Ah-Thiane Loic, Campion Loic, Allouache Nedjla, Meyer Emmanuel, Pommier Pascal, Mesgouez-Nebout Nathalie, Serre Anne-Agathe, Créhange Gilles, Guimas Valentine, Rio Emmanuel, Sargos Paul, Ladoire Sylvain, Mahier Ait Oukhatar Céline, Supiot Stéphane
Department of Radiotherapy, ICO Rene Gauducheau, St-Herblain, France.
Department of Biostatistics, ICO Rene Gauducheau, St-Herblain, France.
Eur Urol Oncol. 2025 Feb;8(1):38-46. doi: 10.1016/j.euo.2024.04.014. Epub 2024 May 11.
The relevance of next-generation hormone therapies and circulating tumor cells (CTCs) are not elucidated in biochemical recurrence after prostatectomy.
To evaluate the combination of abiraterone acetate plus prednisone (AAP), prostate bed radiotherapy (PBRT), and goserelin in biochemically relapsing men after prostatectomy, and to investigate the utility of CTCs.
DESIGN, SETTING, AND PARTICIPANTS: In this single-arm multicenter phase 2 trial, 46 biochemically relapsing men were enrolled between December 2012 and January 2019. The median follow-up was 47 mo.
All patients received AAP 1000 mg daily (but 750 mg during PBRT), salvage PBRT, and goserelin.
The primary outcome was 3-yr biochemical recurrence-free survival (bRFS) when prostate-specific antigen (PSA) levels were ≥0.2 ng/ml. The secondary outcomes included alternative bRFS (alt-bRFS) when PSA levels were ≥0.5 ng/ml and safety assessment. CTC count was assessed.
The 3-yr bRFS and alt-bRFS were 81.5% (95% confidence interval or CI [66.4-90.3%]) and 95.6% (95% CI [83.5-98.9%]), respectively. The most common acute radiotherapy-related adverse effect (AE; all grades was pollakiuria (41.3%). The most common late AE (all grades) was urinary incontinence (15.2%). Grade 3-4 acute or late radiotherapy-related AEs were scarce. Most frequent AEs nonrelated to radiotherapy were hot flashes (76%), hypertension (63%), and hepatic cytolysis (50%, of which 20% were of grades 3-4). Of the patients, 11% had a CTC count of ≥5, which was correlated with poorer bRFS (p = 0.042) and alt-bRFS (p = 0.008). The association between CTC count and higher rates of relapse was independent of the baseline PSA level and PSA doubling time (p = 0.42 and p = 0.09, respectively). This study was nonrandomized with a limited number of patients, and few clinical events were reported.
Adding AAP to salvage radiation therapy and goserelin resulted in high bRFS and alt-bRFS. AEs remained manageable, although a close liver surveillance is advised. CTC count appears as a promising biomarker for prognosis and predicting response to treatment.
Our study was a phase 2 clinical trial that exhibited the efficacy and tolerance of a novel androgen-receptor targeting agent (abiraterone acetate plus prednisone) in patients with prostate cancer who experienced rising prostate-specific antigen after radical prostatectomy, in combination with prostate bed radiotherapy. The results also indicated the feasibility and potential value of circulating tumor cell detection, which constitutes a possible advance in managing prostate cancers.
前列腺切除术后生化复发时，新一代激素疗法与循环肿瘤细胞（CTC）的相关性尚未阐明。
评估醋酸阿比特龙加泼尼松（AAP）、前列腺床放疗（PBRT）和戈舍瑞林联合应用于前列腺切除术后生化复发男性的疗效，并研究CTC的效用。
设计、设置和参与者：在这项单臂多中心2期试验中，2012年12月至2019年1月期间纳入了46例生化复发男性。中位随访时间为47个月。
所有患者均接受每日1000mg的AAP（但在PBRT期间为750mg）、挽救性PBRT和戈舍瑞林。
主要结局为前列腺特异性抗原（PSA）水平≥0.2ng/ml时的3年无生化复发生存（bRFS）。次要结局包括PSA水平≥0.5ng/ml时的替代bRFS（alt-bRFS）和安全性评估。评估CTC计数。
3年bRFS和alt-bRFS分别为81.5%（95%置信区间或CI[66.4-90.3%]）和95.6%（95%CI[83.5-98.9%]）。最常见的急性放疗相关不良反应（AE；所有级别）是尿频（41.3%）。最常见的晚期AE（所有级别）是尿失禁（15.2%）。3-4级急性或晚期放疗相关AE很少见。最常见的与放疗无关的AE是潮热（76%）、高血压（63%）和肝细胞溶解（50%，其中20%为3-4级）。11%的患者CTC计数≥5，这与较差的bRFS（p=0.042）和alt-bRFS（p=0.008）相关。CTC计数与较高复发率之间的关联独立于基线PSA水平和PSA倍增时间（分别为p=0.42和p=0.09）。本研究为非随机、患者数量有限且报告的临床事件较少。
在挽救性放疗和戈舍瑞林中添加AAP可带来较高的bRFS和alt-bRFS。AE仍可控制，尽管建议密切监测肝脏。CTC计数似乎是一种有前景的预后和预测治疗反应的生物标志物。
我们的研究是一项2期临床试验，展示了一种新型雄激素受体靶向药物（醋酸阿比特龙加泼尼松）在根治性前列腺切除术后前列腺特异性抗原升高的前列腺癌患者中联合前列腺床放疗的疗效和耐受性。结果还表明了循环肿瘤细胞检测的可行性和潜在价值，这可能是前列腺癌管理方面的一项进展。
