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临床研究
BP-MRI联合临床预测指标对前列腺癌的诊断价值
黄丹丹 冯倩茹 李增华 夏春华

Cite this article as: HUANG D D, FENG Q R, LI Z H, et al. Diagnosis value of BP-MRI combined clinical predictors for prostate cancer[J]. Chin J Magn Reson Imaging, 2023, 14(10): 90-97.本文引用格式:黄丹丹, 冯倩茹, 李增华, 等. BP-MRI联合临床预测指标对前列腺癌的诊断价值[J]. 磁共振成像, 2023, 14(10): 90-97. DOI:10.12015/issn.1674-8034.2023.10.016.


[摘要] 目的 基于前列腺影像报告和数据系统2.1版(Prostate Imaging Reporting and Data System version 2.1, PI-RADS v2.1)分析双参数磁共振成像(biparametric magnetic resonance imaging, BP-MRI)及其联合临床预测指标对前列腺癌(prostate cancer, PCa)的诊断价值。材料与方法 本研究回顾性分析2020年1月至2022年5月我院171例在进行系统活检前接受多参数磁共振成像(multiparametric MRI, MP-MRI)检查的临床可疑PCa患者病例资料。由两名经验丰富的放射科医师以PI-RADS v2.1评分系统对所有病灶的MR图像进行BP-MRI及MP-MRI评分,并将病灶分为全部病灶组、病灶位于周围带(peripheral zone, PZ)组和病灶位于移行带(transition zone, TZ)组。对PCa组及非前列腺癌(non prostate cancer, No PCa)组的BP-MRI、MP-MRI及各临床预测指标进行单因素分析及多因素分析,确立独立预测因素,并通过受试者工作特性(receiver operating characteristic, ROC)曲线分析两种评分及BP-MRI联合独立预测因素方案的诊断性能。结果 在全部病灶组(PZ+TZ)中,BP-MRI、MP-MRI、年龄、前列腺特异性抗原密度(prostate specific antigen density, PSAD)及游离/总前列腺特异性抗原(free/total prostate specific antigen, f/tPSA)是PCa的独立预测因素,BP-MRI与MP-MRI之间诊断效能差异无统计学意义[ROC曲线下面积(area under the curve, AUC)为0.888、0.886, P>0.05]。联合模型、BP-MRI+f/tPSA、BP-MRI+PSAD的(AUC=0.937, 0.924, 0.915)诊断效能均高于MP-MRI(AUC=0.886),差异具有统计学意义(P<0.05),三者间差异无统计学意义(P>0.05);临床独立预测因素中PSAD诊断效能最高(AUC=0.837);相较于单独应用,各临床独立预测指标联合BP-MRI后诊断准确性明显提升,差异具有统计学意义(P<0.05),而相较于年龄或f/tPSA,BP-MRI联合PSAD的综合临床诊断价值更高;在PZ或TZ组中,BP-MRI(AUC=0.821, 0.908)、MP-MRI(AUC=0.817, 0.908)是PCa的独立预测因素,两者AUC值差异无统计学意义(P>0.05)。结论 BP-MRI与MP-MRI对PCa的诊断效能相当,BP-MRI联合PSAD可提高诊断效能,避免临床不必要活检。
[Abstract] Objective The aim of this study was to assess diagnostic efficacy of biparametric magnetic resonance imaging (BP-MRI) and BP-MRI combined with clinical predictors vs. multiparametric MRI (MP-MRI) for prostate cancer (PCa) based on the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1).Materials and Methods This study retrospectively analyzed 171 patients with clinically suspected PCa who underwent MP-MRI examination before systematic biopsy in our hospital from January 2020 to May 2022. The prostate MR images of all lesions were scored by the two schemes of MP-MRI and BP-MRI based on PI-RADS v2.1. Combined with the results of pathology, the lesions were divided into three groups: all lesions group, lesions located in peripheral zone (PZ) group and lesions located in transition zone (TZ) group. BP-MRI, MP-MRI and clinical predictors were analyzed by univariate and multivariate analysis, and the independent predictors were established. The diagnostic performance of the two schemes and BP-MRI combined with independent predictors was analyzed by the receiver operating characteristic (ROC) curve.Results For all of the lesions (PZ+TZ), the BP-MRI, MP-MRI, age, PSAD, and f/tPSA were the independent predictors of PCa, there was no statistical difference in the diagnostic efficacy between BP-MRI and MP-MRI [area under the curve (AUC): 0.888, 0.886; P>0.05]. Combined model and the combination of BP-MRI and f/tPSA or PSAD (AUC=0.937, 0.924, 0.915) had higher diagnostic efficience than MP-MRI (AUC=0.886). The difference between the AUC value of these combined models and MP-MRI was statistically significant (P<0.05); PSAD had a larger AUC than the other predictors alone (AUC=0.837), the AUC for the combination of BP-MRI and independent predictors is significantly superior to using BP-MRI score and independent predictors alone (P<0.05), and compared with the age or f/tPSA index, combining BP-MRI and PSAD had a higher clinical diagnostic efficacy. For lesions in the PZ or TZ, the two schemes of MP-MRI and BP-MRI were the independent predictors, there was no statistical difference in the diagnostic efficacy between BP-MRI (AUC=0.821, 0.908; P>0.05) and MP-MRI (AUC=0.817, 0.908; P>0.05).Conclusions BP-MRI has equivalent diagnostic efficacy for PCa to MP-MRI, combining BP-MRI with f/tPSA or PSAD can improve diagnostic efficacy and avoid clinically unnecessary biopsies.
[关键词] 前列腺癌;前列腺特异性抗原;前列腺癌成像报告和数据系统;双参数磁共振成像;多参数磁共振成像;诊断
[Keywords] prostate cancer;prostate specific antigen, Prostate Imaging Reporting and Data System;biparametric magnetic resonance imaging;multiparametric magnetic resonance imaging;diagnostic

