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  • If lymph nodes are + after RP: hormonal therapy as a sound tactic

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    Old 02-04-2008, 09:17 AM   #1
    IADT3since2000
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    Thumbs up If lymph nodes are + after RP: hormonal therapy as a sound tactic

    Recently I reviewed a DVD of a talk in January 2006 by Dr. Mark Scholz, one of the leading experts on hormonal blockade therapy, which he refers to as TIP (reminds me of VIP in that Dorris Day/Rock Hudson movie). In the past few years the term "Testosterone Inactivating Pharmaceuticals," TIP, has emerged to describe drugs that reduce testicular production of testosterone, block most of the ability of remaining testosterone to fuel the cancer, or block the conversion of remaining testosterone to DHT, dihydrotesterone, which is far more potent than testosterone as a fuel for the cancer.

    Near the beginning of his talk he gives these very encouraging facts about TIP for men with lymph node positive disease after an RP. I'm particularly impressed because recent reports are documenting success over followup periods of more than a decade. I'll use other terms, such as hormonal blockade, as I still find TIP an awkward term.

    For men with lymph node positive disease who had RPs, immediate hormonal therapy after the RP cuts ten year mortality from 43% without immediate hormonal therapy to 13%. I found a 2006 update of the ongoing study that he cited, now with average (median) survival at nearly a dozen years (11.9 to be exact, with a followup range from 9.7 to 14.5 for surviving patients), and it showed 1.84 times better overall survival, 4.09 times better survival for prostate cancer specifically, and a 3.42 times better progression-free survival. These are obviously huge differences! (Messing, 2006, Lancet)

    This ongoing study included 47 men who were randomized between 1988 and 1993 to receive immediate hormonal therapy and 51 men who were randomized to just being observed, with hormonal therapy given if distant metastases were detected or there were symptoms of recurrence. The hormonal therapy was either a LHRH-agonist drug (like Lupron, Zoladex, etc.) or a bilateral orchiectomy, and after the first year, the patients were assessed semiannually. While the abstract of the 2006 paper did not give the breakdown of numbers surviving at 11.9 years, a breakdown was given in an earlier report from 1999 (Messing, New England Journal of Medicine). It showed that at 7.1 years average follow-up, 7 of the 47 men receiving immediate hormonal blockade had died, which is 15%, versus 18 of 51 men in the observation group, which is 35%. The difference was statistically significant. Moreover, in this 1999 report, 77% of the men in the immediate hormonal blockade group were alive with no evidence of recurrence in contrast to only 18% in the observation group who were alive with no evidence of recurrence. Wow!

    Analysis in the papers indicates that the groups were well-matched for risk characteristics.

    This and other studies appear to me to indicate that patients whose lymph nodes were positive at RP after radical prostatectomy do much better if they do not wait to see if metastases develop but have hormonal therapy soon. There is another similar major clinical series with long-term follow-up with very encouraging results for men who had positive lymph nodes after RPs but were treated with early hormonal blockade, within six months of the RP. Abstracts of several reports on the series can be viewed by using the Government web site [url]www.pubmed.gov[/url] and searching for the surgeon behind the research, Dr. Horst Zincke of the Mayo Clinic in Rochester, Minnesota. This string will find these and others of his studies: "zincke h [au] AND prostate cancer AND adjuvant hormonal therapy AND radical prostatectomy". I just realized that Dr. Charles Myers describes earlier results for both the Zincke and Messing research on pages 51 and 52of his book, "Beating Prostate Cancer: Hormonal Therapy & Diet." Survival graphs in the book make the advantage for adjuvant hormonal therapy stunningly clear.

    While this information is encouraging on its own, we need to keep in mind that hormonal blockade and supportive technology has improved a lot since the last patient in the Messing trial was enrolled in 1993. That means survival odds should be even greater today. For instance, we now have strong evidence that combined and even triple hormonal blockade is much more effective than single hormonal blockade for many of us. We have learned a lot about the effectiveness of intermittent and one cycle hormonal blockade. Arguably the most serious complication of hormonal blockade therapy - lessening of bone density, could not be countered effectively when the earlier patients in this trial were treated in the late 1980s. But the first bisphosphonate - Aredia, was approved in 1991, and there have been several and much improved bisphosphonates approved since then, including Zometa, which, in fact, even helps counter bone mets while maintaining bone density. We also know a lot more about assessing and countering other side effects and complications of hormonal blockade. We have extremely precise and reliable ultrasensitive PSA scans to determine the state of the disease and effectiveness of therapy.

    Has anyone had lymph nodes that turned out to be positive for cancer after an RP? If so, were you put on hormonal blockade therapy, or were you advised about it?

    Jim

    Last edited by IADT3since2000; 02-04-2008 at 09:31 AM. Reason: Added mention of Zincke and Messing research in Myers book. Added right after initial posting.

     
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