A Phase 2 clinical trial at UC Davis Comprehensive Cancer Center has revealed important insights into why some men with aggressive prostate cancer experience high recurrence rates despite treatment, while identifying circulating tumor DNA (ctDNA) as a promising biomarker for personalizing therapy selection. The findings will be presented at the annual American Society of Clinical Oncology (ASCO) conference on June 3 in Chicago.
Novel Approach to High-Risk Prostate Cancer
The pilot trial (NCT04030559) investigated whether administering the PARP inhibitor niraparib before surgery could help prevent cancer recurrence in men with aggressive prostate cancer. Researchers focused specifically on patients with DNA repair gene mutations, aiming to enable more personalized treatment approaches.
A total of 11 men with high-risk prostate cancer and specific genetic biomarkers participated in the study. Each patient received 200 mg of niraparib daily for 90 days before undergoing surgery. The study group had a median age of 68 years and a median prostate-specific antigen (PSA) at diagnosis of 10.7 ng/mL.
Genetic Landscape and Patient Characteristics
The genetic alterations identified in the study population included germline mutations in BRCA2, MSH6, and CHEK2, as well as somatic mutations in ATM, SPOP, KMT2C, and KMT2D, among others. Germline mutations in DNA are inherited, while somatic mutations occur after conception, highlighting the diverse genetic landscape of aggressive prostate cancer.
ctDNA Emerges as Valuable Monitoring Tool
While niraparib did not dramatically shrink tumors before surgery, the study demonstrated the significant potential of genetic testing and blood-based monitoring for understanding and tracking prostate cancer progression. Most notably, circulating tumor DNA biomarker analysis proved useful in tracking tumor evolution and resistance mechanisms in real time. ctDNA consists of small fragments of DNA that cancer cells release into the bloodstream.
"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."
Implications for Future Treatment Strategies
The variable responses observed in the trial, particularly among patients with BRCA2 mutations, underscore the complexity of treating prostate cancer in genetically diverse patient populations. The research team is 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 patient.
The study's emphasis on ctDNA monitoring represents a significant advancement in precision oncology approaches for prostate cancer. This biomarker could potentially help clinicians identify which patients are most likely to benefit from targeted neoadjuvant therapies, moving beyond traditional one-size-fits-all treatment approaches.
The research team included Primo Lara Jr., Nicholas Mitsiades, Mamta Parikh, John McPherson, Kenneth Iczkowski, Irene Mitsiades, and Aedric Lim, reflecting the collaborative nature of this precision medicine initiative.
