Adequate Pelvic Lymph Node Dissection in Radical Cystectomy in the Era of Neoadjuvant Chemotherapy: A Meta-Analysis and Systematic Review

SIMPLE SUMMARY: Bladder cancer is the 10th most common cancer in the world, and its incidence is gradually rising worldwide. Currently, radical cystectomy with pelvic lymphadenectomy and preoperative chemotherapy is the mainstay of treatment for muscle-invasive bladder cancer. The therapeutic role of lymphadenectomy and neoadjuvant chemotherapy is similar in terms of treatment of micrometastatic disease. Therefore, we performed a systematic review and meta-analysis on the impact of adequate lymphadenectomy on patient survival in the era of the multidisciplinary approach. Our results showed a lack of association between adequate lymphadenectomy and overall survival in patients exposed to neoadjuvant chemotherapy. ABSTRACT: Radical cystectomy (RC) with pelvic lymphadenectomy (PLND) serves as the gold-standard treatment for muscle-invasive bladder cancer (MIBC). Numerous studies have shown that the number of lymph nodes (LN) removed during RC could affect patient prognosis. However, these studies confirmed the association between PLND and survival outcomes prior to the widespread adoption of neoadjuvant chemotherapy (NAC). Consequently, this study aimed to investigate the prognostic role of PLND in patients previously pretreated with NAC. A systematic review and meta-analysis were performed using PubMed, Web of Knowledge, and Scopus databases. The selected studies contained a total of 17,421 participants. The meta-analysis indicated a significant correlation between adequate PLND and overall survival in the non-NAC group. However, a survival benefit was not observed in patients undergoing RC with preoperative systemic therapy, regardless of the LN cut-off thresholds. The pooled HR for ≥10 and ≥15 LN were 0.87 (95% CI 0.75–1.01) and 0.87 (95% CI 0.76–1.00), respectively. The study results suggest that NAC mitigates the therapeutic significance of PLND, as patients pre-treated with NAC no longer gain oncological benefits from more extensive lymphadenectomy. This highlights the analogous roles of NAC and PLND in eradication of micrometastases and in prevention of distal recurrence post-RC.