MSK Metastatic Urothelial Carcinoma cfDNA (CALGB 90601, 2025)

Overview

Pretreatment plasma cell-free DNA (cfDNA) cohort of 201 patients with metastatic urothelial carcinoma (mUC) nested within the phase 3 CALGB 90601 (Alliance) randomized trial (NCT00942331) of first-line gemcitabine/cisplatin with or without bevacizumab. Released via cBioPortal per the data availability statement of Guercio et al. 2025 PMID:40256659.

Composition

  • 201 patients with metastatic urothelial carcinoma (bladder primary 76%, upper tract 20%, other 3.5%); drawn from 506-patient CALGB 90601 trial; 212/506 (42%) consented to blood collection with successful cfDNA sequencing in 201/212 (95%) PMID:40256659.
  • Median OS 14 months (95% CI 13–18) on chemo+bevacizumab; 16 months (95% CI 15–18) on chemo+placebo PMID:40256659.
  • 107 patients (53%) had matched archival tumor sequencing via MSK-IMPACT PMID:40256659.
  • Cancer type: metastatic BLCA (urothelial carcinoma).

Assays / panels (linked)

Papers using this cohort

  • PMID:40256659 — Guercio et al. 2025: ctDNA features (TERT promoter, PIK3CA, ERBB2 alterations, and ³√VAF₇₅ₚc) as candidate prognostic biomarkers for mUC patients receiving cisplatin-based chemotherapy; DDR gene alterations (ERCC2) were not associated with improved outcomes in this underpowered analysis.

Notable findings derived from this cohort

  • 87.1% (175/201) of samples harbored ≥1 alteration in queried genes; most frequent: TERT 57%, TP53 ~52%, FGFR3 19%, KDM6A 18%, ERBB2 14% PMID:40256659.
  • Higher pretreatment ctDNA VAF associated with shorter OS (multivariable HR 2.51, 95% CI 1.26–5.00; p=0.009) and shorter PFS (HR 2.18, 95% CI 1.02–4.67; p=0.045) PMID:40256659.
  • TERT promoter alterations associated with shorter OS (multivariable HR 1.59, 95% CI 1.15–2.19; p=0.005) PMID:40256659.
  • PIK3CA alterations (17% cfDNA) associated with shorter OS (HR 1.91, 95% CI 1.20–3.04; p=0.006) PMID:40256659.
  • ERBB2 alterations (14% cfDNA) associated with shorter OS (HR 1.64, 95% CI 1.08–2.49; p=0.019) PMID:40256659.
  • Oncogenic DDR gene alterations detected in 27/201 (13%) cfDNA samples (ATM 5.5%, ERCC2 4.5%, BRCA1 3%, BRCA2 1%); no significant association with response, OS, or PFS PMID:40256659.
  • cfDNA detected numerically higher alteration rates than matched archival tumor for PIK3CA (17% vs 13%), RB1 (14% vs 12%), ERCC2 (6.5% vs 4.7%), BRAF (5.6% vs 4.7%), and KRAS (5.6% vs 3.7%) in the 107-patient concordance subset PMID:40256659.

Sources

  • cBioPortal study blca_msk_2025. Data available per: Guercio BJ, et al. Circulating Tumor DNA Features Associated with Outcomes in Metastatic Urothelial Carcinoma Treated with Gemcitabine-Cisplatin: Results from the Phase III Alliance CALGB 90601 Trial. Eur Urol. 2025. PMID:40256659.

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