Extended versus standard lymph node dissection for urothelial carcinoma of the bladder in people undergoing radical cystectomy

RATIONALE: We are currently uncertain of the benefits and harms of standard pelvic lymph node dissection (PLND) compared to extended PLND in the treatment of urothelial carcinoma of the bladder. OBJECTIVES: To assess the effects of extended versus standard PLND in people undergoing cystectomy to treat muscle-invasive (cT2 and cT4a) and treatment-refractory, non-muscle-invasive (cT1 with or without carcinoma in situ) urothelial carcinoma of the bladder. SEARCH METHODS: We conducted a comprehensive literature search using multiple databases (CENTRAL, PubMed, Embase, Web of Science, and LILACS), trial registries, and conference proceedings published up to 24 September 2025, with no restrictions on language or publication status. ELIGIBILITY CRITERIA: We included randomized controlled trials (RCTs) in which participants underwent radical cystectomy for muscle-invasive or therapy-refractory non-muscle-invasive urothelial carcinoma of the bladder with either an extended PLND with an upper extent reaching as far as the inferior mesenteric artery, or a standard PLND up to the bifurcation of the internal and external iliac artery, with otherwise the same anatomical boundaries. OUTCOMES: Critical outcomes were time to death from any cause (assessed at five years), time to death from bladder cancer (assessed at five years), and Clavien-Dindo classification of surgical complications grade III-V (assessed up to 90 days' postoperatively). Important outcomes were time to recurrence (assessed at five years), Clavien-Dindo I-II complications (assessed up to 90 days' postoperatively), and disease-specific quality of life. RISK OF BIAS: We used the Cochrane RoB 2 tool to assess the risk of bias in the included studies. SYNTHESIS METHODS: We conducted statistical analyses according to the guidance in the Cochrane Handbook for Systematic Reviews of Interventions. We combined the results for each outcome using a meta-analysis with a random-effects model. We employed GRADE to evaluate the certainty of the evidence. INCLUDED STUDIES: We included two RCTs with 993 randomized participants (extended PLND 490, standard PLND 503). Both studies were published in full text. The median age of both groups was similar, ranging from 67 to 69 years for the extended group and 68 years for the standard group. All participants had locally completely resectable, invasive urothelial bladder cancer. SYNTHESIS OF RESULTS: Overall, the certainty of evidence for most outcomes was moderate to low, primarily downgraded due to imprecision. Time to death from any cause Extended PLND may result in little to no difference in time to death from any cause as compared to standard PLND (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.75 to 1.30; 2 studies, 993 participants; low-certainty evidence). Based on the control event risk of 43.0% at five-year follow-up, this corresponds to 3 fewer deaths from any cause (95% CI 86 fewer to 88 more) per 1000 participants. Time to death from bladder cancer Extended PLND likely extends the time to death from bladder cancer as compared to standard PLND (HR 0.65, 95% CI 0.44 to 0.97; 1 study, 401 participants; moderate-certainty evidence). Based on the control event risk of 35.0% at five-year follow-up, this corresponds to 106 fewer deaths from bladder cancer (95% CI 177 fewer to 8 fewer) per 1000 participants. Clavien-Dindo grade ≥ 3 complications (up to 90 days) Extended PLND likely increases Clavien-Dindo grade ≥ 3 complications as compared to standard PLND (risk ratio [RR] 1.22, 95% CI 1.06 to 1.41; 2 studies; 993 participants; moderate-certainty evidence). Based on the control event risk of 39.0% at 90-day follow-up, this corresponds to 86 more complications (95% CI 23 more to 160 more) per 1000 participants. Time to recurrence Extended PLND may result in little to no difference in time to recurrence as compared to standard PLND (HR 0.96, 95% CI 0.71 to 1.31; 2 studies, 993 participants; low-certainty evidence). Based on the control event risk of 40.0% at five-year follow-up, this corresponds to 12 fewer recurrences (95% CI 96 fewer to 88 more) per 1000 participants. Clavien-Dindo grade ≤ 2 complications (up to 90 days) Extended PLND likely results in similar Clavien-Dindo grade ≤ 2 complications as compared to standard PLND (RR 0.85, 95% CI 0.73 to 1.00; 2 studies, 993 participants; moderate-certainty evidence). Based on the control event risk of 40.2% at 90-day follow-up, this corresponds to 60 fewer complications (95% CI 108 fewer to 0 fewer) per 1000 participants. Disease-specific quality of life No studies reported this outcome. AUTHORS' CONCLUSIONS: This updated systematic review synthesizes the evidence from the two available RCTs in this field. We found that extended PLND likely improves bladder cancer-specific survival; however, it may result in little to no difference in overall survival or recurrence-free survival. Extended PLND likely increases severe complications (Clavien-Dindo grade ≥ 3), while likely showing similar rates of minor complications (grade ≤ 2) at 90-day follow-up compared to standard PLND. These findings underscore the trade-offs of potential oncologic benefits of extended PLND versus the increased risk of serious complications in patients undergoing radical cystectomy. FUNDING: None REGISTRATION: Protocol (2018) available via https://www.crd.york.ac.uk/PROSPERO/view/CRD42018116290 Original review (2019) DOI: 10.1002/14651858.CD013336.