The Truth... What is it?





PROSTATE CANCER...as I see it...
AT
LEXINGTON MEDICAL CENTER

DISCLAIMER

 


General Commentary:

You may have recently gotten good news about your, or even a loved one's (with you either being a partner or at least partially in the role of a caretaker), PSA test results or your prostate biopsy results. If so, that's great for you.....for now!!! I started this web file many years ago. It is impossible for me to keep this file complete and up to date. So, I have decided to do what I can to maintain it. Some of the issues discussed are timeless. The most rapidly changing issues are (1) when should biopsies be performed and (2) how can one identify the favorable cancers.

While nearly all men would get prostate cancer if all lived to be 100, NCI SEER data indicates that only about 0.2% of men (2 out of 1000) over age 65 actually die from prostate cancer.

You still may find the following overview to be of interest since at least one-third of men over fifty years of age will get (deal with) prostate cancer in their lifetimes (probably half of those age 60 or older already have prostate cancer they don't know about). Attempts to screen for this cancer have resulted in 2011 in a crescendo of controversy. But, troublesomeness is not so much in the decision to screen for the cancer or not. Over-diagnosis is not the problem; over-treatment is the problem!

If you have, instead, gotten bad news or are awaiting a final determination, this web area is offered in the hopes of helping you deal with the situation. I advise that you immediately begin to collect your own information about your case in your own personal folder because you may be getting more than one opinion. And, there are neat on-line tools you can use that need such information to calculate an answer to your question. And, if you have a large extended family or network of church or other friends you'd like to "keep posted" about the details of your "journey" as you go through this one of life's trials, check out Caring Bridge (previously linked, above) & create your own free, continually updateable website to which friends & loved ones can post notes which you & each other can read. Of course, e-mail lists & social media are other high-tech relationship builders so that those who care can be kept informed.

Before the discussion below, a huge amount of what follows is about how the "system" goes about placing your cancer situation into one of these 3 pigeon holes of tumor-biology risk (but even this table fails to consider age, other medical problems [co-morbidities], treatment option risks, and personal preferences):

May 2007 Amer. Urological Assn. (AUA) Expert Panel  [here]

 riskiness level:

 factors:

 LOW

 PSA=/<10; & either stage T1c or T2a; & Gleason score/sum 6 or less.

 INTERMEDIATE

 PSA=10-20; or stage T2b (but not qualifying otherwise for higher risk); or Gleason score/sum 7.

 HIGH

 PSA=>20; or stage T2c; or Gleason score/sum 8-10.

   

***REMEMBER: PROSTATE CANCER IS ALMOST NEVER A MEDICAL EMERGENCY!***


MOST CASES OF ELEVATED PSA ARE NOT CANCER!...see below:

In most areas of medicine, scientific and practical research are proposing both new tests and approaches to diagnosis & staging as well as suggesting the discarding of older ways. Whether being acknowledged world-class experts in their specialty or being your highly conscientious local specialists, all doctors grapple with controversy and uncertainty as to what to do or not to do. And, standards of practice evolve (sometimes to more conservative & other times to the more radical) as we learn more. Older doctors have seen, hundreds of times, a proposed latest-most-modern-best-method end up on the waste heap of things later shown to be undependable. This is true whether considering how to advise you about your elevated PSA or advise about an actual biopsy diagnosis of prostate cancer.

If I refer to "our program," I mean all (as of early 2009, only one) of our area urologists who take advantage of the services available at Lexington Medical Center. Who am I? [disclaimer, again] I have put this site together primarily for the benefit of friends and relatives who have asked for my input. It is NOT medical advice. It is not for purposes of soliciting "business". If it can be of help to any others, so be it.

WHAT IS CANCER?

Cancer comes in hundreds of varieties which tend to have particular characteristics based on the organ within which it originates. Pathologists are the physician specialists whose job it is to tell/discern cancer from non-cancer and determine the specific variety. Cancers all have the common feature of variably and relatively uncontrolled growth...their cell "engines" are  hyper-metabolic. "Benign" means tissue change or an overgrowth which doesn't, itself, kill. "Cancer" means an overgrowth known to be able to kill. The ordinary prostate cancer is "acinar" adenocarcinoma; most pathology reports simply call it "adenocarcinoma". Over 80% of prostate cancer cases have either multiple cancers in the gland or cancers with small outgrowths away from the main cancer at the time of cancer diagnosis. And  our (the medical system as a whole) ability to define the ones in that =/< 20% minority which are very localized is largely untested.

WHO HAS PROSTATE CANCER?

If a maximum of 30% of males over age 50 harbor prostate cancer from the very earliest to late stages, then about 6250 men in combined Richland and Lexington counties of South Carolina in 1997 (a total population of 500,000) had prostate cancer (whether they knew it or not), a prostate cancer prevalence of 1.3% of our general population. In 1997, 170 were expected to die, and 300 would be newly diagnosed. Of the remaining 5,780 prostate-cancer-containing men, an unknown proportion are already diagnosed and known. The unknown remainder proportion of the 5780 are unaware and undiagnosed! The PSA test may or may not detect them...but this test has made the chances of detecting cancer early MUCH better! And...be aware...many instances of elevated PSA levels are not due to cancer [false positive test] (somewhere between 7-11% of all men tested will have elevated PSA in the apparent absence of prostate cancer).

Because of PSA testing and the appearance of the "biopsy guns" that easily produce "biopsy cores" becoming widely used in the early 1990s, there has been an explosive increase in DIAGNOSIS of prostate cancer that had always been "out there". It used to be diagnosed mostly when at a metastatic stage and was a fatal disease. Prior to 1975, SEER data indicated that 3% of men die because of prostate cancer; and that was also the death rate in 2000. It has been calculated that at least 1,000,000 additional USA men have had a (earlier?) diagnosis of prostate cancer without any decrease in the death rate (hence the interest in "watch and wait" management, see below).

HOW MIGHT A PATIENT THINK ABOUT THIS SITUATION?

Especially in prostate diseases...most particularly as to prostate cancer...the situation is remindful of you and your doctor each trying to look through a keyhole and decide what all is in the room on the other side of the door.  Your doctor has looked through such key-hole situations thousands of times. Especially if he/she is conscientious and fascinated by looking into those particular types of "rooms" (gray-zone situations), he/she will use... as best as possible...his/her own experience in making the assessment and giving advice. You can help by sharing the uncertainty and realizing that (rather than black and white answers) there are mostly gray zones.

AM I CURED?

It is important, as I'll note below, that you remember that statistics should not "rule" your personal, particular case. Upon getting a full diagnosis, no situation is so bad that it is hopeless. My partner had a friend in another state who called years ago (about 1997) with the unsettling news that, on seeing a doctor for back pain, his PSA screening test came back with results of about 140; his biopsies showed Gleason 5+5=10 cancer. Following treatment, his PSA was undetectable until he died 7-9 years later of a stroke. Another patient contacted me that he just couldn't get on with life after treatment because his cancer was 4+4=8 and the "prognosis" was "bad". I asked what his PSA level was: "It is 0.4...BUT that is up from 0.1!! I'm a dead man! I HAVE to get DNA tests on my biopsy because, if it's aneuploid, I really am dead!!" I'd like everyone to remember that a personal cure is a "CURE" until/if there is a recurrence...consider the concept of : "I'm cured though vulnerable". If there is a recurrence or relapse, a remission or actual cure is again still medically possible...and on and on. On the other hand, you might die tomorrow in an automobile wreck! Are you recruiting God to help you cope? Do you have the services of the Savior (Jesus)? [check out some divine healings]

WHICH ARE YOU?

Some patients want to know a lot about their situation and be involved in decision making. Others prefer to rely almost totally on their doctor's direction. Be sure to let your doctor know which type of person you are!

READING AND PERSONAL RESEARCH:

Factors and data valuably used to help in ongoing decision making in your case may not be useful in giving a prognosis (an estimate of your odds of beating the cancer). You can become seriously confused if you use prognosis data/statistics in the place of decision-making data/statistics.

WHO LOOKS OUT FOR WHOM?

In the evolution of our program, we were all well aware of the great numbers of apparently conflicting studies as to the success and complication rates of various types of treatments. It is even considered controversial as to whether prostate cancer should be diagnosed as early as possible! [An excellent book addressing this and some other health screening issues is Should I Be Tested For Cancer?...maybe not and here's why, by H. Gilbert Welch, M. D. , M. P. H.] [comments below] I think that prostate cancer should be screened for and diagnosed as early as a particular patient and his physician think it is prudent to do so. There is no such thing as over-diagnosis (in the sense of catching cancer too early)! OVERTREATMENT, however, is a real problem in the entire field of medicine! In fact, statistical information for prostate cancer having been considered, we still come down to the very highly specific evaluation of a single individual patient: we direct our pathology & lab with a belief in individualized patient care! Our thinking is almost the opposite of situations limiting patient choice such as less knowledgeable medical "gate keepers", insurance companies, corporations, institutions, government agencies, or other entities requiring strict utilization of their own cost-effective or research protocols. It helps immeasurably to be under the care of a urologist interested in cancer & with time to deal with your questions. A highly significant component of whether "satisfactory results" have been achieved rests on the satisfaction of you, the patient.

HOME TEAM ADVANTAGE:

Because of highly varying attitudes of individual patients toward the issues of cancer, radical surgery, radiation, impotence, pain, and urinary incontinence, no particular treatment is considered automatically "best" based on age and presence and supposed extent of cancer, alone. And, even though there are some outstandingly elite or premier programs in the United States for each type of treatment, it is absolutely unrealistic to expect that every patient can go to such a program. Even if they could, expert programs often have very strict research-protocol criteria for entry into a particular treatment method. Such "premier" programs may feel no ethical, financial, or brotherhood-of-community need at all to take on your particular case for treatment. And, many knowledgeable insiders in health care consider (just as the "home team" has certain advantages in sporting events) that local or near-local care has certain strong advantages. "Home team" has to do with local, "point-of-service"...not long distance...medical care [about "point-of-service pathology"].

:::::::::::::::::::::::::Screening::::::::::::::::::::::::::::


SHOULD YOU EVEN BE SCREENED FOR PROSTATE CANCER?

Americans (and human nature) tend to "want to know"...they don't believe in "ignorance is bliss". But, be warned: I estimate that less than one in 5 who have a positive screening test (elevated PSA) will prove to have prostate cancer by biopsy. Elevations can be due to benign enlargement (BPH), chronic prostatitis ("irritation" in the gland), and several other non-cancerous reasons. "Working up" an elevated PSA test result can cost you time, worry, and money deciding when, where, how, and by whom you are going to get to help you get to the bottom of why the PSA is elevated.

