Targets for improving the state of management of advanced prostate cancer include the development of new diagnostic modalities with better performance in detecting recurrent disease, additional monotherapy or combination treatment options, and strategies for mitigating the risks of androgen deprivation therapy.
"There is no question that we need more effective therapies for advanced prostate cancer," said Dr. Thrasher, professor and chair of urology, University of Kansas Medical Center, Kansas City. "Ideally, however, we want to be able to identify recurrence early and localize the site(s) of metastasis so that we can provide targeted delivery of effective treatment."
Nanotechnology may improve PSA
"The nanotechnology PSA looks promising for earlier detection of recurrence, but then, providing optimal care will depend on being able to determine where the cancer lies to enable targeted intervention. To my knowledge, the performance of the C-choline PET/CT scan for detecting small lymph node metastases with exact topographic allocation is the first of its kind," said Dr. Thrasher.
Therapeutic advances hold promise
Vaccines continue to hold promise for improving the treatment of advanced prostate cancer, and a number of other approaches are being investigated to augment responses with existing treatments or as new alternatives for hormone-refractive disease. Reports being presented at the AUA meeting include a phase I-II study of monotherapy with MDV3100, a novel oral androgen receptor antagonist, in men with castration-resistant prostate cancer. Studies of combination therapy include one exploring docetaxel (Taxotere) plus the anti-VEGF agent bevacizumab (Avastin) as second-line therapy in men with hormone-refractory prostate cancer and PSA relapse. Another group will be presenting initial results from a phase II study using ipilimumab, an anti-CTLA-4 antibody that potentiates T-cell immune responses, combined with androgen ablation versus androgen ablation alone.
"There is a great need for alternatives as initial therapy or for men who have failed ADT. A number of new agents and combination approaches are being investigated, and they are showing promise for expanding our armamentarium and slowing disease progression to improve patient survival," said Dr. Thrasher.
There is also growing interest in the role of selective estrogen receptor modulators in the management of advanced prostate cancer for protecting against bone loss risk in men on ADT. Reports at the AUA meeting will describe reductions in fracture risk with the use of toremifene (Fareston) and show that it may also offer antitumor activity. Other research is showing promising results using the oral bisphosphonate risedronate (Actonel) to prevent bone loss associated with LHRH agonist treatment in men with locally advanced prostate cancer.
Research investigating the new GnRH receptor antagonist degarelix (Firmagon) is continuing. Early data from a study of patients who failed leuprolide acetate (Lupron) suggest degarelix may be superior to current LHRH analogs both in terms of its effect on disease control and safety profile, although confirmation in additional studies is needed.
Information being reported on the recently approved therapeutic cancer vaccine, sipuleucel-T (Provenge), will focus on safety. Investigators will present findings from an integrated analysis of complications associated with sipuleucel-T in four randomized clinical trials showing that it was well-tolerated in populations with castrate-resistant and androgen-dependent disease.
"Currently, men who become resistant to hormonal therapy and chemotherapy are doomed to eventually succumb to their disease. I believe there is great hope about the future availability of vaccine therapy for managing late-stage disease in men who have failed all other options, but also for intervening at an early stage," said Dr. Thrasher.