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

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.

Near‐infrared fluorescence lymph node template region dissection plus backup lymphadenectomy in open radical cystectomy for bladder cancer using an innovative handheld device: A single center experience

“…Four patients were treated with NAC. As shown in a recent meta‐analysis, the prognostic benefit of extended lymphadenectomy in terms of eradication of lymphonodular micrometastases could be reversed by such treatment 5 . Although detection of lymph node metastases is not the main goal of our work, this still has the potential to influence our results.…”

“…ePLND represents an integral part of radical cystectomy in MIBC as it defines adjuvant treatment needs and serves as a diagnostic tool to assess patient's prognosis 3 . It is unclear whether the extension of the standard PLND template leads to a prognostic improvement, 4,5 especially when neoadjuvant chemotherapy was performed. The LEA trial, indicated a 3%–8% occurrence of PLND‐related complications such as lymphocele and lymphedema 6 .…”

Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/SUO Guideline (2017; Amended 2020, 2024)

“…37 More recent observational and cohort studies have varying results with several showing no benefit, but in those that did report an advantage with a more extensive LND, this advantage was noted in patients who had not received NAC. [38][39][40][41] The largest observational study (n [ 19,020) using SEER data did report statistically significant associations between the extent of pelvic LND and cancerspecific mortality (HR [ 0.99; P < .001) and rates of lymph node invasion (OR [ 1.01; P [ .001) in a mixed population of patients with MIBC and NMIBC; however, the effect sizes were very small. 41…”

Influence of Neoadjuvant Chemotherapy on Survival Outcomes of Radical Cystectomy in Pathologically Proven Positive and Negative Lymph Nodes

“…reported only a 15% local response rate in patients with cN+ [7]. Some researchers have argued that the count of excised LNs significantly influences the long-term oncological outcomes in patients with cN+ treated with induction chemotherapy [7,8], whereas the merits of extended pelvic lymph node dissection (PLND) remain debated for patients treated with NAC [9]. Consequently, the oncological outcomes for patients with pathologically verified LNs post-induction chemotherapy may not mirror those post-NAC.…”