Dr. Scholz is the prostate cancer expert on veryWELL.com (an ABOUT.COM brand) Check out his articles at www.verywell.com 

https://www.verywell.com/what-about-sex-after-prostate-surgery-2782250

https://www.verywell.com/prostate-size-matters-2781991

A BETTER PROSTATE CANCER TEST?

FEATURED TODAY IN THE WALL STREET JOURNAL - HEALTH

by @melindabeckWSJ   READ FULL ARTICLE HERE

A BETTER PROSTATE CANCER TEST?
Distinguishing aggressive disease from slow-growing tumors means more patients can forgo treatment.  
Several new prostate-cancer tests aim to reduce needless biopsies and unnecessary treatments by sorting out harmless from aggressive tumors. 30 MILLION U.S. men will have a PSA test. 6 MILLION of them will be found to have elevated PSA levels.  1 MILLION of them will undergo a prostate biopsy.  180,000 men who have biopsies will be diagnosed with prostate cancer. Another 180,000 men will have prostate cancer the biopsy missed.100,000 men with prostate cancer will have low-risk tumors that are unlikely to spread or cause symptoms.  60,000 men with low-risk cancers will undergo surgery or radiation anyway, probably unnecessarily.


mpMRI vs BIOPSY
Mark Scholz, a prostate oncology specialist in Marina del Rey, Calif., maintains that an mpMRI can yield much of the same information as a biopsy and far less invasively. Low-risk prostate cancers barely register, he says, adding, “When patients find out they have a choice between 12 harpoon sticks to the prostate through the rectum or an MRI, they are on board big time.” 

Joel Copeland, 62 years old, has been monitoring his PSA closely for a decade; his two brothers were diagnosed with prostate cancer. He opted for an MRI instead of a biopsy when his PSA bounced up in 2013. “I don’t like needles, but that’s not the point,” Mr. Copeland says. “The point is, biopsies can cause infection and miss cancers.”

SEE Prostate Vanguard Mailing List about Active Surveillance + Prostate Imaging

Testosterone Replacement Therapy (TRT)

BY JEFFREY TURNER, MD


Testosterone (T) preparations have been available for more than 70 years.  In 2013, over 2.2 million Americans were prescribed testosterone.  Interestingly enough, about 1 in 4 men prescribed testosterone do not have a baseline testosterone level drawn as primary care physicians may write the prescription without ordering a blood test first.  In a study of 63,000 men from the Truven Health Marketscan Commercial and Medicare Supplemental Insurance database between 2010 and 2012, 71% of men had their testosterone level checked once, 40% twice, and 29% had no measurement at baseline.  Physicians need to do a better job following men on testosterone replacement. Is testosterone replacement therapy really all that good for anything aside from rejuvenation and virility? 

Let’s break this down to risks and benefits below:

Risks of Prostate Cancer

The most universal risk which has been the controversy of much discussion is the association with prostate cancer.  Clinicians remain concerned that Testosterone Replacement Therapy (TRT) can cause or stimulate prostate carcinogenesis and therefore they are reluctant to prescribe it for the aging male who has a higher risk of prostate cancer.  In the 1940s, Huggins and Hodges discovered the association of testosterone with prostate cancer by demonstrating that castration causes the disease to regress. The reality is that TRT may stimulate the growth of existing prostate cancer cells, but it will not cause cancer to form.  As the general male population grows, so does the risk for prostate cancer--patients should be closely evaluated with digital rectal examinations, PSA checks and prostate imaging such as color Doppler ultrasound.

Risk of Prostate Enlargement

Another controversial topic is the assumption that supplemental testosterone leads to a prostate growth, benign prostate hypertrophy, which leads to worse quality of life due to worsening urinary symptoms.  It has long been assumed that high T levels induce prostate overgrowth, but most studies failed to find the correlation between circulating T levels and BPH.  It has been hypothesized that dihydrotestosterone (DHT) could be more responsible for prostate growth than T.  There have been a number of studies evaluating TRT in hypo-gonadal men with BPH.  The results have suggested that there is actually a trend toward an improvement in urinary symptoms.

Risk of High Red Counts—Polycythemia or Erythrocytosis

Erythrocytosis is the increase in red blood cell mass production which can be the result of testosterone replacement therapy.  This is the most frequent adverse effect associated with TRT.  Recent trials have demonstrated that men on TRT have a 4 times higher chance of having high red blood cell counts.  Some reports have implicated excessively high red blood cell levels with an increased risk for heart attack or stroke. We commonly recommend patients remain on a baby aspirin daily and monitor their blood counts. Some patients may benefit by donating a unit of blood if the levels are too high.

