Utility of a ctDNA Assay in Patients With Node-Positive MIBC Receiving Neoadjuvant Chemotherapy

A recent study correlated targeted exome cell-free tumor DNA (ctDNA) sequencing with pathologic response to neoadjuvant chemotherapy and metastatic recurrence in patients with node-positive (N+) muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy.

Study results were presented at the American Urological Association 2023 Annual Meeting.

Previous research has shown ctDNA to be associated with disease progression, worse overall survival, and disease recurrence in patients with bladder cancer.

Andrew B. Katims, MD, and colleagues prospectively identified patients with cT2-3N1-2M0 bladder cancer who received neoadjuvant chemotherapy prior to radical cystectomy. Plasma samples were collected before chemotherapy, mid-treatment, after chemotherapy completion, and 3 months after radical cystectomy. Researchers analyzed samples using MSK-ACCESS, a ctDNA platform designed to identify somatic mutations in 129 cancer-associated genes.

Researchers noted that primary bladder tumors were sequenced using targeted exome sequencing.

A total of 31 samples from 9 patients were analyzed. Among those samples, neoadjuvant chemotherapy regimens included gemcitabine and cisplatin alone (78%) or with paclitaxel (22%). Seven patients had more than 1 detectable mutation before treatment.

The most altered genes detected in both tissue and ctDNA included TERT, TP53, ARID1A, RB1, KDM6A, and ATM. Four patients had a complete response, 1 had a partial response, and 4 were nonresponders. All nonresponders had disease recurrence after radical cystectomy (median time to recurrence, 3 months).

Among the 7 patients who underwent on-treatment MSK-ACCESS analysis, 2 had detectable ctDNA. The patient who had a partial response had detectable ctDNA postchemotherapy, with 1 mutation identified that was not detectable at 3 months. All nonresponders had detectable ctDNA postchemotherapy.

Additionally, researchers noted that patients with recurrence as well as nonresponders had a significantly higher mutation count 3 months after radical cystectomy compared with responders (median mutation count, 7 vs 0, respectively). Two patients who had a complete response had detectable ctDNA at 3 months postchemotherapy but have not experienced disease recurrence.

Researchers concluded that clearance of ctDNA after neoadjuvant chemotherapy correlated with pathologic complete response. All patients in the study with residual disease at radical cystectomy had detectable ctDNA postchemotherapy, and N+ disease correlated with persistent ctDNA detected at 3 months postchemotherapy.