黄丹丹    冯倩茹    李增华    夏春华 *  

合肥市第一人民医院南区(合肥市滨湖医院)放射科,合肥 230000

通信作者:夏春华,E-mail:xiachunhua3775@sina.com

作者贡献声明:夏春华参与设计本研究的方案,对稿件重要内容进行了修改,获得了安徽省卫生健康委科研项目基金项目、合肥市第六周期医学重点学科建设项目(磁共振成像诊断)资助;黄丹丹起草和撰写稿件,获取、分析或解释本研究的数据;冯倩茹、李增华获取、分析或解释本研究的数据,对稿件重要内容进行了修改;全体作者都同意发表最后的修改稿,同意对本研究的所有方面负责,确保本研究的准确性和诚信。


基金项目: 安徽省卫生健康委科研项目 AHWJ2021b141 合肥市第六周期医学重点学科建设项目(磁共振成像诊断) 合卫医秘〔2022〕157号
收稿日期:2022-08-30
接受日期:2023-10-09
中图分类号:R445.2  R737.25 
文献标识码:A
DOI: 10.12015/issn.1674-8034.2023.10.016
本文引用格式:黄丹丹, 冯倩茹, 李增华, 等. BP-MRI联合临床预测指标对前列腺癌的诊断价值[J]. 磁共振成像, 2023, 14(10): 90-97. DOI:10.12015/issn.1674-8034.2023.10.016.

0 前言

       在世界超过一半的国家中,前列腺癌(prostate cancer, PCa)是老年男性生殖系统最常见的恶性肿瘤[1]。据美国癌症协会估计,2022年其发病率居首位,死亡率仅次于支气管肺癌[2]。由于血清前列腺特异性抗原(prostate specific antigen, PSA)具有较高的诊断敏感度和较低的检测成本,广泛应用于PCa的筛查。然而,临床经验表明,PSA对PCa的诊断特异度不高。经直肠超声(transrectal ultrasound, TRUS)引导下前列腺系统活检(systematic biopsy, SB)目前被国际指南推荐为检测临床可疑PCa的金标准[3],但存在血尿和尿路感染等不良反应。仅通过PSA筛查及SB检测临床可疑癌经常导致对良性病变或临床非显著性PCa(clinically insignificant PCa, CiPCa)的过度诊疗以及对临床显著性PCa(clinically significant PCa, CsPCa)的漏诊[4, 5, 6]

