Update on Bladder Preservation Therapies for Muscle-Invasive Bladder Cancer - Beyond the Abstract

Standard management of muscle-invasive bladder cancer (MIBC) entails radical cystectomy (RC) with the removal of bilateral pelvic lymph nodes. Adding neoadjuvant chemotherapy to standard management has been shown to increase absolute survival by 5% at 5 years.1 Although RC with bilateral pelvic lymph node dissection (PLND) remains the standard of care for the majority of patients with MIBC, the procedure is associated with high morbidity and mortality.2 These concerns have sparked investigations into therapies that preserve the bladder. Patients who have sought bladder preservation typically fall into two categories: 1) patients who are medically inoperable and unfit for surgery, or 2) patients with cancer confined to the bladder who wish to avoid radical surgery.


The ideal candidates for bladder preservation include those with small solitary tumors (less than 5cm), no lymph node metastases, no carcinoma in situ (CIS), no hydronephrosis, and with favorable bladder function at baseline.3 Various unimodal and multimodal therapies exist for bladder preservation in the setting of MIBC (Table 1). Trimodal therapy (TMT)—maximal transurethral resection of bladder tumor (mTURBT), chemotherapy, and radiation therapy—is the bladder preservation therapy with the most evidence for use.  In carefully selected patients, TMT has shown comparable efficacy to RC in treating MIBC.4
 
When evaluating trials of TMT, it is important to note the eligibility criteria and whether included patients were medically inoperable or not. Furthermore, heterogeneity of chemoradiotherapy regimens and surveillance protocols makes a comparison of trials difficult. At the authors’ institution, patients receive a single course of chemoradiation with 60-64Gy and either 5-fluorouracil + mitomycin or gemcitabine twice-weekly. Surveillance consists of cystoscopy every three months up through year 2, then every six months through year 4, and annually thereafter.

Table 1. Single modality versus multimodality therapies for bladder preservation in MIBC

Single modality versus multimodality therapies for bladder preservation in MIBC

As opposed to RC, partial cystectomy (PC) affords bladder preservation while maintaining the ability to carefully assess surgical margins and perform PLND if necessary. Although early PC series demonstrated poor outcomes, latter PC series with more selective inclusion criteria showed outcomes comparable to RC.5,6 Because of the possibility of local recurrence after PC due to remaining foci of disease, combinations with other treatment modalities have been investigated. Tetramodal therapy involves maximal TURBT followed by chemoradiation and consolidative PC and has been shown to be highly efficacious, although in studies with smaller sample size.7

Any discussion of bladder preservation therapy must also include quality of life considerations. Adverse outcomes related to TMT are largely gastrointestinal and genitourinary but are likely underreported given inconsistent use of patient-reported outcomes in trials.8 Notably, TMT trials have shown a superior patient-reported quality of life and an increase in quality-adjusted life years as compared to RC.

The last two decades have afforded many advancements and improvements in bladder preservation therapies for patients with muscle-invasive bladder cancer. Opportunities for innovation include further investigation of tetramodal therapy, incorporation of predictive biomarkers for diagnostic and therapeutic purposes, and the use of promising immunotherapies. In summary, efforts to promote bladder preservation have resulted in multimodal therapies that maintain quality of life while not compromising overall and cancer-specific survival. Bladder preservation is particularly useful in patients who are ineligible for radical surgery or who do not wish to undergo the morbidity the bladder removal.

Written by: Judy Hamad, BS, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, and Angela Smith, MD, MS, Director of Urologic Oncology, Associate Professor of Urology, University of North Carolina at Chapel Hill Department of Urology, Chapel Hill, North Carolina

References:

  1. Vale, C. L. "Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data: Advanced Bladder Cancer (ABC) Meta-analysis Collaboration." European urology 48, no. 2 (2005): 202-206.
  2. Rosario, D. J., M. Becker, and J. B. Anderson. "The changing pattern of mortality and morbidity from radical cystectomy." BJU international 85, no. 4 (2000): 427-430.
  3. Spiess, Philippe E., Neeraj Agarwal, Rick Bangs, Stephen A. Boorjian, Mark K. Buyyounouski, Peter E. Clark, Tracy M. Downs et al. "Bladder cancer, version 5.2017, NCCN clinical practice guidelines in oncology." Journal of the National Comprehensive Cancer Network 15, no. 10 (2017): 1240-1267.
  4. Arcangeli, G., L. Strigari, and S. Arcangeli. "Radical cystectomy versus organ-sparing trimodality treatment in muscle-invasive bladder cancer: A systematic review of clinical trials." Critical reviews in oncology/hematology 95, no. 3 (2015): 387-396.
  5. Kassouf, Wassim, David Swanson, Ashish M. Kamat, Dan Leibovici, Arlene Siefker-Radtke, Mark F. Munsell, H. Barton Grossman, and Colin PN Dinney. "Partial cystectomy for muscle invasive urothelial carcinoma of the bladder: a contemporary review of the MD Anderson Cancer Center experience." The Journal of urology 175, no. 6 (2006): 2058-2062.
  6. Smaldone, Marc C., Bruce L. Jacobs, Arlene M. Smaldone, and Ronald L. Hrebinko Jr. "Long-term results of selective partial cystectomy for invasive urothelial bladder carcinoma." Urology 72, no. 3 (2008): 613-616.
  7. Koga, Fumitaka, Kazunori Kihara, Soichiro Yoshida, Minato Yokoyama, Kazutaka Saito, Hitoshi Masuda, Yasuhisa Fujii, and Satoru Kawakami. "Selective bladder‐sparing protocol consisting of induction low‐dose chemoradiotherapy plus partial cystectomy with pelvic lymph node dissection against muscle‐invasive bladder cancer: oncological outcomes of the initial 46 patients." BJU international 109, no. 6 (2012): 860-866.
  8. Ploussard, Guillaume, Siamak Daneshmand, Jason A. Efstathiou, Harry W. Herr, Nicholas D. James, Claus M. Rödel, Shahrokh F. Shariat et al. "Critical analysis of bladder sparing with trimodal therapy in muscle-invasive bladder cancer: a systematic review." European urology 66, no. 1 (2014): 120-137.
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