Department of Urology, Fudan University Shanghai Cancer Center, China.
Shanghai Genitourinary Cancer Institute, China.
Mol Oncol. 2022 Dec;16(22):4011-4022. doi: 10.1002/1878-0261.13320. Epub 2022 Oct 20.
The success of the PROfound, IPATential150, and TheraP trials promoted the transition from sequential treatment to therapeutic targets (TTs)-guided precision treatment in metastatic castration-resistant prostate cancer (mCRPC). The objective of this study was to evaluate the prevalence and prognostic value of TTs from these three trials. All included Chinese mCRPC patients underwent circulating tumor DNA (ctDNA) sequencing, PTEN status assessment, and dual-tracer [ Ga-prostate-specific membrane antigen (PSMA) and F-fluorodexyglucose (FDG)] positron emission tomography/computed tomography (PET/CT). Previous treatment with cabazitaxel, Lu-PSMA or olaparib was unallowed. Patients with known significant sarcomatoid or spindle cell or neuroendocrine small cell components were also excluded. TTs were defined as positive as follows: (a) high PSMA and no PSMA-/FDG+ disease on dual-tracer PET/CT scans; (b) defects in homologous recombination repair (HRR) genes in ctDNA; and (c) loss of PTEN immunohistochemistry staining in tumor tissue. The prevalence and prognostic value on progression-free survival (PFS) of TTs were evaluated. A total of 106 consecutive mCRPC patients were included. The prevalence of positive PET/CT, HRR defect, and PTEN loss was 30%, 29% and 16%, respectively. Sixty-three patients had at least one TT. Metastatic volume (odds ratio = 5.0; P = 0.017) was the only independent factor of positive TT in multivariate analysis. Seventy-four patients received abiraterone after TT screening. Patients with positive PET/CT (P = 0.011) and HRR defect (P = 0.002) had a significantly shorter PFS after receiving abiraterone than patients with negative TTs. However, PTEN status was unrelated to PFS, which may be due to a less number of patients with PTEN loss (P = 0.952). Overall, patients with any positive TTs had a significantly shorter PFS after abiraterone than patients with negative TTs (P = 0.009). Nearly 60% of Chinese patients with mCRPC who had a poor prognosis on abiraterone were candidates for precision treatments based on the specific criteria of TTs.
PROfound、IPATential150 和 TheraP 试验的成功推动了转移性去势抵抗性前列腺癌（mCRPC）从序贯治疗向治疗靶点（TTs）指导的精准治疗的转变。本研究的目的是评估这三项试验中 TTs 的流行率和预后价值。所有纳入的中国 mCRPC 患者均接受了循环肿瘤 DNA（ctDNA）测序、PTEN 状态评估以及双示踪剂[Ga-前列腺特异性膜抗原（PSMA）和 F-氟脱氧葡萄糖（FDG）]正电子发射断层扫描/计算机断层扫描（PET/CT）。先前接受卡巴他赛、Lu-PSMA 或奥拉帕利治疗的患者不允许入组。已知有明显的肉瘤样、梭形细胞或神经内分泌小细胞成分的患者也被排除在外。TTs 的定义如下：（a）双示踪剂 PET/CT 扫描显示高 PSMA 且无 PSMA-/FDG+疾病；（b）ctDNA 中存在同源重组修复（HRR）基因缺陷；（c）肿瘤组织中缺乏 PTEN 免疫组化染色。评估 TTs 在无进展生存期（PFS）上的流行率和预后价值。共纳入 106 例连续 mCRPC 患者。阳性 PET/CT、HRR 缺陷和 PTEN 缺失的患病率分别为 30%、29%和 16%。63 例患者至少有一个 TT。多变量分析显示，转移体积（比值比=5.0；P=0.017）是唯一独立的阳性 TT 因素。74 例患者在 TT 筛查后接受了阿比特龙治疗。阳性 PET/CT（P=0.011）和 HRR 缺陷（P=0.002）的患者接受阿比特龙治疗后的 PFS 明显短于 TT 阴性患者。然而，PTEN 状态与 PFS 无关，这可能是由于 PTEN 缺失的患者较少（P=0.952）。总体而言，任何阳性 TT 的患者接受阿比特龙治疗后的 PFS 明显短于 TT 阴性患者（P=0.009）。在中国 mCRPC 患者中，近 60%的阿比特龙预后不良的患者符合 TTs 特定标准，可作为精准治疗的候选者。
