Level 2: Mid-level evidence
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 (Bria E et al.Cancer. 2009;115:3446-3456) or with prostate cancer with high metastatic risk (Bolla M et al. Lancet Oncol. 2010;11:1066-1073).
The efficacy of ADT plus radiation therapy has now been evaluated in an unblinded trial that involved 2,028 men with less advanced disease (Jones CU et al. N Engl J Med. 2011;365:107-118). Patients with stage T1b, T1c, T2a, or T2b prostate adenocarcinoma and prostate-specific antigen (PSA) ≤20 ng/mL were randomized to radiation therapy plus ADT for four months vs. radiation therapy alone. ADT, started two months before radiation therapy, included flutamide (Eulexin) 250 mg orally t.i.d. plus either goserelin (Zoladex) 3.6 mg subcutaneously monthly or leuprolide (Lupron) 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 ≤10 ng/mL, and clinical stage T1 or T2a were classified as low-risk (n=685). Men with Gleason score 7 or Gleason score ≤6 with PSA 10-20 ng/mL or clinical stage T2b were classified as intermediate-risk. The remainder of patients, who had Gleason scores between 8 and 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, number needed to treat=15). 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 flushes (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.
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