Adjuvant chemotherapy for muscle invasive urothelial carcinoma of the bladder
- Jonathan E Rosenberg, MD
Jonathan E Rosenberg, MD
- Associate Attending Physician
- Associate Professor
- Section Head, Non-Prostate Genitourinary Malignancies
- Memorial Sloan-Kettering Cancer Center
- Weill-Cornell Medical College
- Joaquim Bellmunt, MD, PhD
Joaquim Bellmunt, MD, PhD
- Director, Bladder Cancer Center
- Dana-Farber Cancer Institute
- Dana-Farber/Brigham and Women's Cancer Center
- Associate Professor, Harvard Medical School
- Cora N Sternberg, MD, FACP
Cora N Sternberg, MD, FACP
- Department of Medical Oncology
- San Camillo and Forlanini Hospitals
- Rome, Italy
Bladder cancer is the most common malignancy involving the urinary system. Urothelial (transitional cell) carcinoma is the predominant histologic type, particularly in the United States and Europe, where it accounts for 90 percent of all bladder cancers. In other areas of the world, non-urothelial carcinomas are more frequent. (See "Epidemiology and risk factors of urothelial (transitional cell) carcinoma of the bladder", section on 'Epidemiology'.)
The identification of active chemotherapy regimens in patients with metastatic urothelial carcinoma resulted in the use of both neoadjuvant and adjuvant chemotherapy. Neoadjuvant chemotherapy is associated with a survival advantage for patients with locally advanced bladder cancer, but clinicians are not yet able to identify those patients most likely to benefit from treatment , which raises the concern that some may be overtreated. As a result, many clinicians and patients opt for definitive surgery rather than neoadjuvant chemotherapy. For those patients who undergo primary surgery, adjuvant treatment may be offered, especially to patients at high risk for recurrence based on pathologic staging.
The role of adjuvant chemotherapy in patients with locally advanced urothelial carcinoma of the bladder will be reviewed here. The surgical approach to bladder cancer and the role of neoadjuvant chemotherapy are discussed separately. (See "Overview of the initial approach and management of urothelial bladder cancer" and "Radical cystectomy and bladder-sparing treatments for urothelial bladder cancer" and "Neoadjuvant treatment options for muscle-invasive urothelial bladder cancer".)
RATIONALE FOR ADJUVANT CHEMOTHERAPY
For patients with muscle invasive bladder cancer, cystectomy alone is associated with an overall cure rate that ranges from 50 to 65 percent, though it can be as high as 80 percent in patients who have pT2 disease . In comparison, patients with locally advanced disease are at risk for worse outcomes. The five-year survival rate in patients with invasion beyond the bladder muscle is approximately 40 percent, while the survival for patients with lymph node involvement is approximately 35 percent.
Given the benefit of chemotherapy in the neoadjuvant setting and the poor prognosis of patients following surgical resection, adjuvant chemotherapy is often used in patients with high-risk bladder cancer. Unfortunately, approximately 30 percent of patients experience complications following radical cystectomy that preclude them from receiving adjuvant chemotherapy .
- Sternberg CN, Donat SM, Bellmunt J, et al. Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer. Urology 2007; 69:62.
- Stein JP, Lieskovsky G, Cote R, et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol 2001; 19:666.
- Donat SM, Shabsigh A, Savage C, et al. Potential impact of postoperative early complications on the timing of adjuvant chemotherapy in patients undergoing radical cystectomy: a high-volume tertiary cancer center experience. Eur Urol 2009; 55:177.
- Sternberg CN, Bellmunt J, Sonpavde G, et al. ICUD-EAU International Consultation on Bladder Cancer 2012: Chemotherapy for urothelial carcinoma-neoadjuvant and adjuvant settings. Eur Urol 2013; 63:58.
- Cancer of the Urinary Bladder- SEER Stat Facts http://seer.cancer.gov/statfacts/html/urinb.html (Accessed on April 20, 2012).
- Galsky MD, Hahn NM, Rosenberg J, et al. A consensus definition of patients with metastatic urothelial carcinoma who are unfit for cisplatin-based chemotherapy. Lancet Oncol 2011; 12:211.
- Bamias A, Efstathiou E, Moulopoulos LA, et al. The outcome of elderly patients with advanced urothelial carcinoma after platinum-based combination chemotherapy. Ann Oncol 2005; 16:307.
- Pal SK, Agarwal N, Grivas P, Choueiri T. Adjuvant Chemotherapy for Bladder Cancer: Using Population-Based Data to Fill a Void of Prospective Evidence. J Clin Oncol 2016; 34:777.
- Sternberg CN, Skoneczna I, Kerst JM, et al. Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial. Lancet Oncol 2015; 16:76.
- Leow JJ, Martin-Doyle W, Rajagopal PS, et al. Adjuvant chemotherapy for invasive bladder cancer: a 2013 updated systematic review and meta-analysis of randomized trials. Eur Urol 2014; 66:42.
- Paz-Ares LG, Solsona E, Esteban E, et al. Randomized phase III trial comparing adjuvant paclitaxel/gemcitabine/cisplatin (PGC) to observation in patients with resected invasive bladder cancer: Results of the Spanish Oncology Genitourinary Group (SOGUG) 99/01 study (abstract #LBA4518). J Clin Oncol 2010; 28:18s.
- Cognetti F, Ruggeri EM, Felici A, et al. Adjuvant chemotherapy with cisplatin and gemcitabine versus chemotherapy at relapse in patients with muscle-invasive bladder cancer submitted to radical cystectomy: an Italian, multicenter, randomized phase III trial. Ann Oncol 2012; 23:695.
- Galsky MD, Stensland KD, Moshier E, et al. Effectiveness of Adjuvant Chemotherapy for Locally Advanced Bladder Cancer. J Clin Oncol 2016; 34:825.
- Svatek RS, Shariat SF, Lasky RE, et al. The effectiveness of off-protocol adjuvant chemotherapy for patients with urothelial carcinoma of the urinary bladder. Clin Cancer Res 2010; 16:4461.
- Studer UE, Bacchi M, Biedermann C, et al. Adjuvant cisplatin chemotherapy following cystectomy for bladder cancer: results of a prospective randomized trial. J Urol 1994; 152:81.
- Gallagher DJ, Milowsky MI, Iasonos A, et al. Sequential adjuvant chemotherapy after surgical resection of high-risk urothelial carcinoma. Cancer 2009; 115:5193.
- Lehmann J, Kuehn M, Fischer C, et al. Randomized phase III study of adjuvant versus progression-triggered treatment with gemcitabine (G) after radical cystectomy (RC) for locally advanced bladder cancer (LABC) in patients not suitable for cisplatin-based chemotherapy (CBC) (AUO-trial AB22/00). J Clin Oncol 21, 2013 (suppl 6; abstr 250).
- RATIONALE FOR ADJUVANT CHEMOTHERAPY
- PATIENT SELECTION
- Medical fitness
- Definition of high risk
- IMPACT ON THE OUTCOMES
- EORTC Intergroup trial 30994
- Observational studies
- CHOICE OF ADJUVANT TREATMENT
- Cisplatin-based combination therapy
- Alternative chemotherapy options
- Adjuvant immunotherapy
- SUMMARY AND RECOMMENDATIONS