AACR 2023: Biomarkers May Predict Response to Neoadjuvant Chemotherapy in Bladder Cancer

By: Joshua D. Madera, MS
Posted: Monday, May 1, 2023

The ability to identify which patients with muscle-invasive bladder cancer will respond to neoadjuvant cisplatin-based chemotherapy may now be a feasible strategy, according to a presentation given at the American Association for Cancer Research (AACR) Annual Meeting 2023 (Abstract 2167/9). However, additional investigative efforts with larger patient populations are warranted to further substantiate these results, suggested Maria L. Ascierto, PhD, of Saint John’s Cancer Institute, Santa Monica, California, and colleagues.

A total of 13 patients with muscle-invasive bladder carcinoma were recruited for the study. Tumor biopsies were collected from all patients before the administration of neoadjuvant cisplatin-based chemotherapy and were subjected to RNA sequencing. Following the completion of neoadjuvant cisplatin-based chemotherapy, patients were classified based on whether they achieved a pathologic complete response (n = 8) or not (n = 5). In addition, peripheral blood samples were collected at baseline and after neoadjuvant cisplatin-based chemotherapy to measure the number of neutrophils and lymphocytes.

A total of 1,119 transcript differences were identified on RNA sequencing between those with a pathologic complete response and those without. Patients who achieved a pathologic complete response had increased expression of tumor microenvironment genes that regulate dendritic cell activation (XCR1 and CCL5), formation of tertiary lymphoid structures, and B-cell function (CD19, CLEC4D, and CXCR5). In contrast, patients without a pathologic complete response had elevated levels of interleukin-8, and the tumor microenvironment genes that regulate cell adhesion and DNA repair (DMC1, HFM1, POLB, RAD54B, and RPA4). Furthermore, improved survival rates were observed in patients with elevated gene expression of CXCR5 and XCR1 and decreased expression of POLB. Moreover, despite the lack of a significant difference in neutrophil and lymphocyte counts at baseline, after the completion of neoadjuvant cisplatin-based chemotherapy, elevated lymphocytes were seen in those with a pathologic complete response, and reduced neutrophils were observed in those without a response.

Disclosure: The study authors reported no conflicts of interest.

AACR Annual Meeting 2023

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