Urothelial carcinoma in situ response to cisplatin-based neoadjuvant chemotherapy, or lack thereof: Impact on patient selection for organ preservation in muscle-invasive disease?

Abstract

Introduction: Neoadjuvant cisplatin-based chemotherapy (NACT) followed by radical cystectomy improves urothelial bladder cancer survival [1]. Complete pathological response on cystectomy pathology (pT0N0) is associated with the best survival outcomes [2]. Rates of complete response have increased with improved adoption of NACT calling into question the need for radical cystectomy or perhaps use of organ preservation protocols. In patients with papillary bladder tumors, carcinoma in situ (CIS) has been shown to influence progression and develop into invasive urothelial carcinoma [3]. Furthermore, in patients with invasive urothelial carcinoma, concurrent CIS has been reported in roughly 45% to 65% of cases [4]. Thus, we sought to determine the response rate of CIS to NACT to determine if the presence of CIS should factor into excluding patients from organ preservation.

Methods: A review of our prospectively maintained bladder cancer database was performed among patients undergoing preoperative cisplatin-based chemotherapy followed by cystectomy between 2007 and 2017. Presence of CIS before and after radical cystectomy was assessed. Random bladder biopsies or transurethral resection (TUR) with enhanced imaging for CIS (Cysview) were not routinely utilized in the preoperative setting.

Results: One-hundred eighty-three patients were identified that underwent preoperative cisplatin chemotherapy. A total of 96 (52.4%) unique patients had documented CIS in the entire cohort. Forty-eight (50%) patients were noted to have CIS on TUR. Of these 48 patients, 26 (54.1%) were noted to have residual CIS on final pathology. An additional 48 patients were found to have CIS on final pathology that was not diagnosed on TUR, making a total of 74 (77.1%) patients with CIS refractory to NACT on cystectomy pathology.

Conclusions: CIS seems to respond poorly to cisplatin-based neoadjuvant chemotherapy. If organ preservation protocols are considered, a thorough assessment for CIS with enhanced photodynamic detection cystoscopy or random bladder biopsies should be considered. Residual cisplatin-refractory disease, even if noninvasive CIS, may lead to poor outcomes. Future molecular classifiers may assist in disease signatures to help guide treatment protocols.

Keywords: Bladder cancer; Carcinoma in situ; Neoadjuvant chemotherapy; Urothelial carcinoma.