SCREENING IMPLIES DEALING WITH RESULTS:

If you are then proven to have prostate cancer, there are a number of different treatments (see below), treatment combinations, treatment facilities, and treating doctors to choose from...a potential source of worry and confusion. Some authorities feel that between 2-23% of the cancers are "insignificant" (too small) at the time of initial diagnosis. By that definition, the first sprig of crabgrass or kudzu is "insignificant". Would you rather kill that first sprig...or at least monitor the sprig... or later try to deal with it after it has spread larger or taken over your yard? Monitoring implies things like watching the PSA velocity & other facets of "watch & wait". Either approach may ultimately spare your yard of an overwhelming infestation. There is yet no way to know in advance for absolute certainty  how big your cancer is. And we, and others, have shown that a big cancer can be in your prostate gland when the biopsy series shows only a single tiny spot of cancer and/or when the PSA is still in the normal range. Finally, the cancer treatments can potentially (not necessarily definitely) lead to (variably manageable) problems with pain/irritation, incontinence, and impotence...a potential negative which some would consider to be a small price for the chance to gain control over a potentially life threatening disease. Others prefer to watch & wait.

GET SCREENING TESTED WHILE YOU ARE WELL!

If a man has (by direct blood kin) a father, an uncle, or a brother who has or had prostate cancer, screening should begin at an early age (for example, age 30-40) with a combination of serum total PSA blood test (Prostate Specific Antigen (PSA)) and digital rectal examination (DRE). In the absence of any such family history, at least the PSA blood test should be utilized on a periodic basis beginning at 40 years in blacks and 50 years in all others. Even if the PSA test result is normal (20% of cancer cases had a PSA less than 4), it is advisable for every man to also have a DRE by age 50. On the other hand, a high percentage of elevated PSAs are not due to cancer...the PSA test, therefore, has a high "false-positive" (for cancer) rate. The  transrectal ultrasound (TRUS) volume/size of the average normal prostate is 20 cc (20 grams...the size of a walnut); a gland is "enlarged" at 30 cc or larger. The PSA level is somewhat related to gland size: 98% of men with a 25 gram (or smaller) prostate have a PSA of 4 or less. If total serum PSA is greater than 10, the cancer likelihood is high enough that many would advise biopsy on that PSA height basis alone.

A fairly small percentage of men run elevated total PSA levels in the absence of biopsy procedures being able to find a cancer...sometimes referred to as PSA "high rollers". This can be extremely frustrating to all concerned. One of my physician friends is currently in this category. Another acquaintance ran a PSA in the 30's for years and had a biopsy series about every other year for maybe 8 years prior to dying with pneumonia. These folks tend to have a stable level with very low PSA velocity. The e-coil MRI (below) or the more high resolution body-coil MRIs may help find the cancer; see "PSA parameters", below.

An example of a test "going by the wayside" (what follows is a 1997 paragraph): I believed that the proprietary "ProstAsure index"  artificial neural network (ANN) test was an unknown/undisclosed manipulation of the patient's age and several lab parameters (including serum total PSA) promoted with misleading marketing brochures. And, because the marketing seemed dishonest to me, I didn't trust the "test". I was disappointed that a renowned prostate surgeon lent his name to this type of unethical marketing in the late 1990s. The test by Global Health Net, Savannah, Ga., does not seem to be available as of a check on it in early 2005.

:::::::::::::::::::::::::Diagnosis::::::::::::::::::::::::::::


WARNING!!! THE FIRST STEP...DIAGNOSIS... IS CRUCIAL!

If you are to have maximized ability to catch the cancer early AND to weigh potential treatment choices, it is crucial to be biopsied well, to have the biopsies be processed for maximum useful information, and to have the information made correctly available for staging and treatment maneuvers. We believe that our pathology program meets these goals; and it was available through all of the Columbia-area urology groups (until about 2006) and the radiology group at Lexington Medical Center. In S. C. and across the nation as of early 2009, most urology groups send the biopsies to owned labs elsewhere for financial advantages or contracted labs to process & ship slides back to urologist offices & have a pathologist not truly connected with the local medical community drive by and make diagnoses in the urologist's office. Worse, a study published in 2011 among academic centers (not point-of-service practices) documented a false-negative (missed seeing the cancer) rate of 1.7% and false positive (over-diagnosis of cancer when not cancer) rate of 0.5%. This arrangement, while possibly being financially advantageous to the urology practice, detours around a very important factor in behalf of the patient: Point of Service Pathology (the value of the diagnosis being made by community pathologists credentialed on the local hospital medical staff & actually being citizens of that community). With advance notice, we may be able to work with a urologist elsewhere to use our system. And our duplicate diagnostic biopsy slides diagnosed locally can be sent ahead for second-opinion evaluation should a patient elect treatment at a program anywhere else in the world. 

Findings justifying (or being indications for) biopsy:

  • if you have an abnormal DRE

  • if you have a PSA velocity greater than 0.75 ng/mL/yr
     
  • if your total serum PSA is greater than 4 ng/mL (if you're 60 years old or older)
     
  • if your total serum PSA is greater than 3 ng/mL (if you're less than 60 years old)

Where indications reflect that it is prudent to do so, prostate tissue biopsies are then undertaken. In patients at higher risk for cancer, the above indications or "triggers" may be "pulled" at a lower level.

PSA PARAMETERS:

The previous general upper limit of normal had been 4 ng/mL. But, in 2004, the NCCN lowered it to 2.5, especially for the mass screenings that had become common. Many set "normal" with age-adjusted grades from less than 2 for men younger than 41 and up to less than 4.5 at age 65. Should the screening PSA blood test be abnormal, the patient could be knowledgeably examined with DRE and ultrasound (U/S). When elevated, there are other parameters which can be considered.

  • Serum free vs. total PSA: In the elevated PSA range up to 20, the "free serum PSA" to "total (or 'bound') serum PSA" ratio may add some focus toward the likelihood of cancer or not. A ratio of .24 or less (24% or less), especially .15 or less (15% or less), means a greater likelihood that the total PSA elevation is due to cancer.  As already noted above, the ratio of "free PSA" and "bound PSA" (see above) may prove to be helpful tests, too. The lower the percent "free PSA," the greater the likelihood of cancer...especially if lower than 15% (but, "silent" chronic periglandular prostatitis can also do this). So, a ratio target below .2 (20%) or less may signal "do biopsies".    
     
  • Density (PSAD): A clear elevation of the "PSA density" (when PSA is 10 or less, PSA value divided by an estimate of the prostate gland volume/size (here)...below 0.15 is comforting, 0.15-0.18 is concerning, & 0.18 or higher warrants a biopsy)...this parameter is less reliable with very large glands whose size can "dilute out" the likelihood of biopsies finding any of cancer (some now tackle this situation with "saturation biopsies"...as many as 20 biopsies taken from the gland at one surgical encounter, either transperineally or transrectally). Only your urologist...who has knowledge of the size of your gland...is in the position to follow PSA density. As of 2005, there is evidence that a man's PSA density (when total PSA is 10 or less) above 0.18 means that there is a 24-fold greater chance that he has a Gleason 7 or higher prostate cancer...a possible way to select only "bad [high risk] cancers" for biopsy.   
     
  • Velocity (PSAV): Prior to a decision to biopsy, the PSA blood test can be periodically monitored (checking the "PSA velocity" &/or doubling time...the best way to catch those hidden cancers with PSA in the normal range), possibly in conjunction with or following an empirical course of antibiotic therapy (in case the elevated PSA is due to infectious prostatitis). Your doctor can follow velocity (but so can you).  [on-line calculator at MSKCC link, below...upper right of page, click on "prostate cancer prediction tool"; next page, at bottom of "disclaimer, click "I accept"; next page, scroll down to & click on "PSA doubling time" and then add in values & dates for your series of PSA test results]. In 7/2004, a velocity of >.75 ng/mL/year was an indication for biopsy when PSA is less than 4 and DRE exam "non-suspicious". By August 2007, the target suggesting "now do biopsies" has lowered to a rate 0.6 or greater for all.
     
  • Doubling time (PSADT): it takes about 35 years for a man with an ordinary gland to double his PSA value; it takes about 20 years for a case of benign BPH to double. An average cancer case caught early doubles every 4-5 years

CORE BIOPSIES:

A standard 1990s in-the-urologist's-office biopsy protocol (begun in 1989) which was believed by many to give the highest chance of detecting any prostate cancer which might be present is called the transrectal (biopsy device inserted through the rectum..."up the butt") "sextant biopsy series"* (on each of the right and left sides, a biopsy is taken of the apex, the mid portion and the base of the gland...six separate biopsies in a pattern) performed with biopsy "guns" under U/S image guidance. The patient begins to get prepared the day before. Each biopsy occurs with such mechanical rapidity that a very high percentage of patients consider the procedure not objectionably painful. So, anti-pain medicine is usually not used for 6 cores or less. Should the first set of biopsies fail to detect cancer, one study shows an additional 30% discovery with a second sextant series. By 2004, some had recommended repeat diagnostic attempts by the transperineal "saturation" approach (see below). Depending on personal preference or specific situations in an individual patient case (such as PSA 10 or less and/or a large gland...some would recommend as many as 18 cores for a gland larger than 80 cc.), urologists may utilize a different biopsy protocol*. Such additional protocols (additionally attempting to biopsy midline, far-lateral, and/or transition zone areas of the gland) are said to have increased the finding of cancer by 30% (by 2006, many of our urologists send 8-14 cores per case). In the PSA range of 2-10, the Vienna nomogram came out in 2005 as a means to help select the number of transrectal biopsies to obtain in a patient with negative DRE & based on patient's age and gland size. Our radiologists began doing temporary nerve blocks prior to biopsies on all of their cases in about March 2007.

Patient preparation consists of the patient:

  • completely emptying the rectum with an enema (such as Fleets phospho) about an hour before the biopsies; and, 
  • starting an oral antibiotic to begin the day before or no less than about 2 hours before the biopsies (note here).


When clinical suspicion or fear of malignancy is particularly high, a "saturation biopsy" approach may be taken under sedation, or with local nerve block, or even general anesthesia, performing 20-50 or more biopsies. We see up to 20 during office-based TRUS; greater numbers are said to be done transperineally through the skin. Something akin to this has been used in selection of cases for "focal cryoablation", see below.