       PCa诊疗中的一个持续挑战是早期准确诊断,以降低侵袭性PCa的死亡率,同时最大限度地减少误诊,免除不必要的治疗与活检。与未经MRI检查的系统活检相比,基于MRI检查的诊断途径已经被证实PCa检出率更高,从而避免不必要的活检,已经在临床上广泛应用。目前临床上无创性评估PCa应用最广泛的是前列腺癌成像报告和数据系统(Prostate Imaging Reporting and Data System, PI-RADS)。2019年PI-RADS v2.1版本[7]发布,PI-RADS v2.1指南推荐的多参数MRI(multiparametric MRI, MP-MRI)方案,包括动态对比增强MRI(dynamic contrast enhanced MRI, DCE-MRI)、扩散加权成像(diffussion-weighted imaing, DWI)以及T2WI,研究证实了其对PCa的诊断效能[8, 9],但MP-MRI作为筛查工具存在成像时间长、检查成本高及对比剂过敏风险等缺陷[10, 11],另外,DCE-MRI在PCa诊断中的价值仍存在争议[12, 13]。因此,无须DCE-MRI的简化双参数MRI(biparametric MRI, BP-MRI)成为近年研究热点。

       已有相关研究[14, 15]表明,PI-RADS对PCa具有良好的检出率且具有可重复性,能够做到长期随访。在BP-MRI对PCa诊断效能方面,目前国内相关研究[16, 17]探讨了BP-MRI及其联合部分临床预测指标对CsPCa的临床诊断价值,研究样本局限于CsPCa可能会导致对两种评分方案对PCa的早期临床诊断价值分析出现偏差,且未指出相对于MP-MRI,BP-MRI是否具有临床应用价值。本研究在PI-RADS v2.1框架下,联合BP-MRI与传统临床预测指标,对比并探讨相对传统扫描方案,BP-MRI对PCa的诊断效能及临床应用价值。

1 材料与方法

1.1 研究对象

       本回顾性研究遵循《赫尔辛基宣言》,经合肥市滨湖医院伦理委员会批准,免除受试者知情同意,批准文号:2022-003-01。回顾性分析239例2020年1月至2022年5月在我院行前列腺MP-MRI检查患者的临床病例及影像学资料。纳入标准:(1)出现临床症状,如排尿困难或尿流减弱、中断;PSA升高(>4 ng/mL);经直肠指检或超声检查后临床怀疑PCa需要进行前列腺活检者。(2)所有患者MR检查后1个月内行经会阴超声系统活检,每一针标本均明确标注具体穿刺部位,病理结果明确。排除标准:(1)既往有前列腺内分泌治疗、穿刺活检及经尿道电切等药物或手术治疗史;(2)PSA>100 ng/mL,游离前列腺特异性抗原(free prostate specific antigen,fPSA)>50 ng/mL,或无具体参数值患者;(3)临床或影像资料不全;(4)图像质量差,模糊或存在伪影者,无法确保评分准确性者。

1.2 扫描仪器与检查方法

       使用德国西门子Trio 3.0 T磁共振扫描仪器,体部相控阵线圈作为接收线圈。扫描序列包括:横/矢状位T2WI、横断位DWI(b=50, 1500 s/mm2)、DCE-MRI。DWI序列扫描完成后传输到西门子后处理工作站自动生成表观扩散系数(apparent diffusion coefficient, ADC)图,平扫完成后开始DCE-MRI扫描,自手背静脉注射0.2 mmol/kg对比剂钆喷酸葡胺注射液(Gd-DTPA,GE药业,美国),流率2.0 mL/s,注射完毕以相同的速率用20 mL生理盐水冲洗,注射完成后立即开始持续进行DCE-MRI数据采集,整个DCE-MRI扫描历时约4 min 30 s。研究中包含的序列扫描参数如表1所示。

表1  MR扫描序列参数
Tab.1  MR scan parameters

1.3 图像分析

       由两名受过培训的具有5年及以上经验的中级职称腹部影像诊断医生对病灶进行定位并分为病灶位于周围带(peripheral zone, PZ)组,病灶位于移行带(transition zone, TZ)组;在不知道病理结果及患者PSA水平条件下,以PI-RADS v2.1[7]为标准独立评估每个病灶的BP-MRI及MP-MRI评分(图12),当评分结果不同时协商取得一致。MP-MRI评分方案遵循PI-RADS v2.1评分准则;BP-MRI评分在去除DCE的MP-MRI图像上进行,包含横、矢状位T2WI及横断位DWI图像,在BP-MRI评分中TZ病灶评分准则不变,因为TZ病灶评分仅由T2WI及DWI序列确定,只有当病灶位于PZ且主要序列DWI评分为3时,T2WI≥4代替DCE早期强化阳性决定最终评分,3分升级为4分。BP-MRI具体评分方案见表2