Risk of Obstructive Sleep Apnea

Frequently reported in various literature is the association of worsening sleep apnea symptoms for men on testosterone replacement.  There has been only one randomized control trial to date that addresses this association and it showed that obese men with severe sleep apnea may worsen their oxygenation with TRT at relatively high doses.  This study evaluated injection formulations of testosterone. So far transdermal formulations have not been similarly implicated.

Risk of Infertility

Testosterone replacement leads to inhibition of the pituitary gland located at the base of the brain which can potentially suppress the production of sperm.  Hence, cases of TRT-induced male infertility have been reported. This impact appears to be transient and disappears once TRT is stopped.

Improved Sexual Function

A decreased libido and/or potency remains one of the most common reasons that men desire testosterone replacement.  TRT can certainly improve sexual function in those who have erectile dysfunction primarily due to a low level of testosterone.  Patients need to recognize that there are a series of other reasons for being impotent that are unrelated to low levels of testosterone which must also be investigated as well before concluding that TRT will be the optimal corrective measure.

Improved Cardiovascular Effects

The association of TRT with heart attacks has been very controversial. We must not forget that men with low T levels are at higher risk for poor health due to being more frail and susceptible to other medical issues including obesity and diabetes. As a result, they become more prone to adverse cardiovascular outcomes.  Four out of five of the most recent meta-analyses demonstrated neither a protective or harmful effect of TRT on cardiovascular events. In men with heart failure, it has been demonstrated that low T levels are an independent risk factor for worse outcomes.  Studies also demonstrated that men with heart failure who supplemented with testosterone had a better exercise capacity, oxygen levels, and less fatigue.

Improved Metabolic Effects

Large scale data exists to document the association of low T and worsening blood sugar levels along with a higher chance of developing diabetes. TRT can improve body composition and help to reduce fat which can lead to better control of diabetes.

Reversal of Osteoporosis

Lower testosterone levels are associated with a higher risk of bone fractures and worsening bone health.  TRT has been demonstrated to have a positive effect on bone mineral density.

Improvement in Chronic Kidney Disease

Low T is very common (approximately 50%) in men undergoing dialysis for end stage renal disease. Reduced T levels have in men on hemodialysis have been tied to higher rates of all-cause cardiovascular mortality.   Studies suggest that TRT may improve the levels of a hormone called erythropoeitin (EPO). This hormone stimulates improved production of red blood cells which in turn increases levels of red blood cell mass, energy, stamina, and overall well-being.

Conclusion

It is clear to see that testosterone replacement offers a multitude of benefits which span past merely increasing one’s libido or potency.  The bottom line remains that patients on testosterone supplementation must have close follow-up including both clinical and laboratory evaluation to ensure they are gaining benefit and not placing themselves at increased risk from potential adverse effects.  Physicians must clearly discuss the risks and benefits of supplementation along with employing routine monitoring of PSA, testosterone levels, blood counts, digital rectal examination, and color Doppler ultrasound. 

Modern Taxotere Chemotherapy for Prostate Cancer

BY MARK SCHOLZ, MD


In prostate cancer, the word “chemotherapy” is essentially synonymous with Taxotere (docetaxel). Taxotere is by far the most common chemotherapy medicine for prostate cancer. Taxotere is an active agent that is also employed for the treatment of breast cancer and lung cancer.  Jevtana, which has many similarities to Taxotere, more than any differences, is the second most commonly used type of chemotherapy. Taxotere (and Jevtana) are administered intravenously every three weeks in a cyclical fashion.

These agents are typically used to treat advanced metastatic prostate cancer. Men with preexisting bone pain usually notice significant improvement within a week or two of starting therapy.  Another sign that the Taxotere is working is PSA levels decline.  If the PSA does not decline immediately, Taxotere should still be continued for at least two or three cycles before concluding the treatment is not working. An initial increase in PSA for 30-60 days is not an indication to stop Taxotere because on occasion men have a bump upward in the PSA, a “flare” from the dying cancer cells.  However, if the PSA continues to rise after three cycles, it indicates that the Taxotere is not working.

Cancer response rates can be further improved by using Taxotere in combination with Carboplatin.  Carboplatin is also administered intravenously and can be conveniently administered at the same time as the Taxotere. In patients who have normally functioning bone marrow and normal kidney function, a small dose of Carboplatin, say 200 mg, can be safely administered along with full-dose Taxotere.  Carboplatin is well-tolerated though occasional side effects include low-grade nausea, numbness in the hands or feet and tiredness.

Taxotere administered in combination is with Avastin and Revlimid is another very active combination that will induce a cancer response in most men. Avastin, which is FDA-approved for colon cancer but not prostate cancer, is an angiogenesis inhibitor given intravenously every two weeks.  It is generally well-tolerated but requires concomitant blood thinners due to a higher risk of blood clots.  Avastin can also cause slow wound healing and can't be used before or after surgery. Revlimid oral agent that is FDA-approved for a type of bone cancer called myeloma.  Like Avastin, it also functions by blocking new blood vessel growth. When using Revlimid in combination with Taxotere and Avastin we typically limit the Revlimid dosage to 5 mg daily.  Side effects at this dose range are rare though occasionally platelet counts can be suppressed.

