A retrospective comparison of patients with localized muscle-invasive bladder cancer who achieved complete downstaging or noninvasive downstaging prior to radical cystectomy following either neoadjvuant chemotherapy or transurethral resection revealed that the former approach was associated with a relative survival benefit. The findings from this study were published in Urologic Oncology.
While radical cystectomy is the recommended surgical approach for patients diagnosed with muscle-invasive bladder cancer, rates of 5-year mortality are 40% to 50% in this group of patients.
A number of randomized clinical trials have demonstrated improved survival rates in patients with localized muscle-invasive bladder cancer following treatment with neoadjuvant chemotherapy prior to radical cystectomy, particularly in the subgroup achieving pathologic T0 disease. However, other studies have shown that disease downstaging can also occur in patients with muscle-invasive bladder cancer undergoing transurethral resection before radical cystectomy.
Of the 24,763 patients registered in the National Cancer Database between 2004 and 2014 who underwent radical cystectomy for the treatment of clinically localized muscle-invasive bladder cancer, only 3838 (15.5%) were treated with neoadjuvant chemotherapy prior to radical cystectomy.
Of the 1781 and 1015 patients who achieved noninvasive downstaging (pT0/Tis/TaN0) and complete downstaging (pT0N0), respectively, prior to undergoing radical cystectomy, 757 and 1024 patients in the former group and 465 and 560 patients in the latter group were treated with multiagent neoadjuvant chemotherapy and with transurethral resection only, respectively.
A key study finding was that the proportions of patients achieving complete/noninvasive downstaging were significantly higher for those treated with neoadjuvant chemotherapy compared with transurethral resection. For example, 12.13% and 2.63% of patients treated with neoadjuvant chemotherapy and transurethral resection, respectively, achieved complete downstaging (P <.001). This relative downstaging benefit of neoadjuvant chemotherapy over transurethral resection was also observed in the subgroup of patients with clinical T2 disease who achieved complete downstaging (ie, 14.07% versus 3.08%).
At a median follow-up of 21.3 months, overall survival (OS) was significantly longer in patients achieving disease downstaging following treatment with neoadjuvant chemotherapy compared with transurethral resection. For example, in the subgroup of patients achieving complete downstaging, the 5-year OS rates were 80% and 70%, respectively (hazard ratio [HR], 0.52; 95% CI, 0.35−0.76). Similar results were observed in the subgroup achieving noninvasive downstaging, and treatment with neoadjuvant chemotherapy was found to be an independent predictor of OS in patients with localized muscle-invasive bladder cancer achieving either complete or noninvasive downstaging.
Study limitations mentioned by the study authors included the absence of information on the specific agents included in the neoadjuvant chemotherapy regimens and details related to the transurethral resection procedures.
In their concluding comments, the study authors noted that “these findings highlight the importance of research efforts to identify predictors of response to neoadjuvant chemotherapy; even in the patient population expected to achieve complete downstaging.”
Cajipe M, Wang H, Elshabrawy A, et al. Pathological downstaging following radical cystectomy for muscle-invasive bladder cancer: Survival outcomes in the setting of neoadjuvant chemotherapy versus transurethral resection only [published online January 16, 2020]. Urol Oncol. doi: 10.1016/j.urolonc.2019.12.019