Gleason Score in Diagnosing Prostate Cancer

The following is an excerpt from a January 12th, 2016 blog called Prostate Snatchers by Mark Scholz, M.D.

The latest craze in medical technology is genetic analysis of tumor cells (GAT).  “The scientific progress that has been made with GAT in my opinion is the second most exciting area of advancement in medical technology today (see below for more about the first most exciting area).”  GAT technology is already being commercialized for use in the medical marketplace in products like Prolaris and Oncotype. (For a review of both, see Godanprostate.net November 27,2015 post).  These technologies are able to predict the aggressiveness of prostate cancers, enabling us to differentiate between the men who need immediate treatment and those who can postpone treatment safely.

“The predictive power of GAT is certainly exciting, but there is already an effective form of genetic testing available that has been around for more than 40 years, the Gleason scoring system. The Gleason system relies on the visual appearance of cells under the microscope to draw conclusions about their inner genetic makeup. In the medical world, using the visual appearance of the cancer cells is called phenotypicanalysis. GAT is genotypicanalysis.”

“So how can Gleason score draw conclusions about the underlying genetic potential for tumor aggressiveness simply by looking at the appearance of cells under a microscope?  The answer is to do a comparison of the visual appearance of cancer cells with the appearance of normal prostate cells. Normal cells in the prostate perform varied functions but still work together as a team.  Specifically, healthy cells form into definable structures called glands.  In these glands some cells manufacture prostatic fluid, a complex liquid comprising the ejaculate for the sperm to swim in.  Other cells organize to form ducts, a piping system to drain the fluid from the outer periphery of the gland and channel it into the middle of the prostate so that a large quantity of fluid can be expelled through the urethra at just the right moment.  All of these different cells work as a team and coexist in the prostate functioning together in a structured glandular arrangement.”

“When a trained pathologist looks at tumor cells under the microscope he grades them by the degree of cellular disorder.  He is asking himself the question, ‘How much do these cells retain the normal glandular characteristics of the prostate gland?’  If a cross section of the tumor looks like an unbroken sheet of uniform cells, the cancer is high-grade; the cells have lost their ability to cooperate with each other and form glands. The cancer cells have been honed down into little race cars with only one mission, to aggressively pursue its own replicative destiny. When tumors have this appearance they are graded as a Gleason 9 or 10.  On the other hand, if the appearance of the tumor shows residual glandular components, it is less aggressive, perhaps a Gleason 7.”  Gleason 6 cancer looks almost like normal prostate gland tissue. 

“Predicting future tumor behavior is obviously very important. How fast will it grow?  Is it likely to spread? How well can it be expected to respond to treatment?  As a result of decades of experience, doctors have learned to use the Gleason scoring system to accurately predict the long-term outcome in individual patients. The new GAT tests represent an important additional refinement, further enhancing our ability to predict the future behavior of an individual cancer. GAT holds one even bigger promise.  In the future we believe GAT testing will be a powerful aid in the selection of targeted therapy, i.e., picking cancer treatments with anticancer activity tailored to individual tumor types.  This hope, however, will have to be postponed until our limited armamentarium of effective treatments is further expanded.”

“Now, what is it that I” (Dr. Scholz) “consider to be the most exciting area of medical progress? Since I am an impatient type of guy, someone who is looking for quick results, I find immunotherapy more exciting than GAT. To fully exploit the potential of GAT we will need to invent new pills for each of the myriad of genetically different tumor types. Immunotherapy on the other hand comes with its own ‘built-in’ GAT system that enables it to target the unique genetic signature of individual cancer cells. The immune system is so smart, all we have to do is ‘flip the switch on’ and starts cranking out genetically targeted anticancer therapy. Recent developments in the field of immunology are truly mind-boggling and hold promise for a big revolution in cancer therapy within the next 5-10 years.”

Aspirin May Cut Prostate Cancer Death Risk; Two Reports;

In a study presented at the January 2016 meeting of the American Society of Clinical Oncology (ASCO), researchers from Harvard’s School of Public Health concluded that “men with prostate cancer who took aspirin regularly after diagnosis had a significantly reduced risk of death.”  Taking aspirin more than three times a week was associated with a 39% lower risk of dying from the disease compared to men who reported less frequent aspirin use.  The study evaluated data from 22,071 men who took part in the Physicians’ Health Study and who were tracked from 1982 to 2009.  Taking aspirin prior to a prostate cancer diagnosis was not shown to be beneficial as “aspirin use did not appear to affect the risk of prostate cancer development or rate of diagnosis.  It also did not affect the frequency of diagnosis of high-grade cancer or locally advanced cancer.  But it was proposed that in addition to its cardiovascular benefits, “regular aspirin use may inhibit lethal prostate cancer possibly by preventing cancer progression.”  Regular use was associated with a 24% lower risk of developing lethal prostate cancer.  It was noted that a recommendation to begin aspirin regimen solely for prevention of lethal prostate cancer is not warranted based on this study alone.  More work is needed to identify the particular subsets of men most likely to benefit from aspirin and to determine the optimal aspirin dose.  It was also learned that the results seen with aspirin did not extrapolate to the use of celebrex.  For more details, see the following link.

