Genetic Testing and Blood-Based Monitoring Improve Understanding and Tracking of Prostate Cancer

Many men with aggressive prostate cancer face high recurrence rates despite undergoing treatment. Now, findings of a new study suggest that specific gene mutations may be key to understanding these outcomes and could pave the way for more personalized therapies.

A Phase 2 clinical trial being conducted at UC Davis Comprehensive Cancer Center (Sacramento, CA, USA) is evaluating the use of niraparib (ZEJULA), a PARP inhibitor, administered before prostate cancer surgery. Researchers aim to determine whether this approach can prevent cancer recurrence, particularly in men whose tumors exhibit DNA repair gene mutations. In this pilot study, 11 men with high-risk prostate cancer and identified gene mutations received 200 mg of niraparib daily for 90 days prior to surgery. The median age of participants was 68 years, with a median prostate-specific antigen (PSA) level at diagnosis of 10.7 ng/mL. Genetic alterations observed included germline mutations in BRCA2, MSH6, and CHEK2, as well as somatic mutations in ATM, SPOP, KMT2C, and KMT2D.

While the treatment did not significantly reduce tumor size before surgery, the study highlighted the potential of genetic testing and blood-based monitoring in understanding and tracking prostate cancer. Notably, circulating tumor DNA (ctDNA) analysis proved effective in monitoring tumor evolution and resistance mechanisms in real time, according to the findings presented at the annual American Society of Clinical Oncology (ASCO) conference. The research team is now continuing to analyze the data to better understand why some cancers resist treatment and how to design future therapies that are more tailored to each individual.

“This study shows how complex prostate cancer can be, especially in men with certain gene mutations,” said Marc Dall’Era, chief of UC Davis Health’s Department of Urologic Surgery and lead researcher. “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.”

Related Links:
UC Davis Comprehensive Cancer Center