Pathologist "reading" your biopsies:

But, will the pathologist SEE the cancer? And, will their lab operation assure that specimen mix-up does not happen. Our group experience is based on processing a large volume of prostate biopsies (over 500 cases per year) since late 1990. It takes an expertly trained, sharp eye to notice the very tiny spots of cancer in these tiny biopsy cores. Because it is a difficult task, not all of the pathologists in our group were, early on, considered to have the particular personality type PLUS enough experience to "read" prostate biopsies. The most likely danger is in failing to see the cancer in a set of cores. And, it is not enough to just make the binary decision that a case set of biopsies is either just positive or negative for cancer. The scrutiny must be so concentrated and intense that each cancer spot which is present in any of the cores will be found in all cancerous cores. If only some are found, the report could result in under-staging. A lesser, but still real, problem is that of over-diagnosis of prostate cancer. A third danger is that another patient's cancerous biopsies be mixed up and diagnosed as YOUR biopsies. So, we recommend that biopsies be diagnosed by a pathology group with (1) pathologists thoroughly embedded in the fabric of local community interests (not just as employees of a commercial...usually distant...company; I recommend that your biopsies be read by Point of Service Pathologists), (2) external peer review (members of a hospital medical staff, for example), and (3) who regularly deal in a large volume of prostate cases. Some groups with lesser volume and experience protect against misdiagnosis by having all cases "read" by at least 2 pathologists (double reading).

As already stated, the biopsy procedure and biopsy specimen processing and interpretation are extremely important and represent the fundamental foundation for all subsequent decisions. If the urologist is able to avoid tangentially biopsying the gland (and is able to keep the exact biopsy sites well documented), and if the blot-paper, agar-pre-embedding biopsy orientation technique is used (currently [2012], the only pathology group that I know of offering this process in the world is Pathology Associates of Lexington, P. A.....see June 1996 issue Journal of the South Carolina Medical Association*), then one has an optimal chance to actually find the cancer if it is in any biopsy cores. And, in the cancerous cases, one has an excellent opportunity to get an idea of both the quantity and spatial relationships of any diagnosed cancer as a basis to judge cancer size (a great advantage when considering the W&W treatment option, below).

AND, having kept these small tissue biopsy specimen cores perfectly oriented as to which end is deep and which is peripheral (toward the capsule), one might also be able to estimate the closeness of the cancer to the prostatic capsule (we pathologists must be very careful to microscopically confirm blot paper orientation of the cores...the biopsy cores sometimes come out of the needle end-over-end onto the blot paper).

I believe that the alternative core marking system using dyes on the core ends is less dependable because the dye can mask subtle tissue variations that could otherwise help one detect a miss-oriented biopsy core; and fragmented cores can't be kept oriented.

Though these very small biopsy tissue cores allow the pathologist to view only a very small amount of tissue under the microscope, we have studied over 600 cases and found that the cancer detection rate, surprisingly, is about the same as long as the aggregate length of the series of cores on a case is greater than 2.6 cm. Yet we tend to agree with Dr. Stamey that a sextant series is (we say "optimal"; Stamey says "adequate") most encouraging to a search for cancer which seems negative when the cores add up to 5.0 cm. or more in total length.

The Gleason "grade" for primary treatment decision making is interpreted from the biopsies, see below.*

Biopsy problems with "ASAP":

In about 5% of cases in which the biopsy set is not clearly benign, one will find a microscopic cluster of "suspicious glands"...ASAP (atypical small acinar proliferations). About 75% of that 5% can be clarified in-house (in our lab) by using the IHC stain for 34BE12 (keratin 903...K903 or k903) on the biopsy slide. About 10% of that 5% group...after collaboration by two or more of our pathologists...are felt likely to be definitively diagnosable by an acknowledged world-class expert in order to be more sure of a particularly difficult diagnosis; and sometimes we seek that expert opinion right away...other times we await the direction of your urologist or treating or biopsying doctor. Rarely, even the expert remains uncertain of the correct diagnosis, and re-biopsy is possibly necessary. It usually takes such an expert consult less than a week to FAX an answer to us. The other 15% of that 5% group remain in the ASAP category which must then be followed in a variety of ways by those patients' urologists. Re-biopsy may eventuate, sometimes following attempts to "see" the hidden/occult cancer (if a cancer truly be present) with e-coil MRI. Various studies show that from 21-49% of re-biopsied ASAP cases result in a cancer diagnosis.

CRUCIAL POINT: Patience needed!

You MUST BE PATIENT! Accuracy of diagnoses and special studies depend on tedious, methodical efforts; high-pressure pressing for information runs the risk of increasing the chance for error. An analogy: you can't force a gallon of water through a common drinking straw in less than a minute without serious risk of rupturing the straw! 

##########Now, How Bad Is It?###########

SO, WHAT NOW?

Having now diagnosed prostate cancer, a great deal of effort and physician contemplation is now to be directed toward determining whether the cancer is "CLINICALLY SIGNIFICANT" (dangerous in view of your likely future lifespan) versus "NOT CLINICALLY SIGNIFICANT". The Humphrey Formula attempts to alert that a cancer is not likely "clinically insignificant". The Kattan nomogram attempts to predict the likelihood that a cancer is indolent and non-aggressive (the kind that one might "watch & wait" as to deciding treatment). A "basic" and an "enhanced" calculator of the Kattan nomogram is an online MSKCC nomogram that calculates likelihood of indolent cancer (our graphic shows the 1992 TNM stage criteria [the 1997 criteria only two T2 choices, T2a...one lobe/gland-half involved...and T2b, both lobes/halves with cancer]) & some other risk data.

How bad is your situation?

         Treatment recommendations/decisions rest on three broad parameters:

  1. the patient's general health status: the healthy do better than less healthy.
  2. a best estimate of the cancer stage and grade: low stage/low grade does better than high stage/high grade...and, along these lines, whether the cancer is compact (and can be "shot" with an expertly aimed rifle bullet) or is poorly compact (clues = Gleason 4 or 5 component, perineural space invasion, or capsule penetration seen on biopsy or e-coil MRI). Poorly compacted is more likely to be fired on with a "shotgun blast" or "carpet bombing".
  3. the patient's age: younger tend to be healthier & do better than older.

The above three are rules of thumb. Don't be insulted or feel discriminated against...these are generalities. You may be able to provide valuable decision making input to your doctor. If you haven't already...or maybe you want to restate it, then you might be sure to speak up about your philosophy or inclinations (what you fear the most...be brutally honest with your doctor) toward treatment and other decisions. The following staging and grading procedures are considered in addition to an individual patient's particular desires and in consideration of likely remaining life span (had there not been any diagnosis of cancer).


:::::::::::::::::::::::Cancer Staging::::::::::::::::::


Measures:

By way of the height of elevation of PSA levels*; by bone scans*; by ultrasound (U/S) examination*; and by DRE*, the majority of staging (how big is it and how far has it spread?) information is gained. Rule of thumb: "curative" treatment is attempted with cancers believed to be confined (or confinable) to the prostate gland. Note this 1992-criteria staging graphic.

  1. PSA levels: the higher the PSA, the more likely cancer has spread out of the gland.
  2. Bone scan: prostate cancer strongly tends to go to the bones; a positive scan (there are many false positive cases) could mean cancer has gone to the bones.
  3. U/S positivity: an insensitive, but sometimes positive method to show cancer escape from the gland.
  4. endo-rectal-coil MRI positivity: a parameter that can pick up extra-capsular extension.
  5. DRE positivity: an insensitive, but sometimes-positive method to feel both cancer size and escape from the gland.

Also, our unique biopsy processing potentially allows specific interpretation as to the relationship of the cancer to the prostate capsule.  And it also allows estimates of quantity of cancer (the more the cancer, the greater the likelihood it has gotten out of the gland) AND percentages of the Gleason grade patterns (that is, patterns 3, 4, or 5).

MRI: In addition, to maximally avoid under-staging (erroneously thinking we're dealing with a "better" situation when such is not correct), the endo-rectal-coil Magnetic Resonance Imaging (e-coil MRI)* can be utilized and has been part of our hospital's diagnostic array since October 1995 (by 2009, we use a high resolution body-coil MRI in those who are not too obese in order to avoid the discomfort of the endorectal device). In addition, the body-coil MRI* (previously being the ordinary resolution & now the high resolution MRI) is employed to check the pelvic lymph nodes status. In our program, the prostate biopsy findings are uniquely and carefully correlated by a graphic (graphic report example) provided by us to the diagnostic radiologist for maximum interpretation of the e-Coil MRI images. We have been enhancing this MRI accuracy as of 1 Jan. 1999 through the addition of the "phased-array coil". This allows "dual acquisition" of computerized images by the endorectal probe and an external, small acquisition apron placed on the lower abdomen...such dual input is able to eliminate a great amount of "imaging noise" and produce images with much sharper contrast. The combination of fully-oriented biopsy interpretation and e-coil MRI correlated interpretation allows the greatest opportunity to optimize pre-treatment planning: information is gained as to tumor size, exact tumor location, the relationship of the tumor to the capsule, the relationship of the tumor to neurovascular bundles; and all of this allows for a more precise interpretation of stage (a graphic demonstrating the TNM staging system) (from Harvard Med. School and Hosp. of the U. of Penn..."Endorectal Coil MRI..." Urology vol. 51, #3, pages 449-454, in 1998).

Dual acquisition e-coil MRI is helpful in 4 patient situations:

  1. When doctor desiring to locate a likely target for biopsy in PSA "high rollers" (see "screening", above).
  2. Those who appear to have small cancers (by biopsy findings and normal-range or only mild elevations of PSA) without "significant" Gleason 4 or 5 component, in whom radical surgery (or even "watch & wait") is desired but want extra assurance that cancer has not penetrated the prostate capsule...has not already progressed to level T3 disease.
  3. Those who seem, on the basis of a lot of biopsy positivity for cancer, to have a lot of cancer (large cancer size) but without high PSA levels, without significant Gleason 4 or 5 component, and who desire radical surgery or closely focused radiation therapy (seeds, 3DCRT, IMRT, IGRT) but want extra assurance that cancer has not penetrated the prostate capsule...has not already progressed to level T3 disease; and,
  4. those incidentally found to have "a little bit of cancer" in their TURP specimen (to help give an idea of the extent of cancer in the gland as an alternate to biopsies; TURP removes tissue in the center of the gland and toward the base...cancer usually in gland periphery).

Yet, even as of July 1999 *(still, in 2007, I think our program is the only one in S. C....certainly central S. C....using this), there continues to be a strong impression among many of our area urologists that e-coil MRI "is not that good"..."you don't hear anything mentioned about it in state, regional, or national continuing education meetings."

Additionally, where radical prostatectomy is contemplated and node sampling may be required, laparoscopic* pelvic lymph node biopsies may be obtained prior to any major surgery (we don't see this done anymore as of about 2003); or, the nodes can be tested during surgery by frozen section (we commonly participated in this but not frequently since late 2005) exam * or as part of the ordinary postoperative pathology staging exam done on all removed tissue.

