Surveillance with plasma ctDNA in non-muscle invasive bladder cancer.

Abstract

864 Background: Non-muscle invasive bladder cancer (NMIBC), constitutes 70% of all bladder cancer. Routine surveillance methods for detecting patients at risk of progression to muscle-invasive or metastatic disease are invasive and may delay intervention. Circulating tumor DNA (ctDNA) analysis presents a non-invasive alternative for monitoring minimal residual disease, potentially allowing for earlier detection of disease progression or recurrence. This study evaluates the role of plasma ctDNA in the early detection and monitoring of high-risk NMIBC. Methods: Eleven high-risk NMIBC patients were enrolled in this study. All patients underwent standard transurethral resection of bladder tumors (TURBT) before enrollment. Blood samples were collected prior to initiation of intravesical therapy and then every three months for two years (from January 12, 2022, to February 1, 2024). Plasma ctDNA was analyzed using Natera's Signatera, employing multiplex PCR and next-generation sequencing to detect tumor-specific mutations. Individual mutation profiles were established via whole-exome sequencing of tumor and matched normal tissue. Detection of ctDNA was compared with results from routine cystoscopy, urine cytology, and upper-tract imaging. Disease outcomes of interest included relapse, progression to muscle-invasive disease, and metastasis. Results: Of the eleven high-risk patients, one patient developed diffuse bilateral upper tract high-grade recurrence followed by metastatic disease that was preceded by positive ctDNA. Another patient was noted to have muscle-invasive disease again following the detection of ctDNA and subsequently underwent radical cystectomy. This patient eventually developed metastasis six months later. One patient elected to withdraw from the study. In our study, 20% of patients with high-grade papillary NMIBC had detectable ctDNA nine months post-diagnosis. Notably, both patients with positive ctDNA had normal findings on routine surveillance. However, they eventually progressed to stage IV urothelial carcinoma. In contrast, ctDNA was undetectable in the remaining eight patients, all of whom remained recurrent free to-date. These findings suggest ctDNA may serve as an early predictor of relapse and progression, with a number needed to test of 5 to prevent one delayed identification of disease progression. Conclusions: Plasma ctDNA analysis shows promise as a non-invasive tool for identifying NMIBC patients at risk of disease progression. Early ctDNA detection may enable more personalized treatment approaches, improving patient outcomes. Larger studies are warranted to confirm these findings and support the integration of ctDNA into standard NMIBC surveillance protocols.