THE "NEW" PROSTATE CANCER INFOLINK

Some data presented a few weeks ago at the annual meeting of the European Association for Urology appear to have surprised not only the study’s authors, but pretty much everyone else as well. A report on these data appear in the April 1 issue of Renal & Urology News.

The presentation by Towe et al. was based on a study carried out at the University of California, Irvine. The study enrolled 834 men, all diagnosed with low-risk prostate cancer; all treated by robot-assisted radical prostatectomy; and all followed for a reasonable (but not a long) period of time.

The report on Renal & Urology News doesn’t tell us the time frame over which these patients were treated. However, we understand that the study started to enroll patients in 2008. We have been unable to identify this study on the ClinicalTrials.gov web site.

Here is a summary of the core findings:

• The average (median) follow-up was 33 months or 2.75 years.
• All surgeries were carried out by the same physician.
• Of the 834 men in the cohort
  • 152 (18.2 percent) were treated with testosterone replacement therapy (TRT) at some point after their surgery.
  • 682 men (81.8 percent) did not get TRT post-surgery.
• Among the men who did get TRT,
  • 15/152 (9.9 percent) had a biochemical recurrence during follow-up.
  • 4/152 (2.6 percent) had a biochemical recurrence within 12 months post-surgery.
• Among the men who did not get TRT,
  • 160/682 (23.5 percent) had a biochemical recurrence during follow-up.
  • 81/682 (11.9 percent) had a biochemical recurrence within 12 months post-surgery.
• TRT was associated with a median delay of 18 months in time to disease progression.

Biochemical recurrence was defined by Towe et al. according to standard criteria post-surgery: two consecutive PSA level of 0.20 or higher.

Dr. Thomas Ahlering, the study’s senior author was reported, in a statement released by the EAU, as saying:

This is not what we set out to prove, so it was a big surprise: not only did testosterone replacement not increase recurrence, but it actually lowered recurrence rates. While the testosterone is not curing the cancer per se, it is slowing the growth of the cancer, giving an average of an extra 1.5 years before traces of cancer can be found. We already know that testosterone can help with physiological markers such as muscle mass, better cholesterol and triglyceride levels and increased sexual activity, so this seems to be a win-win.

We need to recognize that the men in this study received treatment for their prostate cancer some time after active surveillance started to become a recognized option as first-line management for low-risk prostate cancer here in the US.

There are all sorts of unanswered questions about this study which may get answered when the full paper is published; for example:

• How many of the patients were low risk at diagnosis, but turned out to be higher risk based on their post-surgical pathology?
• How many of the patients were hypogonadal (i.e., had a lower than normal serum testosterone level) at the time of diagnosis and prior to surgery?
• Why were specific patients given TRT? Were there specific reasons?

We note that in the report on this presentation on the UroToday web site, it states that the patients who were given TRT were “carefully selected”, but the report gives no further details.

In the statement issued by the EAU, Ahlering is also quoted as stating that:

We’re not suggesting that treatment methods be changed just yet, but this puts us at the stage where we need to question the taboo against testosterone use in prostate cancer therapy — especially for low-risk patients after radical prostatectomy. We need the oncology/urology community to begin to review testosterone use.

Of course the only truly accurate way to resolve issues like this will be through large, randomized clinical trials. That may be difficult in a case like this, particularly since there has now been such a major shift away from the use of radical prostatectomy as a first-line treatment for men with low- and very low-risk forms of prostate cancer.

We note that in the reports available at this time, there is no indication that the patients enrolled into this study were carefully evaluated to ensure that they really did meet criteria for low-risk disease (as would be done customarily, today, for patients being placed on an active surveillance protocol). This is not a criticism of the study. It is merely an observation suggesting that a significant percentage of these patients probably did turn out to have higher-risk disease when re-evaluated based on the pathological findings post-surgery.

For some 70 years now, the urology community has being having a love-hate relationship with TRT. On the one hand, most urologists (and some other physicians) are very willing to prescribe TRT for men who either have demonstrably low serum T levels or who feel that they have low libidos or loss of physical stamina. On the other hand, most urologists are also loathe to give any amount of TRT to a man who is at high risk for, has been diagnosed with, or has been treated for prostate cancer (based on the work of Huggins and colleagues back in the 1940s which really only applied to men with metastatic prostate cancer).

From a purely biochemical — as opposed to a clinical — perspective, we know that what is important in the way that living organisms work is commonly the balance of hormonal levels in that organism — not the absolute levels of individual hormones. It is long past time for the whole issue of hormonal balance and patient risk in the management of prostate cancer to be given a thorough scientific overhaul, and that could lead to a clinical overhaul as well.

Filed under: Uncategorized | Tagged: low risk, replacement, serum, surgery, testosterone, TRT |