Rapid progress was recently made in the treatment of prostate cancer, especially metastatic castration-resistant prostate cancer. At the NCCN 18th Annual Conference, Dr. Philip W. Kantoff reviewed the data supporting the use of abiraterone acetate, enzalutamide, cabazitaxel, sipuleucel-T, and radium-223 (pending approval), and offered recommendations for their sequential use in different settings. Dr. James L. Mohler described factors that dictate who should receive treatment, when they should receive it, and how to treat in the setting of prostate-specific antigen elevation. He explained how better treatment decisions will result from individualized estimation of threat-to-life posed by prostate cancer, chance of cure by treatment, and treatment risks.
New Developments in the Management of Prostate Cancer
Philip W. Kantoff and James L. Mohler
New Agents in Metastatic Prostate Cancer
Atish D. Choudhury and Philip W. Kantoff
Discoveries of molecular mechanisms and therapeutic targets in metastatic castration-resistant prostate cancer (CRPC) have led to significant advancements in the development of effective agents in this setting, with diverse mechanisms of action. Within the past 2 years, 5 agents have been approved for the treatment of patients with metastatic CRPC (cabazitaxel, abiraterone, sipuleucel-T, denosumab, and enzalutamide), and another (Alpharadin) has shown overall survival benefit in a phase III trial. This article summarizes the phase III data showing clinical benefit from these agents, highlights other promising therapies in phase III studies as single agents (PROSTVAC-VF, ipilimumab, cabozantinib), discusses important unanswered questions regarding these therapies, and provides a schema for their use based on current regulatory approval and how this is likely to evolve as data from ongoing studies are reported. Although curative interventions in metastatic CRPC still do not exist, the hope is that optimization of therapeutic strategies can reduce the morbidity and mortality associated with this disease.
Early Versus Delayed Initiation of Salvage Androgen Deprivation Therapy and Risk of Prostate Cancer–Specific Mortality
Brandon A. Mahal, Ming-Hui Chen, Andrew A. Renshaw, Marian J. Loffredo, Philip W. Kantoff, and Anthony V. D'Amico
Background: This study sought to ascertain whether there is an association between prostate cancer (PC)–specific mortality (PCSM) and timing of salvage androgen deprivation therapy (ADT) among men with short versus long prostate-specific antigen doubling times (PSA-DTs). Methods: The study cohort was selected from 206 men with localized unfavorable-risk PC randomized to radiation therapy (RT) or RT plus 6 months of ADT between 1995 and 2001. A total of 54 men who received salvage ADT for PSA failure after a median follow-up of 18.72 years following randomization defined the study cohort. The Fine-Gray competing risks regression model was used to analyze whether the timing of salvage ADT was associated with an increased risk of PCSM after adjusting for age, comorbidity, known PC prognostic factors, and previously identified interactions. Results: After a median follow-up of 5.68 years (interquartile range, 3.05–9.56) following salvage ADT, 49 of the 54 men (91%) died, of which 27 from PC (54% of deaths). Increasing PSA-DT as a continuous covariate (per month increase) was associated with a decreasing risk of PCSM (adjusted hazard ratio [HR], 0.33; 95% CI, 0.13–0.82; P=.02). Among men with a long PSA-DT (≥6 months), initiating salvage ADT later (PSA level >12 ng/mL, upper quartile) versus earlier was associated with an increased risk of PCSM (adjusted HR, 8.84; 95% CI, 1.99–39.27; P=.004), whereas for those with a short PSA-DT (<6 months; adjusted HR, 1.16; 95% CI, 0.38–3.54; P=.79) this was not true. Conclusions: Early initiation of salvage ADT for post-RT PSA failure in men with a PSA-DT of ≥6 months may reduce the risk of PCSM.
