Urine cytology NGS comparable to tumor biopsy in identifying UTUC mutations


Urine cytology specimen NGS was found to be a feasible and valid method of assessing genomic alterations in patients with upper tract urothelial carcinoma.

Next-generation sequencing (NGS) via urine cytology specimens may represent a valid, minimally invasive profiling tool for assessing genomic alterations in upper tract urothelial carcinoma (UTUC), according to a poster presented during the 2021 Society of Urologic Oncology Annual Meeting.1

Specifically, researchers concluded that the overall success rate of NGS of urine cytology specimens from UTUC was 86% and that the derived genomic profiles were similar to those obtained via ureteroscopic biopsies and radical nephroureterectomies.

Wesley Yip, MD

Wesley Yip, MD

“Many times, genomic profiling is from tissue from FFPE cell blocks–obtaining tissue requires invasive surgical procedures, and DNA is often moderately degraded,” explained Wesley Yip, MD, urologic oncology fellow at Memorial Sloan Kettering, in a presentation of the findings. “Our group has previously shown that urine cytology specimens, at least in the context of [patients with] non-muscle invasive bladder cancer treated with BCG, present a potential source for genomic analysis. So, we asked the question: ‘Can genomic profiling upper tract tumors be performed through cytology specimens.’”

Researchers compared a total of 14 urine cytology specimens from UTUC tumors with paired tissue specimens including ureteroscopic biopsies and radical nephroureterectomies. The 20 most frequently altered genes in the urine cytology samples were consistent with the gene alterations present in the tissue samples. In both specimen groups, TERT (in cytology vs tumor specimen, 50% vs 67%, respectively), KMT2D (50% vs 67%), and FGFR3 (42% vs 58%) represented the most prevalent genomic mutations.

The tumor specimen findings yielded a total of 124 gene alterations, with TERT (67%), FGFR3 (58%), KMT2D (67%), and STAG2 (50%) as the most prominent mutations. The average tumor mutation burden was 12.3 (range, 2.6-61.4) in this collection of samples. Other prevalent mutations included CREBBP (33%), CCND1, FLT4, and KMT2C (all 25%), and ELF3, PRKD1, MAPKAP1 (all 20%).

Urine cytology specimen findings identified a total of 66 genomic alterations and the TMB average was 8 (range, 2.6–16.7). The most common alterations identified in this collection included FGFR3 (42%), KMT2D (50%), and TERT (50%). Other prevalent alterations included STAG2 (33%) and PIk3CA (25%).

“We demonstrate an 86% success rate of next generation sequencing of urine cytology specimens from upper track tumors. There are similar genetic profiles between the urine cytology, specimens and tissue specimens are there from biopsy or radical nephroureterectomy,” concluded Kip. “This demonstrates that urine cytology is actually a useful minimally invasive tool but has some room for improvement. Sequencing these specimens has the potential for risk stratification and treatment response monitoring.”


1. Yip W, Reisz P, Tracey A, et al. Feasibility and validation of genomic profiling of upper tract urothelial carcinoma from urine cytology specimens. Presented at: SUO 22nd Annual Meeting; December 1-3, 2021; Orlando, Florida. Poster 120.

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