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Journal of Central South University Medical Sciences logoLink to Journal of Central South University Medical Sciences
. 2023 Dec 28;48(12):1812–1819. [Article in Chinese] doi: 10.11817/j.issn.1672-7347.2023.230268

18F-PSMA-1007 PET/CT联合前列腺特异性抗原衍生指标对灰区前列腺癌的诊断价值

Diagnostic value of 18F-PSMA-1007 PET/CT combined with prostate specific antigen derived indicators in gray area prostate cancer

GUO Sheng 1,2, ZHOU Chuan 2, ZHANG Yunfeng 1, WANG Dong 1, NIU Tao 1, ZHOU Fenghai 3,
Editor: 田 朴
PMCID: PMC10930754  PMID: 38448374

Abstract

Objective

The incidence of prostate cancer is increasing every year, and precision diagnosis and treatment can help reduce unnecessary prostate punctures for prostate cancer patients in the gray area. This study aims to investigate the diagnostic value of 18F-prostate specific membrane antigen (PSMA) imaging combined with prostate specific antigen (PSA)-derived indicators for gray zone prostate cancer.

Methods

A total of 107 patients who underwent 18F-PSMA PET/CT imaging for suspicious prostate cancer with tPSA of 4 to 10 μg/L (PSA gray zone) in a hospital were retrospectively included, and were divided into a prostate cancer group and a non-prostate cancer group based on pathological findings. Patients underwent PSA testing, 18F-PSMA, and abdominal ultrasound, and age, tPSA, fPSA, f/tPSA, prostate volume, PSA density (PSAD), maximum standardized uptake value (SUVmax), and molecular imaging prostate specific membrane antigen (miPSMA) score were compared between the 2 groups. Multivariate logistic regression was used to analyze the influencing factors the diagnosis of gray zone prostate cancer. Receiver operating characteristic (ROC) curves were constructed to evaluate the efficacy of PSAD and SUVmax alone and in combination in diagnosing gray zone prostate cancer.

Results

The volume of the prostate cancer group [42.00(34.00, 58.00) cm3 vs 49.00(41.27, 60.41) cm3] was smaller than that of the non-prostate cancer group (Z=-2.376, P=0.017), and the PSAD [(0.18±0.06) μg/(L·cm3) vs 0.15±0.05 μg/(L·cm3)] and SUVmax [18.63(8.03, 28.57) vs 9.33(5.90, 13.52)] were higher than those in the non-prostate cancer group (both P<0.05). The percentage of miPSMA score ≥2 in the prostate cancer group was higher than that in the non-prostate cancer group (χ 2=40.987, P<0.001). PSAD (OR=22.154, 95% CI 1.430 to 873.751, P=0.042) and SUVmax (OR=1.301, 95% CI 1.034 to 1.678, P=0.009) were independent influential factors for the diagnosis of prostate cancer in the gray zone. The optimal cut-off values of PSAD and SUVmax were 0.22 μg/(L·cm3) and 8.02, respectively, and the AUCs for the diagnosis of prostate cancer in the gray zone alone and in combination were 0.628 (95% CI 0.530 to 0.720, P<0.05) and 0.806 (95% CI 0.718 to 0.876, P<0.05), 0.847 (95% CI 0.765 to 0.910, P<0.05), with sensitivities of 41.03%, 76.92%, and 74.36% and specificities of 79.41%, 89.71%, and 92.65%, respectively.

Conclusion

PSAD and SUVmax are increased in patients with gray zone prostate cancer, and the combination of PSAD and SUVmax is of high value in diagnosing gray zone prostate cancer.