A study using these three agents in combination that showed very high response rates was published by Dr. Figg from the National Cancer Institute.  This same study also reported a high frequency of fairly notable side effects including numbness of the hands and feet as well occasional cases of jaw damage, a condition called osteonecrosis.  Despite these significant problem, Dr. Figg reported that the vast majority of the men achieved significant remissions and that the remissions tended to be quite long lasting.  

Aggressive combination protocols like these require various supportive measures to be successful.  Defending against low white blood cell counts with an immune stimulator such as Neulasta should be considered routine. Neulasta is a powerful medicine that stimulates the bone marrow to manufacture white blood cells more quickly and in greater numbers. Side effects are rare but occasionally, serious but transient episodes of lower back pain can occur.

Another bone marrow stimulator, Aranesp, can defend against the development of progressive anemia. Anemia is a common in men with prostate cancer and can be due to hormone therapy, chemotherapy, or even from the prostate cancer invading the bone marrow. Symptoms of anemia are shortness of breath and fatigue. Timely and appropriate use of Aranesp helps to maintain normal red blood cell counts and can reduce the need for blood transfusions.

Taxotere usage has been greatly postponed in men with metastatic prostate cancer ever since the FDA approval of Xtandi and Zytiga. These agents induce meaningful remissions with far fewer side effect than Taxotere.  However, patient tend to have a rapid and virulent progression of the cancer after Zytiga and Xtandi stop working.  Taxotere, possibly in combination with Carboplatin should probably be implemented quickly in most cases. 

Memorials: Peter Grimm, MD and Jay Cohen, MD

BY MARK SCHOLZ, MD

I am sad to report the passing of two giant contributors in the prostate cancer realm, Dr. Peter Grimm and Dr. Jay Cohen. 

Dr. Grimm was the Director of the Prostate Cancer Center of Seattle which pioneered seed implantation for prostate cancer. He was instrumental in establishing the Seattle Prostate Institute in 1997. Along with his colleagues, Dr. John Blasko and Dr. Haken Ragde, he trained over 6000 physicians worldwide in how to administer seed implants. Their team has treated over 10,000 patients since 1985. Over one thousand centers now perform seed implantation, which is now a treatment of choice for many men with prostate cancer.   Dr. Grimm completed his graduate training in radiation oncology at UCLA. 

Dr. Grimm’s technical endeavors, such as the development of six US patented devices, have led to continuous improvements in the equipment widely used in prostate brachytherapy. He has served as one of fifteen physicians on the Medicare Practicing Physicians Advisory Board in Washington DC and served on the American Society of Therapeutic Radiation Oncology economic committee. He was the CEO of ProQura, and served on advisory boards for many seed implant companies. As lead editor, Dr. Grimm and members of the Prostate Cancer Results Study Group published a collaborative book on prostate cancer, The Prostate Cancer Treatment Book. His curriculum vitae included over 80 scientific articles and book chapters on prostate cancer.  

Dr. Grimm received an Outstanding Achievement awards from the American Brachytherapy Society, Midwestern University, and the Northwest Osteopathic Foundation. Born and raised in Seattle, he had a lifelong passion for preserving wild salmon. He was a board member of Long Live the Kings, a non-profit organization dedicated to preserving wild salmon in the Northwest. In a cooperative effort with the Hood Canal Salmon Enhancement Group and Washington State Department of Wildlife, he has released over 3 million wild salmon.  He also serves as a board member for Pacific Northwest College. He leaves behind his spouse Dawn Winters, PhD and two children, Robyn Vera, DO a radiation oncology physician in Olympia Washington and Justin Grimm, an IT specialist.

I am also saddened to report that Dr. Jay S. Cohen passed away in December 2015. My interactions with Dr. Cohen were related to his excellent book on prostate cancer: Prostate Cancer Breakthroughs. However, outside of the prostate cancer world, his researching and writing skills were eclectic and broad. Among his many and varied interests were his extensive research on the causes of medication side-effects. He published his findings in eight books, leading medical journals, and articles and publications such as Newsweek, Bottom Line Health, The New York Times, The Washington Post, Consumer Reports, Wall Street Journal. Another of his books, Over Dose: The Case Against the Drug Companies was favorably reviewed by the Journal of the American Medical Association.  Dr. Cohen was an Adjunct Associate Professor of Psychiatry and the Chairman of the Medical Advisory Committee of the Erythromelalgia Association, and a Fellow of the American College of Nutrition. He lived in Del Mar, CA for over 40 years. He is survived by his son Rory Cohen and daughter-in-law Alana Cohen, and a nephew, Hal Cohen.