 

 

 

Predicting Prostate Cancer’s Future Behavior

Developing an accurate prognosis, i.e., predicting how a man’s cancer is likely to behave in the future, is the first and most important step toward optimal care. Future predictions are often looked at with some suspicion. With prostate cancer, however, our power to anticipate future cancer behavior is quite accurate unless there is a lack of thoroughness in gathering information.  One system designed to evaluate the risk of prostate cancer recurrence following localized treatment was formulated in 1998 by Dr. Anthony D’Amico.  For a summary of the D’Amico system, see this link.

The Size of the Tumor
Tumor size is a universally important prognostic sign for almost all types of cancer including prostate cancer. The method for incorporating tumor size into the Anthony D’Amico’s staging system relies on the degree of PSA elevation, the tumor grade and on how the prostate “feels” with the finger of a trained practitioner. These indicators are useful but don’t incorporate information from modern imaging. Imaging provides accurate information about tumor size and the presence or absence of extracapsular extension. These are very powerful prognostic predictors and it would be foolish to disregard their importance. As things stand presently these indicators are often used to divide the low, intermediate and high risk D’Amico categories into “favorable” and “unfavorable” subcategories, each with a different spectrum of recommended treatment options.

Knowing Past Treatments Tells Something about Future Prognosis
Historically, since the total number of available treatments is relatively limited, practitioners have used a sequential “trial and error” treatment methodology that administers the standard treatment options in a fairly predictable sequence. For example, it is not uncommon for men to start with surgery or radiation. When a relapse occurs, standard hormone therapy (Lupron) is often started and given intermittently or continuously. Hormone therapy usually controls the disease for an average of 10 years. When Lupron stops working, immunotherapy with Provenge may follow. After Provenge, more potent hormone therapy with Xtandi or Zytiga is started. If these two agents prove ineffective, chemotherapy with Taxotere (docetaxel®) or radiation with Xofigo would be considered next.  The whole point of presenting the treatment sequence described in this paragraph is to convey the idea that the number of previous treatments communicates important information about that patients’ future prognosis. Having “failed” Lupron, for example, bespeaks of a much more worrisome prognosis compared to the situation where Lupron continues to be effective.

Response to Lupron, The Mother of All Metrics
The quality of the “response” to Lupron is actually one of the most powerful prognostic metrics available. The degree of PSA decline after Lupron is incredibly important. How low the PSA drops after starting Lupron is called the “PSA nadir.” The specific PSA threshold used to determine a “good response” is less than 0.1. Believe it or not, there is a huge difference in prognosis between a man on Lupron for six months who has a PSA of 0.1 versus a man whose PSA levels off at 1.0.

An Established History is also a Prognostic Indicator
Another somewhat obvious prognostic indicator that is often overlooked and almost never discussed in textbooks has to do with the prognosis of men who have been diagnosed years ago — over time it is apparent that things are turning out much better than what might have been expected based on their initial indicators. For example, take the case of a man who started off with a panoply of bad indicators—tumor is in the lymph nodes and Gleason 10—but after aggressive treatment remains in remission for 5 years. The fact that things have gone well for five years counts big-time in his favor going forward. Remember, the original prognostic predictors of a Gleason 10 were just that, predictors. No predictor is 100% accurate. Five years of established history is a stronger predictor than the original Gleason score. The fact that things have gone well for five years, strongly indicates that the future is for that individual is bright. Such individuals may have “beaten the odds.”

The Location of the Tumor in the Body
Another extremely important indicator of prognosis, something that even laypeople anticipate by simple common sense, is the location of the cancer in the body. Location says volumes about how things are likely to progress in the future. For example, consider the following sequence of progressively more serious cancer sites:

•Contained within the prostate
•Extended into the seminal vesicle
•Spread to the lymph nodes
•Bone metastases
•Liver metastasis

Each of these locations is very important for determining prognosis.

This short blog is just an introduction to some of the “profiling” methods utilized in generating an accurate prognosis. Space limitations preclude discussion here about other known prognostic factors such as the size of the prostate gland, genetic tests and PSA doubling time. The D’Amico risk categories constitute the backbone of useful prognostic information. However, the additional prognostic information beyond the D’Amico risk categories that are discussed in this blog, provide additional useful information necessary for determining an accurate prognosis. An accurate prognosis is the starting point for accurate selection of treatment.

The preceding blog was posted on Dec 30th, 2015 by Mark Scholz, MD on his site entitled “Prostate Snatchers” to which I recommend a subscription.