Long-term follow-up data showed ePLND significantly reduces the risk of metastasis in ISUP GG 3-5 prostate cancer with radical prostatectomy.
Extended pelvic lymph node dissection (ePLND) demonstrated a significant improvement in metastasis-free survival (MFS) compared with limited pelvic lymph node dissection (lPLND) in patients with biopsy ISUP grade group (GG) 3-5 prostate cancer undergoing radical prostatectomy, according to long-term data from a phase 3 trial (NCT01812902) presented at the
In the biopsy ISUP GG 3-5 subgroup, the 2026 analysis showed an HR of 0.26 (95% CI, 0.07-0.93; P = .026) favoring ePLND for MFS. This represented a meaningful improvement from the 2021 analysis of the same subgroup, which had an HR of 1.01 (95% CI, 0.12-8.76; P = .996), reflecting the accruing benefit seen with extended follow-up. The updated median follow-up time was 130.6 months (IQR, 107.8-146.5).
The trial enrolled patients with D'Amico intermediate- or high-risk prostate cancer (≥cT2b, PSA ≥10 ng/mL, or Gleason score ≥7) who had no bone metastasis, no prior radiotherapy or hormonal treatment, no other malignant neoplasm, and no prior abdominal or pelvic surgery.
A total of 364 patients were assessed for eligibility; 300 were randomly assigned 1:1 to ePLND (n = 150) or lPLND (n = 150). Enrollment occurred from May 2012 through December 2016, and 11.3% of patients were lost to follow-up in each arm.
The ePLND template included the obturator, external iliac, internal iliac, common iliac, and pre-sacral nodes bilaterally, yielding a median of 17 (IQR, 13-24) lymph nodes removed. The lPLND template was limited to the obturator fossa bilaterally, yielding a median of 3 (IQR, 2-5) nodes. Patients with pathologic lymph node metastases (N+) were significantly more likely to be identified in the ePLND arm (17% vs 3.4%; P < .001).
The primary end point was biochemical recurrence–free survival (BRFS), designed to detect a minimum 15% advantage in 5-year BRFS with ePLND. Secondary end points were MFS and cancer-specific survival (CSS).
In the overall intention-to-treat population of 300 patients, the updated 2026 analysis showed no significant difference in BRFS (HR, 0.92; 95% CI, 0.66-1.29; P = .638; ePLND median NR vs lPLND median 155 months) or MFS (HR, 0.6; 95% CI, 0.32-1.15; P = .124). Cancer-specific survival and overall survival were also similar between arms (CSS: HR, 1.18; 95% CI, 0.36–3.85; P = .788; OS: HR, 0.99; 95% CI, 0.62-1.58; P = .973).
The benefit of ePLND emerged specifically in patients with biopsy ISUP GG 3-5, a subgroup comprising 31 patients in the ePLND arm and 38 in the lPLND arm. In this group, BRFS also remained significantly better with ePLND at the 2026 update (HR, 0.54; 95% CI, 0.29-0.99; P = .046), consistent with the previously reported 2021 BRFS benefit (HR, 0.48; 95% CI, 0.26-0.91; P = .024). The 2026 update now extends this advantage to MFS in the same subgroup, a finding that was not present in the earlier analysis.
For risk of radiotherapy (RDT) in the ISUP GG 3-5 subgroup, median time to RDT was 43.7 months in the lPLND group and was NR in the ePLND group (P = .098). Secondary treatment rates were also numerically lower in the ePLND arm, with radiotherapy used in 37.3% of ePLND vs 44.7% of lPLND patients overall, and androgen deprivation therapy in 22% vs 26%, respectively.
ePLND was associated with significantly greater surgical burden compared with lPLND. Operative time was longer with a median of 215 minutes vs 162 minutes, respectively (P < .001), estimated blood loss was higher at 750 mL vs 600 mL, respectively (P < .001), and hospital stay and time to drain removal were each longer at a median of 2 days each vs 1 day each, respectively (P < .001). Early perioperative complications within 90 days occurred more frequently with ePLND (31.3% vs 20.7%; P = .035), and symptomatic lymphocele was observed exclusively in the ePLND group (4% vs 0%; P = .029).
The trial findings were contextualized against 2 recent publications supporting the oncologic role of ePLND. A multicentric longitudinal study published in the Journal of Urology found significant MFS benefit with PLND in high-risk (HR, 0.57; P = .02) and intermediate-risk (HR, 0.48; P = .023) patients vs radical prostatectomy alone.2 A large randomized analysis published in European Urology reported significantly better MFS in patients randomized to ePLND vs lPLND (HR, 0.82; 95% CI, 0.71-0.98; P < .0001), with no difference in biochemical recurrence — reinforcing the pattern observed in the current trial.3
The 2026 AUA/ASTRO guideline amendment now states that investigators performing pelvic lymphadenectomy should perform an extended dissection, citing improved staging accuracy, while noting that a survival benefit has not been consistently demonstrated across populations.1 The updated data support consideration of ePLND as a standard of care in ISUP GG 3-5 patients undergoing radical prostatectomy, and that current guidelines should incorporate these updated long-term results, the study authors concluded.
Disclosures: Lestingi served as a speaker for AstraZeneca and received personal fees outside of this work.
