Department of Radiation Oncology, Shanghai Changhai Hospital, 12520Naval Medical University, Shanghai, China.
Department of Urology, Shanghai Changhai Hospital, 12520Naval Medical University, Shanghai, China.
Cancer Control. 2022 Jan-Dec;29:10732748221120462. doi: 10.1177/10732748221120462.
The optimal treatment for oligometastatic prostate cancer (OMPC) is still on its way. Accumulating evidence has proven the safety and feasibility of radical prostatectomy and local or metastasis-directed radiotherapy for oligometastatic patients. The aim of this trial is to demonstrate the safety and feasibility outcomes of metastasis-directed neoadjuvant radiotherapy (naRT) and neoadjuvant androgen deprivation therapy (naADT) followed by robotic-assisted radical prostatectomy (RARP) for treating OMPC.
The present study will be conducted as a prospective, open-label, dose-escalation, phase I/II clinical trial. The patients with oligometastatic PCa will receive 1 month of naADT, followed by metastasis-directed radiation and abdominal or pelvic radiotherapy. Then, radical prostatectomy will be performed at intervals of 4-8 weeks after radiotherapy, and ADT will be continued for 2 years. The primary endpoints of the study are safety profiles, assessed by the Common Terminology Criteria for Adverse Events (CTCAE) 5.0 grading scale, and perioperativemorbidities, assessed by the Clavien-Dindo classification system. The secondary endpoints include positive surgical margin (pSM), biochemical recurrence-free survival (bPFS), radiological progression-free survival (RPFS), postoperative continence, and quality of life (QoL) parameters.
The optimal treatment for OMPC is still on its way, prompting investigation for novel multimodality treatment protocol for this patient population. Traditionally, radical prostatectomy has been recommended as one of the standard therapies for localized prostate cancer, but indications have expanded over the years as recommended by NCCN and EAU guidelines. RP has been carried out in some centres for OMPC patients, but its value has been inconclusive, showing elevated complication risks and limited survival benefit. Neoadjuvant radiotherapy has been proven safe and effective in colorectal cancer, breast cancer and other various types of malignant tumors, showing potential advantages in terms of reducing metastatic stem-cell activity, providing clinical downstaging, and reducing potential intraoperative risks. Existing trials have shown that naRT is well tolerated for high-risk and locally-advanced prostate cancer. In this study, we hope to further determine the optimal irradiation dose and patient tolerance for genitourinary, gastrointestinal and systemic toxicities with the design of 3+3 dose escalation; also, final pathology can be obtained following RP to further determine treatment response and follow-up treatment plans.
Chinese Clinical Trial Registry, ChiCTR1900025743. http://www.chictr.org.cn/showprojen.aspx?proj=43065.
寡转移前列腺癌（OMPC）的最佳治疗方法仍在探索中。越来越多的证据证明了根治性前列腺切除术和局部或转移灶定向放疗治疗寡转移患者的安全性和可行性。本试验旨在证明转移灶导向新辅助放疗（naRT）和新辅助雄激素剥夺治疗（naADT）联合机器人辅助根治性前列腺切除术（RARP）治疗 OMPC 的安全性和可行性。
本研究将作为一项前瞻性、开放标签、剂量递增、I/II 期临床试验进行。寡转移 PCa 患者将接受 1 个月的 naADT，然后进行转移灶导向放疗和腹部或盆腔放疗。然后，在放疗后 4-8 周间隔进行根治性前列腺切除术，ADT 将继续进行 2 年。该研究的主要终点是通过美国国家癌症研究所不良事件通用术语标准（CTCAE）5.0 分级量表评估的安全性特征，以及通过 Clavien-Dindo 分类系统评估的围手术期并发症。次要终点包括切缘阳性（pSM）、生化无复发生存（bPFS）、影像学无进展生存（RPFS）、术后控尿、生活质量（QoL）参数。
OMPC 的最佳治疗方法仍在探索中，这促使人们为这一患者群体探索新的多模式治疗方案。传统上，根治性前列腺切除术被推荐为局限性前列腺癌的标准治疗之一，但随着 NCCN 和 EAU 指南的推荐，其适应证多年来一直在扩大。一些中心已经对 OMPC 患者进行了 RP，但其价值尚无定论，显示出并发症风险升高和生存获益有限的情况。新辅助放疗已被证明在结直肠癌、乳腺癌和其他各种恶性肿瘤中是安全有效的，在降低转移干细胞活性、提供临床降期和降低潜在术中风险方面具有潜在优势。现有试验表明，naRT 对高危和局部进展性前列腺癌具有良好的耐受性。在这项研究中，我们希望通过 3+3 剂量递增设计进一步确定最佳照射剂量和患者对泌尿生殖、胃肠道和全身毒性的耐受性；此外，还可以通过 RP 获得最终的病理结果，以进一步确定治疗反应和随访治疗计划。
中国临床试验注册中心，ChiCTR1900025743。http://www.chictr.org.cn/showprojen.aspx?proj=43065。
