Targeted Sequencing of Non-schistosomal Squamous Cell Carcinoma of the Urinary Bladder – Expert Commentary

Squamous cell carcinoma of the urinary bladder associated with non-schistosomiasis (NSR-SCCUB) is an uncommon tumor subtype distinct from urothelial carcinoma (UC). NSR-SCCUB type is slightly more prevalent in men and is associated with chronic bladder irritation from chemotherapy, chronic bladder infections, or indwelling catheters. In addition, patients with these tumors tend to have a higher T stage at diagnosis (T2). Anatomically, the bladder's trigone and lateral walls are commonly affected.

Genomic characterization of NSR-SCCUB is incomplete. A recent study by Al Ezzi et al. in PLOS ONE used the Oncomine targeted sequencing panel to examine NSR-SCCUB from 11 patients at the Princess Margaret Cancer Center. The investigators collected demographics, disease characteristics, therapy approaches, and outcomes. The Kaplan-Meier method was used to calculate disease-free and overall survival rates (OS).

The median age was 71 years (45–86), with a male predominance (63.6 %). At diagnosis, nine patients (81.8%) had muscle-invasive disease, one (9.1%) had non-muscle-invasive disease, and one (9.1%) had advanced disease. Nine (81.8%) patients had radical cystectomy with pelvic lymph nodes dissection. Eight (72.7%) patients had pT3 or pT4 with N0. The Median OS was 12.5 months on average (95 % confidence interval [CI]: 7.7–17.2 months). Targeted sequencing identified genomic alterations in the TERT promoter (72.7 %), TP53 (72.7 %), PIK3CA (27.3 %), CREBBP (18.2 %), FBXW7 (18.2 %), and PTEN (18.2 %). Copy number alterations of EGFR and CCND1 were found in 18.2 % of patients, respectively. Additional variations in FGFR3, CDKN2A, RADS1D, KRAS, SLX4, NF2, RB1, MAPK1, BRCA2, ATM, ARID1A, and AKT1 were found at lower frequencies.

The study is limited by its small sample size. Overall, the spectrum of genomic alterations in cancer-associated genes in NSR-SCCUB is broadly similar to that of UC. Comprehensive analysis using whole-genome sequencing and RNA sequencing is likely necessary to identify more subtle but biologically important molecular differences between these tumors.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York


  1. Al-Ezzi EM, Veitch ZW, Salah SH, Van der Kwast TH, Stockley TL, Selvarajah S, Zhang T, Sridhar SS, Sacher AG, Fallah-Rad N, Kulkarni GS, Zlotta AR, Finelli A, Hansen AR. Genomic characterization of non-schistosomiasis-related squamous cell carcinoma of the urinary bladder: A retrospective exploratory study. PLoS One. 2021 Dec 1;16(12):e0259272. doi: 10.1371/journal.pone.0259272. eCollection 2021. PMID: 34851968

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