Keywords: prostate cancer, prostate specific antigen density, prostate specific membrane antigen imaging, maximum standardized uptake value


前列腺癌是老年男性最常见的实体器官恶性肿瘤,也是发达国家癌症死亡率的主要原因[1]。目前,总前列腺特异性抗原(total prostate specific antigen,tPSA)水平仍然是临床上前列腺癌主要的筛查方法之一,其诊断前列腺癌的灵敏度较高,但特异度较低。而对于tPSA为4~10 µg/L(PSA灰区)的可疑前列腺癌患者[2],无论是tPSA等前列腺特异性抗原(prostate specific antigen,PSA)相关指标,还是传统影像学检查的诊断效果均不理想。一项包含104例患者的研究[3](前列腺癌68例,良性前列腺增生36例)发现PET/CT诊断前列腺癌的敏感性明显优于传统影像学检查。PET/CT技术融合PET功能代谢图像和CT解剖图像的独特优势[4],让临床一线工作者在了解细胞代谢信息的同时也能获得精准的解剖定位,使得这种诊断方法成为前列腺癌检测的重要工具。前列腺特异性抗原密度(prostate specific antigen density,PSAD)可以提高PSA对前列腺癌的诊断效能。本研究旨在探讨18F-前列腺特异性膜抗原(prostate specific membrane antigen,PSMA)显像联合PSA衍生指标PSAD和最大标准摄取值(maximum standardized uptake value,SUVmax)在灰区前列腺癌(tPSA 4~10 μg/L)筛查中的诊断价值,以期为早期诊断前列腺癌提供参考依据,同时减少患者不必要的穿刺。

1. 对象与方法

1.1. 对象

回顾性收集2020年1月至2022年12月在甘肃省人民医院就诊且怀疑为前列腺癌的患者共151例,年龄(69.05±7.82)岁,tPSA值为4.13~10.00 μg/L,平均7.38 μg/mL,中位值为7.75 μg/L。根据病理学检查结果将患者分为前列腺癌组和非前列腺癌组。所有患者入院后均完成18F-PSMA-1007 PET/CT显像。纳入标准:1)tPSA值为4~10 μg/L;2)所有患者均于穿刺前或术前行18F-PSMA-1007 PET/CT检查且图像资料清晰;3)PSA检测前无直肠指检、留置导尿、手术、服用药物等前列腺治疗史;4)腹部超声或泌尿系超声资料完整;5)病理结果完整。排除标准:1)图像资料不完整影响感兴趣区(region of interest,ROI)勾画;2)合并其他肿瘤;3)接受过内分泌治疗。本研究已通过甘肃省人民医院伦理委员会批准(审批号:2021-260),所有患者检查前均签署知情同意书。

1.2. 仪器与方法

1.2.1. tPSA的检测和PSAD的计算

患者于入院当日清晨进行tPSA和fPSA的检测,并计算f/tPSA。PASD根据PSAD=tPSA/前列腺体积(prostate volume,PV)进行计算。超声检查在横断面测量前列腺最大左右径,在矢状面测量最大前后径和上下径。PV=前列腺前后径×左右径×上下径×0.52。

1.2.2. 18F-PSMA-1007PET/CT显像参数

PET/CT显像均采用美国GE公司的Discovery STE PET/CT扫描仪,18F-PSMA-1007由美国GE公司的MINItrace回旋加速器及陕西正泽公司的18F放射性药物多功能合成模块制备。通过肘静脉注射已经制备好的纯度大于98%的18F-PSMA-1007药物(无需空腹),剂量为3.7 MBq/kg。注射完成后,嘱咐患者休息、多饮水、多排尿。在120 min后,进行PET/CT检查,扫描范围从颅底到股骨中部。CT扫描参数设置为:电压120 kV,电流110 mA,球管单圈旋转时间为0.5 s,扫描厚度为5 mm。PET扫描2~5 min,共采集6至7个床位。根据CT图像对PET图像进行衰减校正,得到冠状、矢状、轴位及最大密度投影(maximum intensity projection,MIP)图像。

