Plasmacytoid variant of bladder cancer defines patients with poor prognosis if treated with cystectomy and adjuvant cisplatin-based chemotherapy

Abstract

BackgroundSince the definition of different histologic subtypes of urothelial carcinomas by the World Health Organization (WHO) 2004 classification, description of molecular features and clinical behavior of these variants has gained more attention.MethodsWe reviewed 205 tumor samples of patients with locally advanced bladder cancer mainly treated within the randomized AUO-AB05/95 trial with radical cystectomy and adjuvant cisplatin-based chemotherapy for histologic subtypes. 178 UC, 18 plasmacytoid (PUC) and 9 micropapillary (MPC) carcinomas of the bladder were identified. Kaplan Meier analysis and backward multivariate Cox’s proportional hazards regression analysis were performed to compare overall survival between the three histologic subtypes.ResultsPatients suffering from PUC have the worst clinical outcome regarding overall survival compared to conventional UC and MPC of the bladder that in turn seem have to best clinical outcome (27.4 months, 62.6 months, and 64.2 months, respectively; p=0.013 by Kaplan Meier analysis). Backward multivariate Cox´s proportional hazards regression analysis (adjusted to relevant clinicopathological parameters) showed a hazard ratio of 3.2 (p=0.045) for PUC in contrast to patients suffering from MPC.ConclusionsHistopathological diagnosis of rare variants of urothelial carcinoma can identify patients with poor prognosis.

Plasmacytoid urothelial carcinoma (PUC): Imaging features with histopathological correlation

“…15 Future studies are required to validate this imaging finding in comparison to high-grade conventional The Canadian Urological Association (CUA) recognizes PUC as an aggressive bladder malignancy, with guidelines suggesting early cystectomy as treatment for non-muscle invasive disease; however, in a recent study by Keck et al, PUC demonstrated a poor prognosis when treated with cystectomy and cisplatin-based chemotherapeutics. 16,17 These findings are similar to our institutional experience, in which PUC intraoperatively demonstrates a high burden of disease with extensive spread along pelvic fascial planes, with an extremely poor prognosis and significant challenges to any attempted surgical management. To our knowledge, no alternative chemotherapeutic regimen has been validated in this population; however, future therapy may be tailored to specific molecular markers, with human epidermal growth factor receptor type 2 (HER2) recently suggested as a potential therapeutic target in PUC.…”

“…To our knowledge, no alternative chemotherapeutic regimen has been validated in this population; however, future therapy may be tailored to specific molecular markers, with human epidermal growth factor receptor type 2 (HER2) recently suggested as a potential therapeutic target in PUC. 17,18 In our series, approximately half of patients who underwent radical cystectomy had a prior TUR in which a diagnosis of PUC was not suggested at histopathology. The majority of these patients demonstrated foci of PUC on a background of high-grade urothelial carcinoma, and failure to prospectively diagnose PUC may have been secondary to undersampling.…”

Neoadjuvant Chemotherapy in Urothelial Bladder Cancer: Impact of Regimen and Variant Histology

“…The role of NACT in other variants is yet to be determined and the small numbers of micropapillary and other less common but aggressive variants in our study preclude meaningful individual analysis. Conflicting [13,[27][28][29] as well as plasmacytoid disease [14,30]. Due to the small numbers of patients with rare VH, it is clear that collaborative research efforts between institutions will be required to advance our understanding of the molecular drivers of these variants and design new clinical approaches.…”

“…High-risk features are proposed to assist with selection criteria, although concerns have been raised regarding overtreatment and loss of a window of curability in patients that are unlikely to respond and were potential surgical cures [12]. Concerns of chemoresistance have especially been raised about patients with variant histology (VH) [13][14][15].…”

Immunochemical and molecular assessment of urothelial neoplasms and aspects of the 2016 World Health Organization classification

“…Some variants are known to be highly aggressive, such as plasmacytoid, micropapillary, sarcomatoid and poorly differentiated UC, but some entities are still under‐recognized and underdiagnosed. Reporting these entities is of major interest in regard to treatment and molecular classification, as some of these subtypes will not respond to cisplatin‐based chemotherapies …”