Characterizing trends in treatment modalities for localized muscle-invasive bladder cancer in the pre-immunotherapy era
Muscle-invasive bladder cancer (MIBC) is an aggressive disease for which treatment strategies are continuously evolving. We characterized trends in treatment modalities for MIBC from 2004 to 2013 (the “pre-immunotherapy era”) and identified predictors of receiving the current standard of care treatment: neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC).
We used the National Cancer Database to identify individuals diagnosed with clinically localized MIBC from 2004 to 2013. We calculated the yearly prevalence of NAC followed by RC, RC as first treatment, trimodal therapy, chemotherapy and/or radiation alone, and no treatment. We then identified factors associated with receiving NAC prior to RC.
There was a notable increase in the use of NAC followed by RC over the study period, from 3.68% in 2004 to 14.83% in 2013 (P < 0.001). Factors associated with decreased odds of receiving this regimen included being older, Black, uninsured, less educated, and more burdened by comorbidities. Rates of trimodal therapy and chemotherapy and/or radiation alone remained relatively constant (approximately 5 and 17%, respectively). There was a consistent decline in the proportion of patients who did not receive any treatment, down to 34.20% in 2013.
Trends in localized MIBC treatment have evolved substantially since the early 2000s, and certain patient characteristics are associated with lower odds of receiving the current standard of care. This serves as a foundation from which to judge the impact of the upcoming immunotherapy era on the treatment landscape for this disease.
KeywordsBladder cancer Epidemiology Health services
Quoc-Dien Trinh supported by the Brigham Research Institute Fund to Sustain Research Excellence, the Bruce A. Beal and Robert L. Beal Surgical Fellowship, the Genentech Bio-Oncology Career Development Award from the Conquer Cancer Foundation of the American Society of Clinical Oncology, a Health Services Research pilot test grant from the Defense Health Agency, the Clay Hamlin Young Investigator Award from the Prostate Cancer Foundation, and an unrestricted educational grant from the Vattikuti Urology Institute.
SAF protocol/project development, data collection or management, data analysis, manuscript writing/editing. SSH protocol/project development, data collection or management, data analysis, manuscript writing/editing. MJK data collection or management, data analysis. APC data analysis, manuscript writing/editing. SB data collection or management, data analysis. PG data collection or management, data analysis. MAP data analysis, manuscript writing/editing. ASK data analysis, manuscript writing/editing. MS data analysis, manuscript writing/editing. TKC data analysis, manuscript writing/editing. QDT protocol/project development, data collection or management, data analysis, manuscript writing/editing.
Compliance with ethical standards
Conflict of interest
QDT reports honoraria from Bayer and Astellas and research funding from Intuitive Surgical. ASK reports consulting fees from Sanofi and Profound Medical; GPS is a consultant for BMS, Exelixis, Bayer, Sanofi, Pfizer, Novartis, Eisai, Janssen, Amgen, Astrazeneca, Merck, Genentech, Astellas/Agensys, and reports research support to institution from Bayer, Amgen, Boehringer-Ingelheim, Merck, Sanofi, Pfizer.
Research involving human participants and/or animals
We used completely de-identified data from the National Cancer Database. No identifiable humans were involved. Our study did not involve animals. Thus, our study was exempt from formal review by the Brigham and Women’s Hospital institutional review board.
All patient data were de-identified/anonymous and collected from hospitals that gave their informed consent to collect this information for the database.
- 16.von der Maase H, Hansen SW, Roberts JT et al (2000) Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol 18(17):3068–3077CrossRefPubMedGoogle Scholar
- 20.Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK (2011) International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol 29(16):2171–2177CrossRefPubMedGoogle Scholar
- 23.Birtle AJ, Chester JD, Jones RJ (2018) Results of POUT: a phase III randomised trial of perioperative chemotherapy versus surveillance in upper tract urothelial cancer (UTUC). J Clin Oncol 36 (suppl 6S; abstr 407) Google Scholar
- 24.Neoadjuvant pembrolizumab in combination with gemcitabine therapy in cis-eligible/ineligible UC subjects (NCT02365766). https://www.clinicaltrials.gov/ct2/show/NCT02365766. Accessed 27 Feb 2018
- 25.Pre-surgical study evaluating anti-PD-L1 antibody (durvalumab) plus anti-CTLA-4 (tremelimumab) in patients with muscle-invasive, high-risk urothelial carcinoma who are ineligible for cisplatin-based neoadjuvant chemotherapy (NCT02812420) https://www.clinicaltrials.gov/ct2/show/NCT02812420. Accessed 27 Feb 2018
- 29.SEER cancer stat facts: bladder cancer https://seer.cancer.gov/statfacts/html/urinb.html. Accessed 1 Mar 2018
- 30.Mak RH, Hunt D, Shipley WU et al (2014) Long-term outcomes in patients with muscle-invasive bladder cancer after selective bladder-preserving combined-modality therapy: a pooled analysis of Radiation Therapy Oncology Group protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol 32(34):3801–3809CrossRefPubMedPubMedCentralGoogle Scholar