1.3. 图像分析

由2名经验丰富的核医学科医师进行盲法分析PET/CT成像结果,并达成一致的诊断意见。采用三维勾画法在PET/CT融合图像上勾画前列腺病灶的ROI,手动排除周围非癌组织和器官(如膀胱和直肠)。系统自动计算出前列腺病灶的SUVmax。根据Eiber等[5]提出的PROMISE标准的方法来勾画病灶,该标准提出参考血池、脾和腮腺的平均摄取程度(SUVmean)为基准,与前列腺病变作比较,即在轴位图像上,将直径为3 cm的圆形ROI置于正常脾中心测量脾;将直径2 cm的圆形ROI置于主动脉弓中心测量血池;将直径1.5 cm的圆形ROI置于腮腺右侧中心测量腮腺;将直径1.0 cm的圆形ROI置于前列腺摄取最高处的中心测量前列腺病灶。根据分子成像前列腺特异性膜抗原(molecular imaging prostate specific membrane antigen,miPSMA)评分标准对病灶部位的PSMA PET摄取进行量化,miPSMA评分标准如下:腮腺以上得分为3,脾与腮腺之间得分为2,血池与脾之间得分为1,血池以下得分为0。miPSMA评分≥2时诊断为前列腺癌,miPSMA评分≤1时诊断为良性前列腺病变。

以病理诊断为金标准,计算miPSMA评分诊断前列腺癌的灵敏度、特异性、阳性预测值、阴性预测值及准确性。构建受试者操作特征(receiver operating characteristic,ROC)曲线,评估PSAD、SUVmax单独及联合诊断灰区前列腺癌的效能。

1.4. 统计学处理

采用SPSS 26.0统计分析软件及MedCalc 20.0软件进行数据分析。符合正态分布的计量资料以均数±标准差( x¯ ±s)表示,组间比较采用独立样本t检验;不符合正态分布的计量资料以中位数(第1四分位数,第3四分位数)[M(P 25, P 75)]表示,组间比较采用非参数秩和检验。采用单因素及多因素logistic回归分析诊断灰区前列腺癌的影响因素。检验水准α=0.05,P<0.05为差异有统计学意义。

2. 结 果

2.1. 一般资料

最终纳入107例患者。病理结果显示39例为前列腺腺泡癌(前列腺癌组),其余68例为良性病变(非前列腺癌组),包括前列腺增生伴炎症4例、前列腺增生改变64例。

2.2. PET/CT显像

107例患者中,40例患者miPSMA评分≥2(3分者26例,2分者14例),诊断为前列腺癌,典型影像学表现见图1;67例miPSMA评分≤1(1分者52例,0分者15例),诊断为良性前列腺病变。前列腺病灶SUVmax值为3.23~58.23,平均值为13.60,中位数为9.34。最终以前列腺穿刺活检或术后病理为金标准,通过miPSMA评分诊断前列腺癌的灵敏度、特异性、准确性、阳性预测值、阴性预测值分别为76.92%(30/39)、85.29%(58/68)、82.24%(88/107)、75.00%(30/40)、86.56%(58/67)(表1)。

图1.

图1

168岁男性前列腺腺泡癌患者的 18F-PSMA-1007 PET/CT表现

Figure 1 18F-PSMA-1007 PET/CT findings in a patient with prostate acinic carcinoma (male, 68 years old)

A: PET/CT fusion image; B: PET image; C: CT image; D: MIP image. PSMA: Prostate specific membrane antigen; MIP: Maximum intensity projection.

表1.

miPSMA评分标准对前列腺癌的诊断效能

Table 1 Diagnostic efficacy of miPSMA scoring criteria for prostate cancer

miPSMA 病理结果/例 合计/例
+ -
合计 39 68 107
+ 30 10 40
- 9 58 67

miPSMA:分子成像前列腺特异性膜抗原。

2.3. 2组年龄、tPSAfPSA等指标的比较

前列腺癌组的PV低于非前列腺癌组,PSAD、SUVmax、miPSMA评分均高于非前列腺癌组(均P<0.05),年龄、tPSA、fPSA、f/tPSA与非前列腺癌组的差异均无统计学意义(均P>0.05,表2)。

表2.

