Interlesional response heterogeneity is associated with the prognosis of abiraterone treatment in metastatic castration-resistant prostate cancer.

IF 12.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Med Pub Date : 2024-08-10 DOI:10.1016/j.medj.2024.07.020

Jian Pan, Junlong Wu, Beihe Wang, Bin Zhu, Xiaohang Liu, Hualei Gan, Yu Wei, Shengming Jin, Xiaoxin Hu, Qifeng Wang, Shaoli Song, Chang Liu, Dingwei Ye, Yao Zhu

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Abstract

Background: Interlesional response heterogeneity (ILRH) poses challenges to the treatment of metastatic castration-resistant prostate cancer (mCRPC). Currently, there are no prospective clinical trials exploring the prognostic significance of ILRH on paired positron emission tomography/computed tomography (PET/CT) in the context of abiraterone therapy.

Methods: In this prospective study, we enrolled patients with mCRPC treated with abiraterone (ClinicalTrials.gov: NCT05188911; ChiCTR.org.cn: ChiCTR2000034708). ⁶⁸Ga-prostate-specific membrane antigen (PSMA)+¹⁸F-fluorodeoxyglucose (FDG) PET/CT and circulating tumor DNA (ctDNA) monitoring were performed at baseline and week 13. Patients were grouped by their early ILRH measurement. The primary endpoint was to evaluate the predictive role of ILRH for conventional progression-free survival (PFS) through the concordance index (C-index) assessment. Conventional PFS was defined as the time from medication to conventional radiographic progression, clinical progression, or death.

Findings: Ultimately, 33 patients were included with a median follow-up of 28.7 months. Baseline+week 13 PSMA PET/CT revealed that 33.3% of patients showed ILRH. Those patients with hetero-responding disease had significantly different PFS compared to the responding and non-responding groups (hazard ratio: responding group = reference, hetero-responding group = 4.0, non-responding group = 5.8; p < 0.0001). The C-index of ILRH on paired PSMA PET/CT (0.742 vs. 0.660) and FDG PET/CT (0.736 vs. 0.668) for conventional PFS was higher than that of PSA response. In an exploratory analysis, PSMA-/FDG+ lesions at week 13 were identified as a strong surrogate for poor conventional PFS (p = 0.039).

Conclusions: ILRH on both baseline+week 13 PSMA and FDG PET/CT strongly associated with conventional PFS.

Funding: This study was funded by the Ministry of Science and Technology of China and Shanghai.

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转移性阉割耐药前列腺癌患者间反应异质性与阿比特龙治疗的预后有关。

背景：间期反应异质性（ILRH）给转移性去势抵抗性前列腺癌（mCRPC）的治疗带来了挑战。目前，还没有前瞻性临床试验探讨在阿比特龙治疗过程中，成对正电子发射断层扫描/计算机断层扫描（PET/CT）显示的ILRH的预后意义：在这项前瞻性研究中，我们招募了接受阿比特龙治疗的mCRPC患者（ClinicalTrials.gov：NCT05188911；ChiCTR.org.cn：ChiCTR2000034708）。在基线和第13周进行68Ga-前列腺特异性膜抗原（PSMA）+18F-氟脱氧葡萄糖（FDG）PET/CT和循环肿瘤DNA（ctDNA）监测。根据早期ILRH测量结果对患者进行分组。主要终点是通过一致性指数（C-index）评估ILRH对常规无进展生存期（PFS）的预测作用。常规无进展生存期被定义为从用药到常规放射学进展、临床进展或死亡的时间：最终有 33 名患者纳入研究，中位随访时间为 28.7 个月。基线+第13周PSMA PET/CT显示，33.3%的患者出现ILRH。与有反应组和无反应组相比，有异质性反应的患者的 PFS 有显著差异（危险比：有反应组 = 参考值，异质性反应组 = 4.0，无反应组 = 5.8；P 结论：基线+第 13 周 PSMA PET/CT 均显示 ILRH 的患者的 PFS 有显著差异：基线+第13周PSMA和FDG PET/CT上的ILRH与常规PFS密切相关：本研究由中国科技部和上海市共同资助。

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来源期刊

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

期刊介绍： Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.