Researchers have identified distinct subgroups of men with high-risk prostate cancer (PCa) who experience different outcomes following treatment with a combination of high-dose radiation therapy and androgen-deprivation therapy (ADT), according to a new report in BMC Urology (2017;17:60).

In a study of 547 patients, Daniel N. Cagney, MD, of St. Luke’s Radiation Oncology Network in Dublin, Ireland, and colleagues found that patients with a single high-risk factor (favorable high-risk subgroup) had better outcomes than those with multiple high-risk factors (unfavorable high-risk subgroup) following treatment with a combination of external beam radiation therapy (EBRT) and ADT. The favorable high-risk subgroup had a 5-year distant metastasis-free survival (DMFS) rate similar to that of patients with intermediate-risk PCa.

The 2015 National Comprehensive Cancer Network (NCCN) guidelines define high-risk PCa as a biopsy Gleason score of 8–10, a PSA level greater than 20 ng/mL, or clinical stage T3a disease.

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In the new study, all patients underwent EBRT and 98% received ADT. The investigators defined 4 subgroups based on NCCN criteria: patients with 1 high-risk factor (favorable risk subgroup); patients with 2–3 high-risk factors (unfavorable risk subgroup); patients with 2–3 NCCN criteria for intermediate-risk disease; and patients with very high-risk disease. The main outcomes were biochemical recurrence-free survival (bRFS) and DMFS.

For the entire study population, the median EBRT dose was 74 Gy, and the median ADT duration was 8 months. The median follow-up was 62.3 months. The 2-year bRFS rate was 87%; the 2- and 5-year DMFS rates were 95% and 85%, respectively.

For the favorable, unfavorable, and very high-risk subgroups, the estimated 2-year bRFS rates were 91.6%, 78.8%, and 79.4%, respectively, Dr Cagney and his colleagues reported. The 5-year bRFS rates for the favorable, unfavorable, and very high-risk subgroups were 69.2%, 66.2%, and 58.2%, respectively. The 5-year rates of DMFS were 88.0%, 81.2%, 78.4%, and 93.7% for the favorable, unfavorable, very high-risk, and intermediate-risk patients, respectively. The estimated 10-year DMFS rates were 66.7% and 54.5% for the favorable and unfavorable subgroups, respectively. The estimated 5-year and 10-year DMFS rates for the very high-risk group were 78.4% and 57.4%, respectively.

“These results highlight the heterogeneity within high-risk prostate cancer,” the authors wrote. “This is one of the first series from Europe in patients with high-risk prostate cancer treated with radiotherapy that has sought to sub-classify high-risk disease.”

On multivariate analysis, significant predictors of shorter bRFS were biopsy Gleason score of 8–10, higher PSA level, shorter duration of ADT, and lower radiation dose. Predictors of shorter DMFS were biopsy Gleason score, higher PSA level, and lower radiation dose.

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Cagney DN, Dunne M, O’Shea C, et al. Heterogeneity in high-risk prostate cancer treated with high-dose radiation therapy and androgen deprivation therapy. BMC Urol 2017;17:60. doi: 10.1186/s12894-017-0250-2