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

Tuesday, February 25, 2014

Xtandi (enzalutamide), the Star of the 10th Annual Genitourinary Meeting


The GU-ASCO meeting kicks off the first of five annual prostate cancer meetings that are on my calendar to attend every year. The other four meetings are hosted by the American Urological Association (AUA) in May, the PCRI meeting in September, the American Society of Therapeutic Radiation Oncology (ASTRO) that is also in September and the Prostate Cancer Foundation retreat (PCF) that occurs in November.  
Since GU-ASCO is the first meeting of the year, the new scientific research presented sets the tone for the whole Year.  This year’s meeting was dominated by the release of a report showing that Xtandi, a potent oral anti-cancer agent, prolongs life compared to placebo when administered prior to the chemotherapy drug Taxotere (a previously published study has already shown that Xtandi prolongs survival when used after Taxotere).
It’s exciting to see an effective pharmaceutical agent get expanded access. This will lead to a greater number of men benefiting with prolonged survival and better quality of life. The bare bones of this groundbreaking report are summarized here:
Abstract #1: Enzalutamide in men with chemotherapy-naive metastatic prostate cancer. Results of the phase III PREVAIL study.
In this randomized, double-blind, placebo-controlled, multinational phase 3 study, chemotherapy-naive patients with metastatic hormone-resistant disease were treated with either enzalutamide or placebo.
Results: A total of 1,717 men were enrolled. Final results showed a significant benefit of enzalutamide over placebo with a 30% reduction in risk of death and an 81% reduction in risk of radiographic progression or death. At the time of the analysis, 28% of enzalutamide patients and 35% of placebo patients had died.
The findings of this study almost certainly indicate that the FDA will approve Xtandi for use prior to Taxotere and in the near future,  Xtandi will compete head to head with Zytiga and Provenge, both of which are already FDA-approved for men in the pre-chemo category.
The fact that FDA approval is almost guaranteed means that doctors are going to start asking a very important question:  What is the optimal way to sequence these three medications?
Presently there is no clear answer about whether Zytiga should be before Xtandi or vice versa. However, there are several very strong arguments that Dendreon’s product, Provenge, a medication that works by stimulating the immune system, should go first:

1.   Provenge only takes 6 weeks to administer, so there is no problem adding other anticancer agents after Provenge administration is complete.

2.   Immune treatments in general are thought to work better when initiated at an earlier stage, before the cancer becomes more entrenched and starts to suppress immune function.

3.   Provenge changes the immune system in a fashion that keeps working indefinitely after the initial 6-week treatment period is passed.

4.   Because insurance only pays for Provenge in men with rising PSA levels, starting Xtandi or Zytiga, both effective in lowering PSA, can substantially delay the initiation of Provenge.   
There seems to be broad consensus that Provenge should be first in line.  The real question then is, “What should come second, Xtandi or Zytiga?”

At the GU-ASCO meeting there were a number of reports, including a report from our office, that show reduced anticancer effects of Xtandi when used after Zytiga.  This is hardly surprising since the phenomena of progressively increasing cancer resistance with each cycle of therapy have been known about for 30 years. Preliminary reports also show a reduced Zytiga response-rate when it is used after Xtandi.

While these reports document that the first agent selected is likely to be used for a much longer time period than the agent that follows, so far there are no studies evaluating whether sequencing  affects overall survival.  Xtandi clearly has reduced anticancer activity after Zytiga. The same, however, has also been observed in reports evaluating Zytiga in men who have previously failed Xtandi.

The jury is still out. Until further comparative studies are performed, no one knows if there is an advantage to using Zytiga first or Xtandi first.  Presently however, I think most experts are assuming that Xtandi and Zytiga seem to have similar overall anti-cancer potency, the preference of sequencing one agent over the other to be first in line is unlikely to have a major impact on overall longevity.

Tuesday, February 18, 2014

Taking Charge of Your Treatment


The condition known as “selective inattention” plagues our understanding:  We hear what we want to hear. I can think of no way around that defect. Some things just have to be repeated. And repeated, until they sink in.

I am now approaching my 82nd birthday, and my long and often humbling affiliation with prostate cancer began when I was fifty-eight. A slightly elevated PSA and a “lump” in my prostate led to a biopsy that the urologist evaluated as “suspicious for well-differentiated adenocarcinoma.” The intervening years have given me a profound education in taking responsibility (and at times failing to take responsibility) for decisions that have affected not only my health but also my emotional well-being.

If you have just been diagnosed with prostate cancer, you are walking into the middle of what my oncologist and writing partner, Mark Scholz, MD, calls “a medical minefield.”  Choosing a medical team that will lead you safely through the prostate cancer minefield is arguably the most important decision you will ever make.  And taking an active role in your team is the second most important. You are the person who has cancer, and a passive, “Whatever you say, doc,” attitude will not serve you well.