ProstaScint* studies...radioimmunoscintigraphy... in nuclear medicine are a newly approved (about 2002) way to pre-operatively look for lymph node or bone metastases: an antibody is locked to a radioactive tracer, and the antibody attaches most avidly only to prostate cancer cells. The aggregated attached molecules then "light up" any PSA-positive cells so that the nuclear medicine camera can "see" it. It is said to be 15 fold better than CT scans and 5 times better than body-coil MRI scans in detecting lymph node metastases and exact recurrence locations...and may find a metastasis even when serum PSA not elevated. It is a test with a considerable false negative rate but low false positive rate. We have even picked up an unexpected isolated skull metastasis in one case in late 2004.

PET Scanner* studies use an F18 radioactive glucose injection, "FDG", to locate "hypermetabolic" tissue...such found areas almost always being cancer (for example, finding cancerous lymph nodes)( very expensive instrument and support personnel; available in relatively few cities). At Lexington as of Sept. 2002; full PET scanner here as of 2003.

"Coincidental" Scanner** studies use a much less expensive arrangement to perform...using the same isotope...almost the same search that the PET Scanner performs, but with a little less detection ability. As a "poor-man's PET scanner," this test is available in many more locations.

The above measures are often not warranted. In some situations, some additional diagnostic determinations are used in trying to factor in some risk information relative to the likelihood that pre-treatment staging might not be "what it seems": additional tumor characterizations may be performed on the cancer in the biopsy specimens, as follows:

 

ADDITIONAL KEY OBSERVATIONS:

CANCER GRADE: HOW BAD, HOW VICIOUS, AN ACTOR IS YOUR CANCER?

But, the additional key question revolves around whether it is a "better" or "worse" (meaner) cancer...the GRADE of the cancer (remember, "grade" is determined by the pathologist). If the tests on the biopsy suggest a "worse" cancer, this can influence a change in treatment choice. If the biopsy shows a "better" cancer, then we continuously know and keep in mind that there still could be undiscovered/undisclosed "worse" cancer in the untested areas of the gland (the gland still being in you). Grading is according to the Gleason system.

Gleason (sum) score:

Gleason reporting details:

Latest prostate pathology textbooks suggest the following reporting rules, to include separate scores for each separately labeled biopsy core having any cancer:

  •   if only one pattern, report such as 3 + 3 =6.
     
  • if two patterns, at least report perceived dominant first and minority one second (we try to estimate percentages & it is VERY valuable in cases with a score of 7, such as:
      4 (60%) + 3 (40%) = 7.
     
  • if 3 patterns:
     
    in biopsies: sum the dominant plus the highest grade pattern of the next two (even if highest is quantitative minority), such as:  3 (50%) + 5 (4%) + 4 (46%) = 8.
     
    in radical prostatectomy: only requires summing the two most prevalent patterns...but one should mention any 3rd (minority) 5 pattern because higher PSA failure rate.

Gleason score "badness":

One way to try to grasp the concept of "grade" expressed as a Gleason "sum" or "score" is to think of dogs and wild wolves. A domestic, nice lap dog usually doesn't bite...it may bark a lot and be scary. It's bites could hurt, and rarely there is a death due to such dogs [these are like "sum" 2 thru 5, well differentiated]. If at least trained and controlled, larger, common pet dogs seldom kill but do so more than the lap dogs [these are like the "sum" 6, moderately differentiated]. "Sum" 7 is more like a German Shepherd, Rottweiler, or pit-bull, capable of killing...it is just hard to know which are "nice" and which are killers. "Sum" 8 thru 10 are like a pack of hungry, wild wolves, and you are alone at the camp site. You are in need of weapons, and you need them now !!!

Note the % dead in 15 years IF NO TREATMENT at all:

1.     Gleason score (sum) 2 thru 4,.... 4-7% dead in 15 years

2.     Gleason score 5,............ 6-11% dead in 15 years

3.     Gleason score 6,............18-30% dead in 15 years

4.     Gleason score 7 (but 4 + 3 = 7 is worse than 3 + 4 = 7),............ 42-79% dead in 15 years.

5.     Gleason score 8 thru 10,... 60-87% dead in 15 years

Has the "horse" gotten out of the barn already?

What is the probability, by Gleason score alone,  that the cancer is still locked inside the prostate gland? If biopsies show:

1.     Gleason score 2 thru 4,......... 74% probable that it's "locked" in the prostate.

2.     Gleason score 5,................. 58% probable that it's locked in the prostate.

3.     Gleason score 6,................. 53% probable that it's locked in the prostate.

4.     Gleason score 7,................. 29% probable that it's locked in the prostate...(but 4 + 3 = 7 is worse than 3 + 4 = 7).

5.     Gleason score 8 thru 10,........ only 17% probable that it's locked in the prostate.

 

What if you consider Gleason plus other factors?

You can take your Gleason score, PSA value, and the stage assigned so far by your urologist and see a more specific probability rating of (1) still locked in the gland, vs. (2) probably out of the gland, vs. (3) probably gone to lymph nodes by going to the Partin Tables (nomogram) in the Johns Hopkins web site. Or with biopsy pathology report alone (if it contains sufficient detail), you can use the Hamburg algorithm to see your risk that cancer has gone to the pelvic nodes.

What about proportion of Gleason 4 & 5 pattern?

Dr. Stamey, as have others, showed in 1999 (JAMA 281:1395-1400, April 21, 1999) that the percentage of any Gleason 4 or 5 component and cancer volume/size are the strongest predictors of disease progression. He translated the study to give meaning to the Gleason grade within an ADEQUATE (sextant or more, aggregate biopsy length of 5.0 or greater centimeters...2 inches) set of biopsies, as follows:

  • Bad-grade cancer: If the biopsy-revealed that cancer had 20% or more Gleason 4 or 5 component, then the gland remaining in you has about a 90% certainty of also containing this much "bad" component and, therefore, has a significantly increased surgical treatment failure-to-cure rate. This strongly suggests an increased failure likelihood for other types of closely focused treatments (low-penetration seeds, too tightly focused 3dCRT, IMRT...even if image guided IGRT, nerve-sparing radical surgery, PBT, or too conservative cryosurgery). And these cases are not candidates for "watch and wait" unless there are compelling reasons to very carefully do so. Some will use the above in such cases and concomitantly cover with androgen deprivation therapy.
     
  • Good-grade cancer: If biopsies have no 4 or 5 component, then there is 90% certainty that the gland remaining in you has no "bad" component and, such patients might expect only a 5.6% likelihood of treatment failure.
     
  • Uncertain cancer: If biopsies have some Gleason 4 or 5 component, but less than 20%, it is a gray zone.

NOTE: While Gleason percentages seem to be a powerful bit of information, your doctor must specifically consider all other of YOUR factors!

Gleason score has an influence on choice and intensity of treatments. As some rough and quickly potentially obsolete examples:

1.     Gleason score 2 thru 6: might choose "watch and wait", or ordinary external radiation dose, or radical prostatectomy , or radiation seeds, or treatments relying on high probability the cancer is still locked in the gland. Will probably not need added hormone suppression. So, the pathologist must be careful to not undergrade the Gleason score. Gleason 6 or less often best candidates for "focused" treatment...shoot it with a rifle.

2.     Gleason score 7: might choose ordinary external radiation dose, or radical prostatectomy , or radiation seeds, or treatments relying on high probability the cancer is still locked in the gland. Hormone suppression therapy possibly needed. It is so important that the pathologist detect ANY Gleason 4 or 5 component, because that information will likely cause your doctor to add on hormone suppression (giving a 50% increase in survival advantage) and be a factor against using just seeds or other intensely focused treatments.

3.     Gleason score 8 thru 10: will likely choose "shot gun" or "carpet bombing" approach of increased external radiation dose, or possible radical prostatectomy , or probably not radiation seeds or treatments relying on high probability the cancer is still locked in the gland. Hormone suppression therapy probable.

The Gleason grade is assigned by a pathologist* looking at the biopsies under a microscope; and it is a numerical assignment of the cancer pattern scores, it usually being expressed as numbers (such as, 3 + 3 = 6). Pattern scores range from 1 to 5, and the major (the greatest quantity) pattern plus the minor (the lesser quantity) pattern are added up to calculate the grade "sum". A grade "sum" of 5 or lower is "better"; a 7 or higher is "worse". A 6 is "average". The American Joint Committee for Cancer Staging, 5th Ed.: "sum" 2 thru 5 is "well differentiated"; 5 thru 6 is "moderately differentiated"; 7 is "moderate to poorly differentiated"; and 8 thru 10 is "poorly differentiated". Some consider any major or minor pattern score component of 4 or 5 as being worse. Therefore, you might occasionally see a cancer scored, as an example, 3 (60%) +5 (5%) +4 (35%)+=8...in order to let your doctors know that there is also a little bit of Gleason 5 pattern in the cancer. Studies have shown that, left entirely untreated, the following are the percentages (also see above) of survivors at 15 years after diagnosis (but keep in mind that scores on biopsies may under-represent the score of what remains in the gland, see below): Gleason scores 2 thru 4, 93-97%; Gleason score 5, 89-94%; Gleason score 6, 70-82%; Gleason score 7, 30-58%; and Gleason score 8-10, 13-40%.

Former Mayo Clinic pathologist, Dr. David Bostwick, reported over a decade ago a tendency for pathologists to under-grade (diagnose it "better" than it actually is) the Gleason score (Am. J. Surg. Path. 22:1169-1170, 1998). I feel that under-grading is more likely from pathologists seeing an insufficient volume of prostate cases and/or lacking a primary interest in prostate cancer. Our group has standardized our scores...and guarded against undergrading...by way of training time one of our group spent with Dr. Gleason plus tutorial time another of our group spent one-on-one with Dr. John McNeil at Stanford: these experiences are integrated into the practice of our group. The group then underwent comparison grading on numerous cancer cases. And we have access to, and practice on, the Johns Hopkins grading tutorial. Yet the toughest place for consistency is between a pattern 3 & 4...which makes the difference between a score of 6-8. I think it wise to let the report express any reservation about choosing an interpretation of Gleason 6 rather than 7. We always assign a Gleason score to your cancer. The higher the score, the more likely the cancer is out of the gland.

