Editor’s Note San Francisco experiment

Innovation in one’s work prevents boredom but also can be stressful. Just prior to the two-day audio recording that led to this program, I questioned my judgment in attempting to effectively moderate the dozen loquacious clinical research leaders who gamely agreed to participate in our Second Annual Prostate Cancer Update Think Tank, held in May during the American Urological Association meeting in San Francisco.

Most of the attendees had already participated in our Prostate Cancer Update audio series; however, that format is much more controlled and after 16 years of interviewing research leaders one-on-one, I pretty much know what to expect.

Recording and editing a Think Tank was a totally different story and something our group has never done before. Since only one faculty member could speak at a time, I was quite nervous that these esteemed leaders would feel muzzled and I would quickly resemble a frantically waving police person on a wild Italian traffic circle.

Fortunately, technology was on my side. Faculty members were provided with networked laptop computers, granting them the opportunity to constantly input comments while others spoke. This also helped me to direct traffic and “green light” those who typed provocative comments.

The edited audio result of this educational endeavor is divided into three segments:

1. Adjuvant endocrine therapy for men with high-risk localized tumors

Bill See presented an update of the most important evolving research database on this question: the Early Prostate Cancer Trials of high-dose bicalutamide. To continue the theme of data that isn’t as straightforward as we would like it to be, the Scandinavian portion of this mega-trial showed improved survival in men with high-risk tumors treated with bicalutamide, but decreased survival in men with low-risk tumors. Statistical fluke? That doesn’t seem likely, but time will tell.

The group also watched a web replay of Richard Peto’s presentation from the “Best of Oncology” session of the last ECCO meeting in Belgium. (web link) During this compelling lecture, the renowned and recently knighted Oxford statistician (affectionately known to friends as “Sir Richard”) compared his unpublished international meta-analysis of adjuvant endocrine therapy for prostate cancer to a series of similar analyses in breast cancer, and concluded that the treatment benefits are about the same.

Peto notwithstanding, tamoxifen and other endocrine therapies are utilized routinely in the adjuvant breast cancer setting but relatively infrequently in men treated with radical prostatectomy. Yes, PSA is available to allow early therapy at relapse, but as Judd Moul so eloquently stated, we have no data to tell us that treating at early PSA progression results in the same survival benefit as it does immediately post-op.

Ed Messing — the only Think Tank member besides me to attend Peto’s closed 2003 Oxford meeting where he first unveiled these data — re-presented to the group his oft-quoted ECOG trial in node-positive patients. That study demonstrated a persuasive survival benefit to adjuvant castration, although patient accrual was very modest. One of his key conclusions is that no data are available to determine if the same benefit would have been observed if therapy had been delayed until PSA progression.

2. Management of PSA-only relapse

Judd Moul started the debate by noting his embarrassment that virtually no prospective randomized trial evidence exists to support physicians and patients facing this challenging situation. While retrospective data he presented from his CPDR database suggests that earlier endocrine therapy in these men results in delayed clinical progression, survival data are not mature enough to draw conclusions.

The Think Tankers seemed to uniformly support Judd’s risk-stratified approach to decision-making for biochemical progression, but they also agreed that, to a great extent, clinicians are “flying by the seat of their pants” when managing these patients.

Laurence Klotz further complicated the discussion by presenting a new analysis suggesting that maximal androgen blockade may be more effective than previously believed, if the antiandrogen utilized is bicalutamide.

3. Chemoprevention

Ian Thompson presented the somewhat ambiguous data from his trial using finasteride, which was published in the New England Journal of Medicine last year. The good news is that fewer prostate cancers were diagnosed in patients treated with finasteride; the bad news is that more high-grade tumors were also observed in these men.

Listeners to our series often comment in emails that they enjoy hearing the experts squirm in their seats when I ask what research data like this means to patient care. Ian and the other attendees seem to conclude that in a man with a BPH indication or semi-indication for finasteride, these data suggest you can “kill two birds with one stone” with finasteride, assuming potential sexual dysfunction is not a major concern.

Sex or no sex, I don’t know how comforting these data will be to men at high risk. Thank God that Eric Klein and the SELECT gang got that study done. Hopefully, when those data are mature, we will have a better option (or options).

With all these controversies and data glitches, our educational experiment at times felt more like stop-and-go traffic than a smooth country ride, but embedded within the back-and-forth are a number of audio nuggets that I believe will assist in patient care. If nothing else, perhaps this program will further motivate us to enroll more patients in clinical trials so that we can obtain answers to these critical questions.

For this print supplement to our program, we have included an edited version of four of the most provocative presentations in the meeting. The PowerPoint slide files of these lectures are enclosed on the first CD and www.ProstateCancerUpdate.net.

Needless to say, we would very much like to know whether the enclosed program resonates with our loyal listeners, and your feedback on the Think Tank educational concept is welcomed and appreciated.

— Neil Love, MD
NLove@ResearchToPractice.net

Select Publications

Iversen P et al; Casodex Early Prostate Cancer Trialists’ Group. Is the efficacy of hormonal therapy affected by lymph node status? Data from the bicalutamide (Casodex) Early Prostate Cancer program. Urology 2004;63(5):928-33. Abstract

Messing EM et al. Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med 1999;341(24):1781-8. Abstract

Moul JW et al. Early versus delayed hormonal therapy for prostate specific antigen only recurrence of prostate cancer after radical prostatectomy. J Urol 2004;171(3):1141-7. Abstract

Peto R. Breast and prostate cancer: 10 year survival gains in the hormonal adjuvant treatment trials. Presentation, Best of Oncology, European Cancer Conference 12, 2003. No abstract available

See W et al. Immediate treatment with bicalutamide 150mg as adjuvant therapy significantly reduces the risk of PSA progression in early prostate cancer. Eur Urol 2003;44(5):512-7. Abstract

Thompson IM et al. The influence of finasteride on the development of prostate cancer. N Engl J Med 2003;349(3):215-24. Abstract