Prostate Cancer, Version 1.2014
James L. Mohler, Philip W. Kantoff, Andrew J. Armstrong, Robert R. Bahnson, Michael Cohen, Anthony Victor D’Amico, James A. Eastham, Charles A. Enke, Thomas A. Farrington, Celestia S. Higano, Eric Mark Horwitz, Mark H. Kawachi, Michael Kuettel, Richard J. Lee, Gary R. MacVicar, Arnold W. Malcolm, David Miller, Elizabeth R. Plimack, Julio M. Pow-Sang, Sylvia Richey, Mack Roach III, Eric Rohren, Stan Rosenfeld, Eric J. Small, Sandy Srinivas, Cy Stein, Seth A. Strope, Jonathan Tward, Patrick C. Walsh, Dorothy A. Shead, and Maria Ho
The NCCN Guidelines for Prostate Cancer provide multidisciplinary recommendations on the clinical management of patients with prostate cancer. This report highlights notable recent updates. Radium-223 dichloride is a first-in-class radiopharmaceutical that recently received approval for the treatment of patients with symptomatic bone metastases and no known visceral disease. It received a category 1 recommendation as both a first-line and second-line option. The NCCN Prostate Cancer Panel also revised recommendations on the choice of intermittent or continuous androgen deprivation therapy based on recent phase III clinical data comparing the 2 strategies in the nonmetastatic and metastatic settings.
Prostate Cancer, Version 2.2014
James L. Mohler, Philip W. Kantoff, Andrew J. Armstrong, Robert R. Bahnson, Michael Cohen, Anthony Victor D’Amico, James A. Eastham, Charles A. Enke, Thomas A. Farrington, Celestia S. Higano, Eric Mark Horwitz, Christopher J. Kane, Mark H. Kawachi, Michael Kuettel, Timothy M. Kuzel, Richard J. Lee, Arnold W. Malcolm, David Miller, Elizabeth R. Plimack, Julio M. Pow-Sang, David Raben, Sylvia Richey, Mack Roach III, Eric Rohren, Stan Rosenfeld, Edward Schaeffer, Eric J. Small, Guru Sonpavde, Sandy Srinivas, Cy Stein, Seth A. Strope, Jonathan Tward, Dorothy A. Shead, and Maria Ho
Prostate cancer has surpassed lung cancer as the most common cancer in men in the United States. The NCCN Guidelines for Prostate Cancer provide multidisciplinary recommendations on the clinical management of patients with prostate cancer based on clinical evidence and expert consensus. NCCN Panel guidance on treatment decisions for patients with localized disease is represented in this version. Significant updates for early disease include distinction between active surveillance and observation, a new section on principles of imaging, and revisions to radiation recommendations. The full version of these guidelines, including treatment of patients with advanced disease, can be found online at the NCCN website.
Prostate Cancer, Version 3.2012 Featured Updates to the NCCN Guidelines
James L. Mohler, Andrew J. Armstrong, Robert R. Bahnson, Barry Boston, J. Erik Busby, Anthony Victor D’Amico, James A. Eastham, Charles A. Enke, Thomas Farrington, Celestia S. Higano, Eric Mark Horwitz, Philip W. Kantoff, Mark H. Kawachi, Michael Kuettel, Richard J. Lee, Gary R. MacVicar, Arnold W. Malcolm, David Miller, Elizabeth R. Plimack, Julio M. Pow-Sang, Mack Roach III, Eric Rohren, Stan Rosenfeld, Sandy Srinivas, Seth A. Strope, Jonathan Tward, Przemyslaw Twardowski, Patrick C. Walsh, Maria Ho, and Dorothy A. Shead
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer provide multidisciplinary recommendations for the clinical management of patients with prostate cancer. These NCCN Guidelines Insights highlight notable recent updates. Abiraterone acetate is a first-in-class hormonal agent that represents a new standard of care for patients with metastatic castration-recurrent prostate cancer who have previously received docetaxel (category 1 recommendation). Abiraterone acetate also received category 2B recommendations in the prechemotherapy setting for asymptomatic patients or symptomatic patients who are not candidates for docetaxel. The NCCN Prostate Cancer Panel also added new indications for existing agents, including the option of sipuleucel-T as second-line therapy. In addition, brachytherapy in combination with external beam radiation therapy with or without androgen deprivation therapy is now an alternative for patients with high-risk localized tumors or locally advanced disease.