Of 2463 patients with urothelial cancer who underwent comprehensive genomic profiling, 39% harbored ≥1 tier 1-2 genomic alterations.
Comprehensive genomic profiling shows that more than one-third of patients with upper tract and bladder urothelial cancer have tier 1-2 genomic alterations, defined as those that potentially can benefit from approved or investigational targeted therapies.1
Using a modified European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets, of 2463 patients with urothelial cancer who underwent comprehensive genomic profiling, 39% harbored ≥1 tier 1-2 genomic alterations, and 29% had a tier 3 genomic alteration “that provides a strong rationale for clinical trial consideration,” according to researchers led by Andrea Necchi, from Fondazione IRCCS-Istituto Nazionale dei Tumori, Milan, Italy.
For their study, which appears in European Urology, tumor tissue samples for comprehensive genomic profiling were obtained from 479 patients with upper tract urothelial cancer and 1984 with bladder urothelial cancer. The distribution of genomic alterations was as follows:
There were no differences in tumor mutational burden–high (≥20 mut/Mb) or microsatellite instability–high (MSI-H) status between primary tumor and metastatic sites, but upper tract urothelial cancer was enriched for MSI-H relative to bladder urothelial cancer (3.4% vs 0.8%; P <.001).
Genomic profiling of cell-free circulating tumor (ct)-DNA was performed for 126 patients. Overall, there was a 69% positive percent agreement between ctDNA and tumor tissue, and 71% of cases shared at least 1 mutation. This concordance decreased with greater time lapse between acquisition of the 2 specimens.
According to the authors, “This study provides an additional rationale for the routine incorporation of ctDNA assays in clinical trials and possibly in clinical practice, especially when a recently obtained tumor tissue sample is not available and/or to complement tumor tissue analysis.”
They continued, “Outside of clinical trials, our study findings have potential implications for the selection of erdafitinib [Balversa], a pan-FGFR inhibitor, which currently has accelerated approval by the US Food and Drug Administration for the treatment of platinum-treated advanced urothelial carcinoma. The potential roles of ctDNA as a putative prognostic biomarker and its ability to detect actionable genomic alterations in patients with and without available tumor tissue are experiencing growing interest among investigators.”
1. Necchi A, Madison R, Pal SK, et al. Comprehensive genomic profiling of upper-tract and bladder urothelial carcinoma [published online August 26, 2020]. Eur Urol Focus. doi: 10.1016/j.euf.2020.08.001