Previous research has suggested that androgen deprivation therapy (ADT) improves survival when added to radiotherapy in men with locally advanced (stage T3 or T4) prostate cancer (Cancer 2009 Aug 1;115(15):3446) or prostatic adenocarcinoma with high metastatic risk (Lancet Oncol 2010 Nov;11(11):1066). The efficacy of ADT plus radiation therapy has now been evaluated in a new unblinded trial with 2,028 men with less advanced disease. Patients with stage T1b, T1c, T2a or T2b prostate adenocarcinoma and prostate-specific antigen (PSA) level ? 20 ng/mL were randomized to radiation therapy plus ADT for 4 months vs. radiation therapy alone. ADT, started 2 months before radiation therapy, included flutamide 250 mg orally 3 times daily plus either goserelin 3.6 mg subcutaneously monthly or leuprolide 7.5 mg intramuscularly monthly.
Patients were stratified to low-, intermediate-, and high-risk categories based on multiple factors. Men with Gleason score ? 6, PSA level ? 10 ng/mL and clinical stage T1 or T2a were classified as low-risk (685 patients). Men with Gleason score 7 or Gleason score ? 6 with PSA level 10-20 ng/mL or clinical stage T2b were classified as intermediate (1,068 patients). The remainder of patients, who had Gleason scores 8-10 were classified as high-risk (although these patients had less advanced disease than the patients in the previous trials).
Median follow-up was 9.1 years. In the intermediate-risk group, addition of ADT was associated with significantly increased 10-year overall survival (61% vs. 54%, p = 0.03, NNT 15) (level 2 [mid-level] evidence). Disease-specific mortality at 10 years for this group was 3% vs. 10% (p = 0.004, NNT 15) and the 10-year rate of biochemical failure 22% vs. 32% (p
< 0.001, NNT 10). In the low-risk group, there were no significant differences in either overall survival (67% vs. 64%) or disease-specific mortality (3% vs. 1%). There were also no significant differences in either overall survival (53% vs. 51%) or disease-specific mortality (12% vs. 14%) in the high-risk group. Hot flashes (55%) and grade 1 hepatic toxic effects (16%) were the most common adverse events in the ADT group prior to radiotherapy. There were no significant differences in acute or late radiation-induced toxic effects (N Engl J Med 2011 Jul 14;365(2):107).
For more information, see the Androgen deprivation therapy for prostate cancer topic in DynaMed.