Addition of Metastasis-Directed Therapy to Intermittent Hormone Therapy for Oligometastatic Prostate Cancer

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As reported in JAMA Oncology by Tang et al, the phase II EXTEND (External Beam Radiation to Eliminate Nominal Metastatic Disease) trial has shown that the addition of metastasis-directed therapy to intermittent hormone therapy improved progression-free survival in patients with oligometastatic prostate cancer.

Study Details

In the trial, 87 patients with no more than five metastases who had received hormone therapy for at least 2 months were randomly assigned at three U.S. centers between September 2018 and November 2020 to receive metastasis-directed therapy consisting of definitive radiation therapy to all sites of disease and intermittent hormone therapy (n = 43) or hormone therapy alone (n = 44). Hormone therapy consisted of a luteinizing hormone-releasing hormone agonist or antagonist with or without a second-generation androgen receptor–targeting agent. Patients had a planned break in hormone therapy at 6 months after enrollment, with treatment then withheld until disease progression.

The primary endpoint was progression-free survival, with progression defined as death or radiographic, clinical, or biochemical progression. A key predefined secondary endpoint was eugonadal progression-free survival, defined as the time from achieving a eugonadal testosterone level (≥ 150 ng/dL) until disease progression.

Key Findings

Median follow-up was 22.0 months (range = 11.6–39.2 months). Median progression-free survival was not reached in the metastasis-directed therapy group vs 15.8 months (95% confidence interval [CI] = 13.6–21.2 months) in the control group (hazard ratio [HR] = 0.25, 95% CI = 0.12–0.55, P < .001). Hazard ratios for progression-free survival favored the metastasis-directed therapy group in all subgroups according to baseline prostate-specific antigen level, disease stage, no or any prior primary treatment, use of second-generation antiandrogens, number of metastatic lesions, and duration of hormonal therapy prior to enrollment.

Recovery to eugonadal testosterone levels occurred in 52 patients. Median eugonadal progression-free survival was not reached in the metastasis-directed therapy group vs 6.1 months (95% CI = 3.7 months to not estimable) in the control group (HR = 0.32, 95% CI = 0.11–0.91, P = .03).

No grade ≥ 4 adverse events were observed. A total of six grade 3 events were reported, consisting of three in the metastasis-directed therapy group (in three patients) and three in the control group (in two patients). A total of 16 grade 2 adverse events were reported, consisting of 12 in the metastasis-directed therapy group (in seven patients) and 4 in the control group (in one patient).

The investigators concluded: “In this randomized clinical trial, [progression-free survival] and eugonadal [progression-free survival] were significantly improved with combination treatment compared with hormone treatment only in men with oligometastatic prostate cancer. Combination of [metastasis-directed therapy] with intermittent hormone therapy may allow for excellent disease control while facilitating prolonged eugonadal testosterone intervals.”

Chad Tang, MD, of the Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was supported by grants from the Cancer Prevention & Research Institute of Texas and the National Cancer Institute. For full disclosures of the study authors, visit

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