Potential of uMRD to Predict Recurrence in BCG-Unresponsive NMIBC

Prior research has demonstrated that urinary measurable residual disease (uMRD) profiling shows potential to predict recurrence and evaluate response to therapy. uMRD profiling determines mutations connected with urothelial carcinoma through next-generation sequencing.

Research from Vikram M. Narayan, MD, and colleagues sought to determine the ability of uMRD to specify molecular response to nadofaragene firadenovec in patients with high-grade (HG) bacillus Calmette-Guérin (BCG)-refractory or relapsed non-muscle invasive bladder cancer (NMIBC).

The phase 2, open-label study was presented at the 2024 American Urological Association Annual Meeting.

In the multicenter trial, 43 patients with BCG-unresponsive NMIBC underwent treatment with intravesical nadofaragene firadenovec. The study’s primary end point was 12-month HG-recurrence-free survival (RFS).

Of the patients, 35 were evaluable, and initial pathological stages included Ta (n=3), T1 (n=9), and Tis (n=23), with 6 patients reporting concomitant carcinoma in situ (CIS). The TP53, TERT, PIK3CA, ARID1A, PLEKHS1, ELF3, and ERBB2 mutated genes were identified the most in pretreatment urine (n=32).

Across both pre- and postinduction collections, uMRD was able to identify patients with high (72%) and low (28%) recurrence risk. The postinduction RFS rate was 100% for low-risk patients and 38% for high-risk patients (P=.038) at 12 months. For low-risk patients, the preinduction RFS rate was 56%, and it was 22% for those who were high risk (P=.097).

Researchers characterized the quantitative drug response through matched pre- and postinduction urine (n=15) and labeled patients as MRD negative (7%), MRD complete responder (13%), MRD partial responder (27%), MRD stable (20%), or MRD refractory (33%).

Of the patients, those in the MRD negative and complete responder cohorts did not recur on study; however, 7 of 12 patients in the differing cohorts did recur.

“uMRD enables quantitative assessment of molecular response to drug treatment,” the researchers wrote. “uMRD-determined pretreatment disease burden assessment can support stratification of control and intervention arms in future treatment trials.”