Recent Advances Revolutionize Treatment of Metastatic Prostate Cancer

Ravi A Madan; Philip M Arlen


Future Oncol. 2013;9(8):1133-1144. 

In This Article


Although the development of docetaxel raised hopes for rapid progress in the treatment of mCRPC, nearly a decade had passed before new advances in mCRPC therapy came to fruition. The rediscovery of the importance of the AR and the focus on secondary androgen production has led to the development of modern hormonal therapies that appear to be significant improvements over their predecessors. Abiraterone is now approved for use in all mCRPC patients, not just those who have had prior chemotherapy, and approval of enzalutamide will probably follow, pending final results from studies in mCRPC chemotherapy-naive patients.

Many studies evaluating these new hormonal agents in non-metastatic and newly diagnosed prostate cancer patients are already underway. The tolerability of enzalutamide is certainly an attractive benefit for patients with asymptomatic and non-metastatic disease. Additional studies using CYP17 lyase inhibitors (including abiraterone) with limited or no use of prednisone would also be appropriate for patients in this population. Long-term steroid exposure is a concern for non-metastatic patients, who may have survival rates reaching 5–10 years with their disease. Limiting supplemental steroids in this population is therefore desirable. These trials could determine the clinical impact of new hormonal therapies and whether their impact is more appreciated by their use earlier in the disease course. Meanwhile, there are significant advances in the development of next-generation ARAs and agents that can suppress secondary androgen production.

The impact of immunotherapy in mCRPC should not come as a complete surprise. In retrospect, prostate cancer's indolent disease course and the numerous tumor antigens identified make prostate cancer an ideal target for immunotherapy. Although sipuleucel-T has been FDA approved for several years, clinicians need to become more familiar with how to use this new therapy in order to maximize its potential clinical benefit. This need becomes urgent when one considers that both Prostvac and ipilimumab are being utilized in ongoing Phase III trials in mCRPC that could lead to further immunotherapeutic options in the next several years. Furthermore, the negligible toxicity profile of therapeutic cancer vaccines, the ability of hormonal therapies and radiation to enhance immune responses, and the potential to induce long-lasting immunologic effects have led to immunotherapy trials in earlier stages of prostate cancer, with the goal of augmenting the clinical impact seen in late-stage disease. These trials could establish the future utility of immunotherapy in adjuvant disease and non-metastatic prostate cancer, in addition to mCRPC.