图1  男,86岁,前列腺癌。血清PSA为17.0 ng/mL,f/tPSA为1.56 ng/mL,PSAD为0.09 μg/(L∙mL),BP-MRI及MP-MRI均评分为5分。1A:T2WI显示移行带前缘片状边界不清的中等低信号病灶(箭,蓝色标记),长径>1.5 cm;1B:高b值DWI显示病灶明显高信号(箭,蓝色标记);1C:ADC图病灶明显低信号(箭,蓝色标记);1D:DCE-MRI显示病灶显著强化(箭,蓝色标记);1E、1F:分别为在
Fig. 1  Male, 86 years old, patient with PCa, serum PSA 17.0 ng/mL, f/tPSA 1.56 ng/mL, and PSAD 0.09 μg/(L∙mL), both BP-MRI and MP-MRI scored 5 points. 1A: T2WI shows a homogeneous and moderately hypointense lesion in the anterior part of transition zone (arrow, blue mark) with longest diameter being >1.5 cm; 1B: The lesion is hyperintense on DWI (b=1500 s/mm2) (arrow, blue mark); 1C: The lesion is hypointense on the ADC images (arrow, blue mark); 1D: Positive enhancement is seen on the DCE (arrow, blue mark). 1E, 1F: The maximum transverse diameter, anterior-posterior diameter and maximum superior-inferior diameter of the prostate are measured on the transverse and sagittal T2WI, respectively; 1G: Pathological section (HE ×100) shows the result of prostate system biopsy in 10 o'clock direction is PCa located in transitional zone, and the Gleason score is 4+4. PCa: prostate cancer; PSA: prostate specific antigen; f/tPSA: free/total prostate specific antigen; PSAD: prostate specific antigen density; BP-MRI: biparametric magnetic resonance imaging; MP-MRI: multiparametric magnetic resonance imaging; DWI: diffussion-weighted imaing; ADC: apparent diffusion coefficient; DCE: dynamic contrast enhanced.
图2  男,73岁,前列腺癌。血清PSA为5.76 ng/mL,f/tPSA为0.89 ng/mL,PSAD为0.15 μg/(L∙mL),BP-MRI及MP-MRI均评分为4分。1A:T2WI显示右侧周围带局限性边界不清低信号病灶(箭,蓝色标记),T2WI评分3分;2B:高b值DWI上病灶明显高信号(箭,蓝色标记),长径<1.5 cm;2C:ADC图上病灶明显低信号(箭,蓝色标记),DWI序列评分4分;2D:DCE-MRI病灶明显强化(箭,蓝色标记);2E、2F:分别为在横、矢状位T2WI上测量前列腺最大横径、前后径及最大上下径;
Fig. 2  Male, 73 years old, patient with PCa, serum PSA 5.76 ng/mL, f/tPSA 0.89 ng/mL, PSAD 0.15 μg/(L∙mL), both BP-MRI and MP-MRI scored 4 points. 2A:T2WI shows a homogeneous and moderately hypointense lesion in the right transition zone (arrow, blue mark) with diameter being <1.5 cm; 2B: The lesion is hyperintense on DWI (b=1500 s/mm2) (arrow, blue mark); 2C:The lesion is hypointense on the ADC images (arrow, blue mark); 2D: Positive enhancement is seen on the DCE (arrow, blue mark). 2E, 2F: The maximum transverse diameter, anterior-posterior diameter and maximum superior-inferior diameter of the prostate are measured on the transverse and sagittal T2WI, respectively; 2G: Pathological section (HE ×100) shows the pathological result of prostate system biopsy in 7-8 o'clock direction is PCa located in the peripheral zone, and the Gleason score is 4+4. PCa: prostate cancer; PSA: prostate specific antigen; f/tPSA: free/total prostate specific antigen; PSAD: prostate specific antigen density; BP-MRI: biparametric magnetic resonance imaging; MP-MRI: multiparametric magnetic resonance imaging; DWI: diffussion-weighted imaing; ADC: apparent diffusion coefficient; DCE: dynamic contrast enhanced.
表2  BP-MRI评分方案
Tab.2  The BP-MRI scoring protocol

1.4 数据收集

       收集所有纳入患者入院一周内PSA、fPSA、游离/总前列腺特异性抗原(free/total prostate specific antigen, f/tPSA)以及前列腺体积(prostate volume, PV)、PSAD数据[PSAD=PSA/PV;单位为μg/(L•mL)],其中PV(单位mL)=前列腺最大横径(单位cm)×最大前后径(单位cm)×最大上下径(单位cm)×0.52,由5名具有5年及以上经验的中级职称腹部影像诊断医生经过培训后,按照PI-RADS v2.1指南推荐测量方式在横断位T2WI上测量最大横径及最大前后径,在矢状位T2WI上测量最大上下径(图12),最终结果取平均值。

