Higher Gleason Score and ADT Efficacy

A recent finding shows that men with a Gleason score of 9–10 prostate cancer may derive a smaller survival benefit from androgen deprivation therapy (ADT) compared with those with Gleason score of 8. However, in the men with a Gleason 8, ADT is associated with an approximately 20% decrease in all-cause mortality. These are among the findings of a new analysis published in European Urology.

This finding came from David Yang, MD, of Harvard Medical School and the Harvard Radiation Oncology Program in Boston, and colleagues who conducted a retrospective study of more than 20,000 men from the National Cancer Database (NCDB). 

All individuals they evaluated had localized or locally advanced, Gleason score 8–10 prostate cancer who received external beam radiation therapy (EBRT) between 2004 and 2012. In this cohort, 78% of men with Gleason score 8 disease and 87% of men with Gleason 9–10 disease had ADT. 

After conducting a multivariable analysis, Yang et al. found that ADT was associated with a significant improvement in overall survival for men with a Gleason score of 8  but not for men with a Gleason score of 9–10. Also, a higher Gleason score (8, 9, or 10) was associated with a decreasing benefit from ADT. However, the authors cautioned that the study is limited by the relatively short follow-up of a median of 4.0 years.

Based on the results of the study, intensification multiple treatment modalities of therapy should be considered for men with prostate cancer with a Gleason score of 9–10, the authors concluded. They also encourage the enrollment of such men in clinical trials or potentially adding novel anti-androgens or docetaxel. Both of these therapies have been shown to be effective in castration-resistant and castration-sensitive settings, according to the authors.

Neil Desai, MD, who is an assistant professor of Radiation Oncology at the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center in Dallas, said this is a provocative study that contradicts the commonly held belief that ADT improves outcomes in high-grade prostate cancer, irrespective of specific grade.