Noninvasive early detection and recurrence monitoring for non-muscle-invasive bladder cancer via urine tumor DNA.

e16586 Background: Traditional methods for the detection and surveillance of non-muscle-invasive bladder cancer (NMIBC) were generally invasive, costly, and not effective for early-stage, low-grade, and minimal residual disease (MRD) tumors. Whether urine tumor DNA could be used to early detect urothelial carcinoma and monitor MRD with high sensitivity should be explored. Methods: We conducted a perspective study to determine the performance of utLIFE-UC (our previously reported urine tumor DNA multidimensional bioinformatic predictor) in early detection and recurrence monitoring of NMIBC (Trial No. ChiCTR2300072635). We prospectively recruited 49 patients initially diagnosed with NMIBC. Urine samples were collected prior to transurethral resection of bladder tumor (TURBT) and repeat TURBT (Re-TURBT) if needed. Postsurgical samples were collected every 3-6 months when patients underwent routine cystoscopy. The utLIFE-UC score > 60 indicates a positive clinical significance. Results: Overall, utLIFE-UC could discriminate NMIBC with high sensitivities of 91.8% (45/49), both in different T stages (Ta, 84.0%; T1, 100%; P = 0.110) and grades (low-grade, 88.2%; high-grade, 93.3%; P = 0.613). Twenty patients underwent Re-TURBT, of whom 8 cases had residual tumor. The utLIFE-UC correctly diagnosed 8 of 8 (100%) patients with residual tumor. In addition, the assay showed a high NPV of 100%, implying that it may aid in avoiding Re-TURBT in patients predicted to have no residual tumor. Notably, utLIFE-UC score before Re-TURBT in patients with multiple tumors (MT) was markedly increased than that of patients with single tumor (ST) (P = 0.028). MRD-positive rate in MT patients was 100%, whereas 50% of ST patients were MRD-negative. During follow-up, recurrence status of 27 patients was collected, and 18.5% (5/27) of them recurred. The median follow-up time was 211 days (range 39 to 326 days). For patients receiving Re-TURBT, all the tumors with MRD-negative results before Re-TURBT, had no recurrence, further supporting the possible unnecessity of Re-TURBT in this population. The prognostic value of postsurgical utLIFE-UC results in NMIBC was explored. MRD-positive patients showed a worse recurrence-free survival than MRD-negative ones (median 200 days vs unreached; P = 0.001). However, it was not observed the correlation between prognosis and clinical features, including age, sex, tumor number, T stage, and grade. Compared to clinical confirmed recurrence, utLIFE-UC could predict recurrence with a median lead time of 100 days (range 17 to 140 days; P = 0.056). Conclusions: TheutLIFE-UC assay for early diagnosis, MRD detection and surveillance in NMIBC is a noninvasive and effective approach, which may contribute to reducing the burden of cystoscopy and invasive examination. Clinical trial information: ChiCTR2300072635 .