Utility of Tumor-Informed Circulating Tumor DNA for Monitoring Treatment Response in Nonmetastatic, Locally Advanced Penile and Primary Urethral Cancers.

Objective: Tumor-informed circulating tumor DNA (ctDNA) testing has not been evaluated in monitoring patients with primary urethral cancer (PUC) or penile squamous cell carcinoma (pSCC). We investigated whether serial ctDNA monitoring correlated with clinical response in these rare genitourinary malignancies in the nonmetastatic, locally advanced setting.

Methods: Sixty-six ctDNA tests using a tumor-informed molecular residual disease assay from 13 patients with PUC or pSCC were reviewed. All patients were treated with curative intent and followed with standard imaging and ctDNA testing. ctDNA decrease or clearance was considered concordant if associated with radiographic stability or surgical downstaging. Disease progression was evaluated for concordance with positive or increasing ctDNA results. Fisher exact testing for univariable analysis and Cox regression modeling for ctDNA changes were used.

Results: Mean age was 68 (59-77) years and median follow-up was 74.6 weeks (11.3-195.3). Seven had pSCC and six had PUC. Treatment and surveillance schedules were variable, but generally, patients had ctDNA testing every 3-4 months relative to radiographic imaging or treatment/surgical intervention. ctDNA results were concordant in 65 of 66 times points (98.5%) on the basis of radiographic disease status and/or surgical downstaging. Odds ratio (OR) analysis was evaluated on the basis of all available ctDNA tests analyzed collectively across all time points. Positive ctDNA tests had an OR for progression of 36.75 (4.51-299.52, P < .0001) and negative ctDNA OR for progression was 0.027 (0.0033-0.222, P < .0001).

Conclusions: Our data suggest that tumor-informed ctDNA levels are concordant with surveillance imaging and pathologic staging for PUC and pSCC. This preliminary report not only develops support of tumor-informed ctDNA in better understanding treatment response but also serves as a basis for further prospective studies.