You need to be aware that over-diagnosis and over-treatment of prostate cancer are rampant. There are many reasons that so many doctors over-treat and over-test, not the least of which is that most of them are reimbursed for how much care they deliver. In fact hospitals, doctors, medical equipment manufacturers, pharmaceutical companies—all organizations that derive their revenue from cancer diagnosis and treatments--have a deeply vested interest in the “more-treatment-is-better treatment” paradigm. However, in the great majority of cases prostate cancer is very slow growing, so there is no reason to panic, or to act precipitously. So that for 9 out of 10 men reading this blog, “active-surveillance” should be your first step on this cancer journey as you weigh your treatment options—which must include the possibility of living with prostate cancer untreated.

You also need to be aware of the “Hammer Syndrome:” If you’re a hammer the whole world looks like a nail. To the surgeon the best option looks like surgery. A radiation oncologist will see radiation as the answer. A medical oncologist is more likely to suggest drugs. It can’t be repeated too often: Before you reach any treatment decision take the time to do as much research as possible, and make sure you explore every option. Do not go to just one doctor and say, “Treat me.” Get a second opinion. Ask questions. And don’t be pressured by anyone to hurry a decision.  Weigh all the pros and cons of each treatment recommended, and look carefully at prostate cancer from the potential cure versus quality-of-life perspective. Far too many men rush into radical treatment for what is typically a non-life-threatening condition when their number one priority should be guarding and preserving quality of life.

Few of us have any objective way to judge whether a particular doctor has the medical knowledge, skill and experience to treat our specific case with success.  I have dodged some major bullets over the years, but eventually it was my good fortune to fall into Mark’s compassionate and capable hands. And I can tell you that confidence in your doctor and belief in your chosen treatment are two of the great intangibles in a successful recovery. And guess what? Your successful recovery may include living a long and productive life with a chronic form of prostate cancer. At least, it has worked for me.

Tuesday, February 11, 2014

I Am Not a Urologist


In February, while attending the tenth annual GU-Oncology meeting, I was surprised to see my name listed on large posters around the meeting hall (along with about 30 other physicians).  The hosts of the meeting were honoring a very small group of doctors who have attended every single American Society of Clinical Oncology Genitourinary (ASCO-GU) meeting since the meeting’s inception 10 years ago.

A Prostate Cancer World Populated by Surgeons
It’s not surprising that at a meeting of 2,500 attendees, only 30 doctors were honored. This was not a urology meeting, as is typical with most prostate cancer meetings. This meeting was hosted by the American Society of Clinical Oncology*, an association of medical oncologists. Only 30 doctors were on the list because medical oncologists who consistently attend meetings focused on prostate cancer are rare. The prostate cancer world is run by urologists, who are surgeons. Urologists have dominated prostate cancer for 100 years, dating back to when surgery was the only effective cancer treatment available.

What is a Medical Oncologist?
I tend to assume that all my patients know that I am a medical oncologist, not a urologist. However, when I speak to patients, I frequently discover that men fail to understand the difference. The following short list might be help helpful.

Medical Oncologists:  

1.    Take leadership of a medical team comprised of medical doctors from various specialties

2.    Are trained to manage all types of cancer

3.    Supervise multimodality therapy (surgery, radiation, immune, hormonal and chemotherapy)

4.    Are board certified in internal medicine as well as medical oncology

5.    By observing patient outcomes, learn through first-hand experience which surgeons and radiation doctors are the most skilled

6.    Are trained in how to administer multiple different types of medications—both for cancer treatment and for overall health needs—safely, in combination

7.    Have no innate preference for surgery over radiation, since they perform neither

1.    Are trained first and foremost as surgeons

2.    Are trained to care of numerous noncancerous maladies of the genitourinary tract (kidney stones, erectile dysfunction, bladder infections, prostate enlargement, vasectomies, repair of congenital anomalies, urinary leakage, etc.)

3.    Have no internal medicine training

4.    Have a rudimentary understanding of cancer treatment (outside of doing surgery)
Let’s take up the issue of leadership. In this complex modern era, good medical outcomes require a coordinated team effort that maximizes the participation of all the different medical specialties. Five specialties commonly participate in prostate cancer management: urology, radiation oncology, radiology (reading scans), pathology (reading biopsy specimens under the microscope) and medical oncology.  Obviously, any kind of team, medical or otherwise, performs best with knowledgeable and experienced leadership. With almost every other type of cancer (besides prostate cancer) medical oncologists take the lead.

Longstanding Tradition Makes Prostate Cancer the Exception to the Rule
It’s surprising to most people that university medical oncology fellowship programs (like USC, where I trained) offer no training in the management of early-stage prostate cancer. This role has been totally abdicated to the urologists. While advanced-stage prostate cancer patients do transfer their care to oncologists somewhat more frequently, this happens in only half the men with advanced disease.

