Findings of a multi-institutional cohort study provide further evidence that favorable outcomes can be achieved by carefully selected patients with muscle-invasive bladder cancer who forgo radical cystectomy after achieving a clinical complete response to neoadjuvant chemotherapy.
Chicago-Findings of a multi-institutional cohort study provide further evidence that favorable outcomes can be achieved by carefully selected patients with muscle-invasive bladder cancer (MIBC) who forgo radical cystectomy after achieving a clinical complete response to neoadjuvant chemotherapy (NAC).
Considering the limitations of the available research and the need to optimize methods for selecting and monitoring patients for conservative management, however, radical cystectomy after NAC should remain the standard of care, according to the authors.
The study included 148 patients treated at Columbia University Medical Center and Memorial Sloan Kettering Cancer Center, both in New York. During median follow-up of 55 months (range, 5-145 months), 71 patients (48%) experienced a recurrence in the bladder, including 16 with M1 disease and 55 with nonmuscle-invasive (NMI) disease. Eleven of the 71 patients and four others had a systemic recurrence. Twenty-seven patients underwent salvage cystectomy, which prevented cancer-specific death in 75% of those who underwent the procedure after MIBC relapse and in 93% operated on after NMIBC relapse.
For the overall population, rates for 5-year disease-specific survival, overall survival, cystectomy-free survival, and recurrence-free survival were 90%, 86%, 76%, and 64%, respectively.
“To our knowledge, ours is the largest study investigating outcomes of patients with MIBC who forgo radical cystectomy after having a complete response to NAC. Its results are consistent with previous research showing high survival rates in this population and match those seen for patients in a SWOG trial who were pT0 after NAC and underwent immediate radical cystectomy, which suggests radical cystectomy may not provide benefit in the setting of a complete response to NAC,” said Patrick Mazza, clinical research coordinator in the department of urology, Columbia University Medical Center, working with James M. McKiernan, MD, and co-authors.
“While the findings are encouraging, more work is needed to understand the safety of implementing this conservative management approach,” Mazza added.
Next: Outcome predictors identified
Outcome predictors identified
The study also sought to identify outcome predictors and found that survival was significantly worse among patients who relapsed with MIBC compared to those without a muscle-invasive relapse.
In addition, univariate analysis showed that hydronephrosis at diagnosis was associated with both muscle-invasive recurrence and cancer-specific death. On multivariate analysis, the presence of carcinoma in situ at diagnosis was predictive of intravesical recurrence.
“Either of these findings at diagnosis would be reasons to exclude patients from conservative management,” Mazza said.
“All patients in our study had solitary, small- to medium-sized muscle-invasive lesions, with no nodal or distant metastases, urothelial cell carcinoma or mixed histology (no small cell), and a complete TURBT both prior to and following NAC,” he added. “These characteristics seem to be predictive of successful bladder sparing, but it should also be noted that the patients in our study were treated at two centers of urologic oncology expertise. The treatment approach they received, and in particular the extent of TURBT, may not be deliverable at the majority of centers or community hospitals.”
A prospective trial enrolling patients who have a complete clinical response to NAC and randomizing them to cystectomy or surveillance would be needed to definitively determine whether or not cystectomy provides a survival benefit or if a bladder-sparing approach can be safely implemented.
Recognizing that it may not be feasible to conduct such a trial, the investigators suggested that developments to improve patient selection and follow-up may enable bladder sparing to become an acceptable option.
“We believe there is a need to identify genomic biomarkers that are predictive of durable cT0 status and low risk of invasive relapse as well as novel imaging methods that can provide assurance that cT0 disease equals pT0 disease,” Mazza told Urology Times.