Sometimes Going Fishing with the Doctor Isn’t So Much Fun

BY A PATIENT OF MARK SCHOLZ, MD

When you go fishing, you can bring up all kinds of things besides fish—old rubber boots, pieces of a broken net and discarded trash. Once I caught an eel.  You never know what you will drag in when you drop your line overboard. 

The same analogy holds true for diagnostic testing in the medical world. Investigative studies can have unintended consequences. Of course the studies seem justified at the time. We presume that the doctor is being rightfully conscientious by using all the tools of modern medicine, “fishing” for the right answers.

Dr. Scholz asked me to relate the story of an extended medical fishing trip that started with my dermatologist for my annual, too-much-California-sun screening. While talking to my dermatologist, I mentioned some itching on my arms.  He gave me a few samples of lotion and referred me to my internist for further evaluation and blood testing to “make sure” the itching wasn’t a symptom of something more serious. My internist ordered some lab work (which was normal) but recommended that I have a routine chest x-ray since itching can be associated with lung cancer.  This suggestion may have occurred to him because he knew that lung cancer caused my mother’s death.  Since I hadn’t had a chest x-ray in years, I thought, “why not?”

In retrospect, the chest x-ray may have been a mistake.  Because that’s when the boat left the dock and the fishing really began in earnest.  Two days later, the chest x-ray revealed a “suspicious” spot on my lung. So, to identify what it was, a CT was ordered.  The spot was benign. “Whew!” It was only a bone artifact (the end of a rib visible due to the angle of the x-ray).  But…. the CT scan showed a suspicious spot in the liver, which shouldn’t have been there and was large enough to be of concern.  So, an MRI of the abdomen was ordered.  The MRI revealed that the liver spot was nothing but a harmless hemangioma, a collection of blood vessels that are common and mean nothing.  Another big relief. But…. guess what else the MRI found?  At the top end of the scan in my lower neck, it showed some abnormalities in my thyroid “that could not be ignored.”  So, a thyroid ultrasound was ordered.  It revealed two nodules that looked benign and would have been ignored completely if there had only been one.  But the only way to really know what types of cells the nodules consisted of was by doing a needle biopsy or an exploratory surgery. 

Yikes!  When would I get off this merry-go round?  Who could imagine that simply mentioning some itching to a dermatologist would lead me face to face with the possibility of thyroid cancer.  However, the doctor was kind enough to offer another alternative.  Because of the known, slow-growth rates of typical thyroid cancers, active surveillance and re-testing at future intervals was also an option, and the one I have selected.

So, six months later, a second thyroid ultrasound—my fifth imaging test—showed no changes from the previous test.  The fishing trip finally seems to be over.  I am back in the waiting pool anticipating next year’s medical expedition, much the same as the next round of prostate screening tests I am scheduled to undergo early in 2017.  Now, routinely surveilling my thyroid is going to be just like my prostate.  If next year’s fishing trip doesn’t run down any new tributaries and is uneventful, I expect it may even be possible to extend by a year or two the time the frequency of testing.

My medical fishing trip was not much fun.  Personally, I’d rather spend my time working, biking or walking, or doing almost anything besides waiting for the next set of results from the last odd thing that showed up unexpectedly. But life goes on and it isn’t possible to know precisely how it will end.  My recommendation—Give careful consideration to your doctor’s invitation to go fishing.  Take control over your medical destiny and ask you doctors if close surveillance is an alternative to further testing. 

Crila, A Solution to Old Men’s Urinary Problems?

BY MARK SCHOLZ, MD

As we get older, we run into all kinds of difficulties.  Poor hearing, sexual dysfunction, memory problems and arthritic joints, just to name a few. Bladder issues in particular can be troublesome, interrupting sleep, making us dread long drives or forcing us to visit the bathroom at an inopportune time.

As a prostate oncologist taking care of many men who are in their 60s and 70s, it’s no surprise that I hear a lot about urinary difficulties. These problems are often thought to result from prostate enlargement, otherwise known as BPH. The swollen gland ends up pinching the urinary passage way (called the urethra).  Slow urination and incomplete emptying of the bladder are the result. 

Prostate gland enlargement with incomplete bladder emptying can frequently be solved with common prescription medications like Flomax, Rapaflo and Uroxatrol which relax the muscles in the wall of the urethra and help to open up the passageway.  Proscar and Avodart can shrink the prostate but they also tend to shrink your libido. The most popular treatment is a nonprescription—Saw Palmetto an herbal product that works by relaxing the muscles in the urethra.

