Marvaso Giulia, Corrao Giulia, Zaffaroni Mattia, Vincini Maria Giulia, Lorubbio Chiara, Gandini Sara, Fodor Cristiana, Netti Sofia, Zerini Dario, Luzzago Stefano, Mistretta Francesco Alessandro, Venetis Konstantinos, Cursano Giulia, Burla Tiziana, Mazzocco Ketti, Cattani Federica, Petralia Giuseppe, Fusco Nicola, Pravettoni Gabriella, Musi Gennaro, De Cobelli Ottavio, Tang Chad, Ost Piet, Palma David A, Orecchia Roberto, Jereczek-Fossa Barbara Alicja
Division of Radiation Oncology, IEO European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy.
Division of Radiation Oncology, IEO European Institute of Oncology, IRCCS, Milan, Italy.
Lancet Oncol. 2025 Mar;26(3):300-311. doi: 10.1016/S1470-2045(24)00730-7.
Metastasis-directed therapy by stereotactic body radiotherapy (SBRT) has been shown to improve clinical outcomes in the oligometastatic prostate cancer setting. We aimed to investigate whether short-course androgen deprivation therapy (ADT) and SBRT at all oligometastatic sites versus SBRT alone improves clinical progression-free survival in men with metachronous oligorecurrent hormone-sensitive prostate cancer.
The RADIOSA study was a single-centre, randomised, open-label, controlled phase 2 trial done in the European Institute of Oncology, IRCCS, Milan, Italy. Key eligibility criteria were histologically proven initial diagnosis of adenocarcinoma of the prostate, biochemical progression after radical local prostate treatment, nodal relapse in the pelvis, extra-regional nodal relapse, bone metastases at next-generation imaging with a maximum of three lesions, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and age 18 years or older. Participants were stratified according to prostate-specific membrane antigen doubling time (≤3 vs >3 months), metastases localisation (node vs bone), and diagnostic imaging (positron emission tomography vs MRI) and were randomly assigned (1:1) using a computer-generated random number to SBRT alone or SBRT in combination with 6 months of ADT. For SBRT treatment, a schedule of 30 Gy in three fractions every other day (with the equivalent dose in 2 Gy fractions being 98·6 Gy, considering α/β ratio of 1·5 Gy and biologically effective dose of >100 Gy), or equivalent regimens depending on disease site location, was administered. Patients in the SBRT with ADT group received 6 months of ADT with a luteinising hormone-releasing hormone analogue within 1 week before the start of SBRT. The allocated treatment was not masked. The primary outcome measure was clinical progression-free survival. All analyses followed a modified intention-to-treat principle, consisting of all patients assigned to a treatment group who had available data. The trial is registered at ClinicalTrials.gov, NCT02680587, and is complete.
Between Aug 1, 2019, and April 30, 2023, 218 patients were assessed for eligibility, 113 were excluded, and 105 were enrolled and randomly assigned to an intervention (52 to SBRT only and 53 to SBRT with ADT). Three patients were lost to follow-up and 51 patients in each group were assessed for the primary outcome. The median age at study enrolment was 70 years (IQR 65-75); data on race and ethnicity were not collected. With a median follow-up of 31 months (IQR 16-36) for both groups, the median clinical progression-free survival was 15·1 months (95% CI 12·4-22·8) for the SBRT group versus 32·2 months (22·4-not reached) for the SBRT with ADT group (hazard ratio 0·43 [95% CI 0·26-0·72], p=0·0010]). One gastrointestinal grade 1 adverse event (SBRT group) and one genitourinary grade 3 adverse event (left ureter stenosis, SBRT with ADT group) were reported, with no late toxicities observed. 22 grade 1 ADT-related adverse events were reported, all of which had resolved at the last follow-up. No treatment-related deaths were recorded.
To our knowledge, the RADIOSA trial represents the first randomised trial in the metachronous oligometastatic hormone-sensitive prostate cancer setting to report improved clinical progression-free survival with the combination of SBRT and a short course of ADT, although carefully selected patients might still benefit from SBRT alone. By demonstrating improved clinical progression-free survival, the RADIOSA trial reinforces the role of metastasis-directed therapy in delaying systemic treatment escalation. Additionally, it underscores the need for further studies to determine the optimal duration of ADT and identify biomarkers predicting response to SBRT alone.
Italian Association of Cancer Research.
立体定向体部放疗（SBRT）的转移灶定向治疗已被证明可改善寡转移前列腺癌患者的临床结局。我们旨在研究在异时性寡复发性激素敏感性前列腺癌男性患者中，对所有寡转移部位进行短程雄激素剥夺治疗（ADT）联合SBRT与单纯SBRT相比，是否能改善无临床进展生存期。
RADIOSA研究是在意大利米兰欧洲肿瘤研究所（IRCCS）开展的一项单中心、随机、开放标签、对照2期试验。主要入选标准为经组织学证实的前列腺腺癌初始诊断、根治性局部前列腺治疗后生化进展、盆腔淋巴结复发、区域外淋巴结复发、新一代影像学检查发现的骨转移且最多三个病灶、东部肿瘤协作组（ECOG）体能状态为0 - 1以及年龄18岁或以上。参与者根据前列腺特异性膜抗原倍增时间（≤3个月与>3个月）、转移灶定位（淋巴结与骨）和诊断成像（正电子发射断层扫描与MRI）进行分层，并使用计算机生成的随机数按1:1随机分配至单纯SBRT组或SBRT联合6个月ADT组。对于SBRT治疗，采用每隔一天分三次给予30 Gy的方案（考虑α/β比值为1.5 Gy且生物等效剂量>100 Gy时，2 Gy分次的等效剂量为98.6 Gy），或根据疾病部位采用等效方案。SBRT联合ADT组的患者在SBRT开始前1周内接受6个月的ADT及促性腺激素释放激素类似物治疗。分配的治疗未设盲。主要结局指标为无临床进展生存期。所有分析遵循改良意向性分析原则，包括所有分配至治疗组且有可用数据的患者。该试验已在ClinicalTrials.gov注册，注册号为NCT02680587，且已完成。
2019年8月1日至2023年4月30日期间，对218例患者进行了资格评估，113例被排除，105例入组并随机分配至干预组（52例接受单纯SBRT，53例接受SBRT联合ADT）。3例患者失访，每组51例患者接受了主要结局评估。研究入组时的中位年龄为70岁（四分位间距65 - 75岁）；未收集种族和民族数据。两组的中位随访时间均为31个月（四分位间距16 - 36个月），单纯SBRT组的中位无临床进展生存期为15.1个月（95%CI 12.4 - 22.8），而SBRT联合ADT组为32.2个月（22.4 - 未达到）（风险比0.43 [即95%CI 0.26 - 0.72]，p = 0.0010）。报告了1例1级胃肠道不良事件（SBRT组）和1例3级泌尿生殖系统不良事件（左输尿管狭窄，SBRT联合ADT组），未观察到晚期毒性反应。报告了22例1级ADT相关不良事件，所有这些事件在最后一次随访时均已缓解。未记录与治疗相关的死亡病例。
据我们所知，RADIOSA试验是异时性寡转移激素敏感性前列腺癌领域的首个随机试验，报告了SBRT与短程ADT联合应用可改善无临床进展生存期，尽管经过精心挑选的患者可能仍可从单纯SBRT中获益。通过证明无临床进展生存期得到改善，RADIOSA试验强化了转移灶定向治疗在延迟全身治疗升级方面的作用。此外，它强调需要进一步研究以确定ADT的最佳持续时间，并识别预测单纯SBRT反应的生物标志物。
意大利癌症研究协会。
