Germline Testing in Upper Tract Urothelial Carcinoma: A Nationwide Claims-Based Analysis

Upper tract urothelial carcinoma (UTUC) is the third most common malignancy associated with Lynch syndrome (LS). Various guidelines endorse universal germline testing in patients diagnosed with UTUC. We evaluated the utilization of germline testing in UTUC using a nationwide claims database.

We queried the MarketScan database for patients with newly diagnosed UTUC between January 2015 and June 2023. The primary outcome was receipt of germline testing, defined as claims for multigene hereditary cancer panel testing after diagnosis. Univariable and multivariable logistic regression models were used to identify independent associations of testing.

Of 4,783 patients with newly diagnosed UTUC, 216 (4.5%) patients underwent germline testing, with no meaningful change across the study period. On multivariable analysis, prior Lynch-spectrum cancer was independently associated with germline testing (odds ratio [OR], 3.00 [95% CI, 2.14 to 4.22]), as was male sex (OR, 1.37 [95% CI, 1.01 to 1.86]). Northeast residence was associated with lower odds of postdiagnosis testing compared with the South (OR, 0.54 [95% CI, 0.34 to 0.85]). Among patients diagnosed before age 50 years, a stand-alone criterion for genetic evaluation, only 5.6% underwent germline testing. LS diagnosis after UTUC diagnosis was ultimately claimed in eight patients across the entire cohort.

Germline testing in UTUC is performed in fewer than 1 in 20 patients and remains low even in patients meeting established clinical criteria for evaluation. Structural integration of germline evaluation into upper tract urothelial carcinoma care pathways is needed.