2组年龄、tPSAfPSAf/tPSA等的比较

Table 2 Comparison of age, tPSA, fPSA, and f/tPSA between the 2 groups

组别 n 年龄/岁* tPSA/(µg·L-1)† fPSA/(µg·L-1)* f/tPSA*
前列腺癌组 39 71.00(66.00, 76.00) 7.45±1.45 1.39(1.17, 2.01) 0.15(0.11, 0.22)
非前列腺癌组 68 68.50(61.52, 73.00) 7.45±1.75 1.46(1.00, 1.97) 0.19(0.13, 0.24)
Z/t/χ 2 -1.856 0.001 -0.262 -1.468
P 0.063 0.999 0.793 0.142
组别 PV/cm3* PSAD/(µg·L-1·cm-3)† SUVmax* miPSMA评分
≥2 <2
前列腺癌组 42.00(34.00, 58.00) 0.18±0.06 18.63(8.03, 28.57) 30 9
非前列腺癌组 49.00(41.27, 60.41) 0.15±0.05 9.33(5.90, 13.52) 10 58
Z/t/χ2 -2.376 -2.434 -3.039 40.987
P 0.017 0.018 0.002 0.000

*数据以中位数(第1四分位数,第3四分位数)表示;†数据以均数±标准差表示。tPSA:总前列腺特异性抗原;fPSA:游离前列腺特异性抗原;PV:前列腺体积;PSAD:前列腺特异性抗原密度;SUVmax:最大标准化摄取值;miPSMA:分子成像前列腺特异性膜抗原。

2.4. 诊断灰区前列腺癌影响因素的单因素及多因素logistic回归分析

以前列腺疾病患者的病理诊断结果是否为前列腺癌为因变量,年龄、tPSA、fPSA、f/tPSA、PV、PSAD、SUVmax及miPSMA评分作为自变量进行单因素及多因素logistic回归分析。单因素结果显示PV、PSAD、SUVmax、miPSMA评分是诊断灰区前列腺癌的影响因素(均P<0.05,表3)。将单因素分析中有统计学意义的影响因素(由于PSAD与PV有直接关系,为避免影响因素重复将PV剔除)作为自变量进行多因素logistic回归分析,结果显示PSAD(OR=22.154,95% CI 1.430~873.751,P=0.042)和SUVmax(OR=1.301,95% CI 1.034~1.678,P=0.009)是诊断灰区前列腺癌的独立影响因素(表4)。

表3.

诊断灰区前列腺癌影响因素的单因素logistic回归分析

Table 3 Univariate logistic regression analysis of influencing factors of prostate cancer in gray-zone PSA

变量 β SE OR(95% CI) P
年龄 0.044 0.025 1.045(0.995~1.097) 0.079
tPSA 0.001 0.123 1.000(0.786~1.273) 0.999
fPSA -0.054 0.314 0.947(0.512~1.753) 0.863
f/tPSA -4.404 2.696 0.012(0.000~2.413) 0.102
PV -0.030 0.015 0.971(0.943~1.000) 0.047
PSAD 3.601 1.524 36.644(1.850~725.976) 0.018
SUVmax 0.366 0.069 1.442(1.260~1.650) <0.001
miPSMA评分 2.962 0.512 19.333(7.094~52.692) <0.001

tPSA:总前列腺特异性抗原;fPSA:游离前列腺特异性抗原;f/tPSA:游离前列腺特异性抗原与总前列腺特异性抗原的比值;PV:前列腺体积;PSAD:前列腺特异性抗原密度;SUVmax:最大标准化摄取值;miPSMA:分子成像前列腺特异性膜抗原。

表4.

