BLOGGERS: MARK SCHOLZ, MD & RALPH H. BLUM

The co-authors of Invasion of the Prostate Snatchers, blog alternate posts weekly. We invite you to post your comments.

Tuesday, May 10, 2016

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

Tuesday, March 22, 2016

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. 

Tuesday, March 8, 2016

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. 

Tuesday, February 23, 2016

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.