Pan Jian, Zhu Bin, Wu Junlong, Ni Xudong, Li Xiaomeng, Jin Shengming, Ma Weiwei, Liu Xiaohang, Hu Xiaoxin, Gan Hualei, Wang Hongkai, Wang Beihe, Zhang Qing, Song Shaoli, Liu Chang, Ye Dingwei, Zhu Yao
Department of Urology, Fudan University Shanghai Cancer Center, No. 270 Dong'an Road, Shanghai, 200032, People's Republic of China.
Shanghai Genitourinary Cancer Institute, Shanghai, China.
Eur J Nucl Med Mol Imaging. 2025 Apr 16. doi: 10.1007/s00259-025-07278-z.
The differences in imaging between prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and conventional imaging (CI) significantly impact disease staging, subsequently influencing the scope and clinical efficacy of stereotactic body radiotherapy (SBRT). In this multicenter retrospective study, we aimed to explore the effect of homologous recombination repair (HRR) gene status on the imaging differences between PSMA PET/CT and CI, which may have important implications for treatment selection.
A total of 1214 newly diagnosed hormone-sensitive prostate cancer (HSPC) patients with ≤ 5 CI-defined distant metastatic lesions were included. All patients underwent PSMA PET/CT, CI, and circulating tumor DNA testing for 19 HRR genes. The PSA response was defined as achieving a PSA level of < 0.1 ng/ml after 6 months.
The median PSA level was 22.7 ng/ml. In the comparison of bone metastasis detection rates, the proportion of patients with higher detection rates on PSMA PET/CT than on CI was similar between BRCA mutation carriers and those with other HRR gene mutations (43.6% vs. 39.3%, p = 0.554), yet significantly higher in both groups compared to non-mutation carriers (20.5%, p = 0.00001). Similar results were observed in the analysis of metastasis detection rates for distant lymph nodes and regional lymph nodes. In non-metastatic HSPC patients without PSMA-positive distant disease who accepted radical prostatectomy (RP), patients without HRR gene mutations exhibited a significantly higher PSA response rate compared to HRR gene mutated patients (96.9% vs. 90.2%, p = 0.003).
HRR gene alterations were significantly associated with a higher number of PSMA-positive metastases in newly diagnosed HSPC with ≤ 5 CI-defined distant metastases and worse outcomes in non-metastatic HSPC accepting RP. This finding suggests that HRR gene status should be considered as a potential indicator for recommending PSMA PET/CT in the design of clinical trials involving SBRT and in shaping imaging strategies.
前列腺特异性膜抗原（PSMA）正电子发射断层扫描/计算机断层扫描（PET/CT）与传统成像（CI）在影像学上的差异对疾病分期有显著影响，进而影响立体定向体部放疗（SBRT）的范围和临床疗效。在这项多中心回顾性研究中，我们旨在探讨同源重组修复（HRR）基因状态对PSMA PET/CT与CI之间影像学差异的影响，这可能对治疗选择具有重要意义。
共纳入1214例新诊断的激素敏感性前列腺癌（HSPC）患者，其CI定义的远处转移病灶≤5个。所有患者均接受了PSMA PET/CT、CI检查以及针对19个HRR基因的循环肿瘤DNA检测。PSA反应定义为6个月后PSA水平<0.1 ng/ml。
PSA中位数水平为22.7 ng/ml。在骨转移检出率的比较中，BRCA突变携带者与其他HRR基因突变携带者中，PSMA PET/CT检出率高于CI的患者比例相似（43.6%对39.3%，p = 0.554），但两组与非突变携带者相比均显著更高（20.5%，p = 0.00001）。在远处淋巴结和区域淋巴结转移检出率分析中观察到类似结果。在接受根治性前列腺切除术（RP）的无PSMA阳性远处疾病的非转移性HSPC患者中，无HRR基因突变的患者与HRR基因突变的患者相比，PSA反应率显著更高（96.9%对90.2%，p = 0.003）。
在新诊断的CI定义的远处转移≤5个的HSPC患者中，HRR基因改变与更多的PSMA阳性转移显著相关，并且在接受RP的非转移性HSPC患者中预后更差。这一发现表明，在涉及SBRT的临床试验设计以及制定影像学策略时，HRR基因状态应被视为推荐PSMA PET/CT的潜在指标。
