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Considerations in Selecting Patients for Trimodal Therapy for Muscle-invasive Bladder Cancer

Key findings

  • Multiple patient- and tumor-related factors contribute to the choice between trimodal therapy (TMT) or radical cystectomy for patients with muscle-invasive bladder cancer
  • Candidates for TMT must be able to tolerate radiosensitizing chemotherapy, pelvic radiation and repeated cystoscopic surveillance, and be relied on to attend repeated follow-up visits
  • Candidates for TMT must also have reasonable lower urinary tract function, assessed using validated voiding symptom questionnaires and cystoscopy; uroflowmetry, post-void residual bladder scan or formal urodynamics are additional options
  • Imaging of the bladder is preferably performed prior to transurethral resection of the bladder tumor to avoid artifact from the resection
  • The ideal patients and tumors for TMT include those without hydronephrosis, without presence of extensive carcinoma in situ, those in whom the tumor can be maximally resected transurethrally and those without tumor extension into the distal ureter

Trimodal therapy (TMT) is now a well-accepted option for many patients with muscle-invasive bladder cancer. This approach involves maximal transurethral resection of the bladder tumor (TURBT) followed by concomitant radiation therapy and radiosensitizing chemotherapy as an alternative to radical cystectomy with urinary diversion.

In Urologic OncologyAdam S. Feldman, MD, MPHdirector of the Combined Harvard Urologic Oncology Fellowship, urologic oncologist at Massachusetts General Hospital Cancer Center and faculty member of The Carol and James Herscot Center for Tuberous Sclerosis Complex at Massachusetts General Hospital, and colleagues recently reviewed the critical roles of the urologist in making TMT successful. These include thorough TURBT, re-resection to assure no residual or recurrent disease, ongoing surveillance and proper management of any local recurrence.

The first key, though, is appropriate patient selection. Summarized here are the factors that should most strongly influence the decision between TMT and radical cystectomy with or without neoadjuvant chemotherapy.

Patient Factors

Key factors in positive outcomes for TMT include:

  • Patient preference for bladder preservation vs. surgical resection
  • Ability to tolerate radiosensitizing chemotherapy
  • Ability to tolerate pelvic radiation (e.g., note prior pelvic radiation, baseline bowel function and history that suggests an inability to tolerate potential gastrointestinal side effects of radiation, such as inflammatory bowel disease or history of colovesical fistula)
  • Voiding function, lower urinary tract symptoms and bladder capacity
  • Results of uroflowmetry and post-void residual bladder scan (optional)
  • Ability to tolerate repeated cystoscopic surveillance and predicted ability to attend follow-up visits

A patient with very poor bladder and lower urinary tract function may have difficulty during and after TMT that the procedure is actually detrimental to the quality of life. Occasionally, it must be asked whether the bladder is worth saving.

Tumor Factors

Imaging of the bladder is preferably performed prior to TURBT:

  • Contrast-enhanced CT with delayed-phase CT urography aids assessment of the upper tracts; cross-sectional CT can be used to estimate tumor volume and the extent of bladder and transmural involvement
  • MRI provides excellent resolution for assessing the tumor, bladder wall and associated adjacent structures for local staging

Relative contraindications to TMT are:

  • Tumor extension into the ureter beyond the level of the intramural tunnel (tumor merely overlying the ureteric orifice or extending just within the ureteral tunnel can often be managed with TMT)
  • Hydronephrosis (but hydronephrosis is a risk factor for T2 disease even in patients undergoing radical cystectomy, so it may not be an absolute contraindication to TMT if the tumor can be thoroughly resected transurethrally)
  • Predicted inability to achieve complete TURBT (e.g., clinical T3b/T4 disease or an overly large tumor) if the patient can tolerate radical cystectomy
  • An extensive amount of carcinoma in situ (CIS) throughout the bladder (a small amount of peripheral CIS usually does not preclude TMT)
  • Extensive tumor burden involving the majority of the bladder
  • Invasive tumor involving a bladder diverticulum that cannot be resected transurethrally
  • Prostatic stromal invasion or CIS of the prostatic urethra in men who are candidates for radical cystectomy
  • In women, extensive and circumferential distal bladder neck involvement

The review also discusses techniques for TURBT, how best to document the primary tumor location for radiation planning, repeat TURBT and biopsy after chemoradiation, treatment of noninvasive recurrences, and choosing between continent/incontinent urinary diversions and orthotopic neobladder in patients who need salvage cystectomy.

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Adam S. Feldman, MD, MPH, and colleagues review the patient-related and tumor-related factors that should most strongly influence the decision between trimodal therapy and radical cystectomy for patients with muscle-invasive bladder cancer.