Investigators have created a DNA damage and repair (DDR) pathway profiling method that may be used in the management of patients with high-risk prostate cancer, according to an article published in JAMA Oncology.1

In the study, 1090 patients with high-risk prostate cancer who had undergone prostatectomy were split up into a training cohort (n = 545) and 3 pooled validation cohorts (n = 232, 130, and 183).

Investigators profiled 9 DDR pathways using 17 gene sets from data obtained from prostatectomy samples and followed-up for a median of 10.3 years. DDR pathway profiles were studied and gene mutations from published cohorts analyzed.

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Results revealed distinct DDR pathways and enrichment was weakly correlated with clinical variables including age, Gleason score, prostate-specific antigen level, but 13 of the 17 sets were strongly correlated with androgen receptor pathway enrichment.

Prognostic ability of the signature for metastasis-free survival was stronger in younger patients (HR, 1.67; 95% CI, 1.12 – 2.50) than in older patients (HR, 0.77; 95% CI, 0.29 – 2.07).

“As a biomarker of disease progression, DDR pathway profiling may be used to select patients for earlier treatment intensification with approaches such as adjuvant radiation or systemic therapy and may represent an avenue toward improved personalization of therapy for prostate cancer patients,” the authors concluded.


  1. Evans JR, Zhao SG, Chang SL, et al. Patient-level DNA damage and repair pathway profiles and prognosis after prostatectomy for high-risk prostate cancer [published online ahead of print January 7, 2016]. JAMA Oncol. doi: 10.1001/jamaoncol.2015.4955.