Does neoadjuvant or induction systemic therapy modify the association between pelvic lymph node dissection metrics and survival after radical cystectomy for bladder cancer? A systematic review and meta-analysis

The incremental survival value of higher lymph node yield (LNY) or extended pelvic lymph node dissection (PLND) during radical cystectomy in the systemic therapy era remains uncertain. Because LNY is a postoperative count rather than a direct measure of anatomical dissection boundaries, we evaluated LNY-threshold and anatomical-template evidence separately and explored whether their survival associations differed according to neoadjuvant or induction systemic therapy exposure. This PROSPERO-registered systematic review and meta-analysis (CRD420261398389) was reported according to PRISMA 2020. PubMed/MEDLINE, Web of Science, Embase, ClinicalTrials.gov, and reference tracking were searched. Six studies were included in the quantitative synthesis. GRADE certainty was very low for all comparisons. Prespecified DerSimonian-Laird random-effects models were supplemented by restricted maximum-likelihood models with Hartung-Knapp adjustment. In LNY-threshold studies, higher LNY was associated with better overall survival (OS) in no-neoadjuvant-chemotherapy cohorts (three studies; HR 0.723, 95% CI 0.557–0.938; I² = 72.0%) but not clearly in neoadjuvant-chemotherapy-treated cohorts (four studies; HR 0.878, 95% CI 0.754–1.023; I² = 3.8%). Anatomical-template studies showed no clear OS advantage for extended over standard PLND in systemic-therapy-treated (two studies; HR 0.924, 95% CI 0.722–1.183) or no-neoadjuvant/no-induction strata (two studies; HR 1.184, 95% CI 0.897–1.563). The paired ratio-of-HRs analysis did not demonstrate effect modification (all paired studies: 1.073, 95% CI 0.748–1.540). Hartung-Knapp sensitivity intervals were wider, including the null for all comparisons. Very-low-certainty, limited, and heterogeneous aggregate evidence raises, but does not confirm, the hypothesis that the prognostic association between higher LNY and OS may be weaker after neoadjuvant systemic therapy. Formal effect modification was not demonstrated. Contemporary anatomical-template evidence does not show a clear survival advantage for routine extension beyond standard PLND, which remains important for staging and local control.