A comparative analysis of radical cystectomy with perioperative chemotherapy, chemoradiation therapy, or systemic therapy in patients with clinically advanced node-positive bladder cancer (cN2/N3)

Harshit Garg; Mukund Bhandari; Furkan Dursun; Michael A Liss; Dharam Kaushik; Robert S Svatek; Ahmed M Mansour

doi:10.3389/fonc.2023.1157880

A comparative analysis of radical cystectomy with perioperative chemotherapy, chemoradiation therapy, or systemic therapy in patients with clinically advanced node-positive bladder cancer (cN2/N3)

Front Oncol. 2024 Jan 11:13:1157880. doi: 10.3389/fonc.2023.1157880. eCollection 2023.

Authors

Harshit Garg¹, Mukund Bhandari², Furkan Dursun¹, Michael A Liss^{1

3}, Dharam Kaushik^{1

3}, Robert S Svatek^{1

3}, Ahmed M Mansour^{1

3

4}

Affiliations

¹ Department of Urology, University of Texas Health, San Antonio, TX, United States.
² Department of Population Health Science, University of Texas Health, San Antonio, TX, United States.
³ Department of Urology, University of Texas Health San Antonio/MD Anderson Mays Cancer Center, San Antonio, TX, United States.
⁴ Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.

Abstract

Introduction: The management of non-metastatic clinically advanced lymph nodal (cN2/N3) bladder cancer (Stage IIIB) could involve radical cystectomy, chemoradiation, or systemic therapy alone. However, a definitive comparison between these approaches is lacking. This study aims to compare the outcomes of patients undergoing radical cystectomy with pelvic lymph node dissection (RC-PLND), chemoradiation therapy (CRT) or systemic therapy (including immunotherapy) (ST) only in patients with stage IIIB bladder cancer.

Materials and methods: A retrospective analysis of the National Cancer Database for patients with stage IIIB urothelial bladder cancer was done from 2004-2019. Patients were classified as Group A: Those who received RC-PLND with perioperative chemotherapy, Group B: Those who received CRT, and Group C: Those who received only ST alone. The primary outcome was overall survival (OS). Inverse probability weighting (IPW)-adjusted Kaplan Meier curves were utilized to compare overall survival (OS) and cox multivariate regression analysis was used to identify predictors for OS.

Results: Overall, 2,575 patients were identified. They were classified into Group A (n=1,278), Group B (n=317) and Group C (n=980). Compared to Group B, patients in Group A were younger (SMD=19.6%), had lower comorbidities (SMD=18.2%), had higher income (SMD=31.5%), had private insurance (SMD= 26.7%), were treated at academic centres (SMD=29.3%) and had higher percentage of N2 disease (SMD=31.1%). Using IPW-adjusted survival analysis, compared to Group C, the median OS was significantly higher in Group A (20.7 vs 14.2 months, p<0.001) and Group B (19.7 vs 14.2 months, p<0.001) but similar between Group A and Group B (20.9 vs 19.7 months, p=0.74). Both surgery (HR=0.72 (0.65-0.80), p<0.001) and CRT (0.70 (0.59-0.82), p<0.001) appeared to be independent predictors for OS on cox-regression analysis. The major limitations include bias due to retrospective analysis and non-assessment of cancer-specific survival.

Conclusion: In stage IIIB bladder cancer with advanced lymph nodal disease, both RC and CRT offer equivalent survival benefits and are superior to systemic therapy alone.

Keywords: bladder cancer; concurrent chemoradiation; locally advanced bladder cancer; overall survival; radical cystectomy.