Addition of Androgen Deprivation Therapy to Radiation Therapy May Improve Survival in Patients with Intermediate-Risk Localized Prostate Cancer

DynaMed Weekly Update - Volume 6, Issue 30

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.