Benefit of Neoadjuvant Cisplatin-based Chemotherapy for Invasive Bladder Cancer Patients Treated with Radiation-based Therapy in a Real-world Setting: An Inverse Probability Treatment Weighted Analysis

Ronald Kool; Alice Dragomir; Girish S Kulkarni; Gautier Marcq; Rodney H Breau; Michael Kim; Ionut Busca; Hamidreza Abdi; Mark Dawidek; Michael Uy; Gagan Fervaha; Fabio L Cury; Nimira Alimohamed; Jonathan Izawa; Claudio Jeldres; Ricardo Rendon; Bobby Shayegan; Robert Siemens; Peter C Black; Wassim Kassouf

doi:10.1016/j.euo.2024.01.014

Benefit of Neoadjuvant Cisplatin-based Chemotherapy for Invasive Bladder Cancer Patients Treated with Radiation-based Therapy in a Real-world Setting: An Inverse Probability Treatment Weighted Analysis

Eur Urol Oncol. 2024 Feb 6:S2588-9311(24)00040-3. doi: 10.1016/j.euo.2024.01.014. Online ahead of print.

Authors

Ronald Kool¹, Alice Dragomir², Girish S Kulkarni³, Gautier Marcq⁴, Rodney H Breau⁵, Michael Kim³, Ionut Busca⁶, Hamidreza Abdi⁵, Mark Dawidek⁷, Michael Uy⁸, Gagan Fervaha⁹, Fabio L Cury¹⁰, Nimira Alimohamed¹¹, Jonathan Izawa¹², Claudio Jeldres¹³, Ricardo Rendon¹⁴, Bobby Shayegan⁸, Robert Siemens⁹, Peter C Black⁷, Wassim Kassouf¹⁵

Affiliations

¹ Department of Urology, McGill University Health Centre, Montreal, QC, Canada; Department of Abdominal Surgery, Division of Urologic Oncology, Erasto Gaertner-Cancer Center, Curitiba, Brazil.
² Department of Urology, McGill University Health Centre, Montreal, QC, Canada.
³ Department of Surgery (Urology), Princess Margaret Cancer Centre and the University Health Network, University of Toronto, Toronto, ON, Canada.
⁴ Department of Urology, McGill University Health Centre, Montreal, QC, Canada; Urology Department, Claude Huriez Hospital, CHU Lille, Lille, France; CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, University of Lille, Lille, France.
⁵ Division of Urology, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada.
⁶ Department of Radiation Oncology, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada.
⁷ Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
⁸ Division of Urology, McMaster University, Hamilton, ON, Canada.
⁹ Department of Urology, Queen's University, Kingston, ON, Canada.
¹⁰ Department of Urology, McGill University Health Centre, Montreal, QC, Canada; Department of Radiation Oncology, McGill University Health Centre, Montreal, QC, Canada.
¹¹ Division of Medical Oncology, University of Calgary, Calgary, AB, Canada.
¹² Division of Urology, Western University, London, ON, Canada.
¹³ Division of Urology, University of Sherbrooke, Sherbrooke, QC, Canada.
¹⁴ Department of Urology, Dalhousie University, Halifax, NS, Canada.
¹⁵ Department of Urology, McGill University Health Centre, Montreal, QC, Canada. Electronic address: wassim.kassouf.med@ssss.gouv.qc.ca.

PMID: 38326142
DOI: 10.1016/j.euo.2024.01.014

Abstract

Background: Neoadjuvant chemotherapy (NAC) improves survival for patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy. Studies on the potential benefit of NAC before radiation-based therapy (RT) are conflicting.

Objective: To evaluate the effect of NAC on patients with MIBC treated with curative-intent RT in a real-world setting.

Design, setting, and participants: The study cohort consisted of 785 patients with MIBC (cT2-4aN0-2M0) who underwent RT at academic centers across Canada. Patients were classified into two treatment groups based on the administration of NAC before RT (NAC vs no NAC).

Outcome measurements and statistical analysis: The inverse probability of treatment weighting (IPTW) with absolute standardized differences (ASDs) was used to balance covariates across treatment groups. The impact of NAC on complete response, overall, and cancer-specific survival (CSS) after RT in the weighted cohort was analyzed.

Results and limitations: After applying the exclusion criteria, 586 patients were included; 102 (17%) received NAC before RT. Patients in the NAC subgroup were younger (mean age 65 vs 77 yr; ASD 1.20); more likely to have Eastern Cooperative Oncology Group performance status 0-1 (87% vs 78%; ASD 0.28), lymphovascular invasion (32% vs 20%; ASD 0.27), higher cT stage (cT3-4 in 29% vs 20%; ASD 0.21), and higher cN stage (cN1-2 in 32% vs 4%; ASD 0.81); and more commonly treated with concurrent chemotherapy (79% vs 67%; ASD 0.28). After IPTW, NAC versus no NAC cohorts were well balanced (ASD <0.20) for all included covariates. NAC was significantly associated with improved CSS (hazard ratio [HR] 0.28; 95% confidence interval [CI] 0.14-0.56; p < 0.001) and overall survival (HR 0.56; 95% CI 0.38-0.84; p = 0.005). This study was limited by potential occult imbalances across treatment groups.

Conclusions: If tolerated, NAC might be associated with improved survival and should be considered for eligible patients with MIBC planning to undergo bladder preservation with RT. Prospective trials are warranted.

Patient summary: In this study, we showed that neoadjuvant chemotherapy might be associated with improved survival in patients with muscle-invasive bladder cancer who elect for curative-intent radiation-based therapy.

Keywords: Bladder cancer; Radiotherapy; Urinary tract neoplasm.