1.5 穿刺活检

       所有纳入患者均在MRI检查后1个月内,以MRI图像为参照,行经会阴超声引导下前列腺“10+X”系统穿刺活检,对MRI图像上可疑病灶由一名不参与评分的影像科医师确认位置并与超声科穿刺操作医师沟通后行额外“+X针”穿刺,穿刺完成后由超声科操作医师记录穿刺进针深度及位置,由影像科医师在MRI图像上标注每一针穿刺位置,由病理科报告病理结果。

1.6 统计学方法

       使用SPSS 22.0(国际商业机器公司,美国)及MedCalc 18.2.1(MedCalc Software Ltd)、Graphpad Prism 10.0(Graphpad software公司)软件对数据进行统计分析。对符合正态分布的数值变量数据用均数±标准差(x¯±s)表示,PCa与No PCa组间比较采用两独立样本间t检验;不符合正态分布的数值变量数据采用中位数和上下四分位数[M (P25, P75)]表示,组间比较采用Mann-Whitney U检验。应用组内相关系数(intra-class correlation coefficient, ICC)检验评估5名医师间测量PV数据的一致性。将差异有统计学意义(P<0.05)的临床指标纳入多因素logistic回归分析,得出PCa独立预测因素,以穿刺病理结果为金标准绘制受试者工作特征(receiver operating characteristic, ROC)曲线评价两种评分方案及BP-MRI评分方案联合独立预测因素对三组PCa的诊断效能,计算ROC曲线下面积(area under the curve, AUC)值、敏感度、特异度、阳性预测率、阴性预测率及最大约登指数,并对不同方案间诊断效能进行Z检验,分析差异有无统计学意义(P<0.05)。

2 结果

2.1 一般资料

       本研究最终纳入171例患者(171例病灶),58例病灶位于PZ,113例位于TZ。其中PCa 59例(34.5%),28例(47.5%)定位于PZ,31例(52.5%)定位于TZ;良性病变112例(65.5%),其中良性前列腺增生症66例(58.9%),急、慢性前列腺炎46例(41.1%),30例(26.8%)定位于PZ,82例(73.2%)定位于TZ。统计结果显示全部病灶中除fPSA外纳入的临床指标及两种评分差异有统计学意义(P<0.05);病灶位于TZ组,纳入的所有临床指标及两种评分差异均有统计学意义(P<0.05);病灶位于PZ组,年龄、f/tPSA、PSAD、BP-MRI及MP-MRI评分差异具有统计学意义(P<0.05);统计分析结果详见表35

表3  全部病灶组患者临床资料
Tab.3  Clinical data of patients in all the lesion group
表4  移行带病灶组患者临床资料
Tab. 4  Clinical data of patients in the transitional zone lesion group
表5  周围带病灶组患者临床资料
Tab. 5  Clinical data of patients in the peripheral zone lesion group

2.2 不同医师间PV测量结果一致性分析

       因本次使用原始数据,因而使用单一度量标准结果,ICC为0.990,ICC>0.8,表明医师间测量结果一致性好(表6)。

表6  医师间前列腺体积测量结果一致性
Tab. 6  The Consistency of prostate volume measurements between physicians

2.3 MRI评分结果比较

       BP-MRI与MP-MRI两种评分方案的唯一区别在当病灶位于PZ且DWI评分为3分时,BP-MRI评分方案免除DCE-MRI,在病灶T2WI评分≥4时则将评分升级,否则维持不变。结果显示两种评分方案[1~2分82例(48.0%)及5分32例(18.7%)]的例数相同,MP-MRI评分方案结果有24例(14.0%)为3分,33例(19.3%)4分,BP-MRI评分方案结果有27例(15.8%)为3分,30例(17.5%)4分。

       MP-MRI评分结果显示,4例位于PZ DWI评分3分的病例因DCE早期强化阳性,升级为4分,2例最终病理结果为局灶性/弥漫性慢性前列腺炎,BP-MRI评分为(DWI)3分+(T2WI)4分=4分,(DWI)3分+(T2WI)3分=3分;1/4例穿刺结果为良性前列腺增生,BP-MRI评分3分;1/4例穿刺结果为PCa,GS评分3+4,此例BP-MRI评分3分。

