Urothelial Carcinoma (MSK, Clin Cancer Res 2023)

Overview

Single-institution MSK cohort of 1,421 urothelial carcinoma patients (1,507 tumors) profiled with MSK-IMPACT tumor sequencing and, for a treated subcohort, serial MSK-ACCESS cfDNA, assembled to characterize FGFR2/3 alterations and real-world erdafitinib outcomes (PMID:37682528).

Composition

• Cancer types: BLCA and UTUC (PMID:37682528).
• Disease-state breakdown: 504 NMIBC, 526 MIBC, 187 localized upper-tract, 228 distant metastatic specimens (PMID:37682528).
• Erdafitinib-treated subcohort: 32 metastatic patients treated 8/2019–7/2022, with serial cfDNA on 27 (PMID:37682528).

Assays / panels (linked)

• MSK-IMPACT — FDA-authorized targeted tumor panel (PMID:37682528).
• MSK-ACCESS — 129-gene cfDNA assay, >15,000x, 0.1% VAF threshold (PMID:37682528).

Papers using this cohort

• PMID:37682528 — Guercio et al., Clin Cancer Res 2023.

Notable findings derived from this cohort

• Oncogenic FGFR3 alterations in 39% NMIBC, 14% MIBC, 43% localized UTUC, 26% metastatic specimens (PMID:37682528).
• Only 1/1,507 tumors carried an actionable FGFR2 alteration (an FGFR2:MARVELD3 fusion of unclear significance) (PMID:37682528).
• Primary/metastatic FGFR3 status discordant in 7/27 (26%) paired cases (PMID:37682528).
• FGFR3-altered tumors inversely associated with ERBB2, TP53, and RB1; frequently co-altered with CDKN2A, CDKN2B, and KDM6A (PMID:37682528).
• Real-world erdafitinib ORR 40%, median PFS 2.8 mo, median OS 6.6 mo (n=32) (PMID:37682528).
• Serial cfDNA identified acquired TP53 (5/27), AKT1 (1/27), and second-site FGFR3 kinase-domain mutations (V553M, N540S) as putative erdafitinib resistance drivers (PMID:37682528).

Sources

• PMID:37682528 — Guercio et al., “Clinical and Genomic Landscape of FGFR3-Altered Urothelial Carcinoma and Treatment Outcomes with Erdafitinib,” Clin Cancer Res 2023.

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