"For profit" Commercial Labs and Advertising:

I don't believe that the Wall-Street-owned or privately owned commercial or entrepreneurial labs & their employee pathologists are sufficiently grounded in a local community of referral doctors (or bonded in local citizenry with the local population) to have the kind of "point-of-service" attitude & concern that is in the best interest of patients...particularly on (1) some of these critical Gleason determinations and (2) the finding of small quantities of cancer in the biopsies. You can always request (just call the diagnosing lab and make an official request...or have your urologist's office do it) that any lab obtain a second opinion on your case. We would be happy to give second opinions [how to]; or, you can have them obtained from expert uropathologists in centers such as Johns Hopkins,  Mayo Clinic, Cleveland Clinic, Stanford, and others. Studies attempting to portray reliability of commercial diagnostic lab assignment of Gleason scores by comparing biopsy scores with scores found in radical prostatectomy specimens are of limited value (but, Dr. Stamey's, above, is valuable) because they do not account for all of the cancer cases not resulting in radical prostatectomy. I believe that for-profit commercial labs who use this type of deceptive and misleading advertising are using unethical and deliberately-misleading tactics.

 

Perineural Space Invasion:

Proliferation Rate (how fast it is growing):

Ki67 proliferation marker: this third biopsy determination can be an added double-check on the Gleason score. This is an immunohistochemical (IHC) marker stain which can be applied to the malignant biopsy if there is debate as to the correct Gleason score...especially as to whether there actually is significant 4 component. There must be a minimum of 500 stainable cancer cells. If greater than 7.5% of the cancer nuclei are positive, a study elsewhere of almost 100 patients showed that their tumors behaved aggressively (like Gleason 8-10). Immediately after the published study of 8/98, we used this test on a case of 4(70%) + 3(30%)=7 in order to see if we should better just interpret the case as an 8. We have seldom seen the need to perform this test . However, in late 2003, a report came out to the effect that increased rates of treatment failure happen when the rate of Ki67 positive nuclei is 7.1% or higher.

DNA testing:

The fourth biopsy determination is "DNA ploidy"***: a determination of "diploid" is "better"; any other determination may be "worse"; ploidy has to do with chromosome status. Many consider that the DNA ploidy is just another way of reflecting the Gleason score and is not an independent signal of "better" or "worse". DNA ploidy can be very difficult to determine accurately on tiny spots of cancer within these hair-like biopsy cores (and may...no one is certain...only be of use when treatment is non-surgical). We have only rarely attempted this test; and we can only currently attempt a determination on RE-BIOPSY specimens solely used for DNA analysis. (We are almost never involved in such DNA requests).

P27 proliferation "brake" marker:

Another marker coming out in late 1998 is for P27...said to be a cell protein which modifies the rate of cell proliferation...holding proliferation somewhat in check. Initial work suggests that tumors low on P27...having "weak brakes"...grow and spread faster and easier than tumors with adequate levels. This is determined on biopsies (we have never had a request for this test as of Sept. 2010).

rt-PCR-PSA test:

I was disappointed that the American Cancer Society, about 3/96, reported this test to the media as if it were the greatest break-through ever. We have significant doubts that this blood test can play any reliable role in pretreatment staging estimates because the technique detects and amplifies extremely minute quantities of PSA protein antigen. The idea was that, if the test was "positive", cancer had already gotten into the bloodstream. The significance of such is totally unknown because it could be that this cancer antigen is periodically shed into the blood by cancer still restricted to the gland. 

Summarize Your Cancer Riskiness Situation:

  • FAVORABLE/better situation : (a) good life expectancy otherwise, (b) Gleason score/sum 6 or less, (c) PSA 10 or less; and (d) staging T1c (positive biopsy & negative DRE) to T2A (palpable...positive DRE...& in half a lobe or less)...no evidence of node or distant metastasis (the above affirmed May 2007 AUA...J. Urol. 177:2106-2131). I would personally also want to have the e-coil MRI to be sure no obvious capsule invasion or malignant component that is MRI-visible but not producing its share of PSA.  In "favorable", all treatment options are in play, including expectant management if: (1) patient can stand the idea & (2) small lesion...no worse than T1c (controversial if younger than 60)...(best if evidence =/<0.5cc of cancer, something like cancer in 2 or fewer cores of at least 12 cores [unless gland not large enough for 12 biopsies] and no core more than 50% cancer...PSA density =/< 0.15ng/ml/cc). There has been a series of research studies attempting to find other concretely objective analyses that can confirmatorily suppliment the above favorable parameters [check highly technical examples HERE].
     
  • intermediate/uncertain: good life expectancy otherwise; Gleason score/sum 7; PSA 10-19; and staging T2B/T2C. 
     
  • poor/worse/high-risk: good life expectancy otherwise; Gleason score/sum 8-10; PSA 20 or more; and staging T3 or worse.

Summary Point:

Your doctors try to categorize your cancer situation as "better", "worse", or "uncertain" in order to plan your treatment and management.

HOW LONG WILL I LIVE?

No one can truly tell you how much time you have left; if pushed by patients or family, many doctors provide educated guesses. Remember, you could live to age 100; or, you could die in a wreck next week...with or without cancer.


:::::::::::::::::::::::::Treatments::::::::::::::::::::::::::


Statistics speak for a large group...you are singular/unique! So, statistics are only a guess for you:

It is vitally important for the patient to understand that published statistics as to various treatments only represent a source of IMPERFECT, after-the-fact, possibly-seriously-outdated information. And that his own case is not, itself, part of some statistical analysis. You, the patient, represent a statistical universe of only one case! Therefore, a tremendous amount of the patient's contribution to treatment decisions and his ultimate satisfaction rests with his own understanding of what he fears the most (cancer, surgery, radiation, chemo, "not knowing") and what he suspects he can best tolerate. Remember, he is now facing "dealing with" cancer for the rest of his life. How can you rest easiest while dealing with it? Take the factor of impotence: taking away any treatment or proposed treatment, even taking away the fact of cancer, this dysfunction is extremely related to both mental and blood vessel factors, anyway. In short, don't get "hung up" on statistical figures much beyond "unlikely", "occurs commonly", and "very likely to occur". Besides, complications, such as impotence, can take on a totally different meaning with drugs like Viagra appearing on the market.

Doctors must consider the ENTIRE You:

Treatments are selected or advised according to an overall analysis of the patient and situation, a key bit of info being hard for us pathologists to know is (1) such as the Charlson co-morbidity index (CCI)...what kind of medical "shape" you are in... to help in treatment choices [online calculator]. Then there is a careful analysis of (2) the PROBABLE stage (how big and how far the cancer has spread) and (3) Gleason grade of the cancer. A treatment strategy may be "for cure"; if the cancer stage is too high, a treatment strategy may be designed "for palliation" (making the best out of a probably fatal situation). In between is a large group treated for "control" of the cancer...to delay progression of a probably-not-fully-curable cancer. Also, one might elect at first to just "control" a cancer for a year or two in order to evaluate treatment options at a later date, potentially taking advantage of future newly approved treatments. Part of a treatment strategy may be directed toward local control or elimination of cancer; another part of the strategy may be for systemic (body-wide) control or elimination of any known or suspected cancer. Finally, one must carefully consider an initial treatment choice, keeping in mind what possible secondary treatments might be available later should the first treatment strategy fail. Following is an incomplete list of initial treatment choices.

TREATMENT-DECISION BLOCK:

Many patients become decision-paralyzed with information gathering and information overload that still leaves them in this gray zone of indecision...it just won't come up black or white! And they fervently desire that an expert were to appear who will say, "We have thoroughly analyzed your case, and there is no question that there is one and only one best treatment for you." Almost always, there is more than one choice: remember, specialists tend to be honestly biased and more confident toward that which they do best. So, you will probably never be a satisfied patient until you accept responsibility for being a full partner in making the choice. Also, remember that you, too, have a prejudiced mind-set (some minds are set against or in favor of certain kinds of treatment just as some gardeners believe in pesticides and some in natural pest control, some in digging weeds...to include all of the roots...out, and some in using herbicides).

FIVE INTERNET SOURCES POSSIBLY HELPING TO ORGANIZE YOUR THINKING TOWARD DECISIONS...COMPUTER DECISION AIDS:

  1. Prostate Cancer Profiler is a site you can register in and plug in your case information and try out some treatment scenarios (can do this for bladder, breast, colonic, prostate, and melanoma skin cancers)  
     
  2. Prostate Cancer Research Institute (PCRI) is a site with lots of decision aids (many on-line nomograms) and educational material...especially pre-treatment decisions such as to "active surveillance" of "low-risk" cancers.
     
  3. CHESS Prostate Cancer Module of the U. of Vermont Medical Center, Fletcher Allen Health Care  System.
  4. National Comprehensive Cancer Network is an informational site which includes decision trees as a decision-making tool. On the home page, point to the  "patients" area near top & note the drop-down list & click on "patient guidelines". It will take you to a new page; scroll down to near the bottom and "click" on Prostate Cancer. This takes you to a page with a menu on the left (or, you can scroll to the bottom and select from a different menu...same topics). Select and "click" on "decision trees".  
     
  5. Memorial Sloan Kettering Cancer Center (MSKCC): Check "nomogram"...pick prostate. There is a pre-treatment tool to help decide among the choices for treatment options; other nomograms help decide prognosis. Others help you insert your PSA levels and testing dates to check the PSA velocity and doubling time.

TREATMENT OPTIONS LIST, PRIMARY DISEASE: 

CH's website thumbnail overview of the common treatment options.

  • Watch and wait:* Also called "watchful waiting", "active surveillance", "proactive monitoring", "expectant management", or "expectant management with curative intent"; PSA checks (PSA velocity) plus close urologist follow-up by way of DRE and U/S (maybe annual biopsies).
  • Surgery:* open, manual or robotic laparoscopic, radical removal with bilateral nerve sparing.
     
  • Surgery:* open, manual or robotic laparoscopic radical removal with one-sided nerve sparing.
     
  • Surgery:* open, manual or robotic laparoscopic radical removal without nerve sparing.
     
  • Radiation:** open-abdomen, operative (retropubic free-hand) radiation seed implant brachytherapy (now probably considered old-fashioned).
     
  • Radiation:** U/S-guided radiation seed implant [permanent] brachytherapy: high penetration isotope (e.g., gold).
     
  • Radiation:* U/S-guided radiation seed implant [permanent] brachytherapy: low penetration isotope (e.g., iodine or palladium).
     
  • Radiation:** U/S-guided high-dose-rate (HDR) [temporary] brachytherapy (hot "seeds" via catheters).
     
  • Radiation:* External beam radiation (2-D) therapy (XRT). With or without initial 3-D field planning (3DCRT), (with**) or without IMRT (3DCRT plus modulating...varying...the dosage, depending on tumor shape variations in your tumor), with or without IGRT (IMRT plus a CT recheck of tumor shape & position at each radiation session).
     
  • Radiation:** Intensity modulated radiation therapy (IMRT)...closely arranges radiation to prostate & relatively spares the surrounding tissue. But, structures move (for example, during breathing). If so in your case, respiratory gating may be used. And image guided techniques at each radiation session may be used with the IMRT (IGRT).
     