However, after doing thousands of color Doppler ultrasound examinations, which by the way is the most precise way to measure the size of the prostate, I have learned that BPH is a less common cause of men’s urinary problems. So what is the primary reason for men’s urinary frustrations? Prostatitis—low grade inflammation of the gland with secondary irritation. What causes prostatitis?  In a minority of cases it is due to bacterial infection. When this type of prostatitis occurs it may improve with antibiotics. But for the vast majority of cases we simply don’t know the cause.  Virus or autoimmune causes have been theorized but nothing has been proven. Our ignorance, however, has nothing to do with its prevalence. It is not widely realized, but almost all men have some degree of chronic inflammation in their prostate glands.

Though we don’t know the precise etiology, anti-inflammatory medications can be quite effective at alleviating the symptoms of prostatitis. Over the counter products like Aleve and Motrin are effective. Celebrex, is a prescription anti-inflammatory agent that is billed as having less stomach irritation. However, unless the pills are used continuously, the inflammation comes back.

Recently, I have been introduced to a natural anti-inflammatory substance discovered in the flower of the Crila plant. Several of our patients tried Crila with notable improvement to their urinary symptoms. So far we have not observed any side effects.  To investigate Crila’s effectiveness further, I have petitioned the manufacturer to provide a 3-month supply of Crila to 15 of our patients at no cost. Patients who have problems with frequent urination, a strong sense of urinary urgency or have to get up frequently at night to urinate may want to consider contacting Sabrina in our office about their eligibility for participating in this clinical trial. 

The Amazing Gleason Score

BY MARK SCHOLZ, MD


Everyone is excited about the latest craze in medical technology—genetic analysis of tumor cells, which I’ll call GAT for short. 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 further 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. This technology is 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 phenotypic analysis. GAT is genotypic analysis.  Drawing conclusions about underlying genetic makeup by simple visual assessment is a pervasive in human experience.  In courtship, we rely on phenotypic analysis of the underlying genetic make-up of potential spouses to form an opinion about their suitability as potential mates.  Perusal of the genetic pool of immediate family members provides further insight.

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,” the type the one that never spreads, 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 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.  I’ll try to address some of these recent advances in an upcoming blog. 

Predicting Prostate Cancer’s Future Behavior

BY MARK SCHOLZ, MD


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.

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 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 is usually follows. After Provenge, more potent hormone therapy with Xtandi or Zytiga is started. If these two agents prove ineffective, chemotherapy with Taxotere or radiation with Xofigo would be considered next.

The whole point of presenting the treatment sequence described in the previous 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 bigtime 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 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 (discussed in a previous blog), 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.

Androgen Deprivation Therapy for Prostate Cancer Causes Alzheimer’s Disease?

BY MARK SCHOLZ, MD


Dr.Kevin Nead authored an article published in the Journal of Clinical Oncology this month.  It created a media sensation and generated multiple calls to the PCRI Helpline.  Last week, three separate articles about this topic were posted on the Yahoo home page at the same time.


It’s no surprise that an article on this topic generates wide-spread interest. About 500,000 thousand men in the United States are undergoing prostate cancer treatment with androgen deprivation therapy (ADT). This treatment works by blocking the male hormone levels delivering notable anticancer efficacy and also proven to prolong life in men with prostate cancer. Despite it’s known effectiveness, a variety of side effects can occur, including memory problems.  The previously reported studies evaluating this phenomenon seem to indicate that when memory deficits occur, they usually reverse after ADT is stopped.
The research published in the Journal of Clinical Oncology, relied on a new method of searching through patient’s medical charts with computers.  No human review of these medical charts were performed. The computer software searched the medical records in an attempt to determine if men on ADT had a higher incidence of Alzheimer’s. The authors report that this new computer searching methodology in detecting a specific medical diagnosis is 74% accurate.


Review of all the charts at Stanford and Mount Sinai hospital unearthed 16,888 prostate cancer patients of which 2,397 were treated with ADT.  After the fancy computer analysis, designed to compensate for multiple factors such as patient age and underlying heart disease (both of which lead to Alzheimer’s more frequently), the conclusion was that the ADT-treated men were twice as likely to have developed Alzheimer’s. A total of about 9 cases would have been expected from normal causes, but 18 were actually detected.  If these conclusions are accepted as gospel truth, an additional 9 out of 2,397 men treated with ADT would equate to an increased risk of less than half of 1%.


The conclusion that there is tiny increase risk of Alzheimer’s with ADT, needs to be put in context based on what we already know about prostate cancer. First, is it possible that these men have reversible memory problems while still taking ADT? There was no attempt in the study made to determine if the “Alzheimer’s” patients were still on ADT when the diagnosis of Alzheimer’s was made. Second, men treated with ADT are substantially sicker than men who don’t need ADT.  There is no way for the computer analysis to compensate for how this may have impacted mental performance. Third, patients getting ADT receive closer medical surveillance and visit physicians more frequently than men who are not receiving ADT.  As such, memory problems are more likely to come to medical attention and be diagnosed when men are on ADT.  Fourth, general anesthesia (from surgery) is known to cause long-term memory problems.  This study did not perform any analysis to determine if surgery was performed with equal frequency in both groups.


