New Study Claims Improved Gene Expression-Based Risk Stratification for Prostate Cancer

Urologists at Cancer Research UK have identified 5 distinct genomic signatures in prostate cancer that can have important implications on treatment decisions.

As the debate on overdiagnosis and overtreatment in cancer patients continues, scientists are working to improve the granularity of molecular signatures that can more precisely drive clinical decisions. With the objective of reducing mortality among prostate cancer patients, extensive screening and early detection have been blamed for unnecessarily aggressive treatment in patients who probably would not even have developed symptoms during their lifetime. In addition to the impact on the patient’s quality of life, overtreatment also burdens healthcare costs.

The prostate-specific antigen (PSA), for example, has historically been used as a biomarker to screen for prostate cancer, but recent recommendations from the American Urological Association advice against pelvic CT scan for asymptomatic men with low-risk prostate cancer (PSA less than 20 ng/mL, Gleason score less than 7, tumor stage T2 or lower). There’s also an emphasis on shared decision making with the patient, all a part of the Choosing Wisely initiative of the ABIM Foundation, which has now been adopted by numerous professional organizations.

In the current study, published in EBioMedicine, scientists evaluated healthy and cancerous tissue from the prostate of 259 men for copy number alterations (CNA) and expression of the transcriptome (complete set of RNA transcripts), to stratify patients into subgroups based on future clinical behavior. The resulting analysis identified 5 distinct subgroups with unique genomic alterations and expression profiles based on 100 discriminating genes, the authors write. The authors conducted short-term and long-term follow-up in these patients and found that the subgroups could consistently predict biochemical relapse. The authors believe that the unique molecular profiles identified by their study can be used for the early detection of aggressive cases in a clinical setting. Urologists could utilize the genetic signature to make treatment decisions in patients classified as low, intermediate, or high risk.

Said study author Alastair Lamb, MD, in a statement “The next step is to confirm these results in bigger studies and drill down into the molecular 'nuts and bolts' of each specific prostate cancer type. By carrying out more research into how the different diseases behave we might be able to develop more effective ways to treat prostate cancer patients in the future, saving more lives.”