2.4 多因素logistic分析结果

       对差异有统计学意义的指标进行多因素分析,结果显示在全部患者中,年龄、PSAD、f/tPSA和BP-MRI、MP-MRI评分是PCa的独立预测因素,BP-MRI和MP-MRI评分是病灶位于PZ组及病灶位于TZ组的独立预测因素。

2.5 诊断效能分析

       BP-MRI和MP-MRI两种评分方案最大约登指数分别为0.678、0.677,对应最佳诊断阈值均为3.5分,因此评分≥4分诊断为PCa阳性。各方案PCa诊断效能的ROC分析结果(图3表7)显示:(1)在全部病例中,相较于独立应用,BP+年龄、BP+PSAD、BP+f/tPSA的诊断准确率明显提高,差异有统计学意义(Z=5.658, P<0.001; Z=2.387, P=0.017; Z=3.826, P<0.001)。联合模型AUC(0.937)>BP-MRI+f/tPSA(0.924)>BP-MRI+PSAD(0.915)>BP-MRI+年龄(0.892)>BP-MRI(0.888)>MP-MRI(0.886),组间比较结果显示BP-MRI与MP-MRI诊断效能相当(图12),差异无统计学意义(P>0.1),而BP-MRI联合独立预测指标对PCa的诊断效能均高于MP-MRI,其中联合模型、BP-MRI+f/tPSA、BP-MRI+PSAD三种方案与MP-MRI间诊断效能差异有统计学意义(Z=2.739, P=0.0062; Z=2.594, P=0.0095; Z=2.568, P=0.0102);联合模型、BP-MRI+f/tPSA、BP-MRI+PSAD较BP-MRI+年龄诊断准确率高,且差异有统计学意义(Z=2.467, P=0.014; Z=1.994, P=0.046; Z=1.944, P=0.045),而前三者组间差异无统计学意义(P>0.05);(2)对于PZ病灶,BP-MRI的AUC值(0.821)>MP-MRI(0.817),差异无统计学意义(P>0.05),MP-MRI较BP-MRI的敏感度及阴性预测率较高(90.0%, 81.3%),但特异度及阳性预测率较低(65.0%, 79.4%);(3)对于TZ病灶,BP-MRI及MP-MRI的诊断效能相同(AUC均为0.908)。

       两种评分分级及与病理结果的差异如图4所示,两种评分方案1~2分及5分结果相同,59例PCa中BP-MRI评分11例假阴性(4例1~2分,7例3分),MP-MRI评分10例假阴性(4例1~2分,6例3分),仅1例位于PZ的病灶因DCE早期强化阳性被MP-MRI单独检出,病理结果为临床低危癌(GS≤3+3);112例良性病变中15例BP-MRI假阳性(11例4分,4例5分),17例MP-MRI假阳性(13例4分,4例5分),3例位于PZ的病灶因DCE强化早期阳性被MP-MRI误诊,病理结果显示10、17例分别为局灶性、多灶性慢性前列腺炎。

图3  ROC曲线。3A:各方案诊断全部病灶组(PZ+TZ)前列腺癌的ROC曲线;3B:年龄、PSAD、f/tPSA诊断全部病灶组(PZ+TZ)前列腺癌的ROC曲线;3C:BP-MRI、MP-MRI诊断病灶位于PZ前列腺癌的ROC曲线;3D、3E:分别为BP-MRI、MP-MRI诊断病灶位于TZ前列腺癌的ROC曲线。ROC:受试者工作特征;PZ:周围带;TZ:移行带;PSAD:前列腺特异性抗原密度;f/tPSA:游离/总前列腺特异性抗原;BP-MRI:双参数磁共振成像;MP-MRI:多参数磁共振成像。
Fig. 3  ROC curves. 3A: ROC curve of all protocols for the diagnosis of prostate cancer in all lesion groups (PZ+TZ); 3B: ROC curve of age、PSAD、f/tPSA for the diagnosis of prostate cancer in all lesion groups (PZ+TZ); 3C: BP-MRI and MP-MRI ROC curves for PZ prostate cancer; 3D, 3E: BP-MRI and MP-MRI ROC curves for TZ prostate cancer. ROC: receiver operating characteristic; PZ: peripheral zone; TZ: transition zone; PSAD: prostate specific antigen density; f/tPSA: free/total prostate specific antigen; BP-MRI: biparametric magnetic resonance imaging; MP-MRI: multiparametric magnetic resonance imaging.
图4  两种评分方案与活检结果的比较,显示了BP-MRI和MP-MRI之间PI-RADS v2.1评分差异以及评分与活检结果之间的关系。BP-MRI:双参数磁共振成像;MP-MRI:多参数磁共振成像;PI-RADS:前列腺影像报告和数据系统;PCa:前列腺癌;No PCa:非前列腺癌。
Fig. 4  Comparison of the two scoring protocols and the results of biopsy. The graph shows changes in the PI-RADS categories between BP-MRI and MP-MRI and the relationship between the PI-RADS categories and biopsy results. BP-MRI: bultiparametric magnetic resonance imaging; MP-MRI: multiparametric magnetic resonance imaging; PI-RADS: Prostate Imaging Reporting and Data System; PCa: prostate cancer; No PCa: non-prostate cancer.
表7  各方案对三组前列腺癌诊断效能对比
Tab. 7  Diagnostic performance of all protocols for prostate cancer

