2579 - Title: Genomic characterization of non-schistosomiasis-related squamous cell carcinoma (NSR-SCC) of the urinary bladder: a retrospective study of potential prognostic and predictive biomarkers

Background

NSR-SCC is a rare subset of bladder tumors distinct from urothelial carcinoma (UC). Most studies that have assessed molecular biomarkers in bladder cancer have been limited to UC. We aim to characterize the genomic profile of NSR-SCC and to correlate genomic alterations with survival outcomes.

Methods

This was a retrospective study of NSR-SCC patients (pts) at Princess Margaret Cancer Centre. Patient demographics, risk factors, disease characteristics, treatment modalities, and survival outcomes were collected for eligible pts. Genomic DNA and complementary DNA were analyzed using Oncomine® V3 assay, a targeted NGS platform. Overall survival (OS) was estimated by Kaplan-Meier (log-rank). Uni- (UVA) and multi-variate (MVA) analysis (Cox-regression) was used to evaluate the impact of patient and genomic characteristics on OS.

Results

We identified 11 pts with NSR-SCC from 2002-2017, with median age 71 years (range 46-86) and 7 were male. Nine pts had muscle invasive, 1 superficial stage and 1 distant metastasis. Nine pts had radical cystectomy and LN dissection. Eight pts had pT3 or pT4 with N0 and 6 were grade 2. Median OS was 12.5 months (95 % CI 7.7- 17.2 months). Common point mutations were identified in TERT (73%), TP53 (73%), PIK3CA (27%), CREBBP (18%), FBXW7 (18%), and PTEN (18%). Amplifications were identified in EGFR (18%), FGF3 (18%), CCND1 (18%), and FGF19 (18%). Additional mutations were detected at a frequency <10%. On UVA, only bladder irritants (e.g. prior radiation, urinary catheter, infection) were associated with improved OS (HR = 0.091; p = 0.031). A limited MVA didn’t identify any significant prognostic genomic abnormalities: TP53 (HR = 2.2; 95%CI: 0.3-17; p = 0.425), TERT (HR = 1.45; 95%CI: 0.2-10.2; p = 0.70) and PIK3CA (HR = 0.46; 95%CI: 0.1- 2.0; p = 0.31).

Conclusions

In this NSR-SCC series, we identified a number of actionable genomic alterations that may be targeted with drugs. No mutation was able to define different prognostic groups. Many of these aberrations were seen in UC. Biomarker driven studies in UC should consider enrollment of NSR-SCC pts who harbor these putative mutations.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Aaron Hansen.

Funding

Astellas.

Disclosure

A.G. Sacher: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self): Merck; Honoraria (self): Genentech-Roche. G. Kulkarni: Advisory / Consultancy: Janssen; Advisory / Consultancy: Astellas; Advisory / Consultancy: Roche; Advisory / Consultancy: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Ferring; Advisory / Consultancy: Sanofi. A. Zlotta: Advisory / Consultancy: Sanofi; Advisory / Consultancy: Ferring; Advisory / Consultancy: Janssen. A.R. Hansen: Advisory / Consultancy, Research grant / Funding (self): Genentech; Advisory / Consultancy, Research grant / Funding (self): Roche; Advisory / Consultancy, Research grant / Funding (self): Merck; Advisory / Consultancy, Research grant / Funding (self): GSK; Advisory / Consultancy, Research grant / Funding (self): Bristol-Myers; Advisory / Consultancy, Research grant / Funding (self): Squibb; Advisory / Consultancy, Research grant / Funding (self): Novartis; Advisory / Consultancy, Research grant / Funding (self): Boston Biomedical; Advisory / Consultancy, Research grant / Funding (self): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (self): AstraZeneca. All other authors have declared no conflicts of interest.