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

• Published in: BJU international Vol. 134; no. 6; pp. 976 - 981
• Main Authors: Flammia, Rocco Simone, Tuderti, Gabriele, Bologna, Eugenio, Minore, Antonio, Proietti, Flavia, Licari, Leslie Claire, Mastroianni, Riccardo, Anceschi, Umberto, Brassetti, Aldo, Bove, Alfredo, Misuraca, Leonardo, D'Annunzio, Simone, Ferriero, Maria Consiglia, Guaglianone, Salvatore, Chiacchio, Giuseppe, De Nunzio, Cosimo, Leonardo, Costantino, Simone, Giuseppe
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.12.2024
• Subjects: Aged; Bladder cancer; Chemotherapy; Chemotherapy, Adjuvant; Clinical trials; complete response; Cystectomy; Female; Humans; Lymph Node Excision; Lymph nodes; Lymph Nodes - pathology; Lymphatic Metastasis; Lymphatic system; Male; Metastases; Middle Aged; muscle‐invasive bladder cancer; neoadjuvant chemotherapy; Neoadjuvant Therapy; Neoplasm Invasiveness; pelvic lymph node dissection; radical cystectomy; Retrospective Studies; Risk Assessment; Survival; Treatment Outcome; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - mortality; Urinary Bladder Neoplasms - pathology; Urinary Bladder Neoplasms - surgery; neoadjuvant chemotherapy; complete response; radical cystectomy; muscle‐invasive bladder cancer; pelvic lymph node dissection
• ISSN: 1464-4096; 1464-410X; 1464-410X
• DOI: 10.1111/bju.16440

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.