At the 2023 ASCO Genitourinary Cancers Symposium, Andrew Katims, MD, Memorial Sloan Kettering Cancer Center, New York, NY, discusses the results of an assessment of the MSK-ACCESS, a cell-free tumor DNA assay among patients with node-positive muscle-invasive bladder cancer, receiving neoadjuvant chemotherapy.

Dr Katims stated, this study found “a high detection rate, and concordance rate, with our cohort of locoregional disease” and “ctDNA may not be a good marker for on-treatment response, but it does correlate with pathological response when assessed after chemotherapy.”

Transcript:

Hello, my name is Andrew Katims. I am a urologic oncology fellow at Memorial Sloan Kettering, and I'm happy to be talking to you today about our study we presented at the 2023 ASCO Genitourinary Cancers Symposium titled, Assessing the Utility of a Cell-Free Tumor DNA Assay in Node-Positive Muscle-Invasive Bladder Cancer Patients Undergoing Neoadjuvant Chemotherapy. Circulating tumor DNA, or ctDNA, is an emerging biomarker in bladder cancer that has utility in detection, response to treatment, and surveillance for recurrence. This is particularly true in the metastatic setting for which there is a 70% to 90% detection rate. Regarding response to treatment, some studies have shown that persistence of ctDNA during or after neoadjuvant chemotherapy is predictive of disease recurrence. However, concordance of ctDNA to tissue genetic alterations is poor, ranging from 16% to 41%. The purpose of this study was to evaluate the utility of MSK-ACCESS, a 129-gene targeted exome ctDNA sequencing platform with up to 20,000 times coverage in a cohort of clinically node-positive bladder cancer patients.

We prospectively identified patients with clinically node-positive bladder cancer by PET scan, biopsy, or CT imaging. Patients were planned for preoperative platinum-based chemotherapy, followed by a radical cystectomy. ctDNA was collected at 4 timepoints: pre-chemotherapy, approximately midway through treatment, post-chemotherapy, and 3 months after radical cystectomy. Tissue from either transurethral resection or radical cystectomy was sequenced with MSK-IMPACT, a 505-gene targeted exome sequencing platform. Ultimately, we identified 12 patients that were eligible for inclusion. There was a pathologic complete response in 42% of patients and nodal down-staging to N0 in 17% of patients. Median recurrence-free survival was 11.5 months. 75% of our cohort had at least 1 detectable mutation on MSK-ACCESS.

Among those that had a positive test, around 80% had at least 1 shared mutation with tissue. The most commonly detected mutations were TP53, TERT promoter, RB1, KDM6A, and FGFR3. If we consider different timepoints, we found that post-chemotherapy clearance of ctDNA was correlated with a pathologic complete response. Additionally, all patients with residual disease at cystectomy had detectable ctDNA. With that, almost all patients had clearance of ctDNA while on-treatment with chemotherapy, and this was not associated with the degree of pathologic down-staging.

These results are exciting for a few reasons. First, we found a high detection rate and concordance rate in our cohort of locoregional disease. This is likely due to the unique opportunity to run both ctDNA and tissue DNA sequencing on parallel platforms. This could lead to future work into targeted therapies based on pre-treatment ctDNA results. Next, we learned that ctDNA may not be a good marker for on-treatment response, but it does correlate with pathologic response when assessed after chemotherapy.

We're excited to continue our work evaluating MSK-ACCESS in the localized and metastatic setting.

Source:

Katims AB, Lenis AT, Shah RH, et al. Assessing the utility of a cell-free tumor (ct)DNA assay (MSK-ACCESS) in patients (pts) with node-positive (N+) muscle-invasive bladder cancer (MIBC) undergoing neoadjuvant chemotherapy (NAC). Presented at 2023 ASCO Genitourinary Cancers Symposium; February 17-19; San Francisco, CA. Abstract 544