Prognostic Impact of Lymph Node Yield in a Phase III Clinical Trial (NRG/RTOG 9601) of Prostate Cancer Patients Treated With Salvage Radiation Following Prostatectomy.

Background: We aim to evaluate whether increased lymph node yield at prostatectomy (RP) is associated with improved outcomes in NRG/RTOG 9601, a randomized clinical trial of men who underwent either radiation (RT) alone or RT + bicalutamide for PSA elevation following RP for pT2/T3 prostate cancer.

Methods: We reviewed available pathology reports for patients in NRG/RTOG 9601 to determine the nodal count at RP. Cox proportional hazards models were used to assess effect of lymph nodes yield, arm (RT alone or RT + bicalutamide), Gleason score, positive margins, and seminal vesicle invasion on the following endpoints: times to local and distant failure and overall and disease-specific survival.

Results: Of 760 patients, 552 (73%, 276 in each arm) had complete data available. Median node count in the entire cohort was 6 (range: 0-33, IQR: 3-9). There were no significant differences between arms in terms of patient demographic or clinical characteristics, including total lymph nodes removed in either arm. There was no significant association between total lymph nodes and overall or disease-specific survival with both arms combined and when adjusting for arm. Notably, interaction analysis revealed that in seminal vesicle invasion, there was a significant association between lymph node yield and OS and DSS (HR = 0.91, 95% CI: 0.83-0.99, p = 0.034; HR = 0.87, 95% CI: 0.77-0.99, p = 0.029, respectively).

Conclusions: Although lymph node yield in NRG/RTOG 9601 did not show association with adverse outcomes in the entire cohort or either arm alone, there was significant association between lymph node yield and adverse outcomes when seminal vesicle invasion was present. The therapeutic benefit of extensive lymph node dissection remains uncertain but could be more relevant in higher risk patients.