A Pilot Study of a Multimodal Treatment Paradigm to Accelerate Drug Evaluations in Early Stage Metastatic Prostate Cancer.

To evaluate a multimodal strategy aimed at treating all sites of disease that provides a rapid readout of success or failure in men presenting with noncastrate metastatic prostate cancers that are incurable with single modality therapy.

Twenty selected men with oligometastatic M1a (extrapelvic nodal disease) or M1b (bone disease) at diagnosis were treated using a multimodal approach that included androgen deprivation, radical prostatectomy plus pelvic lymphadenectomy (retroperitoneal lymphadenectomy in the presence of clinically positive retroperitoneal nodes), and stereotactic body radiotherapy to osseous disease and/or the primary site. Outcomes of each treatment were assessed sequentially. Androgen deprivation was discontinued in responding patients. The primary endpoint was an undetectable prostate-specific antigen (PSA) after testosterone recovery. The goal was to eliminate all detectable disease.

Each treatment modality contributed to the outcome: 95% of the cohort achieved an undetectable PSA with multimodal treatment, including 25% of patients after androgen deprivation alone and an additional 50% and 20% after surgery and radiotherapy, respectively. Overall, 20% of patients (95% confidence interval 3-38%) achieved the primary endpoint, which persisted for 5, 6, 27+, and 46+ months. All patients meeting the primary endpoint had been classified with M1b disease at presentation.

A sequentially applied multimodal treatment strategy can eliminate detectable disease in selected patients with metastatic spread at diagnosis. The endpoint of undetectable PSA after testosterone recovery should be considered when evaluating new approaches to rapidly set priorities for large-scale testing in early metastatic disease states and shifts the paradigm from palliation to cure.

Urology. 2016 Jan 22 [Epub ahead of print]

Matthew J O'Shaughnessy, Sean M McBride, Hebert Alberto Vargas, Karim A Touijer, Michael J Morris, Daniel C Danila, Vincent P Laudone, Bernard H Bochner, Joel Sheinfeld, Erica S Dayan, Lawrence P Bellomo, Daniel D Sjoberg, Glenn Heller, Michael J Zelefsky, James A Eastham, Peter T Scardino, Howard I Scher

Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Urology, Weill Cornell Medical College, New York, NY., Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY., Body Imaging Service and Molecular Imaging & Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Radiology, Weill Cornell Medical College, New York, NY., Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY., Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Biostatistics Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY., Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY. Electronic address: .