Assessing risk of lymph node invasion in complete responders to neoadjuvant chemotherapy for muscle-invasive bladder cancer

Abstract

Objectives: To investigate the lymph node invasion (LNI) rate in patients exhibiting complete pathological response (CR) to neoadjuvant chemotherapy (NAC) and to test the association of CR status with lower LNI and better survival outcomes.

Materials and methods: We included patients with bladder cancer (BCa; cT2-4a; cN0; cM0) treated with NAC and radical cystectomy (RC) + pelvic lymph node dissection (PLND) at our institution between 2012 and 2022 (N = 157). CR (ypT0) and LNI (ypN+) were defined at final pathology. Univariable and multivariable logistic regression analysis was performed to test the association between CR and LNI after adjusting for number of lymph nodes removed (NLR). Kaplan-Meier and Cox regression analyses were used to assess overall survival (OS), metastasis-free survival (MFS) and disease free-survival (DFS) according to CR status.

Results: Overall CR and LNI rates were 40.1% and 19%, respectively. The median (interquartile range [IQR]) NLR was 26 (19-36). The LNI rate was lower in patients with CR vs those without CR (2 [3.2%] vs 61 [29.8%]; P < 0.001). After adjusting for NLR, CR reduced the LNI risk by 93% (odds ratio 0.07, 95% confidence interval [CI] 0.01-0.25; P < 0.001). Kaplan-Meier plots depicted better 5-year OS (69.7 vs 52.2%), MFS (68.3 vs 45.5%) and DFS (66.6 vs 43.5%) in patients with CR vs those without CR. After multivariable adjustments, CR independently reduced the risk of death (hazard ratio [HR] 0.44, 95% CI 0.24-0.81; P = 0.008), metastatic progression (HR 0.41, 95% CI 0.23-0.71; P = 0.002) and disease progression (HR 0.41, 95% CI 0.24-0.70; P = 0.001).

Conclusion: Based on these findings, we postulate that PLND could potentially be omitted in patients exhibiting CR after NAC, due to negligible risk of LNI. Prospective Phase II trials are needed to explore this challenging hypothesis.

Keywords: complete response; muscle‐invasive bladder cancer; neoadjuvant chemotherapy; pelvic lymph node dissection; radical cystectomy.