Feasibility and tissue concordance of genomic sequencing of urinary cytology in upper tract urothelial carcinoma Journal Article


Authors: Katims, A. B.; Gaffney, C.; Firouzi, S.; Yip, W.; Aulitzky, A.; Pietzak, E. J.; Donat, S. M.; Bochner, B. H.; Donahue, T. F.; Herr, H. W.; Dalbagni, G.; Al-Ahmadie, H.; Kim, K.; Solit, D. B.; Lin, O.; Coleman, J. A.
Article Title: Feasibility and tissue concordance of genomic sequencing of urinary cytology in upper tract urothelial carcinoma
Abstract: Background: There is limited ability to accurately diagnose and clinically stage patients with upper tract urothelial carcinoma (UTUC). The most easily available and widely used urinary biomarker is urine cytology, which evaluates cellular material yet lacks sensitivity. We sought to assess the feasibility of performing next-generation sequencing (NGS) on urine cytology specimens from patients with UTUC and evaluate the genomic concordance with tissue from primary tumor. Methods: In this retrospective study, we identified 48 patients with a diagnosis of UTUC treated at Memorial Sloan Kettering Cancer Center (MSK) between 2019 and 2022 who had banked or fresh urine samples. A convenience cohort of matching, previously sequenced tumor tissue was used when available. Urine specimens were processed and the residual material, including precipitated cell-free DNA, was sequenced using our tumor-naïve, targeted exome sequencing platform that evaluates 505 cancer-related genes (MSK-IMPACT). The primary outcome was at least 1 detectable mutation in urinary cytology specimens. The secondary outcome was concordance to matched tissue (using ANOVA or Chi-Square, as indicated). Results: Genomic sequencing was successful for 45 (94%) of the 48 urinary cytology patient samples. The most common mutations identified were TERT (62.2%), KMT2D (46.7%), and FGFR3 (35.6%). All patients with negative urine cytology and low-grade tissue had successful cytology sequencing. Thirty-six of the 45 patients had matching tumor tissue available; concordance to matched tissue was 55% overall (131 of the total 238 oncogenic or likely oncogenic somatic mutations identified). However, in 94.4% (n = 34/36) of patients, the cytology had at least 1 shared mutation with tissue. Eleven (30.6%) patients had 100% concordance between cytology and tissue. Conclusions: Sequencing urinary specimens from selective UTUC cytology is feasible in nearly all patients with UTUC. Prospective studies are underway to investigate a clinical role for this promising technology. © 2023
Keywords: retrospective studies; prospective study; prospective studies; cytology; pathology; retrospective study; bladder tumor; urinary bladder neoplasms; feasibility study; feasibility studies; genomics; upper tract urothelial carcinoma; carcinoma, transitional cell; transitional cell carcinoma; next-generation sequencing; humans; human
Journal Title: Urologic Oncology: Seminars and Original Investigations
Volume: 41
Issue: 10
ISSN: 1078-1439
Publisher: Elsevier Inc.  
Date Published: 2023-10-01
Start Page: 433.e19
End Page: 433.e24
Language: English
DOI: 10.1016/j.urolonc.2023.07.007
PUBMED: 37640571
PROVIDER: scopus
PMCID: PMC11177811
DOI/URL:
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is Jonathan A. Coleman -- Source: Scopus
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MSK Authors
  1. Jonathan Coleman
    346 Coleman
  2. Guido Dalbagni
    325 Dalbagni
  3. Sherri M Donat
    174 Donat
  4. David Solit
    780 Solit
  5. Oscar Lin
    310 Lin
  6. Bernard Bochner
    469 Bochner
  7. Harry W Herr
    595 Herr
  8. Timothy Francis Donahue
    72 Donahue
  9. Kwanghee   Kim
    43 Kim
  10. Eugene J Pietzak
    116 Pietzak
  11. Wesley Yip
    12 Yip
  12. Andrew Barry Katims
    13 Katims
  13. Christopher Daniel Gaffney
    15 Gaffney