  • Radiation: Cyberknife (highly focused robotically aimed external radiation with gating...sometimes called "radiosurgery)...has advantages over the Gammaknife. Not any surgery at all.
     
  • Radiation:** Proton Beam Therapy (PBT).
     
  • Medical:* combined hormonal deprivation (CHD), sometimes known as "total androgen blockade".
     
  • Freezing:* ultrasound guided cryosurgery, both as to total gland cryoablation or as focal cryoablation.
     
  • HFU: High frequency ultrasound (street lingo = "high foo")
     
  • Planned combination sequences.*
    a.  Pre-radical-surgery neoadjuvant CHD.*
    b.  Combination seeds and XRT.*,**
    c.  Other sorts of combinations.*,**
  • Fall-back" combination sequences or salvage procedures.*,**
  • Other treatment maneuvers:*,**
    a.  Bilateral orchiectomy (castration)*
    b.  Radioactive strontium*
    c.  Spot XRT to bone lesions*
    d.  Vaccine therapy (Johns Hopkins University)*
    e.  Anti-proliferation therapy with calcitrol: alone or in combination with CHD, this anti-proliferation drug has been used to slow the growth of tumor...a delay-progression tactic.
    f.   Chemotherapy*. even though it's not standard procedure, a piece of metastatic cancer...if it can be surgically obtained...can be forwarded to a laboratory (Oncotech) for extreme drug resistance testing (EDR) so as to avoid toxic chemotherapy that would have a high percentage chance of not working. Our lab participated with Oncotech until about 1999... but almost never as to prostate cancer.
    g.  Super-radical salvage surgery such as total pelvic exenteration (very rarely chosen).** or maybe salvage cryosurgery...cryoablation.

Good layman articles about how they made their choices in May 13, 1996 issue of Fortune magazine. 

Some Rules of Thumb About Each Treatment:

  • Watch and wait (W&W): This "active surveillance" or "expectant management with curative intent" is the only "treatment" which is entirely free of treatment-induced side effects. You must be the type of patient who is totally reliable about playing by the rules. Only if the Gleason score is "better" and if all staging criteria otherwise strongly suggests a small, prostate-gland-confined cancer (a favorable case). Especially if you are old enough or have other serious health issues making it unlikely that you have more than 5-10 years to live, otherwise...AND, if you can tolerate knowing that the cancer resides in you...this could be your choice. All other treatment options continue to remain available at all times while you do "W&W". Dr. Gleason (JAMA 280:1034, 9/98) reports that...based on a study of 767 men; those with a score of 7 to 10 have a high risk of death from the cancer; those with score 5 or 6, have a more modest risk. While you "watch and wait", you have time to "educate" yourself about future game plans. Your risk lies in the imperfection of our ability to be perfectly sure of your cancer stage and "better" versus "worse" Gleason grade and case type/status. W&W is an approach more likely for those aged 75 or older (BUT, some [see PCRI] are working this with much younger, highly motivated men). Or it can work for those who strongly want to avoid treatments and in whom it is estimated that the cancer is no larger than 0.5 cc. and PSA doubling time is known to be higher than 3 years. In one of our nation's most prestigious medical journals is this case diagnosed at age 55 & dramatically cancelled surgery & then re-evaluated & staying with W&W at age 65...all issues discussed...see if your hospital or local public library can get a copy for you if REALLY interested in W&W [reference].

    As sort of a double-check on your decision to W&W (especially if your cancer has any Gleason 4 or 5 component), you might consider monthly to quarterly PSA tests, beginning 3 months after biopsy, during the first decision year: if PSA is stable or barely increasing, this suggests a safe decision. If it is increasing, try to figure how long it would take to double at the present rate [a PSA doubling time is actually usually a logarithmic rate...the PSAdt]. If it looks like it might take only as little as 18-24 months for your PSA to double, then you are in danger of cancer progression in as little as one year. If it looks like the PSAdt is greater than 3 years, then there is a suggestion that the cancer won't progress for more than 3 years [the report on this...Cancer, 1998, 82:342-348... checked on 113 men with starting PSA of 21 or less].

    A December 2004 report (J. Urology, vol. 172, p.2193-96) suggests W&W is reasonable for men with "favorable" cancers of "small volume". Favorable is: PSA less than 10, clinical stage no worse than T2a, and Gleason score no worse than 3 + 3 = 6. Small volume is: T1c, PSA density of 0.15 ng/ml/cm3 or less, and cancer in only 2 or fewer cores and never more than 50% of any positive core. A majority (93%) of the men who fit the W&W criteria in this report were able to just W&W. The W&W program at Johns Hopkins indicates a belief that at least 80% of men who fit this small volume data set actually have small volume cancer; and they confirm the above with at least a 12-core-biopsy pattern, if gland large enough.  Annual biopsies are part of that program...part of the parameters that are "watched" to detect progression. If progression (JHU = more than 2 positive cores or >50% of core cancer, or Gleason changes to 7 or higher or unusual increase in PSA), then treat with curative intent.
  • Radical Surgery: This is a classical "go for the cure" strategy for those desiring to wage their fight with surgery. Best candidates are typically 60 years old or younger. If there has been previous disease scarring or pelvic injury affecting tissues near or about the prostate, any surgery may be fraught with elevated risk of complications. Also, odds are best with those cases showing evidence that the cancer is confined to the prostate gland (lower elevations of PSA, biopsy findings negative for risk markers of extra-glandular spread [cancer in the capsule boundary and/or perineural lymphatic positivity, DRE or e-coil MRI or MRS indication of extra-glandular extension, and a Gleason "sum" or score containing any significant amount of 4 or 5 component]). Magnetic resonance spectroscopy (MRS...MR spec) is becoming available in some places (as of 2006) to help double-check size and location of the cancer (potentially allowing focused...IMRT/IGRT...radiation "boosts" to the localized area)...MRS is in our area as of 2007.

    As of early 2005, open suprapubic (going in above your pubic hair line) radical prostatectomy (OSRP [radical retropubic prostatectomy...RRP]) is the standard most urologists perform...done extra-peritoneally. Simply because training programs teach it far less frequently, transperineal (going in through your bottom between the scrotum and anus) is an option. Transperineal prostatectomy has poorer (no?) access to lymph nodes & should be done by a urologist with regular experience with this approach. The first laparoscopic (avoiding opening the abdomen) prostatectomy in S. C. [S-05-1406] was performed at our hospital. Air is put into the abdominal cavity; resection is done extra-peritoneally. A hot topic (developed at Henry Ford Hospital in Detroit) in early 2005 is "da Vinci" (other robotic assistants are ZEUS, AESOP, & Robodoc) "robotically assisted laparoscopic radical prostatectomy" (RALP), even with nerve sparing. The robotic technique is (as of early 2006) a marketing "flag"; but, it can do some anastomotic "wrist action" that is hard for all human laparoscopic surgeons to do as easily (for the urologist) in a small space. Patient fascination & marketing hype are responsible for many patient choices to go for the "robot". Check these factors before you think you will have an all-knowing R2D2-type robot operating on you! It is way too soon (2007) for longer-term data to prove that RALP has outcome data even equal to OSRP. RALP cannot be performed if other preceding abdominal surgery or disorders have caused scarring (adhesions) in the abdominal "insides". RALP came to our area in 9/2007. By 2012, we know that...as with most endeavors...experience counts greatly with robotics (Fox News "House Calls", Marc Siegel, M. D. 4/15/2012): Dr. David B. Samadi at Mt. Sinai has developed the SMART ("bloodless prostatectomy") technique with amazing positive statistics as to continence & sexual function.

    For persons who are particularly obese, transperineal prostatectomy (entering between scrotum and anus) may be "the method" and usually performed by only a few urologists at major referral centers.

    All choices are major surgery, and blood loss could be significant and require a transfusion (especially with the open methods). However, transfusions of banked blood can be avoided in the hospital which has: an autologous blood program,* intra-operative hemo-dilution blood program,* and a blood-cell-saver program* so that your blood loss is replenished by your own blood. Deep anesthesia is used. There is a lot of current interest in pain management. Some surgeons inject the tissue sites around the prostate with a local agent such as Marcaine and follow this with post-operative pain medications which include an anti-inflammatory component. Additional or alternative post-operative pain is expertly manageable in hospitals with IV patient-demand continuous pain medication (PCA*)...patient-controlled anesthesia...(on it for about 3 days followed by oral medicine for residual pain control) and/or a program of continuous post-operative epidural pain block* (for about 3 days followed by oral-medicine for any residual pain control). However, epidural pain block can sometimes lead to very sluggish intestinal recovery; and, it is very difficult to rationalize discharging a patient from the hospital who cannot yet properly eat or defecate. There is a slight chance of death surrounding the stress of surgery. Hospitalization averages 3-7 days. There is an 80% chance of at least temporary impotence during the 1st post-operative months and a 30-50% chance of permanent impotence. There are both medical and mechanical means of dealing with impotence, if it occurs.*

    Sparing of the nerves to one or both sides of the prostate may decrease the odds of permanent impotence in about 50% of cases. We have had brief experience in about 1997 with CaverMap, an intra-operative electronic stimulator wand-like gimmick for trying to detect the nerves involved with erection. It worked clearly in only 20% of cases. Our surgeons felt that experience and a clear knowledge of anatomy, balanced with a clear knowledge of all of the factors particular to you and your case, are the best approach to a careful and expeditious nerve-sparing procedure. The e-coil MRI exam may be most helpful in planning for radical surgery, particularly in helping to plan the likelihood of successful nerve sparing. The two programs below probably have the greatest experience at nerve-sparing radical prostatectomy.

    Laparoscopic surgery tends to allow a more rapid postoperative recovery. The robotic assistance allows a little better surgical "wrist action" in forming a smoother anastomosis such that the postoperative catheter tends to be removable earlier. These are not guaranteed advantages and may not be big advantages. It will take years to gather data to prove that recurrence rates are no worse than open prostatectomy. I think that the rush by many internet-savvy newly diagnosed prostate cancer patients to fly to places to have robotic-assisted laparoscopic prostatectomy reflects the fascination of the Star Trek generation with the possibility that robots can outperform humans (forgetting that there is a fallible human operating the robot...just as a jet pilot operates a jet airplane). Unless a hospital program can do about 150 or more cases per year, the procedure tends to be sort of "break even", institutionally...unlikely to last in lesser market places.

    Radical surgery is the only treatment allowing us the extra advantage of knowing if what we estimated, "looking through the key hole", was correct...and that comparison only when the surgery specimen is examined by a knowledgeable, interested, and thorough pathologist*. If the "key hole" grade estimate was faulty, we can find out and adjust the management game plan (the grade gets "up-graded") towards the future.