3 讨论

       本研究使用BP-MRI、MP-MRI两种评分方案对入组的病例进行评分,根据评分及穿刺病理结果,首次全面性分析并对比BP-MRI评分方案相对于传统MP-MRI方案对PCa的诊断价值是否相当,评估BP-MRI评分联合各临床独立预测指标对PCa的诊断价值。研究结果表明两种评分方案诊断效能相当,且BP-MRI联合部分临床独立预测指标可明确提高诊断效能。

3.1 全部病灶组中两种评分方案的诊断价值对比及分析

       在全部病灶中,我们的研究结果显示BP-MRI与MP-MRI检测出的PCa数量几乎相同(54例、55例),且BP-MRI和MP-MRI的敏感度及特异度无显著差异(敏感度:81%、83%;特异度:87%、85%)。两者诊断效能差异无统计学意义(P<0.05),这与几项前瞻性临床研究和回顾性荟萃分析报告的结果相似[18, 19, 20, 21]。BASS等[18]对44项研究进行的荟萃分析结果显示,BP-MRI及MP-MRI诊断敏感度分别为84%、89%,特异度分别为79%、74%,Meta回归分析显示这两种方案的诊断价值差异无统计学意义。在ZAWAIDEH等[19]的一项包括264名男性的前瞻性研究中,BP-MRI检出了MP-MRI检测到的117例中的116例癌症,与本研究结果相似。本研究验证了BP-MRI对PCa的检出率良好且具有较高的准确率及特异度,且在不损失诊断准确率的前提下,BP-MRI的社会效益更高[22]

3.2 DCE-MRI序列对PCa诊断价值分析

       根据PI-RADS v2.1指南,DCE序列的缺失可能会使CsPCa的漏诊率增高,有研究发现,DCE可显著提高PZ PCa的检出率[12, 23],ZAWAIDEH等[19]的研究除指出BP-MRI与MP-MRI相当的PCa检出率外,同时表示DCE使MP-MRI具有较高的阴性预测率,是前列腺MRI检查的重要组成部分。本研究中两种方案对PZ病灶的诊断效能差异无统计学意义,DCE阳性在PZ额外检出1例PCa,检出率仅提高1.8%,而3例PZ良性病变被误诊为PCa,误诊率增高18%,导致MP-MRI的假阳性率高而特异度较低(65.0%),这与KUHL等[24]的研究一致,该研究同样指出了相比BP-MRI(33例)、MP-MRI(43例)假阳性率较高。DCE假阳性的原因可能是由于PCa富血供及血管通透性较高的特点[24, 25, 26],相较于正常前列腺组织在DCE上表现为早期明显强化,然而其他良性病变如前列腺炎和良性增生性结节[27]也可以表现出类似现象,本研究中误诊病例穿刺结果显示慢性局限性前列腺炎在误诊病例中占比较高,与此理论相符。同时笔者发现3例位于PZ的假阴性病灶体积较小(长径<10 mm),在其主要判断序列DWI上未见明显异常信号,补充序列DCE早期强化阳性,即DCE可能有助于小病灶的检出。目前,前列腺DCE-MRI诊断价值存在的争议[12, 13, 19, 28, 29],笔者认为可能与检查技术、影像科医生的阅片经验及对评分准则解读的异质性有关,因此对于DCE能否提高对PZ病灶的诊断准确率,以及如何改进检查技术还需进一步的研究。此外已有研究表明高b值(b>1400 s/mm2)DWI可显著提高PCa的检出率,进一步降低DCE的作用[30, 31],因此笔者认为进一步的研究可着重于高b值DWI序列对PCa的诊断效能。对于TZ病变,两种评分准则完全一致,因此诊断效能相同,在本研究结果中,BP-MRI对TZ病变的敏感度(96.4%)较高,特异度较低(71.8%),与一项纳入了5217例患者的大型荟萃分析结果(敏感度、特异度均为80%)存在差异[32],这可能与本研究样本量较小、医师鉴别PCa与良性病变的经验不足有关。

