Concordance of circulating tumor DNA and imaging surveillance in patients with urothelial carcinoma and renal cell carcinoma post-immunotherapy.

Abstract

597 Background: Early detection of recurrence in urothelial carcinoma (UC) and renal cell carcinoma (RCC) may improve patient outcomes. Conventional imaging techniques may not identify early molecular relapses that precede clinical relapse. Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for the early detection of disease relapse. This study aims to evaluate the concordance of molecular relapses by ctDNA and radiographic progression in patients with UC and RCC who are off immunotherapy due to intolerance of side effects or completion of treatment. Methods: We conducted a retrospective study of locally advanced/advanced UC and RCC patients who were treated at The Ohio State University James Cancer Hospital from November 2021 to September 2024. Patients who completed planned immunotherapy followed by imaging and ctDNA surveillance were included. ctDNA levels were measured using the Signatera tissue informed assay at intervals of 4 to 12 weeks. Imaging surveillance schedules were at the treating physician discretion. Patient demographics, clinical characteristics, and ctDNA levels were recorded and analyzed. Results: A total of 36 patients were included: muscle-invasive bladder cancer (MIBC, n = 10), metastatic urothelial carcinoma (mUC, n = 10), locally advanced RCC (n = 4), and metastatic RCC (mRCC, n = 12). The median follow-up was 39.5 weeks (range: 1–138 weeks), with a median age of 67.5 years (range: 41–83 years), and 72.2% were male. At the time of immunotherapy discontinuation, ctDNA was negative in all patients except one mRCC patient (ctDNA 0.95 MTM/mL). During surveillance, 9 patients (25%) - 5 mUC and 4 mRCC - became ctDNA-positive, of which, eight showed radiographic progression, while one mRCC patient (ctDNA 0.15 MTM/mL) did not. None of the 27 patients (75%) that continued to have negative ctDNA had radiographic progression. For the 8 patients with progression, the median time from stopping immunotherapy to ctDNA relapse was 17.5 weeks (range: 11–42 weeks). The median time from ctDNA relapse to imaging-confirmed progression was 22 weeks (range: 13–43 weeks). At progression, ctDNA levels ranged from 0.08 to 136.49 MTM/mL (median: 2.33 MTM/mL). Six of the 20 metastatic patients (30%) relapsed despite negative ctDNA at immunotherapy discontinuation. Conclusions: ctDNA positivity occurs much earlier and is highly concordant with radiographic progression in patients with locally advanced/advanced UC and RCC under post-immunotherapy surveillance. These findings suggest that ctDNA is a promising tool for early disease relapse detection in these patients. Further studies are warranted to validate these results and establish standardized ctDNA surveillance protocols.