Early Detection of Metastatic Progression by Circulating Tumor DNA in Patients Undergoing Bladder-Preserving Trimodality Therapy.

Abstract

Radical cystectomy and trimodality therapy (TMT) are efficacious treatments for muscle invasive bladder cancer. Novel methods for post-treatment surveillance are needed to detect recurrence. This study assesses the value of plasma circulating tumor DNA (ctDNA) for detection of post-TMT recurrence. We performed a retrospective ctDNA analysis in 32 patients with at least one post-TMT ctDNA measurement before any disease recurrence. Patients were stratified as post-TMT ctDNA (+) or ctDNA (-) and assessed for metastasis-free survival and recurrence-free survival (RFS) using Kaplan-Meier and Cox regression methods. At a median follow-up of 181 days (range: 24-522) after the first post-TMT ctDNA measurement, 4 patients (12.5%) were ctDNA (+) and 28 patients (87.5%) were ctDNA (-); 3 of 4 ctDNA (+) patients developed radiographic evidence of metastasis. All 28 ctDNA (-) patients were without metastasis. ctDNA positivity correctly identified all metastatic progression with 100% sensitivity and 93% specificity at 6-month post-TMT ctDNA surveillance. Furthermore, ctDNA-based detection preceded clinical detection of metastasis with a median lead time of 138 days. ctDNA (+) status was associated with worse metastasis-free survival (<i>P</i> < .0001) and RFS (<i>P</i> < .0001). In univariable analysis, ctDNA (+) status was the only variable significantly associated with worse RFS (HR 3.53, 95% CI: 1.11-11.53, <i>P</i> = .03). Plasma ctDNA is a potential biomarker for early detection of metastatic progression after TMT. Our hypothesis-generating findings provide a basis for larger studies to evaluate the utility of ctDNA-guided post-TMT surveillance.