诊断灰区前列腺癌影响因素的多因素logistic回归分析

Table 4 Multivariate logistic regression analysis of influencing factors of prostate cancer in gray-zone PSA

变量 β SE OR(95% CI) P
PSAD 2.985 1.876 22.154(1.430~873.751) 0.042
SUVmax 0.304 0.101 1.301(1.034~1.678) 0.009
miPSMA评分 1.123 1.653 2.543(4.292~32.271) 0.341

PSAD:前列腺特异性抗原密度;SUVmax:最大标准化摄取值;miPSMA:分子成像前列腺特异性膜抗原。

2.5. PSADSUVmax单独及联合诊断灰区前列腺癌的效能

PSAD、SUVmax分别以0.22 μg/(L·cm3)、8.02为最佳截断值,单独及联合诊断灰区前列腺癌的AUC分别为0.628(95% CI 0.530~0.720,P<0.05)、0.806(95% CI 0.718~0.876,P<0.05)、0.847(95% CI 0.765~0.910,P<0.05),灵敏度分别为41.03%、76.92%、74.36%,特异度分别为79.41%、89.71%、92.65%(图2)。

图2.

图2

PSADSUVmax单独及联合诊断灰区前列腺癌的ROC曲线图

Figure 2 ROC curve of PSAD and SUVmax alone and combined in diagnosis of grey area prostate cancer

PSAD: Prostate specific antigen density; SUVmax: Maximum standardized uptake value; ROC: Receiver operating characteristic.

3. 讨 论

tPSA作为临床上筛查前列腺癌的主要指标,其参考值范围为0~4 μg/L。随着PSA水平的升高,患前列腺癌的可能性也增加[6]。然而,tPSA水平的升高不仅仅由单一因素引起,可能受良性前列腺增生、炎症、直肠指检或留置导尿管等潜在因素的影响。因此,tPSA对前列腺癌的诊断作用有一定局限性。研究[7]表明:tPSA在前列腺癌筛查中具有较高的敏感度,但特异度较低,尤其在良性前列腺增生患者中表现更为明显。当tPSA>10 μg/L时,指南建议直接进行前列腺穿刺活检;而当tPSA值处于4~10 μg/L之间时,则需要结合其他检查结果来判断患者是否需要进行穿刺活检[8]。这可能导致不必要的前列腺穿刺活检。因此,有必要探索PSA衍生指标与其他检查结果的结合以提高灰区前列腺癌的诊断敏感度和特异度。

PSAD是通过计算tPSA与前列腺体积的比值得出的指标,可减少前列腺体积对血清PSA的影响,被认为是灰区前列腺癌的理想诊断指标[9]。PSAD值越大,患前列腺癌的风险越高。一项临床荟萃分析[10]发现,PSAD用于诊断灰区前列腺癌的曲线下面积为0.78,敏感度为79%,特异度为57%。而王晓明等[11]的结果显示,PSAD用于诊断灰区前列腺癌的曲线下面积为0.749,敏感度为64.60%,特异度为72.80%。本研究结果显示:前列腺癌组的前列腺体积小于非前列腺癌组,而PSAD值则高于非前列腺癌组。多因素logistic回归分析显示PSAD是诊断灰区前列腺癌的独立影响因素。PSAD用于诊断灰区前列腺癌的曲线下面积为0.628,敏感度为41.03%,特异度为79.41%。这表明PSAD在诊断灰区前列腺癌方面具有较高的价值。与仅使用tPSA作为穿刺活检指征相比,PSAD可以减少不必要的前列腺穿刺活检。