In summary, it is not clear from this JCO article whether the men labeled having Alzheimer’s disease had memory problems while still receiving ADT or whether they had true Alzheimer’s, i.e., long-term irreversible memory problems continuing after the ADT was stopped. There is one thing, however, this study does show: At worst, memory problems serious enough to be labeled as “Alzheimer’s” occur in in less than one out of every 200 men treated with ADT.

Sir Spheres for Liver Metastases from Prostate Cancer

BY MARK SCHOLZ, MD

Cancer that spreads outside the prostate gland is what makes prostate cancer dangerous. Metastatic prostate cancer cells cause malfunction by impeding normal function. Some organs, like lymph nodes for example, continue to function quite nicely, even if the degree of cancer spread is extensive.  Lymph node spread, therefore, is the least dangerous form of prostate cancer metastases.  At the other end of the spectrum is the liver, which is far less tolerant.  The seriousness of bone metastases, the most common site of prostate cancer spread, lies about half way between that of node metastases and liver metastases.


The earliest stages of metastases are microscopic and therefore invisible even with the best available technology. To be detected with the best available PET scan technology, small tumors must measure more than 1/8 of an inch across. For detection with standard CT scans and MRI scans, more than a half-inch sized tumor is necessary. Since the presence of metastases is such a defining issue when describing a cancer’s character, men who are newly-diagnosed are labeled as low, intermediate or high-risk depending on their estimated likelihood of micro-metastatic disease. Liver metastases are extremely rare at the time of initial diagnosis of prostate cancer. When they occur it is usually after many years of ongoing treatment for known metastatic disease in the bone.


Prophylactic treatment with hormone therapy, chemotherapy or radiation to treat the possibility of micro-metastases is common for high-risk prostate cancer and occurs maybe half the time in intermediate-risk prostate cancer. The goal is to cure the micro-metastases at an early stage when they are most susceptible to eradication, thus preventing the future development of detectable metastases which is what makes cancer life threatening.


When talking about prostate cancer, even though this is a blog about metastases, it should always be remembered that many common types of prostate cancer never spread. These low grade “cancers” are genetically distinct and represent a totally different category of disease.  However, when discussing the type of prostate cancer that is capable of metastasis, the following factors impact how dangerous it is:

1. The site of spread.
2. The extent of spread
3. The tumor cell growth rate
4. The efficacy of available treatment

As noted above, the liver is far less tolerant to metastatic invasion than bone or lymph nodes.  In addition, because liver metastases tend to occur in men with advanced disease, tumor growth rates tend to be brisk. Also, the most commonly administered treatments, hormone therapies and chemotherapy, have often already been tried before liver metastases first develop. The advent of liver metastases, therefore, usually represents a very serious and life threatening issue.


Liver metastases may first be suspected when standard blood tests such as ALT, AST or ALP which are components of a hepatic panel blood test, register outside the normal range. Investigation into their cause often leads to doing a CT scan or MRI scan of the abdomen and pelvis to confirm the presence of disease in the liver. Alternatively, a scan may detect abnormal spots in the liver during routine periodic scanning that is being performed as regular surveillance.


Hormone therapy with Lupron, Zytiga and Xtandi, or chemotherapy with Taxotere, Jevtana and Carboplatin, is the standard approach to treatment for liver metastasis.  However, these treatments may have already been tried or may no longer be effective.  Since liver failure is tantamount to death, prostate cancer growth in the liver needs to be stopped immediately, regardless of how the disease is faring in the bones or nodes.


Much that has been learned about the treatment of liver metastases comes from reviewing common methods for managing metastatic colon cancer. The liver is the cancer’s preferred site of metastatic spread for colon cancer.  Treatments that have been employed include surgery, radiation and blockage of the blood supply to the liver by embolization of the arteries, all with variable success.  More recently, radioactive microspheres injected directly into the tumor, called SIR-Spheres, have shown notable efficacy with very tolerable side effects.


Prostate cancer and colon cancer are similar in that they are both adenocarcinomas which means they are derived from glands. Therefore, they are likely to have similar susceptibility to radiation.  As such, we have been administering SIR-Spheres to a limited number of prostate cancer patients with liver metastases.  Results have been encouraging with a notable improvement of survival compared to our historical experience treatment patients with liver metastases without SIR-Spheres.  Our preliminary results using SIR-Spheres in six patients is being presented at the 2016 Genitourinary Cancers Symposium - San Francisco in January 2016.

Active Surveillance: Follow-Up Essential

BY RALPH BLUM

 

A recent UCLA study found that a significant percentage of men diagnosed with low-risk prostate cancer who chose "active surveillance," rather than aggressive treatment in order to avoid the debilitating side effects of surgery or radiation, don't follow up with the required tests and office visits.