    The odds of annoying or significant post-operative complications such as urinary incontinence or urethral stricture are low and manageable.

    BUT: If the pathology exam indicates cancer in the surgical margins or risk that cancer was left behind, XRT can be added postoperatively. It is advised by some to do the XRT without necessarily waiting to see if the PSA  rises. But, don't do it prior to  postoperative recovery from urinary incontinence (usually not prior to 3 months...but I'm told that an early 2006 report suggests that its best not to delay).

    Premier Programs in the U.S. include: Dr. Tom Stamey's @ Stanford University, Stanford, California and Dr. Pat Walsh's @ Johns Hopkins in Baltimore, Maryland.
  • Radiation Seeds: Rule of thumb: if you have previously had a TURP for any reason, you are unlikely to be a candidate for seed implant because the complication rate is so much higher. Called "interstitial radiation therapy" or "brachytherapy", seeds of every type can now be accurately placed into the gland with U/S visualization. Radiation beams into gland from within the gland. The advantage here is the delivery of a compact, high dose of radiation while limiting exposure to surrounding structures such as the rectum. With a decision for seed therapy (whether permanent or HDR), precise prostate volume and shape measurements must now be made with another U/S session, see differences, below. IMRT & IGRT accomplish about the same thing but deliver from externally.

    In order for treatment success rates to be comparable, the 10 year survival rate is the key benchmark. Much data is available on gold seeds, the actual "gold standard" (short half-life, deep gamma penetration) by which any other radiation seed survival data will eventually be compared. However, even with gold seeds, much of that older survival data was based on open-abdomen, operative seed implantation which could not be as accurate as modern transperineal implantation by U/S guidance. Newer isotopes have some attractive features, but survival data has accumulated for a lesser period of years. Note that use of a high-penetration isotope such as gold will not demand as much precision, meticulousness, and compulsiveness of the radiation oncologist and urologist team as will the short-penetration isotopes (iodine or palladium).

    We use palladium seeds. As with e-coil MRI, our pathologist may be asked to render a schematic of the biopsy findings in order that the radiation oncologist physician and the physicist have optimal opportunity to consider and execute any seed additions or special pattern arrangements based on the cancer distribution in the prostate gland as suggested by the biopsy findings [even so, the whole gland is treated under the presumption that prostate cancer tends to be a multifocal disease].

    In our program, real-time ultrasound images and 3D-generated images are evaluated; and the urologist, radiation physicist, and radiation oncologist (in the operating room, at the time of surgery) consider numerous factors in deciding whether or not to over-ride the computer-generated designation of seed placement. There is no delay of days or weeks between measurement and seed placement during which there could be slight prostate changes and , almost certainly, re-positioning of the ultrasound probe slightly differently than at the measurement session. That is, we do measurement, planning, and execution of surgical seed placement all at one sitting. (Be aware that there are at least 3 patterns of seed placement that can be used: uniform, peripheral, and "peripheral plus periglandular").

    After final, time-consuming, meticulous seed placement of upwards of 100 seeds via 24 or more carefully placed needles by the urologist, a permanent image is taken to document correct seed placement; some days later, another image is taken to be sure that the proper seed pattern has continued in place.

    Meticulousness is essential because only a 10-25% under-dosage is said to leave the patient at a 2.3 fold risk of recurrence...25% under-dosage, 6.7 fold risk! And, a lesser level of meticulousness probably means that one should be quicker to use XRT overlay...such double radiation adds 2-3 percentage points of increased risk of serious bowel or bladder injury. Our program relatively seldom uses combination XRT/seeds.

    But, we now have the PSA test to help with early detection of most treatment failures...regardless of the type of treatment... so that one may be safer in opting early for new treatments. NOTE: a phenomenon called "PSA bounce" may be seen in seed-implant PSA follow-up...in as many as 35% of patients. Within a year or two after seed implantation (median 18 months), the PSA having been down, starts to rise for 12 months or more, the median PSA increase being 0.4 ng/ml, with a range of 0.1 to 15.8 ng/ml. About 22 percent of the men had more than one bounce. Biopsies are problematic because cancer cells which have been shocked but not yet eliminated can be seen in the biopsy in "bounce" situations and don't really mean recurrence. A true cancer recurrence rise happens later, at a median of 30 months after seed implant.

    Be warned that some practitioners (elsewhere) of this seed method are known to take on marginal, even contra-indicated cases and almost routinely refer for added XRT (where XRT would have been sufficiently comprehensive alone)...such urologists get their pay for seed treatment and also divest [to the radiation oncologist] themselves of patient follow-up responsibility for at least 2 years! Or, they may much more hurriedly and imprecisely place the seeds and rely on XRT to mop up whatever was missed. They may even have a way to make money from both the seeds and the XRT (RCOG has even come up with an "eye catching" name for their ploy, ProstRcision). Such entrepreneurial types are often beloved by the patients because, in fact, they are expertly sensitive as to how to please patients.

    XRT overlay is legitimately more likely if high confidence the cancer is organ confined but Gleason score is 8 or higher (or there is a "significant" amount of Gleason 4 or 5 component), or evidence of large tumor by imaging (T2b or T2c) or by PSA of 10 or higher, or a biopsy finding of "significant" perineural space invasion...anything suspicious of increased likelihood of minor (microscopic) penetration of the capsule.

    Clearly, interested and focused multidisciplinary collaboration...common sense tells us...should be a real advantage here. We started seeds about 1992 here and ceased in about 2002 & began again in 2007. 

    Premier Programs in the U.S. include: Dr. John Blasko's @ Seattle Prostate Institute, Seattle, Washington.



    [Seedpods info site...urologists doing "seed" implants].....[an example of a free-standing prostate facility]

  • HDR Brachytherapy: Whereas radiation "seeds" are left in place, HDR is administered through a highly radioactive seed which is attached to a wire which is momentarily inserted into the patient's prostate gland through 24 or more hollow-catheter tubes/needles. [a website] These tubes have been initially inserted under U/S guidance, under local anesthesia. Radiation is in place only temporarily, and the amount of radiation can be varied within each tube. Correct tube placement is verified by CAT scan. This radiation procedure is performed during several 60-90 minute intervals over a period of 36-48 hours (the needles must be kept in place the entire time, sutured to the groin). As with stationary/permanent seeds, you may not be a candidate if you have previously had a TURP. The balloon-placement, radioactive liquid HDR method now available in breast and CNS tumors is not applicable to prostate.

    Premier Programs in the U.S. include: Dr. Timothy P. Mate's, Swedish Cancer Institute of the Swedish Medical Center, Seattle, Washington. 
  • Medical: CHD (combined hormonal deprivation) or TAB (total androgen blockade) avoids major surgery and radiation but, while being used, guarantees at least temporary complete impotence. Menopause-like symptoms can be severe. And, there is the theoretical chance that CHD/TAB might stifle/kill only the "better" portions of your cancer and leave behind (or select out for further survival) only any "worse" areas...being left to take over. Dr. Fernand Labrie (a Canadian endocrinologist @ U. of Quebec) is a leading proponent of hormone-only treatment.

    CHD/TAB is beginning to be used as "neo-adjuvant therapy"*to shrink the gland (reduce tumor bulk) prior to surgery, seed implant, 3D-CRT, IMRT or cryo-ablation...reduced size means less tumor to kill and, in the case of any type of radiation, smaller radiation fields (possibly leading to less chance of complication).

    Premier Programs in the U.S. include: Dr. E. David Crawford's @ Univ. of Colorado Health Sciences Center, Denver, Colorado. 
  • Radiation Therapy by External-Beam (Photons/X-rays): XRT has undergone tremendous advances in the past 20 years, even since 1990. The ability to very sharply focus the photon/x-rays beam to make its energy concentrate predominately on a precisely defined internal area has become greatly enhanced and is now available in radiation oncology services which have the equipment.* The volume of treated tissue (when excellent, highly modern equipment is used) more closely corresponds to the target tumor tissue.* So, expert radiation oncologists with such equipment and highly qualified technical teams* have markedly reduced the old side effects and added to cure rates while delivering increased dose to the target area. The cure rate is high in those same situations qualified for radical surgery on the basis of Gleason score and cancer stage, with many experts (both radiation and surgeons) considering excellent XRT to have the same "go for the cure" possibilities as excellent radical surgery. XRT is a way to avoid radical surgery; however, the initial use of XRT nearly always voids the possibility of using radical surgery later (except for "salvage prostatectomy"). But cryosurgery is now available* if XRT fails. Our professional interest and technological equipment is as high quality as nearly any in the country.* The odds of permanent impotence are 20-30%. The odds of annoying or significant complications such as bladder or intestinal injury, urethral strictures, or chronic pain are low and manageable.

    If, by way of higher PSA levels, PSI positivity, higher Gleason score, or other factors one is suspicious that the cancer may have locally and occultly invaded the capsule, one can "unfocus" this treatment to the desired degree.

    Our Radiation Oncology Department utilizes CT scan, 3-D planning and delivery of the external beam therapy as of April of 1997 (3D-CRT...conformal radiation therapy)*. Furthermore, such delivery of XRT includes (as of 2006) use of a multi-leaved columnator, a device which will allow dynamically varying 3-D delivery of even-more-focused radiation to a significantly irregular-shaped and tightly defined target area (intensity modulated radiation therapy...IMRT). Because the XRT beam reshaping is automated and dynamic, patient repositioning is minimized; and each treatment session is time-minimized. Combined with pulse/beam radiation modulation (varying of radiation dose/intensity), certain areas of the prostate... those areas containing definite tumor or tumor closest to the capsule, for example...can receive boosted radiation in a highly optimized manner so as to vary the radiation similar to HDR brachytherapy.** In 2007, we added respiratory gating capability to IMRT. This type of external beam refinement is likely to achieve its most optimized potential when combined with a staging process such as e-coil MRI with oriented prostate biopsy MRI correlation (as is already being practiced in our institution). 

    Also, when studies indicate a very localized cancer, a radiation equivalent of "male lumpectomy (see below...cryosurgery) is possible with high-dose "boost" to that localized area (if MRS meets researchers' hopes, see above...surgical options...it might help select cases for special focal/focused attention).

    The focus of IMRT & IGRT should come very close to what is theoretically possible with protons, below.

