目的:评估高危非转移性前列腺癌(PCa)患者对新辅助化学激素治疗(NCHT)的肿瘤治疗反应的最佳工具仍不确定。我们比较了[68Ga]标记的前列腺特异性膜抗原(PSMA)-11正电子发射断层扫描/计算机断层扫描([68Ga]Ga-PSMA-11PET/CT)的作用,多参数磁共振成像(MPMRI),和前列腺特异性抗原(PSA),并评估了最近的欧洲泌尿外科协会和欧洲核医学协会(EAU/EANM)推荐的PSMAPET/CT标准的实用价值,以评估高风险非转移性PCa患者对NCHT的治疗反应。
方法:这项前瞻性研究包括2021年6月至2022年3月72例接受NCHT并接受根治性前列腺切除术的高危非转移性PCa患者。PSA测试,[68Ga]Ga-PSMA-11PET/CT,所有患者在NCHT前后均进行了mpMRI扫描。用PSA评估对NCHT的治疗反应,RECIST1.1、PERCIST1.0和EAU/EANM推荐标准。术后病理结果为参考标准。有利的病理反应定义为病理完全缓解(pCR)或微小残留病(MRD)。通过灵敏度评估诊断准确性,特异性,正似然比(PLR),负似然比(NLR),阳性预测值(PPV),负预测值(NPV),和科恩的卡帕指数。使用逻辑回归分析来确定[68Ga]Ga-PSMA-11PET/CT衍生参数的独立预测值。
结果:所有病例在NCHT后PSA水平均显著下降。二十四例(33.33%)病例出现良好的病理反应,其中pCR5例(6.94%),MRD19例(26.39%)。根据[68Ga]Ga-PSMA-11PET/CT的结果,EAU/EANM推荐标准显示20例(27.78%)病例有CR,而PERCIST1.0标准显示23例(31.94%)有CR。EAU/EANM推荐标准和PERCIST1.0标准之间有很强的相关性(Pearson'sR=0.857)。灵敏度(75.00%,79.17%与58.33%,58.33%),特异性(95.83%,91.67%与83.33%,68.75%),PLR(18.00,9.50vs.3.50,1.87),NLR(0.26,0.23vs.0.50,0.61),PPV(90.0%,82.6%vs.63.6%,48.3%),和净现值(88.5%,89.8%与80.0%,76.7%)的[68Ga]Ga-PSMA-11PET/CT(包括EAU/EANM推荐标准和PERCIST1.0标准)预测有利的病理反应均优于mpMRI和最低点PSA。PSA预测有利病理反应的κ指数为0.257,RECIST1.1为0.426,PERCIST1.0为0.716,EAU/EANM推荐标准为0.739。多因素分析显示,根治性前列腺切除术前NCHT后最大标准化摄取值(SUVmax)是对NCHT有利病理反应的独立预测因子。
结论:[68Ga]Ga-PSMA-11PET/CT与最低PSA和mpMRI相比,对NCHT的病理反应更好。当[68Ga]Ga-PSMA-11PET/CT用作治疗反应评估工具时,EAU/EANM推荐的标准和PERCIST1.0标准同等地进行以鉴定病理反应者。
The optimal tool to evaluate the tumour therapeutic responses to neoadjuvant chemohormonal therapy (NCHT) in patients with high-risk non-metastatic prostate cancer (PCa) remains uncertain. We compared the role of [68Ga]-labeled prostate-specific membrane antigen (PSMA)-11 positron emission tomography/computerized tomography ([68Ga]Ga-PSMA-11 PET/CT), multiparametric MRI (mpMRI), and prostate-specific antigen (PSA) and assessed the practical value of the recent European Association of Urology and European Association of Nuclear Medicine (EAU/EANM) recommended criteria of PSMA PET/CT to evaluate the therapeutic responses to NCHT in patients with high-risk non-metastatic PCa.
This prospective study included 72 high-risk non-metastatic PCa patients receiving NCHT followed by radical prostatectomy from June 2021 to March 2022. PSA testing, [68Ga]Ga-PSMA-11 PET/CT, and mpMRI scanning were conducted in all patients before and after NCHT. Therapeutic responses to NCHT were evaluated with PSA, RECIST 1.1, PERCIST 1.0, and EAU/EANM recommended criteria. Postoperative pathological results were considered the reference standard. A favourable pathological response was defined as pathologic complete remission (pCR) or minimal residual disease (MRD). Diagnostic accuracy was assessed by sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV), negative predictive value (NPV), and Cohen\'s kappa index. Logistic regression analysis was used to determine the independent predictive value of [68Ga]Ga-PSMA-11 PET/CT-derived parameters.
All cases experienced a marked decrease in PSA levels after NCHT. Twenty-four (33.33%) cases experienced a favourable pathological response, including five (6.94%) cases of pCR and 19 (26.39%) cases of MRD. According to the results of [68Ga]Ga-PSMA-11 PET/CT, EAU/EANM recommended criteria indicated that 20 (27.78%) cases had a CR, whereas PERCIST 1.0 criteria indicated that 23 (31.94%) cases had a CR. There was a strong association between EAU/EANM recommended criteria and PERCIST 1.0 criteria (Pearson\'s R=0.857). The sensitivity (75.00%, 79.17% vs. 58.33%, 58.33%), specificity (95.83%, 91.67% vs. 83.33%, 68.75%), PLR (18.00, 9.50 vs. 3.50, 1.87), NLR (0.26, 0.23 vs. 0.50, 0.61), PPV (90.0%, 82.6% vs. 63.6%, 48.3%), and NPV (88.5%, 89.8% vs. 80.0%, 76.7%) of [68Ga]Ga-PSMA-11 PET/CT (including EAU/EANM recommended criteria and PERCIST 1.0 criteria) to predict favourable pathological responses were all superior to those of mpMRI and nadir PSA. The kappa index to predict a favourable pathological response was 0.257 for PSA, 0.426 for RECIST 1.1, 0.716 for PERCIST 1.0, and 0.739 for EAU/EANM recommended criteria. Multivariate logistic analysis revealed that the post-NCHT maximum standardized uptake value (SUVmax) before radical prostatectomy was an independent predictor of a favourable pathological response to NCHT.
[68Ga]Ga-PSMA-11 PET/CT had a better concordance with a favourable pathological response to NCHT compared with nadir PSA and mpMRI. EAU/EANM recommended criteria and PERCIST 1.0 criteria performed equally to identify pathological responders when [68Ga]Ga-PSMA-11 PET/CT was used as a therapeutic response assessment tool.