3.3 BP-MRI联合临床独立预测指标对PCa的诊断价值

       PSA及PSA相关临床指标(fPSA、f/tPSA、PSAD)在临床PCa的筛查中存在敏感度高而特异度低的问题,与本研究结果相符,本研究纳入的临床指标中f/tPSA、PSAD及年龄是全部病灶组PCa的独立预测因素,为提高PSAD数值的稳定性,对PV的测量结果进行了ICC检验,结果ICC系数信度良好,因此PV及PSAD的数据稳定性及可重复性较高。ROC曲线显示PSAD诊断效能最高(AUC=0.837),且PSAD敏感度及阴性预测率(98.40%, 95.89%)相较于特异度及阳性预测率(62.80%, 56.12%)更好,f/tPSA及年龄对PCa的诊断效能(AUC=0.783, 0.651)和敏感度(77.6%, 69.0%)均显著低于PSAD(AUC=0.837,特异度=77.0%),这一结果说明f/tPSA及年龄作为PCa的独立危险因素,临床上对PCa的准确检出能力欠佳,若在进行PCa诊断决策时f/tPSA及年龄两种因素的权重过大,将导致对良性病变及临床低危癌的不必要活检或对临床显著癌的漏检,此两种临床指标应只作为参考因素参与决策;而PSAD的诊断效能较突出,是因其表示单位体积前列腺组织内PSA的浓度,这减弱了患者前列腺增生等因素的干扰。相对于各临床指标及MRI检查方案的独立应用,本研究结果显示BP-MRI+PSAD(AUC=0.915)>BP-MRI(AUC=0.888)>PSAD(AUC=0.837)、BP-MRI+f/tPSA(AUC=0.924)>BP-MRI(AUC=0.888)>f/tPSA(AUC=0.783)、BP-MRI+年龄(AUC=0.892)>BP-MRI(AUC=0.888)>年龄(AUC=0.651),另外本研究中各联合方案诊断效能均优于MP-MRI,联合模型和BP-MRI+f/tPSA、BP-MRI+PSAD及MP-MRI间的AUC值差异有统计学意义,其中联合模型的诊断效能最高(AUC值0.937),BP-MRI+PSAD的特异度(87.6%)及阳性预测率较高(77.8%),但三者诊断效能组间差异无统计学意义(P>0.05)。即联合方案可提高BP-MRI方案的诊断效能,并弥补临床指标特异度低的缺陷,而相对于年龄、f/tPSA的不稳定性,选择PSAD与BP-MRI进行联合的临床价值更高。但对病灶位于PZ及TZ组PCa,PSA等临床指标是否为预测因素还需要进一步研究。目前,PSA及其相关临床指标在诊断PCa中的价值存在争议[33, 34],但多数研究结果表明联合PSA相关指标尤其PSAD可提高BP-MRI的诊断效能及诊断准确率[35, 36, 37],本研究证实了BP-MRI联合PSAD的临床应用价值。

3.4 局限性及展望

       本研究的局限性:(1)本研究纳入样本量较小,部分研究结果与国内外其他研究存在一定的差异性,将进一步扩大样本量进行深入研究;(2)没有根据病灶的Gleason评分数据进一步分析两种评分系统及联合方案对CsPCa及CiPCa的诊断效能,已有研究表明PI-RADS评分与PCa病理分级相关[38, 39],进一步研究将针对BP-MRI评分结果与PCa Gleason的相关性进行进一步分析。

4 结论

       综上所述,BP-MRI作为扫描更简便且风险较低的检查方案对PCa的诊断价值与MP-MRI相当,且不受病灶定位影响;而在临床预测因素中,联合PSAD后明确提高了诊断效能,可用于临床可疑PCa的筛查,避免不必要活检。

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