    Premier Programs in the U.S. include: Dr. Gerald Hanks' (he retired 2001...now chaired by Alan Pollack) @ Fox Chase Cancer Center, Philadelphia, PA. 
  • Proton-particle Beam (radiation) Therapy: PBT is an external-beam technique and is by far the most expensive type of radiation therapy and is only currently available in about 10 treatment centers in the USA (as of 2011). It is one of the LET (linear energy transfer) treatments. The radiation energy can be focused somewhat more tightly than by other methods because greatest energy is delivered at the end of the calculated path (the Bragg peak). When this form of radiation is used to treat tissue which is totally non-movable, the focus can be extremely precise. However, until methods are available to more precisely and confidently assure that the prostate cancer is definitely confined within the gland, we have significant concern that such tight focusing of the tumor treatment area could leave small nests of tumor out in the untreated shell of surrounding "periprostatic" tissue. Also of significant concern is the fact that the prostate gland (particularly the base or seminal vesicle aspect) is significantly mobile and could shift in and out of the extremely focused treatment target area during the multiple treatments, and that any attempt to keep this from happening may be less precise than one would hope. Furthermore, the urethra, as a highly important normal structure subject to complications, runs right through the target field just as with XRT and radiation seeds. IMRT & IGRT, above, can almost as precisely focus as PBT. By May 2011, one of our urologist had four patients who had been sent to University of Florida PBT program in Jacksonville for PBT and had excellent results!

    Premier Program originally in the U.S. Dr. Carl J. Rossi's @ Loma Linda University Medical Center Department of Radiation Medicine, Loma Linda, California; (also at Harvard University). 
  • Cryosurgery: Rather than inserting radiation seeds, freezing probes are implanted by U/S guidance; and freezing of part of or the entire gland is performed under U/S visualization so as to kill the cancer but avoid damaging surrounding structures. The urethra and rectum are protected by heating devices. Unlike radiation, it is possible to use cryoablation more than once in the same patient. This old treatment has much better modern control with U/S imaging guidance. As of 1995, there is nationwide caution as to its use except when the gland is less than 75 grams size, the patient is older than 70 and refuses other treatments, or there has been local failure of another primary treatment (such as surgery, seeds, CHD, or XRT). There is more current wide-spread acceptance of cryosurgical treatment of cases which fail cure by other primary treatments. My radiation oncology friends tell me that there is an incorrect view circulating that advocates primary treatment by cryosurgery, "Then, if that fails, you can get radiation therapy."...as if radiation therapy becomes an, "Oh, by the way..." ready backup for failed cryosurgery. I'm told that this casual attitude is not so and that "salvage" therapies are what backs up any failed first-line treatment. The following two programs are seriously involved in first-line, primary treatment by cryosurgery.

    (Focal cryoablation ["male lumpectomy"] is promoted under a special method of biopsying by Dr. Gary Onik in Florida as of 2006. In addition to numerous biopsies suggesting a small, localized cancer, I'd also like to see the "PSA density" calculation be nearer toward the upper normal range than far into the elevated zone.)

    Premier Programs in the U.S. include: Dr. Jeff K. Cohen's (Triangle Urological Group) @ Allegheny General Hospital in Pittsburgh, Pa.; Dr. Fred Lee's @ Crittenton Hospital, Rochester, Michigan.
     
  • Planned combination sequence: CHD for a period of time prior to radical surgery is gaining some popularity because of some initial hopes that the maneuver will "mature" certain higher grade cancers down to a lower grade and will "down-stage" certain cancers from a higher stage to a lower stage. Another example would be CHD followed by either of the types of brachytherapy, followed by XRT. 

Post-treatment Testing for Recurrence:

The test for total PSA (see monitoring, below) is the test of choice, and what you are looking for is "biochemical recurrence"...the total PSA level rising to 0.2 or higher. CPDR is developing on-line calculators (nomograms or algorithms) that predict your 5 & 10 year survival likelihoods if your have PSA recurrence [nomogram]. On average, it is said that it takes about 8 years from biochemical recurrence to "clinical recurrence", if no treatment is undertaken. Some of the reporting nomenclature at very low levels can be confusing. If your treatment was seeds, see the scary post-brachytherapy (seed implant) benign "PSA bounce", above.

 

Recurrence = Treatment failure:

 

Treatment failure is more likely if your situation or cancer has:

  • greater than 20% Gleason 4-5 component in biopsies,
     
  • postoperative Gleason scores 8 to 10,
     
  • seminal vesicle invasion,
     
  • large size (a greatest tumor size dimension of 1.0 cm or less tends not to fail [Renshaw, Cancer 83:748-752, 1998]),
     
  • greater than 15% of the radical prostatectomy gland involved or occupied by cancer,
     
  • impressively high pretreatment PSA level (greater than 10 being the beginning of concern),
     
  • positive lymph nodes at surgery,
     
  • impressive amounts of perineural space invasion in a radical surgery specimen,
     
  • evidence of impressive invasion beyond the capsule, or
     
  • evidence of significant (not just minute microscopic, technicality-positivity) surgical margin positivity in a radical surgery specimen,
     
  • advanced stage higher than T2.

Treatment failure is searched for...monitored for...by periodic post-treatment lab testing for total serum PSA levels...tracking the PSA velocity & doubling times. If your treatment was seeds, see the scary post-brachytherapy (seed implant) benign "PSA bounce", above.

Post-treatment PSA Monitoring:

Based on many factors, your treating physician will determine a monitoring schedule. As previously stated, attempting serial following of PSA tests gets more complex if you use several different labs (we allow self-ordered testing in our community [HERE]). In many cases, the post-treatment PSA level does completely disappear or become negative or zero. Again, your treating physician will have a "feel" for whether it falls as low as expected for the particular mode of treatment. This is an area of navigation of the "gray zone". What one looks for, thereafter, is a rising PSA...not just a single level barely higher than the previous. A velocity greater than 0.75 ng/mL/yr or doubling time quicker than 10 months is worrisome. If your treatment was seeds, see the scary post-brachytherapy (seed implant) benign "PSA bounce", above.

All lab tests have detection ranges within which results are reliable and reproducible. Hardly any are able to detect ultra-tiny amounts of any particular agent with reliability. Laymen and many health professionals are miss-educated into the belief that a test can actually be truly negative. In fact, "negativity" is a status assigned when a test is "non-reactive" at a clinically and analytically appropriate detection limit which is set at a dependable cut off. Labs express "negativity" in several ways:

  • "negative"...(practical; not scientifically or legally clear)
     
  • "non-reactive"...(practical; a little more scientific and legally clear)
     
  • "negative at 0.1"...(more professional, scientific, and legally correct/clear)
  • "non-reactive at 0.1"...(more professional, scientific, and legally correct/clear)
     
  • "undetectable at 0.1"...(more professional, scientific, and legally correct/clear)

The above means that an observer or reader of the lab report of the 1st or 2nd has no scientific idea at what level the test would "turn positive". In either of the 3rd, 4th, or 5th, the PSA could "creep" from 0.003 to 0.05 and still appear to be "negative"; only after it rises above 0.1 would it become reliably and reportably positive. And, we know from a practical clinical standpoint that this typical PSA detection limit serves patients perfectly well. Especially in view of the mathematical law of "significant digits",  a more sensitive method is not clinically useful.

FINAL COMMENT:

As you read scientific studies, information from prostate cancer advocacy or support groups, information from the American Cancer Society, and information from personal or any other sources, remember that rapid changes are taking place in the details of each treatment modality, combinations of treatments, who the experts are, and where the premier programs are. You need to be satisfied that: your doctor cares particularly about your situation; you've soul-searched yourself and revealed your TRUE cares and fears to your doctor; you feel confident that your doctor is committed to keeping up with what's available; you have gotten all the reliable information you want to have from sources committed to keeping up with issues important to patients; and, that you are comfortable with testing programs, hospitals, or treatment programs selected for your case. You need to remember that all information sources (including professional persons, programs, and institutions) tend to be at least somewhat biased (for any of hundreds of reasons). You are the customer/consumer/ buyer. Hear your advisors; develop your confidence; help choose your course!

 

*        Available in Lexington Medical Center Program

**      Available in referral from Lexington Medical Center Program

***     Available in referral lab from biopsy material processed in   Lexington Medical Center Lab.

 

SOME INFORMATION SOURCES:

CaP Cure, a private source founded in 1993 by multimillionaire Michael Milken

Prostate Cancer Research Institute in Los Angeles, Calif.

N. Y. Prostate Institute

National Network of Prostate Cancer Support Groups 800-242-2383

American Cancer Society 800-227-2345

US TOO! International, Inc. 803-799-5288

PAACT (Patient Advocates for Advanced Cancer Treatments) 616-453-1477

Attempt to see a copy of the following short article discussing the screening controversy in Oct. 2011: Brett AS & Ablin RJ, "Prostate-Cancer Screening — What the U.S. Preventive Services Task Force Left Out", New England Journal of Medicine, 26 Oct. 2011.

Our pathology group's prostate cancer table of contents page is rich in doctor info (mostly covered above).

An incredible amount of information can be accessed through the Internet. Some institutions (and such as public libraries) may be able to help you with this and the obtaining of other sources of information; our hospital library is eager to be of help in this regard through our Community Health Information Library 803-739-3884.

 

BY THE WAY, have you considered your spiritual status?

(this handout devised July 1995; web site posting June 1998; latest addition 18 May 2012)

 

The second biopsy determination...we always check for this... is a search for PSI: the presence of cancer in microscopic spaces around prostatic nerves ("perineural space invasion"...PSI..."PNS positive").* Some 85% of cancer penetrations out through the prostate gland capsule happen along-side of the nerves coming into the gland (highest concentrations at apex and base as the neurovascular bundle runs along each posterolateral side of the gland). "Positivity" near the capsule ups the odds that tumor has invaded through the gland capsule, whether it can be specifically visualized or not. And its presence may strongly influence treatment choices, it being a soft clue to that particular cancer's ability to scatter beyond local lines of resistance. Treatment choices which are focused (nerve-sparing radical, low-penetration seeds, PBT, cryo., 3D-CRT/IMRT and IGRT tightly focused around the gland) may be more risky in the face of positive PSI (see treatment details, below). Positive PSI on a biopsy has a positive predictive value of 93% that the capsule is at least microscopically penetrated (of 100 cases having a biopsy showing PSI, 93 will have capsular penetration documentable in the radical prostatectomy specimen). Biopsies showing PNS (perineural space) negativity are no guarantee, however, against capsule penetration.

The Gleason grading system subjectively recognizes 5 cancer "patterns" in any positive biopsy core. And, it adjusts for the common fact that prostate cancer most often contains two patterns by creating a Gleason score consisting of the sum of the estimated percentages of the majority pattern plus the minority pattern, such as 3 (60%) + 4 (40%) = 7 (see more, below). Otherwise, it contains one pattern, such as 3 + 3 = 6.  Rarely, the samples show 3 patterns.