Urine Cytology NGS Comparable to Tumor Biopsy in Identifying UTUC Mutations

Targeted Therapies in OncologyJanuary 2022
Volume 11
Issue 1
Pages: 41

Next-generation sequencing samples of urine cytology specimens from upper tract urothelial carcinoma demonstrated an 86% success rate.

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 22nd Annual Meeting of the Society of Urologic Oncology.1

Specifically, investigators 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.

“Many times, genomic profiling is from tissue from formalin-fixed, paraffin-embedded 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 Cancer Center in New York, New York, 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 of upper tract tumors be performed through cytology specimens?”

Investigators compared a total of 14 urine cytology specimens from UTUC tumors with paired tissue specimens including ureteroscopic biopsies and radical nephroureterectomies. Six cytology specimens were obtained after local treatment. Cytology and tissue specimens were then analyzed using NGS with a hybridization-based exon capture assay of 505 cancer-related genes.

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, and MAPKAP1 (all 20%).

Urine cytology specimen findings identified a total of 66 genomic alterations, and the tumor mutational burden 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%).

The investigators noted that the urine cytology molecular landscape was highly concordant with that of the paired tissue. Further, no statistically significant differences in the frequencies of the 20 most commonly altered genes were reported.

“We demonstrate an 86% success rate of next-generation sequencing of urine cytology specimens from upper tract tumors. There are similar genetic profiles present in the urine cytology specimens and tissue specimens that there are from biopsy or radical nephroureterectomy,” Kip concluded. “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.”


Yip W, Reisz P, Tracey A, et al. Feasibility and validation of genomic profiling of upper tract urothelial carcinoma from urine cytology specimens. Poster presented at: 22nd Annual Meeting of the Society of Urologic Oncology; December 1-3, 2021; Orlando, Florida. Accessed December 10, 2021.

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