Highlights of the 2006 Prostate Cancer Symposium
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The 2006 Prostate Cancer Symposium, held in San Francisco February 24-26, was a unique and noteworthy event. Accurately subtitled “A Multidisciplinary Approach”, the three-day symposium brought together “leading experts in the fields of urology and medical, radiation, and surgical oncology… with the goal of increasing the understanding of the diagnostic and therapeutic strategies that can be used in the multimodality treatment of patients with prostate cancer.”

In all, 364 abstracts of papers were presented. Of particular interest were the following subjects that attracted abstracts from several speakers.

  1. Obesity and Prostate Cancer
  2. Cancer Epidemiology, Google, and the promise of a Global Biospecimen Network
  3. Active Surveillance (Watchful Waiting)
  4. HRPC Treatment

Obesity and Prostate Cancer
Dr. Peter R. Carroll of the UC San Francisco Comprehensive Cancer Center reported that obese men are more likely to have positive surgical margins but that their risk of biochemical recurrence, second treatment and prostate-related death appeared to be no different than they are for the non-obese group. He also stated that although diet and supplements may reduce the risk of prostate cancer (PC), it is unknown whether they have an effect in men already diagnosed.

Dr. Stephen J. Freedland of the Duke University School of Medicine reported that Duke researchers have found that “the association between obesity and the risk of being diagnosed with prostate cancer is less clear. Whereas some older studies – particularly those out of Europe – suggested obesity was associated with the risk of being diagnosed with prostate cancer, more recent studies from the United States suggest that obesity may actually be associated with a lower risk of being diagnosed with prostate cancer among certain subsets of men.” (There may be other barriers to diagnosis.)

Cancer Epidemiology, Google, and the Promise of a Global Biospecimen Network
Clinton Leaf of Fortune magazine expanded on his provocative article, “Deadly Caution”, in which he wrote,“ our regulators have fallen prey to a deadly caution. Simply put, the need for certainty in drug approval is killing people. Excessive caution is delaying the availability of potentially helpful treatments for cancer, multiple sclerosis, Parkinson’s, and a host of other ailments; it’s slowing the absorption of new knowledge and diagnostic tools into medical practice; and it’s discouraging the pursuit of vaccines and next generation antibiotics that could save tens of millions of lives.” In his talk at the symposium, he described the need for a data management system for cancer researchers that would link the millions of data points relevant to their work. He concluded that the perfect model for such a global information system already exists: Google.

Active Surveillance (Watchful Waiting)
A number of papers were delivered on this subject. In the first, Dr. Anna Bill-Axelson of the Scandinavian Prostate Cancer Group described a ten-year study from 1989 to 1999. A total of 695 men, 75 or younger, with newly diagnosed PC were randomly assigned to receive either radical prostatectomy (RP) or watchful waiting (WW). Follow up included PSA testing every six months and a bone scan annually. End points were death, occurrence of distant metastases, and occurrence of local progression. Systemic hormone treatment was recommended if metastases were observed. By the end of 2003, no men in the RP arm had died of PC, compared to 50 in the WW arm. However, since the study allowed participants with PSAs approaching 50 ng/mL and Clinical Stage T2 to participate, it is clear that many in the WW group were not good candidates for WW and warranted earlier treatment.

Dr. Leonard Klotz of the University of Toronto described a study with different participant qualifications and quite different results. His study consisted of 299 patients followed with active surveillance with selective delayed intervention. “Patients under age 70 were required to have a PSA less than or equal to 10 and Gleason 6 or less. Patients over 70 were eligible if their PSA was less than 15, and Gleason 7 or less (3+4)… Patients were followed with active surveillance until they met specific criteria defining rapid or clinically significant progression” [PSA doubling time (PSADT) of < 2-3 years].With a median follow-up of 72 months, 65% of the patients have remained on surveillance. At nine years, only two of the 299 patients have died of PC. Dr. Klotz concluded that “The approach of active surveillance with selective delayed intervention based on PSADT represents a practical compromise between radical therapy for all… and watchful waiting with palliative therapy only.”

