Nearly all men with metastatic hormone-sensitive prostate cancer treated with intermittent androgen deprivation therapy (ADT) experience recurrence within 6 mo of testosterone recovery. We conducted a single-arm phase 2 trial to evaluate whether addition of dual androgen receptor pathway inhibitors (ARPIs) and metastasis-directed stereotactic body radiotherapy (SBRT) to intermittent ADT improves recurrence rates for men with between one and five nonvisceral, extrapelvic metastases on prostate-specific membrane antigen positron emission tomography/computed tomography after prior radical prostatectomy. Patients received 6 mo of androgen annihilation therapy (AAT; leuprolide, abiraterone acetate plus prednisone, and apalutamide) and metastasis-directed SBRT. The primary endpoint was the percentage of patients with prostate-specific antigen (PSA) <0.05 ng/ml 6 mo after testosterone recovery (≥150 ng/dl), with the study powered to detect an improvement from 1% to 12%. We enrolled 28 men between March 2021 and June 2022. Median follow-up was 20 mo (interquartile range 16–22). Twenty-six patients (93%) completed SBRT with 6 mo of hormone therapy, of whom six discontinued at least one ARPI; two patients withdrew prematurely. At 6 mo after testosterone recovery, PSA was maintained at <0.05 ng/ml in 13/26 patients (50%, 95% confidence interval 32–67%). Rates of grade 2 and 3 AAT toxicity were 21% and 21%. The results confirm that addition of metastasis-directed SBRT to highly potent systemic therapy can maintain low PSA after testosterone recovery, although further studies are needed to clarify the optimal systemic therapy regimen. We tested a combination of intensified hormone therapy (called androgen annihilation therapy) and radiotherapy targeted at metastases in men with recurrence of metastatic prostate cancer. We found that half of patients were recurrence-free 6 months after their testosterone level recovered, and that less than a quarter of patients experienced a severe drug-related side effect. Overall, this appears to be an effective therapy with acceptable side effects.

中文翻译：

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少发性转移性前列腺癌 (SATURN) 的全身和肿瘤定向治疗：2 期临床试验的主要终点结果

几乎所有接受间歇性雄激素剥夺疗法 (ADT) 治疗的转移性激素敏感性前列腺癌男性在睾酮恢复后 6 个月内都会出现复发。我们进行了一项单组 2 期试验，以评估在间歇性 ADT 中添加双雄激素受体途径抑制剂 (ARPIs) 和转移定向立体定向放射治疗 (SBRT) 是否可以提高患有 1 至 5 个非内脏盆腔外转移的男性的复发率。既往根治性前列腺切除术后进行前列腺特异性膜抗原正电子发射断层扫描/计算机断层扫描。患者接受 6 个月的雄激素消除治疗（AAT；亮丙瑞林、醋酸阿比特龙加泼尼松和阿帕鲁胺）和转移导向的 SBRT。主要终点是睾酮恢复后 6 个月（≥150 ng/dl）前列腺特异性抗原 (PSA) <0.05 ng/ml 的患者百分比，该研究有力地检测到从 1% 到 12% 的改善。我们在 2021 年 3 月至 2022 年 6 月期间招募了 28 名男性。中位随访时间为 20 个月（四分位数间距 16-22）。 26 名患者 (93%) 完成了 SBRT 和 6 个月的激素治疗，其中 6 名患者停止了至少一种 ARPI；两名患者提前退出。睾酮恢复后 6 个月，13/26 名患者的 PSA 维持在 <0.05 ng/ml（50%，95% 置信区间 32-67%）。 2 级和 3 级 AAT 毒性发生率分别为 21% 和 21%。结果证实，在高效全身治疗中添加针对转移的 SBRT 可以在睾酮恢复后维持较低的 PSA，尽管需要进一步研究来阐明最佳的全身治疗方案。我们测试了针对转移性前列腺癌复发的男性的强化激素疗法（称为雄激素消灭疗法）和针对转移灶的放射疗法的组合。我们发现，一半的患者在睾酮水平恢复后 6 个月内没有复发，不到四分之一的患者出现了严重的药物相关副作用。总体而言，这似乎是一种有效的疗法，且副作用可接受。