EBRT works better with ADT for intermediate/high-risk prostate cancer

The EORTC trial 22991 compared EBRT + short-term ADT vs. EBRT alone in intermediate and high-risk men. The preliminary report by Bolla et al. was posted at the 2016 GU Conference. There are more details of the clinical trial available here. There were 819 patients in the European multi-institutional study:

• ·      407 received EBRT only, 403 received EBRT+6 months of ADT
• ·      Radiation dose: 70, 74, or 78 Gy (at discretion of each institution)
• ·      Pelvic node radiation: at discretion of each institution
• ·      75% intermediate risk, 25% high risk

After a median follow-up of 7.2 years,

• ·      5-year biochemical progression-free survival was 82.5% with the ADT, 69.3% without it.
• ·      Improvement was irrespective of radiation dose.
• ·      5-year clinical progression-free survival was improved by 7.9 percentage points.
• ·      Late urinary toxicity was 5.9% with the ADT, 3.6% without it (not statistically significant)
• ·      Severe sexual function impairment was 27.0% with the ADT, 19.4% without it (statistically significant)
• ·      Symptoms of hormone treatment, sexual activity and functioning were impaired at 6 months with ADT, but there was no difference at 2 years.

The authors conclude:

“The addition of 6 months of medical castration to primary irradiation improves BPFS and PFS in intermediate- and high-risk localized T1b-cT2a N0M0 prostatic carcinoma with no persistent detriment on HRQOL or sexual function.”

Unfortunately, this preliminary report doesn’t break out the intermediate and high-risk men separately.

We have previously looked at the DART 01/05 clinical trial that proved that at escalated radiation doses, long-term (28 months) androgen suppression improved cancer control better than short-term (4 months), at least for high-risk men. The benefit of longer duration ADT was not established for intermediate risk men at 5-year follow-up.

Nabid et al. focused on intermediate risk men and found a clear benefit to adding 6 months of ADT rather than none (after 10 years of follow-up).

It now seems clear that short-term androgen suppression improves results in intermediate risk men, while longer androgen suppression is necessary in high risk men. It would be helpful to know whether the improvement in intermediate risk men was only among the subgroup classified as “unfavorable intermediate risk.” ADT seems to have a more powerful effect than radiation dose, but it is unclear if that effect is maintained with therapies like SBRT and brachy boost that treat with much higher biologically effective doses. We are getting closer to defining an optimal duration of adjuvant ADT by risk level, and future trials using genetic classification data may provide better definition.