PSMA在前列腺癌细胞膜上高表达,与正常前列腺组织相比,前列腺癌的PSMA表达上升100~1 000倍[12],PSMA PET/CT对于前列腺癌的诊断具有较高的灵敏度和特异度。李曾等[13]探索18F-PSMA-1007 PET/CT显像在初诊前列腺癌精确评估中的应用,结果显示其灵敏度、阳性预测值和准确率均为100%。然而,在临床实践中,前列腺增生也可能导致PSMA变化,因此有时很难区分前列腺癌与前列腺增生,因此需要一种更准确的诊断方法。目前的PSMA PET显像研究采用视觉分析和半定量分析(如勾画ROI计算SUVmax等)来区分诊断前列腺癌,但由于PSMA PET示踪剂的种类较多(主要是68Ga和18F),导致各研究结果存在一定差异,其参考价值相对较小。因此,需要一种更准确的方法来区分诊断前列腺癌。miPSMA评分可能解决这个问题[5]。通过对miPSMA评分法进行分析,本研究探讨其对前列腺癌的诊断效能。楼云龙等[14]对103例可疑前列腺癌的患者进行18F-PSMA-1007 PET/CT显像,应用miPSMA评分诊断前列腺癌的灵敏度、特异度、准确度、阳性预测值和阴性预测值分别为70.2%、89.1%、88.9%、70.7%和78.6%。本研究应用miPSMA评分诊断前列腺癌的灵敏度、特异度、阳性预测值、阴性预测值和准确度分别为76.92%、85.29%、82.24%、75.00%和86.56%,表明miPSMA评分对于灰区前列腺癌具有较高的诊断价值。本研究的多因素logistic回归分析结果表明miPSMA评分不是灰区前列腺癌的独立影响因素,可能与本研究纳入的样本少有关。研究[15]表明,在PET/CT显像中,前列腺增生常呈弥漫性或轻度摄取,而前列腺癌则常呈局灶性放射性摄取,以SUVmax=7.95作为阈值鉴别两者的灵敏度和特异度分别为85.0%和84.6%。王卓楠等[16]的初步研究显示,18F-PSMA-1007 PET/CT的半定量参数SUVmax对于前列腺病变的良恶性鉴别具有较高的价值,以SUVmax=8.85作为截断值时,灵敏度和特异度分别为69.77%和91.43%。本研究得出鉴别良恶性前列腺疾病的最佳SUVmax阈值为8.02(灵敏度76.92%、特异度89.71%、AUC为0.806)。与之前的研究[16]相比,以SUVmax=8.02作为截断值时,可以获得较为理想的诊断效能。

近年来,越来越多的学者倾向于联合模型的构建,例如MRI联合前列腺特异性抗原衍生指标构建联合模型,其在前列腺癌诊断、分级等方面优于单一预测模型[17-19]。国内外PET/CT研究多数为不同显像剂[20]或与MRI[21]在前列腺癌诊断效能的比较。本研究初步构建了SUVmax多参数灰区前列腺癌风险预测模型。经多因素logistic回归分析显示SUVmax和PSAD是灰区前列腺癌的独立预测因素。所建立的预测模型的ROC曲线下面积为0.847,诊断敏感性为74.36%,特异性为92.65%。相比于单独使用PSAD和SUVmax进行诊断,二者联合诊断灰区前列腺癌的价值更高。

本研究存在一些不足之处:数据仅来自单个中心的回顾性临床研究,样本量较小,因此不能推广应用。未来的研究需要进行多中心和大样本的前瞻性研究,以进一步证明PSAD和SUVmax联合诊断在临床实践中的实用价值。

综上,本研究结果提示灰区前列腺癌患者PSAD、SUVmax增高,PSAD和SUVmax联合诊断对于灰区前列腺癌有较高的诊断价值。

基金资助

甘肃省重点研发计划(21YF5FA016);甘肃省自然科学基金(22JR5RA650)。

This work was supported by the Key Research and Development Project in Gansu Province (21YF5FA016) and the Natural Science Foundation of Gansu Province (22JR5RA650), China.

利益冲突声明

作者声称无任何利益冲突。

作者贡献

郭盛 研究设计,数据分析,论文撰写与修改;张云峰、王东、牛涛 数据采集;周川 论文指导及修改;周逢海 论文指导。所有作者阅读并同意最终的文本。

Footnotes

http://dx.chinadoi.cn/10.11817/j.issn.1672-7347.2023.230268

原文网址

http://xbyxb.csu.edu.cn/xbwk/fileup/PDF/2023121812.pdf

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