The published POP-RT trial randomized patients (n=214) with NCCN high- (~50%) and very high-risk (~50%) prostate cancer306 to IMRT to the whole pelvis (68 Gy in 25 fractions to prostate with 50 Gy to pelvic lymph nodes) versus prostate-only (68 Gy). This currently represents the only trial of elective pelvic nodal irradiation that delivered both modern standard-of-care radiotherapy doses and ADT duration while looking exclusively at high-risk patients. All patients received ADT (surgical or medical) starting eight weeks prior to radiation therapy; medical ADT was via an LHRH agonist and was administered for two years. The trial demonstrated improved 5-year biochemical failure-free survival (HR 0.23, 95% CI 0.10 to 0.52; trial’s primary endpoint), distant MFS (HR 0.35, 95% CI 0.15 to 0.82), and disease-free survival (HR 0.40, 95% CI 0.22 to 0.73) with whole pelvis IMRT, although no difference was detected in OS (HR 0.92, 95% CI 0.41 to 2.05). Despite not showing an OS benefit, the Panel notes that elective nodal irradiation for high-risk patients may be offered given the reasonable morbidity (higher late grade II genitourinary toxicity with whole pelvis radiation but no difference in late gastrointestinal toxicity and no difference in grade III/IV genitourinary or gastrointestinal toxicity noted) as well as the reductions in biochemical failure and distant metastases. The Panel recognizes that neither the previous GETUG-01266 nor RTOG 9413269 trials demonstrated a benefit to elective nodal irradiation, but submits that those studies included variably-defined high-risk sub-groups (and lower risk than the POP-RT trial), used simpler radiation technologies with more limited pelvic fields, included a shorter duration of ADT, and delivered lower doses of radiation to the prostate; collectively, these differences may have blunted the impact of elective regional irradiation; as such, may be less relevant to inform contemporary practice.