Concomitant CIS on TURBT does not impact oncological outcomes in patients treated with neoadjuvant or induction chemotherapy followed by radical cystectomy

© Springer-Verlag GmbH Germany, part of Springer Nature 2018Background: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer improves all-cause and cancer specific survival. We aimed to evaluate whether the detection of carcinoma in situ (CIS) at the time of initial transurethral resection of bladder tumor (TURBT) has an oncological impact on the response to NAC prior to radical cystectomy. Patients and methods: Patients were identified retrospectively from 19 centers who received at least three cycles of NAC or induction chemotherapy for cT2-T4aN0-3M0 urothelial carcinoma of the bladder followed by radical cystectomy between 2000 and 2013. The primary and secondary outcomes were pathological response and overall survival, respectively. Multivariable analysis was performed to determine the independent predictive value of CIS on these outcomes. Results: Of 1213 patients included in the analysis, 21.8% had concomitant CIS. Baseline clinical and pathologic characteristics of the ‘CIS’ versus ‘no-CIS’ groups were similar. The pathological response did not differ between the two arms when response was defined as pT0N0 (17.9% with CIS vs 21.9% without CIS; p = 0.16) which may indicate that patients with CIS may be less sensitive to NAC or ≤ pT1N0 (42.8% with CIS vs 37.8% without CIS; p = 0.15). On Cox regression model for overall survival for the cN0 cohort, the presence of CIS was not associated with survival (HR 0.86 (95% CI 0.63–1.18; p = 0.35). The presence of LVI (HR 1.41, 95% CI 1.01–1.96; p = 0.04), hydronephrosis (HR 1.63, 95% CI 1.23–2.16; p = 0.001) and use of chemotherapy other than ddMVAC (HR 0.57, 95% CI 0.34–0.94; p = 0.03) were associated with shorter overall survival. For the whole cohort, the presence of CIS was also not associated with survival (HR 1.05 (95% CI 0.82–1.35; p = 0.70). Conclusion: In this multicenter, real-world cohort, CIS status at TURBT did not affect pathologic response to neoadjuvant or induction chemotherapy. This study is limited by its retrospective nature as well as variability in chemotherapy regimens and surveillance regimens.Peer reviewedFinal Accepted Versio

Optimal pathological response after neoadjuvant chemotherapy for muscle‐invasive bladder cancer: results from a global, multicentre collaboration

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/170883/1/bju15434_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/170883/2/bju15434.pd

Contemporary update on neoadjuvant therapy for bladder cancer.

Administration of neoadjuvant chemotherapy preceding radical cystectomy in patients with bladder cancer remains a matter of debate. Results of prospective, randomized studies have demonstrated an overall absolute survival benefit of 5% at 5 years, provided cisplatin-based combination regimens are used. Owing to the perception of a modest survival benefit, the medical community has been slow to adopt the use of neoadjuvant chemotherapy. Other reasons for the underuse of neoadjuvant chemotherapy range from patient ineligibility to fear of delaying potentially curative surgery in nonresponders. Instead, several institutions have adopted an individualized, risk-adapted approach, in which the decision to administer chemotherapy is based on clinical stage and patient comorbidity profile. The development of new cytotoxic and targeted therapies, in particular immune checkpoint inhibitors, warrants well-designed prospective studies to test their efficacy alone or in combination in the neoadjuvant setting. Moving forward, genomic characterization of muscle-invasive bladder cancer could offer information that aids clinicians in selecting the appropriate chemotherapy regimen. Following neoadjuvant therapy, every effort should be made to ensure optimal surgery, as surgical margins and the number of removed lymph nodes are prognostic factors; thus, radical cystectomy and a meticulous extended pelvic lymph node dissection should be performed by expert surgeons