Analyzing Mutations, Pathologic Complete Response in MIBC

Previous research from Elizabeth R. Plimack, MD, MS, FASCO, and colleagues demonstrated that in patients with muscle invasive bladder cancer (MIBC), any tumors with ATM, RB1, FANCC, or ERCC2 mutations were likely to respond to treatment with neoadjuvant cisplatin-based chemotherapy (NAC). These patients subsequently reported cancer-free surgical specimens upon cystectomy (pT0).

A recent study from Dr. Plimack and colleagues published in European Urology sought to validate their previous findings.

Researchers evaluated data from the CARIS 592 Gene Panel, including 105 pre-NAC tumor specimens from a large multicenter trial of neoadjuvant gemcitabine and cisplatin or dose-dense methotrexate, vinblastine, Adriamycin, and cisplatin.

The findings showed that upon surgery, a mutation in any of the 4 genes predicted for pT0 (95% CI, 2.05-14.02; P=.0006). Investigators noted that the biomarker was more proficient at predicting the presence of disease (95% CI, 73-94) than the absence of disease (95% CI, 35-62).

“When combined with clinical assessment, these findings help inform patient selection for bladder preservation after cisplatin-based chemotherapy,” the researchers wrote.

Dr. Plimack and colleagues also noted there was no evidence of an association between the treatment arm and the genetic variant regarding pT0.

“The evolution of more effective systemic neoadjuvant therapies in conjunction with innovative tools such as urine-based tests for detection and monitoring patients on bladder surveillance will build on this work toward a goal of avoiding cystectomy in cases where radical surgery is not required to achieve cure,” said Dr. Plimack.