prost8blog

I heard on the news tonight a well known urologist expressing “outrage” at the findings of the task force. No doubt it is in other newscasts as well, but I can only stand to listen to so many… Let’s start by giving you the link to their recommendation which is here. My personal view is that the better recommendation would have been to have men read the document before deciding about being screened, and then make their own decision. I can’t tell you how many times I have had men read a clinical trial (which must explain in 8th grade language, the risks and benefits) consent form and then decline to participate because of the long list of side effects that accompany every drug imaginable. However in the case of PSA testing, these side effect considerations are outweighed by 2 decades of “promoting” screening by well-meaning (and some not-so-well meaning) physicians, often urologists. It is likely these doctors are biased, not because of any personal gain, but because they are on the front line of watching men die from prostate cancer and our long-standing belief is that early detection is the way to cure cancer. We all grew up in the era when Pap smears helped eliminate cervical cancer, and now we have a vaccine that can do even better.

In addition, I have virtually never met a man in my clinic or in our support group who didn’t feel either that 1) screening and treatment saved his life, or 2) that earlier detection/screening WOULD HAVE saved his life. The reality is that neither of these feelings is accurate. Some men who are screened will be treated, suffer the side effects, and never would have needed to know they had cancer. Others will be found “early” yet succumb to cancer that had escaped their prostate long before they were detected by the best techniques. And remember that those of us who have lived through the treatment have a built in emotional bias to think “we did the right thing” as a balm for the side effects we endure. In any event, this won’t be the last of this controversy, so we all have time to ponder the challenges of our “favorite” disease. Personally I applaud the USPSTF for taking a hard look at the evidence and putting it together in a document for all to see, and perhaps that document provides the best way to try and help men be better informed than having a political figure, war hero, or movie star stand before the general public and urge everyone to “get screened”.

Since I have previously written blogs on both the vaccine and the issue of screening (several blogs actually), I will simply pass these on with minimal commentary that follows. In the screening controversy, Europe updated their data showing that screening reduces death from prostate cancer but not overall mortality. My view is that 1) men with some high risk factor (African American, affected first-degree relative, BRCA-2 mutation family, etc) should be screened 2) others should be careful what they are asking for. And my corollary is that there are no screened/treated men who don’t feel either that screening saved their life or WOULD HAVE saved their life if it had been done earlier. But as a public health issue, since the vast majority of men will develop prostate cancer, current screening falls far short of the test we are looking for, and finding “more sensitive” tests is certainly not the answer. We need more SPECIFIC tests for the lethal phenotype.

As for the vaccine, there is a nice review of an alternative interpretation of the data that led to the approval of Provenge. It is worth knowing about, as is the intense interest in this vaccine from the financial community as well as patient advocacy groups. Be sure to read the whole article to get a balanced perspective. If you have the time, I also recommend reading a companion article that is linked on the Reuters page. Negative scientific studies are never published, nor do news writers bother making the few that are published into headlines. Companies like Amgen who have to put their resources where their “beliefs” lie do us a favor when they look into sensational claims.

In my view, the ideal physician is one who combines caring, compassion, empathy and introspection with hard core science. It is all too easy to become fascinated by the “mind over matter” paradigm and delude one’s self into thinking that a positive attitude will solve some very basic problem (like a mutation in DNA…). That said, I have little doubt that patients with a positive attitude generally enjoy their lives and whatever time they have left with friends and families more than those who become obsessed with one disease or another and launch on an endless search for an answer that probably doesn’t exist. My own experience with cancer in my parents, siblings and self has taught me that equanimity is one of the most essential characteristics of the cancer survivor. We all survive (with luck) various insults in our genomes or our environments for only so long, and then we move on. I will turn 65 this summer, and it is hard for me to internalize the reality that (again with luck) I may have only about 20 or so more years to enjoy this wonderful planet. Like everyone else, my mind tells me I will go on forever, but the harsh reality of 20 years is just plain difficult to internalize. Are you kidding me? 1992 seems like only yesterday!

Today I received an email from a colleague with a link to this website that is written by a psychologist. It seems to have lots of good resources, and I recommend it on your journey. Perhaps Dr. Pope will have helped winnow down the avalanche of information out there for you as well. Good luck!

The term oncogene addiction, or “driver mutation” is pretty central to most of the exciting progress being made in drug development for prostate cancer. At the outset, unlike breast cancer, ~95% of men with prostate cancer achieve some sort of remission with simple androgen ablation. This can take the form of surgical castration (orchiectomy), or the same thing can be achieved (lowering the T level in the blood) through administration of gonadotropin hormone releasing hormone analogs. The best known of these is probably leuprolide, but the same thing happens with other analogs, be they agonists, or the more recently marketed antagonist, degarelix. Overall, there is probably little difference which one is used.

The newer drugs are all designed to further inhibit testosterone stimulation in other ways. Examples include the better androgen receptor blockers (AR) like MDV-3100 or ARN-509 which are improvements on the small molecule blockers initially developed like flutamide or the more commonly used bicalutamide. Still in the laboratory phase are potentially even better blockers like a small molecule called EPI-001 that exerts its action not through blocking androgen binding to its receptor, rather blocking the receptor itself from interacting with DNA in the nucleus or with other proteins. Clearly there are many other approaches to the AR that will eventually lead to newer and better drugs. Blocking the cancer cells from making their own testosterone as is done with abiraterone or TAK-700 is a good example.  However, as Peter Nelson outlines in a lovely review article in the Journal of Clinical Oncology this week, additional mechanisms of resistance emerge. He has characterized this as different “states” of prostate cancer cell existence as shown in this figure from his publication:

States of the Androgen Receptor

Of  course it is important to understand that even this level of complexity is far too simple. The feedback loops that are activated when AR is blocked, or when it is no longer active are many and varied and will require a great deal of further work. Already, trials are evaluating mtor inhibitors like temsirolimus in blocking some of these feedback loops.  Nevertheless, it is great to see the increasing knowledge that will lead to suppression of prostate cancer in patients, and as I have often said, in this field if we can keep patients alive long enough to die of a heart attack or some other malady, we can claim it as a “cure”.

The WordPress.com stats helper monkeys prepared a 2011 annual report for this blog. It is somewhat interesting to look at what topics generated the most interest as well as where visitors came from. To all of you who took the time to comment, I thank you for adding to the discussion and look forward to continuing to find topics of interest to bring to your attention in 2012. I sincerely welcome suggestions for topics that you would like to see covered. Just add them as comments to this post and I will try to get through them in coming weeks . Happy New Year!

Here’s an excerpt:

A New York City subway train holds 1,200 people. This blog was viewed about 4,600 times in 2011. If it were a NYC subway train, it would take about 4 trips to carry that many people.

Click here to see the complete report.