Dr. Anthony V. D’Amico of the Dana Farber Cancer Institute reported from his study of 206 men with a median age of 75 that “death from prostate cancer was not observed in men who experienced PSADT greater than 12 months and who had salvage [ADT] initiated at a PSA of about 10 ng/mL,” and that “in the setting of salvage [ADT] initiation at a PSA level of 10 ng/mL, PSA failure did not shorten survival unless the PSADT was less than six months.” He concluded from this study that “Men with a PSADT greater than 12 months could be considered for entry in a prospective randomized study evaluating the effect on survival of initiating [ADT] at a PSA level of 10 ng/mL versus at the time of bone, visceral, or lymph node metastases.”

PCRI co-founder Mark Scholz, MD had led a team that did a retrospective chart review of 154 PC patients with negative bone scans and PSAs < 100 who had started on ADT before January 2000. The study team evaluated the predictive value of Gleason score, initial PSA, PSA doubling time, clinical stage, and ultra-sensitive PSA nadir for their ability to predict early progression to bone metastases within 72 months of starting an anti-androgen and an LHRH agonist. The report described the finding that “Ultra-sensitive PSA nadir (= 0.5 ng/ml) is a more accurate indicator of early progression to bone metastases (90%) than Gleason score (75%) as well as being more sensitive and specific 72% vs. 37% and 95% vs. 86%, respectively).” Moreover, the report concluded, this prognostic information provided by PSA nadir is obtainable within the first eight months of starting ADT in 97% of the patients.

Hormone Refractory Prostate Cancer Treatment
Dr. Cora Sternberg of San Camillo and Florlanini Hospitals in Rome recommended when and how to treat hormone-refractory disease with chemotherapy. She pointed out that both TAX 327 and SWOG 9916 clinical studies demonstrated that a docetaxel regimen can reduce the risk of death by 20-24%. She also mentioned the SPARC trial under way, which will compare satraplatin plus prednisone to prednisone alone. She concluded that “Chemotherapy is clearly indicated for patients who have symptomatic metastatic hormone-refractory prostate cancer. However, only a few small Phase II trials have addressed the optimal sequencing of therapy trials regarding the timing of chemotherapy. Taxotere works after mitoxantrone; mitoxantrone is less effective after docetaxel; and docetaxel is now being combined with several newer biologic and targeted therapeutic agents. Newer approaches and better drugs are clearly needed.”

Dr. Maha Hussain of the University of Michigan described a new generation of clinical trials commencing to evaluate a variety of new agents against traditional targets as well as against entirely new biologic targets as shown below. However, she cautioned, “ It is too soon to assess what roles these agents will play in the treatment of hormone-refractory disease, either as single agents or in novel biotherapy-chemotherapy combinations with more traditional cytotoxic agents such as docetaxel. (For a listing of novel agents being studied in advanced PC, see Table 1 of “Chemotherapy for Prostate Cancer” which appears on page 6 of this issue of Insights.)

Dr. Eric Small of UC San Francisco presented a talk on the rationale for Immunotherapy in PC to induce antibody and/or T-lymphocyte immune responses targeted at cancer cells. He discussed G-VAX, Provenge and CTLA-4 Blockade-based Immunotherapy, all of which have exciting possibilities. He stated that the overall survival benefit seen with Provenge seemed to be significant. There were other papers covering other targets arising out of epigenetics and modification of proteins. EGFR and HER-2 were discussed as potential therapeutic targets. He concluded that “Most emerging immunotherapeutic approaches have been tested in patients with advanced prostate cancer. These patients, however, possess a high frequency of underlying immune suppression, so testing patients with less advanced disease will be important. Additionally, combining various treatment modalities (e.g. antigen presentation together with an immunostimulatory approach) will likely be necessary.”

ASCO Special Lectureship
by Dr. Donald Coffey
In his own inimitable way, Dr. Coffey gave a provocative presentation that asked WHY some treatments work – citing Lance Armstrong as an example. The talk ranged widely, and included self-organization, chaos, and how hyperthermia increases the effect of chemotherapy and radiation. Since cancer cells are sensitive to heat, heat can kill them before it damages normal cells. If you direct the hyperthermia directly to the tumor, you can enhance immunology, radical prostatectomy, and chemotherapy.