Adding four months of androgen deprivation therapy (ADT) to radiation treatment extends survival and delays metastasis in men with unfavorable intermediate-risk prostate cancer, according to a secondary analysis of a Phase 3 clinical trial.
However, that new trial analysis showed there were no such benefits to ADT therapy for men with favorable intermediate-risk prostate cancer undergoing radiation therapy.
These findings support the National Comprehensive Cancer Network recommendations that ADT treatment only be given to patients with unfavorable intermediate-risk prostate cancer.
The study,” Effect of Androgen Deprivation on Long-term Outcomes of Intermediate-Risk Prostate Cancer Stratified as Favorable or Unfavorable,” was published in the journal JAMA Network Open.
Radiation therapy is a prostate cancer treatment strategy that uses high-energy x-rays to target and damage tumor cells. Hormone therapy, also known as androgen deprivation therapy or ADT, aims to reduce the production of androgens, such as testosterone, which fuel cancer cell growth.
The RTOG 9408 trial (NCT00002597), supported by NRG Oncology and the National Cancer Institute, was a Phase 3 clinical trial investigating the effectiveness of radiation therapy with or without four months of ADT in men with localized prostate cancer.
The original analysis found that the short course of ADT increased the proportion of intermediate-risk patients living at least 10 years (to 62%, from 57% with radiation therapy only).
This secondary analysis of the RTOG 9408 data now examined the benefits in patients classified as favorable intermediate-risk (FIR) versus unfavorable intermediate-risk (UIR) prostate cancer.
The classification was based on the number of intermediate-risk factors, the percentage of positive biopsy cores, and the Gleason score — a higher score reflects the increased likelihood cancer will grow and spread quickly.
A total of 377 men classified as FIR and 513 identified as UIR were included in the analysis; all had an average age of 70 years. The outcomes were distant metastasis (cancer that spread), prostate cancer-specific mortality, and all-cause mortality. The median follow-up for this analysis was 17.8 years.
Compared with patients classified as having FIR cancer, the men classified as UIR had a 2.36 times higher risk of distant metastasis, a 1.84 times higher risk of prostate cancer-specific mortality, and an increased risk of all-cause mortality of 1.19 times.
Among men with FIR disease, no significant differences were found in those who received ADT compared with those who did not have the additional therapy with respect to distant metastases, prostate cancer-specific mortality, or all-cause mortality. Over the first 15 years, there was also no difference in survival time (11.0 vs. 10.7 years).
In contrast, in patients with UIR disease, ADT’s addition significantly reduced the risk of distant metastasis (by 52%) and of prostate cancer-specific mortality (by 60%). There was a trend toward improved all-cause mortality but the result was not statistically significant.
In this group, survival time significantly increased from 9.8 years in those without ADT to 10.5 years in men who received ADT.
“To our knowledge, these are the highest-quality data supporting recent changes in the National Comprehensive Cancer Network guidelines recommending radiation without ADT for patients with FIR disease and combined ADT and radiotherapy for patients with UIR disease,” the investigators wrote.
The data support splitting intermediate-risk prostate cancer into favorable and unfavorable subgroups, the scientists said.
“Future studies exploring genomic classifiers to further personalize therapy in intermediate-risk prostate cancer should be performed,” they added.