DNA damage and repair (DDR) pathway profiling revealed patient-level variations and the DDR pathways are rarely affected by mutation. This according to a study of 1,090 men with high-risk prostate cancer, divided into a training cohort and 3 validation cohorts. Researchers found:

• There are distinct clusters of DDR pathways and DDR pathway enrichment is only weakly correlated with clinical variables such as age, Gleason score, and prostate-specific antigen level, while 13 of 17 DDR gene sets are strongly correlated with androgen receptor pathway enrichment.

• In published cohorts, DDR pathway genes are rarely mutated.

• A DDR pathway profile prognostic signature built in the training cohort was significantly associated with biochemical recurrence-free, metastasis-free, and overall survival independent of standard clinicopathological variables.

• Prognostic performance of the signature for metastasis-free survival appears to be stronger in younger patients vs older patients.

Citation: 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.