Purpose:
We investigated the characteristics and outcomes of patients with muscle invasive bladder cancer treated with transurethral resection plus chemotherapy alone in a large observational cohort reflecting the continuum of practice settings in the United States.
Materials and Methods:
In the National Cancer Database from 2004 to 2015 we identified 1,538 patients treated with transurethral resection plus multi-agent chemotherapy as definitive treatment of cT2-T4aN0M0 urothelial carcinoma of the bladder. For comparison purposes we included in study 17,866 patients treated with radical cystectomy with or without perioperative chemotherapy. Baseline characteristics were compared between the 2 groups by multivariable logistic regression. Treatment outcomes were assessed using Kaplan-Meier analysis and a Cox regression model.
Results:
On multivariate analysis several variables, including patient demography (older age, African American race, prior malignancy and lack of insurance), tumor characteristics (higher cT stage) and facility type (nonacademic facilities and lower radical cystectomy volume) were associated with a higher probability of transurethral resection plus chemotherapy for muscle invasive bladder cancer compared to the standard of care. Two and 5-year survival rates in all patients treated with transurethral resection plus chemotherapy were 49.0% and 32.9%, and in patients with cT2 disease the rates were 52.6% and 36.2%, respectively.
Conclusions:
This large population level cohort of unselected patients shows that long-term survival can be achieved in a subset of patients treated with transurethral resection plus chemotherapy alone for muscle invasive bladder cancer. However, the best candidates for this approach remain to be defined. Ongoing clinical trials are now being launched to evaluate the ability of biomarkers to accurately select patients who could be treated with this bladder sparing strategy.
Until now, bladder cancer with muscle invasion is one of the last urological cancer where organ-sparing approaches are rarely offered. Actually, cisplatin-based neoadjuvant chemotherapy (NAC) associated with radical cystectomy and concomitant bilateral pelvic lymph node dissection is actually considered as the standard of care treatment of muscle-invasive bladder cancer (MIBC). The different studies who assessed the impact of NAC reported complete response (ie.; ypT0) in up to 40% of cases on the final cystectomy specimens. These results lead to the hypothesis that some patients who have a complete response after chemotherapy might not require a radical cystectomy to achieve curative outcomes and therefore avoid the morbi-mortality that comes with this procedure.
This latter conservative approach was investigated by Audenet et al. in a large observational cohort using the National Cancer Database (NCDB). From 2004 to 2015, they identified 1,538 patients who had a TURB plus multi-agent chemotherapy for cT2-T4N0M0 bladder cancer without local treatment (radiotherapy or cystectomy) and compared this population to 17,866 patients who received the classical treatment of radical cystectomy ± chemotherapy.
Patients in the arm TURB + chemotherapy alone were significantly older, non-caucasian, uninsured or without private insurance, had higher rates of previous history of malignancy, and a higher clinical T stage (24% cT3-T4 vs. 18% p<0.001). They found that these patients had a significantly lower OS than those treated with radical cystectomy (median 23.9 months 95% CI 21.4-30.2 vs 48.1, 95% CI 46.3-50.2, p<0.001). Interestingly, these patients had a significantly lower 30- and 90-days mortality (0.2% vs. 2.6% and 3.8% vs. 6.5%, respectively) and the OS at 2 and 5 years was respectively 49% and 32.9%. Moreover, for patients treated for a cT2 disease, the OS was improved with 52.6% and 36.2% at 2 and 5 years, respectively. Even if these results do not define a subgroup of patients that may benefit from bladder sparing strategy for the management of MIBC, it is interesting to highlight that almost a third of the patients achieved a 5-year overall survival despite factors that could have impacted negatively the outcomes such as treatment in non-reference centers and/or low volume institutions. This study is the first large observational cohort which showed that TURB plus chemotherapy may be a viable strategy in a subset of patients with the potential for long-term oncological control coupled with a decreased morbidity and mortality as well as potential favorable long-term quality of life compared with radical cystectomy. Prospective trials are essential to confirm these interesting results, and in order to evaluate the real impact of neoadjuvant cisplatin-based chemotherapy following TURB without local treatment.