Short-term adjuvant androgen suppression combined with radiation prolonged biochemical disease-free survival (DFS) among patients with intermediate- or high-risk localized prostate cancer, according to results from the EORTC Trial 22991.1

The treatment of locally advanced prostate cancer commonly includes radiotherapy (RT) and adjuvant androgen suppression; however, the benefit of this combination in patients with intermediate- and high-risk localized prostate cancer has not been established.2-7 In addition, up to 30% of patients with intermediate- or high-risk localized prostate cancer who receive radiation experience biochemical by 5 years.1

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The EORTC initiated trial 22991 to determine the efficacy of 6-month AS plus RT in this population.

“This is a group of patients for whom we need more information about how to best combine RT and ADT, and it also addresses the issue of whether ADT can be avoided simply by increasing the radiation dose,” Mitchell S. Anscher, MD, professor and chairman of the Radiation Oncology Division of Virginia Commonwealth University Massey Cancer Center in Richmond, VA,  told Cancer Therapy Advisor. He is not affiliated with the study.

The trial randomly assigned 819 patients with stage cT1b-c prostate cancer and a prostate-specific antigen (PSA) of at least 10 ng/mL or a Gleason score of at least 7, or stage cT2a with no pelvic lymph node involvement or evidence of metastasis and a PSA of 50 ng/mL or less to receive adjuvant AS and RT, or RT alone. RT dose of 70, 74, or 78 Gy was selected by each center, and RT was defined as 3-dimensional conformal RT or intensity-modulated radiation therapy with an isocentric beam arrangement. In the adjuvant AS arm, depot goserelin was administered subcutaneously every 3 months beginning day 1 of RT.

The primary endpoint was biochemical DFS defined as PSA relapse by the Phoenix criteria or clinical relapse as indicated by imaging or all-cause mortality. Secondary efficacy endpoints included clinical DFS and overall survival (OS). Quality of life was assessed by the EORTC Quality of Life questionnaire with the QLQ-PR25 prostate cancer module at randomization, 6 months, and 1, 2, and 3 years.

At baseline, the median age was 70 years, 74.8% of patients were intermediate risk, and 85.3% of patients had a World Health Organization performance status of 0. The median follow-up was 7.2 years. Assessments, including laboratory and PSA measurements, were repeated every 6 months for 5 years, and annually subsequently.

There was a significant improvement in biochemical DFS in the adjuvant androgen suppression arm; 28.8% of patients who received adjuvant androgen suppression plus RT experience biochemical relapse compared with 49.1% of patients who received RT alone.

As a result, the 5-year biochemical DFS rate was 82.6% for the adjuvant androgen suppression arm (95% CI, 78.4 – 86.1) and 69.8% in the RT alone arm (95% CI, 64.9 – 74.2) with a hazard ratio of 0.52 (95% CI, 0.41 – 0.66; P < .001). The 5-year OS rate was 91.3% (95% CI, 88 – 93.7) for the combination arm compared with 88.4% (95% CI, 84.7 – 91.3) for the RT alone arm.

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The rate of local relapse and identification of metastasis was also reduced in the adjuvant androgen suppression arm. The local relapse rate was 2.1% (95 %CI, 0.7 – 3.6) in the combination arm compared with 6.6% (95% CI, 4.1 – 9.1) in the RT alone arm (HR, 0.37; 95% CI, 0.21 – 0.68; P = .001). In addition, metastases were detected in 4.4% of patients in the combination arm compared with 7.6% in the RT alone arm (P = .05).