Studies show that 50% of men with advanced prostate cancer who succumb to progressive disease die without ever consulting with a medical oncologist!  This practice of urologists holding onto their patient to the bitter end may have been defensible back when the effective treatment options for advanced disease were limited to Lupron, Casodex and palliative spot radiation to the bones. However, forgoing oncology consultation in this modern era of Provenge, Zytiga, Xtandi, Xofigo and Jevtana, all of which are proven to prolong survival, borders on lunacy.

Yet despite there being over two million prostate cancer survivors in the U.S., less than a one-hundred (100) medical oncologists who actually specialize in prostate cancer, and almost all of these are in academia doing clinical or laboratory research. Outside of academia less than ten (10) medical oncologists specialize in prostate cancer fulltime. Three of these are in my office in Marina del Rey. The other free-standing medical oncology clinics that specialize in prostate cancer are listed at

Practice Makes Perfect
Real day-to-day clinic experience treating large numbers of men with one disease—in this case prostate cancer—improves the skill level of the practicing doctors. Skillful doctors are of great value because new medicines are being approved at an ever faster pace. Familiarity with their use can only be achieved at a high-volume prostate cancer clinic. A fulltime prostate oncologist gains practical experience that takes years to appear in textbooks.

Furthermore, prior to FDA approval, new drugs can only be obtained by participating in clinical trials. But it’s dangerous to conclude that every agent under clinical investigation will provide meaningful benefit. While there is no absolute inside information, most of the prostate oncologists in the country know each other so “inside information” can be learned from a simple phone call or a chance meeting at one of the various prostate meetings that occur throughout the year.

Finally, doctors who are involved in managing large numbers of men with prostate cancer also gain experience with the relative skill levels of other physicians on the medical team; the surgeons, pathologists, radiation therapist and the radiologists. Improved patient outcome is not simply the result of picking the right treatment.  You also have to select a doctor with special talent to administer it.

Don’t make the common mistake that urologists and medical oncologists are inter-changeable.  Having a highly trained and skilled surgeon can be lifesaving—when surgery is truly indicated.  However, in this modern era, radical prostatectomy should be the first choice in relatively few men. And even when surgery is the preferred approach, having a surgeon as the overall leader of your team is no longer ideal.

P.S. My apologies for radically digressing from the exciting information shared at the meeting.  My frustration with a world dominated by urologists clearly got the best of me.  I’ll take up the meeting highlights in my next blog (and in even greater detail in the next issue of PCRI Insights).

* As an aside, the acronym, ASCO, in Spanish means nausea, a name some consider apropos since oncologists are the main purveyors of chemotherapy.

Tuesday, February 4, 2014

The Humble Aspirin to the Rescue! Or Does an Aspirin a Day Help Keep Cancer Away?


There is reason to be grateful for this simple “wonder drug,” discovered in the mid-19th century by Friedrich Bayer and his partner, Johann Friedrich Weskott, in Barmen (today a part of Wuppertal), Germany—a modification of salicylic acid or salicin, which is actually a folk remedy found in the bark of the willow plant.

We keep aspirin around. We take it for headaches, to relieve pain, as a deterrent to heart attack and stroke.  Now, a new light illuminates the potential value of this humble drug.  Studies have shown the possible efficacy of aspirin and other non-steroidal anti-inflammatory drugs acting to reduce the risk of dying from cancer. It is suggested that these drugs inhibit the accumulation of somatic genome abnormalities, also known as SGA’s, that result in uncontrolled cancer cell growth. It appears that aspirin acts to slow the speed of mutation.

According to a study published in The Journal of Clinical Oncology, men being treated for prostate cancer who were taking aspirin regularly for other medical conditions were likely to live longer than men who were not taking aspirin.

The 2012 multi-center study was not a randomized controlled clinical trial of the kind that is considered the gold standard, but it adds to an intriguing and growing body of evidence suggesting that aspirin prevents the growth of tumor cells in a variety of cancers, including prostate cancer. Especially in high-risk disease for which there is no very good treatment. The risk of the cancer returning, and of it spreading to the bones, was significantly lower, as was the risk of dying from the disease.

According to Peter Rothwell of Oxford University, one of the leading experts on aspirin and cancer, “Aspirin reduces the likelihood that cancers will spread to distant organs by about 40-50 percent.”

Dr. Kevin S. Choe, assistant professor of radiation at University of Texas Southwestern Medical Center in Dallas and lead author of the paper, said that while it would be ideal to conduct a randomized study, doing so with prostate cancer patients would be difficult because the natural progression of the disease is so slow that you would have to follow men for many years. He added, significantly, that little money is available for research on aspirin because it is cheap and easily available!

One of the problems with aspirin therapy is you have to be patient and consistent, as most studies have found that it only becomes effective in 2-3 years. Also there is a risk-versus-benefit equation due to aspirin’s gastric and bleeding effects. However, cancer survivors concerned about recurrence, and those being treated for cancer worried about metastases should discuss an aspirin regimen with their doctor.