Researchers may have uncovered factors contributing to poor outcomes among patients with prostate cancer, according to recent findings presented by Dall’Era et al at the 2025 ASCO Annual Meeting (Abstract 5104). The findings may lead to the development of novel targeted therapies, particularly in patients who have prostate cancer with certain DNA repair gene mutations.
Study Methods and Results
In a phase II clinical trial (ClinicalTrials.gov identifier NCT04030559), the researchers examined the efficacy of neoadjuvant treatment with the PARP inhibitor niraparib in preventing cancer recurrence in 11 men with high-risk prostate cancer and DNA repair gene mutations. They assigned the participants to receive 200 mg of niraparib daily for 90 days prior to undergoing surgery. The patients involved in the study had a median age of 68 years and a median prostate-specific antigen level at diagnosis of 10.7 ng/mL. The genetic alterations included germline mutations in the BRCA2, MSH6, and CHEK2 genes as well as somatic mutations in the ATM, SPOP, KMT2C, and KMT2D genes.
Although niraparib did not dramatically shrink the patients’ tumors prior to surgery, the researchers discovered that genetic testing and blood-based monitoring could be used to better understand and track the prostate cancer. Of note, circulating tumor DNA (ctDNA) biomarker analysis proved to be effective in tracking tumor evolution and resistance mechanisms in real time.
Conclusions
“This study shows how complex prostate cancer can be, especially in men with certain gene mutations,” underscored lead study author Marc Dall’Era, MD, Chief of the Department of Urologic Surgery at the University of California, Davis Health. “Although responses were variable, especially in patients with BRCA2 mutations, this study points to ctDNA as a promising tool to identify who might benefit from targeted neoadjuvant therapies,” he concluded.
The researchers are currently analyzing the data to evaluate why some cancers resist treatment and how to design future therapies that are more tailored to each individual patient.
Disclosure: The research in this study was funded by Janssen Pharmaceuticals. For full disclosures of the study authors, visit meetings.asco.org.
