Extended vs Limited Pelvic Lymph Node Dissection During Radical Prostatectomy for Intermediate- and High-Risk Prostate Cancer: Early Oncological Outcomes from a Randomized Phase 3 Trial

Background: The role of extended pelvic lymph node dissection (EPLND) in the surgical management of prostate cancer (PCa) patients remains controversial, mainly because of lack of randomized controlled trials (RCT). Methods: In this randomized controlled phase 3 study, men with newly diagnosed clinically localized intermediate- or high-risk PCa who had chosen surgery as their treatment approach were enrolled from Sao Paulo State Cancer Institute, Brazil. Participants were randomly assigned (1:1) to have either extended (EPLND) or limited pelvic lymph node dissection (LPLND) at radical prostatectomy (RP). LPLND included the obturator chain bilaterally, whereas EPLND involved included obturator, external-, internal-, common-iliac and pre-sacral chains bilaterally. The primary endpoint was biochemical recurrence-free survival (BRFS) and the secondary outcomes were metastasis-free survival (MFS), cancer-specific survival (CSS) and histopathologic findings. This trial was registered with ClinicalTrials.gov, number NCT01812902. Findings: Between May 2012 and December 2016, 300 men were enrolled, of which 150 were randomly assigned to EPLND and 150 to LPLND. Median follow-up was 54.3 months. EPLND detected 4.9 times more lymph node metastases (16.8% [n=25] in the EPLND group vs. 3.4% [n=5] in the LPLND group, p<0.001). The median BRFS was 61.4 months in the LPLND group and not reached in the EPLND group (HR 0.91; 95% CI 0.63-1.32; p=0.623). The median metastasis-free survival was not reached in both groups (HR 0.57; 95% CI 0.17-1.8; p=0.345). CSS data were not available because no patient died from prostate cancer prior to the cutoff date. In exploratory subgroup analysis, patients with preoperative biopsy International Society of Urological Pathology (ISUP) grades 3-5 who were allocated to EPLND had improved BRFS (HR 0.33, 95% CI 0.14-0.74, interaction p<0.001). Interpretation: EPLND is not associated with an improvement in biochemical recurrence among men undergoing RP for intermediate- and high-risk localized PCa. Subgroup analyses suggest that preoperative ISUP 3, 4 or 5 biopsy is associated with an improvement in BRFS for patients undergoing EPLND. Trial Registration Number: This trial was registered with ClinicalTrials.gov, number NCT01812902. Funding: Foundation for Research Support of the State of Sao Paulo (FAPESP). Declaration of Interest: Lestingi, Coelho, Pontes, Faraj, Mitre, Cordeiro, Srougi, Nahas: none. Guglielmetti: Personal fees from Janssen; outside the submitted work. Trinh: Personal fees from Astellas, Bayer, InsighTec and Janssen. Grants from Intuitive Surgical; outside the submitted work. Bastos: Grants from Janssen and Astellas; outside the submitted work. Sarkis: Personal fees from Ferring and from MSD - Merck Sharp and Dohme; outside the submitted work. Ethical Approval: All patients participating in the study will sign the ICF and study was approved by the local Research Ethics Committee.