Investigating the Latest Evidence from Phase III Trials Supporting Treatment Options for De novo Clinically Lymph Node-Positive Hormone-Sensitive Prostate Cancer

Purpose of Review The introduction of PSMA-PET/CT scans is expected to increase the incidence of clinically lymph node-positive metastatic hormone-sensitive prostate cancer (mHSPC). The 8th AJCC-TNM classify disease with metastasis limited to pelvic nodes (cN1M0) and nonregional lymph nodes (M1a) as stage IV. To date, there is limited prospective evidence for management of this subgroup. Additionally, no specific recommendations currently exist for managing M1a as a distinct condition but as a part of CHAARTED low volume disease (LVD). Our review examines relevant results from phase III trials examining the management of clinically positive nodal disease over the last decade. Recent Findings STAMPEDE is the only phase III trial that gave recent data about cN1M0 and isolated M1a management. Cohort sub-analysis of the control arm showed improved failure-free survival after local radiotherapy (RT) plus Androgen Deprivation Therapy (ADT), while metastasis-free survival benefit from Abiraterone Acetate with Prednisolone (AAP) addition was noted when compared to standard of care (SOC), awaiting the overall survival (OS) benefit result. The STAMPEDE H arm showed a marginal significance of M1a stratified OS after RT. Future trials, including PEARLS, ALADDIN and STAMPEDE2, are expected to offer more insights. Summary Interventional Phase III trials directed to clinically node positive patients are still needed to aid deciding on the best management, and nodal metastasis number and size impact on prognosis.