New Clues Emerge on Management of Recurrent Nonmuscle Invasive Bladder Cancer After Trimodality Therapy

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Trimodality therapy with maximal transurethral bladder tumor resection (TURBT) followed by chemoradiation is a feasible alternative to radical cystectomy in some patients with muscle-invasive bladder cancer (MIBC). However, even in patients who experience a complete response to trimodality therapy, there is a substantial risk of intravesical recurrence. When patients have recurrent MIBC, salvage radical cystectomy is the standard of care, but when the recurrence is nonmuscle invasive bladder cancer (NMIBC), treatment strategies have been unclear.

Matthew F. Wszolek, MD, chair of Quality and Safety in the Department of Urology, Jason A. Efstathiou, MD, DPhil, director of the Genitourinary Service in the Department of Radiation Oncology at the Mass General Cancer Center, and colleagues at Massachusetts General Hospital recently reviewed the largest cohort of patients to date—85 patients—with NMIBC recurrence after complete response to trimodality therapy. The results were published in The Journal of Clinical Urology. The researchers found that not all patients need immediate radical cystectomy, and adjuvant intravesical bacillus Calmette-Guérin (BCG) had a reasonable toxicity profile and efficacy in this population.

After a complete response to trimodality therapy, NMIBC recurred in 25% of patients. The median time to NMIBC recurrence was 1.8 years. Most recurrences, 82%, developed within the first five years after complete response, but 8% occurred more than 10 years later. The research team notes that those results support the cystoscopic surveillance schedule they use: every three months for two years, every six months for years three to five and, then, yearly for life.

On univariate analysis, carcinoma in situ was associated with recurrent NMIBC (P = .02). However, on multivariable analysis, no risk factor for NMIBC recurrence could be identified, including age, gender, stage, grade, adjuvant chemotherapy or completeness of resection.

Patients with recurrent NMIBC had worse 10-year disease-specific survival than those with no recurrence (72.1% vs 78.4%; P = .002). However, overall survival was similar in the two groups.

Thirty-nine of the patients (46%) received TURBT and adjuvant intravesical BCG, of whom 29 (74%) completed induction therapy and 19 (49%) experienced BCG toxicity. The three-year recurrence-free and progression-free survival rates after induction BCG were 59% and 63%, respectively.

Only 36% of the patients who received induction BCG also received BCG maintenance therapy, the researchers report. They could not determine whether intolerance to induction BCG explained the low use of maintenance BCG.

The team advises surgeons to consider the overall patient health and comorbidities when deciding how to treat recurrent NMIBC after complete response to trimodality therapy. Some patients may be able to avoid radical cystectomy and be initially treated with TURBT and intravesical BCG, ideally including maintenance BCG.

Conversely, patients are strong candidates for immediate radical cystectomy, the team adds, if they have adverse prognostic features such as T1 disease, tumor size 3 cm or greater, concomitant carcinoma in situ and/or lymphovascular invasion, especially if the recurrence is located at the initial MIBC site.

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