 

This is an alarming finding, because not being monitored appropriately puts them in danger of the cancer progressing or metastasizing without their knowledge. Before patients decide on active surveillance as a management option for prostate cancer they should agree with their physician on a strict follow-up schedule to closely monitor the cancer.

 

There is no doubt in my mind that active surveillance is the smart treatment option for low-risk prostate cancer.  With other cancers, or if the prostate cancer is aggressive, the main issue is survival. But with low-risk prostate cancer, since long survival is the norm, the most important consideration is quality of life. Having said that, with active surveillance regular check-ups are essential, because when men are watched closely, treatment can be started at the first sign of cancer progression.

 

So what does active surveillance require? How exactly is it carried out?

 

Different centers have different requirements. At a 2007 Active Surveillance Conference, attended by over 200 of the world's leading prostate cancer experts, the attendees recommended a biopsy after one year, subsequently repeating it every two to three years. But as I have often said, I am not a fan of biopsies. So I prefer to recommend doing a repeat targeted biopsy only on the basis of a PSA and prostate imaging with either color Doppler ultrasound or 3T multi-parametric MRI.

 

Here is an Active Surveillance Protocol that Dr. Mark Scholz recommends:

 

• PSA every three months
• Rectal examination every 12 months
• Color Doppler ultrasound annually
• Multi-parametric MRI annually

Whatever protocol your urologist recommends you need to be committed to following it. It may be inconvenient or uncomfortable but the alternative is aggressive treatment that has the potential to leave you with erectile and urinary dysfunction.

 

There is always the consideration to just treat the cancer and be rid of it. But having lived with this disease for over two decades, with my prostate intact, I am a firm believer in avoiding radical treatment and preserving quality of life as long as possible. And if you have low-risk prostate cancer, bear in mind that the longer you can wait before you submit to radical treatment, the better the odds are that research in the field will have advanced, and treatment will have become more effective and less toxic.                                                                

What’s Going On at the Prostate Cancer Research Institute

BY MARK SCHOLZ, MD
In 2016, the PCRI will celebrate its 20^th anniversary.  The PCRI, founded in 1996 by Dr. Stephen Strum and I, was originally funded by a generous grant from the Daniel Freeman Medical Foundation.  This initial grant was spent on hiring Harry Pinchot, aka Helpline Harry. The helpline format adopted at the PCRI was modeled after the work of Lloyd Ney, the founder of PAACT.  PCRI’s helpline presently has four counselors: Jonathan Levy, Silvia Cooper, Bob Each and Charles Kokaska, all who provide unbiased prostate-cancer-related information, free of charge to the public.


PCRI started doing patient-focused conferences in 2006. Since 2006 this has become an annual meeting. The conference has grown in stature through the years by attracting world-renowned prostate cancer experts who are invited to present the latest information on optimal diagnosis and therapy. DVDs of the presentations are distributed throughout the world.  Partly due to the wonderful moderating presence of Dr. Mark Moyad, the conference has grown to be the largest patient-orientated prostate cancer conference in the world.


PCRI makes its biggest impact via its online presence by providing articles and blogs authored by prostate cancer experts from every specialty. But more importantly, PCRI is presently in entering into a new phase, the development of the SHADEs of Blue organizational format, a methodology to help patients sort through the overwhelming amount of information by reducing it into a more manageable bite-sized format.  As we all know, the internet has solved the problem of getting access to information.  Now the biggest problem patients face is information overload. How does one sort through the deluge of unfiltered information?


The development of the SHADES of Blue program will address this problem of information overload by segregating prostate cancer information into five large categories. Three are for the newly-diagnosed, Low, Intermediate and High-Risk, and two are for men with either relapsed disease or metastatic, hormone-resistant disease. The SHADES program is a big undertaking for a small organization like the PCRI, especially considering that we have expanded our conference schedule by now doing two conferences annually with the addition of the Mid-Year Update in March.


Looking to the immediate future, I never been more excited by the PCRI’s potential for making a positive impact in the lives of men with prostate cancer.   If my suspicious are correct, PCRI’s visibility is truly on the verge of taking a big jump.

Photons or Protons? You Choose

BY RALPH BLUM


Following in the footsteps of robotic surgeons, prostate cancer continues to go high-tech. Radiation, for instance, is no longer just radiation. There are now numerous different ways to deliver it. But the two methods I want to write about here are Intensity Modulated Radiation Therapy (IMRT), and Proton Beam Therapy (PBT).


The predominant method in the U.S. for the past decade is IMRT, a complex procedure that precisely targets the prostate gland with multiple beams of high energy light (photons) at different angles and intensities while significantly lowering the risk of damage to the surrounding tissues and organs.  This greater accuracy in targeting also allows the therapist to maximize the radiation dose to the tumor.  IMRT has at least as effective a cure rate as surgery, and without the risks and side effects of a major surgical procedure.


