Surveillance Versus Metastasis-Directed Therapy With Surgery or Stereotactic Body Radiotherapy (SABR/SBRT) for Oligorecurrent Prostate Cancer: Prospective Randomized Multicenter Phase II Trial

Abstract

Purpose: Retrospective studies suggest that metastasis-directed therapy (MDT) for oligorecurrent prostate cancer (PCa) can improve progression-free survival. This randomized phase II trial assessed the benefit of MDT compared with surveillance. Patients and Methods: In this multicenter, randomized, phase II study, patients with asymptomatic PCa were eligible if they had biochemical recurrence after primary PCa treatment with curative intent, three or fewer extracranial metastatic lesions detected by choline positron emission tomography-computed tomography, and serum testosterone levels > 50 ng/mL. Patients were randomly assigned 1:1 to surveillance or MDT to all detected metastatic lesions using surgery or stereotactic body radiotherapy (SBRT; stereotactic ablative radiotherapy [SABR]). Surveillance consisted of prostate-specific antigen (PSA) follow-up every 3 months, with repeat imaging at PSA progression or clinical suspicion of progression. Random assignment was dynamically balanced by PSA doubling time (≤ 3 v > 3 months) and nodal versus non-nodal metastases. The primary end point was androgen deprivation therapy (ADT)-free survival. ADT was initiated for symptomatic progression, progression to more than three metastases, or local progression of known metastases. Results: Between August 2012 and August 2015, 62 patients were enrolled. At a median follow-up of 3 years (interquartile range, 2.3-3.75 years), median ADT-free survival was 13 months (80% CI, 12 to 17 months) with surveillance and 21 months (80% CI, 14 to 29 months) with MDT (hazard ratio, 0.60 [80% CI, 0.40 to 0.90]; log-rank P = .11). Quality of life was similar between treatment arms at baseline and remained comparable at 3-month and 1-year follow-up. In the MDT arm, six patients developed grade 1 toxicity. No grade 2 to 5 toxicity was observed. Conclusion: ADT-free survival was longer after metastasis-directed therapy than after surveillance alone in oligorecurrent prostate cancer, supporting further evaluation of MDT in phase III trials. Trial registration: ClinicalTrials.gov NCT01558427.