Prostate Cancer Coverage from Every Angle

ctDNA-Targeted Sequencing in Metastatic Prostate Cancer: Real-World Chinese Study

By: Justine Landin, PhD
Posted: Tuesday, June 15, 2021

Mutations in DNA damage repair genes and other driver genes may be important for clinical management of patients with metastatic castration-resistant prostate cancer, according to a multicenter study from China. Distinct gene mutations selectively modulated clinical outcomes, such as progression-free survival rates and responses to standard systemic treatments. This research was published in JNCCN–The Journal of the National Comprehensive Cancer Network.

“Metastatic castration-resistant prostate cancer remains incurable, despite incremental improvements provided by multiple agents,” stated Wei Xue, MD, of Shanghai Jiao Tong University, and colleagues. Further, the authors indicated that the genomic profile of this disease “…is dynamic and evolves with systemic treatments, explaining its diverse molecular signatures at different treatment stages.”

Patients with metastatic castration-resistant prostate cancer from multiple institutions in China were enrolled (n = 292). Blood samples were collected for multigene targeted sequencing of circulating tumor DNA (ctDNA) along with matched biopsied tumor tissue samples. The frequency of genetic mutations in these samples was compared with the Stand Up to Cancer–Prostate Cancer Foundation cohort. Medical reports for each patient were provided from the respective treatment facility. The association between progression free-survival following standard treatments for metastatic castration-resistant prostate cancer was assessed and utilized to investigate potential prognostic factors.

According to the investigators, ctDNA sequencing indicated that 91.7% of mutations were detected in both blood and paired biopsy samples, with the most common alterations in AR, TP53, CDK12, BRCA2, and R1. The likelihood of a CDK12 mutation appeared to be higher in Chinese patients (15.4%) than White patients (5%–7%). CDK12 mutations were associated with rapid disease progression and reduced progression-free survival following abiraterone (P < .001), but not docetaxel, treatment (P > .10). Patients with metastatic castration-resistant prostate cancer and a mutation in DNA damage repair genes, particularly BRCA2, appeared to be more responsive to PARP inhibitors and platinum-based chemotherapy, compared with patients who had other gene defects. 

Disclosure: The study authors reported no conflicts of interest.

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