Standard of Care Versus Metastases-directed Therapy for PET-detected Nodal Oligorecurrent Prostate Cancer Following Multimodality Treatment: A Multi-institutional Case-control Study

Abstract Background Most prostate cancer (PCa) patients with a biochemical failure following primary multimodality treatment (surgery and postoperative radiotherapy) relapse in the nodes. Objective To perform a matched-case analysis in men with lymph node recurrent PCa comparing standard of care (SOC) with metastasis-directed therapy (MDT). Design, setting, and participants PCa patients with a prostate-specific antigen (PSA) progression following multimodality treatment were included in this retrospective multi-institutional analysis. Intervention The SOC cohort ( n =1816) received immediate or delayed androgen deprivation therapy administered at PSA progression. The MDT cohort ( n =263) received either salvage lymph node dissection ( n =166) or stereotactic body radiotherapy ( n =97) at PSA progression to a positron emission tomography-detected nodal recurrence. Outcome measurements and statistical analysis The primary endpoint, cancer-specific survival (CSS), was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched analyses. Results and limitations At a median follow-up of 70 (interquartile range: 48–98) mo, MDT was associated with an improved CSS on univariate ( p =0.029) and multivariate analysis (hazard ratio: 0.33, 95% confidence interval [CI]: 0.17–0.64) adjusted for the year of radical prostatectomy (RP), age at RP, PSA at RP, time from RP to PSA progression, Gleason score, surgical margin status, pT- and pN-stage. In total, 659 men were matched (3:1 ratio). The 5-yr CSS was 98.6% (95% CI: 94.3–99.6) and 95.7% (95% CI: 93.2–97.3) for MDT and SOC, respectively ( p =0.005, log-rank). The main limitations of our study are its retrospective design and lack of standardization of systemic treatment in the SOC cohort. Conclusions MDT for nodal oligorecurrent PCa improves CSS as compared with SOC. These retrospective data from a multi-institutional pooled analysis should be considered as hypothesis-generating and inform future randomized trials in this setting. Patient summary Prostate cancer patients experiencing a lymph node recurrence might benefit from local treatments directed at these lymph nodes.