Having said that, I have recently been checking out Proton Beam Therapy, a form of radiation that targets the tumor with charged particles called protons. Several decades ago, Loma Linda University in California was the first to begin administering PBT. At that time, I had a friend who, at 55, developed prostate cancer and was one of the first patients at Loma Linda when proton therapy was at a very early stage.  Bill has been free of cancer for over twenty years, and only recently had a rise in PSA and is discussing further treatment.


Since then, thanks in part to marketing hype, PBT is becoming increasingly popular.  Now, M.D. Anderson, Harvard, and the University of Florida in Jacksonville, are among the major medical centers that have made PBT available. And The Mayo Clinic is building two proton therapy centers (one in Rochester, one in Arizona) at a cost of $380 million. Naturally PBT costs considerably more than IMRT.


When weighing treatment options, patients generally consider two main factors: potential side-effects, and successful outcome. So how do these two therapies measure up? Well, there is considerable controversy in the urologic community. The good news is both therapies have a high cure rate. Studies that have tried to compare IMRT with Proton therapy indicate that the outcomes are quite similar and that the side effects are comparable.  No large randomized trials have been published that directly compare patient outcomes with the different techniques.  So in the end, a treatment decision usually depends on such variables as patient preference and doctor preference.


It is reasonable, therefore, to keep in mind that any medical center that has invested an astronomical amount of money on equipment will end up wanting to use it.

Biopsy, Not PSA, Leads to Prostate Cancer

BY MARK SCHOLZ, MD

Prostate cancer is way over treated, and the problem starts with over diagnosis.  Once men are diagnosed, the fear of cancer naturally drives them toward radical treatment. In 2011 the US Preventive Services Task Force intervened, trying to stop overtreatment, argued that PSA testing causes more harm than good.

Some have questioned the expertise of the panel because of the lack of representation by urologists, radiation therapists or medical oncologists --the types of doctors usually responsible for treating prostate cancer.  Actually, the credentials of the panel constituents appear entirely appropriate to comment on screening, because this is an area of medicine usually handled by primary care doctors.  The panel members consisted of twelve MD’s and four PhD’s trained in primary care, public health and statistics.

The Task Force agrees that PSA screening may save lives. Their judgment, however, was that too few lives are saved to justify thousands of men getting unnecessary radical treatment. One statistic indicates that a thousand men must be screened to save one life within the next 12 years.

Personally, I agree with the panel in regards to over diagnosis is a root cause of over treatment. However, simply discarding PSA is an oversimplification. PSA can detect a variety of problems infection and benign prostate enlargement. Actually, the majority of men with elevated PSA, don’t have prostate cancer.

No, the real problem is after a PSA test rises. Every year, a million men are advised to have a dozen, large-bore needles jabbed into their rectums “Just to be sure there is no cancer.”  Such behavior sounds ridiculous, but really, it is just the survival instinct in action. People will do practically anything when they fear for their lives.

So if not a biopsy to evaluate an elevated PSA, what’s next?

First, the fear must be faced. Ralph Waldo Emerson says “Knowledge is the antidote to fear.” So let’s look at some basic facts:

• One out of 38 men die of prostate cancer
• One out of seven men are diagnosed with prostate cancer
• In men who are “diagnosed”
  • Five-year survival is 100%
  • Ten-year survival is 99%
  • Fifteen-year survival is 94%
    

Considering it is cancer, survival rates are great! At least these numbers should overcome any urge to rush. Clearly there is plenty of time is to study and learn more. Confusion arises because a minority of prostate cancers can indeed be dangerous. Not as dangerous as lung or pancreas cancer which kill within months. However, demise from prostate cancer certainly qualifies as “dangerous,” even if it is rather infrequent and much postponed.

These statistics reveal something else that is quite useful. Prostate management issues are of long-range nature, like saving for college or for retirement. Just as expert financial planners are limited in the ability to make predictions about economic activity ten years in the future, doctors should be equally humble in their pronouncements about the future of prostate cancer. We don’t know for sure, but we strongly suspect there will be substantial breakthroughs in the diagnosis and treatment of prostate cancer in the next ten years.

For the short term, I think the best way to proceed is with imaging the prostate with a 3Tmulti-parametric MRI or color Doppler ultrasound. Scans are about as accurate as a random biopsy for detecting aggressive cancers and they usually fail to detect the harmless low grade types, which is a good thing. However, if there is a worrisome abnormality, a targeted biopsy with just a couple cores is needed.

Over-diagnosis and over-treatment is not due to PSA. It’s the misguided policy of rushing into an immediate random biopsy whenever there is a slight elevation.  .The random biopsy procedure should be abandoned.  PSA abnormalities should be evaluated with prostate imaging A targeted biopsy can be considered in men who have a distinct abnormality detected by imaging.