Establishment and prospective validation of an SUV(max) cutoff value to discriminate clinically significant prostate cancer from benign prostate diseases in patients with suspected prostate cancer by (68)Ga-PSMA PET/CT: a real-world study.

Background and Aims: The aims of this study were to establish a maximum standardized uptake value (SUVmax) cutoff to discriminate clinically significant prostate cancer (csPCa) from benign prostate disease (BPD) by 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA-11) positron emission tomography/computed tomography (PET/CT) in patients with suspected prostate cancer (PCa), and to perform a prospective real-world validation of this cutoff value. Methods: The study included a training cohort to identify an SUVmax cutoff value and a prospective real-world cohort to validate it. A retrospective analysis assessed 135 patients with suspected PCa in a large tertiary care hospital in China who underwent 68Ga-PSMA-11 PET/CT. All patients were suspected of having PCa based on symptoms, digital rectal examination (DRE), total prostate-specific antigen (tPSA) level, and multiparameter magnetic resonance imaging (mpMRI). The 68Ga-PSMA PET/CT results were evaluated using histopathological results from transrectal ultrasound-guided 12-core biopsy with necessary targeted biopsy as references. Patients with Gleason scores (GS) ≥7 from the biopsy results were diagnosed with csPCa, and patients with negative biopsy and follow-up results were diagnosed with BPD. Receiver operating characteristic (ROC) curve analysis was used to identify the optimal SUVmax cutoff value. The cutoff value was prospectively validated in 58 patients with suspected PCa. The diagnostic benefits of the cutoff value for clinical decision making were also evaluated. Results: According to ROC curve analysis, the most appropriate SUVmax cutoff value for discriminating csPCa from BPD was 5.30 (sensitivity, 85.85%; specificity, 86.21%; area under the curve [AUC], 0.893). The cutoff achieved a sensitivity of 83.33%, a specificity of 81.25%, a positive predictive value (PPV) of 92.11%, a negative predictive value (NPV) of 65.00%, and an accuracy of 82.76% in the prospective validation cohort. Metastases were used as an indicator to reduce false negative results in patients with SUVmax ≤ 5.30. In patients without metastases, an SUVmax value of 5.30 was also the best cutoff to diagnose localized csPCa (sensitivity, 80.43%; specificity, 86.21%; AUC, 0.852). The cutoff discriminated localized csPCa from BPD with a sensitivity of 76.19%, a specificity of 81.25%, a PPV of 84.21%, an NPV of 72.22%, and an accuracy of 78.38% in the prospective validation cohort. The cutoff, combined with metastases, achieved an accuracy of 89.12% in all patients, increasing accuracy by 8.29% and reducing equivocal results compared with manual reading. There was a strong correlation between SUVmax and PSMA expression (rs = 0.831, P < 0.001) and a moderate correlation between SUVmax and GS (rs = 0.509, P < 0.001). The PSMA expression and SUVmax values of patients with csPCa were significantly higher than those of patients with BPD (P < 0.001). Conclusion: We established and prospectively validated the best SUVmax cutoff value (5.30) for discriminating csPCa from BPD with high accuracy in patients with suspected PCa. 5.30 is an effective cutoff to discriminate csPCa patients with or without metastases. The cutoff may provide a potential tool for the precise identification of csPCa by 68Ga-PSMA PET/CT, ensuring high accuracy and reducing equivocal results.

Jiao J ，Kang F ，Zhang J ，Quan Z ，Wen W ，Zhao X ，Ma S ，Wu P ，Yang F ，Guo W ，Yang X ，Yuan J ，Shi Y ，Wang J ，Qin W ... -  《Theranostics》

Fluorine-18-labelled Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography or Magnetic Resonance Imaging to Diagnose and Localise Prostate Cancer. A Prospective Single-arm Paired Comparison (PEDAL).

Multiparametric magnetic resonance imaging (mpMRI) of the prostate is used for prostate cancer diagnosis. However, mpMRI has lower sensitivity for small tumours. Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) offers increased sensitivity over conventional imaging. This study aims to determine whether the diagnostic accuracy of 18F-DCFPyL PSMA-PET/CT was superior to that of mpMRI for detecting prostate cancer (PCa) at biopsy. Between 2020 and 2021, a prospective multicentre single-arm phase 3 imaging trial enrolled patients with clinical suspicion for PCa to have both mpMRI and PSMA-PET/CT (thorax to thigh), with reviewers blinded to the results of other imaging. Multiparametric MRI was considered positive for Prostate Imaging Reporting and Data System (PIRADS) 3-5. PSMA-PET/CT was assessed quantitatively (positive maximum standardised uptake value [SUVmax] >7) and qualitatively (five-point lexicon of certainty). Patients underwent targeted and systematic biopsy, with the technique at the discretion of the treating urologist. Clinically significant PCa (csPCa) was defined as International Society of Urological Pathology grade group (GG) ≥2. The primary outcome was the diagnostic accuracy for detecting PCa, reported as sensitivity, specificity, negative predictive value (NPV), and area under the curve (AUC) of the receiver operating curve. The secondary endpoints included a comparison of the diagnostic accuracy for detecting csPCa, assessing gains in combining PMSA-PET/CT with mpMRI to mpMRI alone. Of the 236 patients completing both mpMRI and PSMA-PET/CT, 184 (76.7%) had biopsy. Biopsy histology was benign (n = 73), GG 1 (n = 27), and GG ≥2 (n = 84). The diagnostic accuracy of mpMRI for detecting PCa (AUC 0.76; 95% confidence interval [CI] 0.69, 0.82) was higher than that of PSMA-PET/CT (AUC 0.63; 95% CI 0.56, 0.70, p = 0.03). The diagnostic accuracy of mpMRI for detecting csPCa (AUC 0.72; 95% CI 0.67, 0.78) was higher than that of PSMA-PET/CT (AUC 0.62; 95% CI 0.55, 0.69) but not statistically significant (p = 0.27). A combination of PSMA-PET/CT and mpMRI showed excellent sensitivity (98.8%, 95% CI 93.5%, 100%) and NPV (96%, 95% CI 79.6%, 99.9%) over mpMRI alone (86.9% and 80.7%, respectively, p = 0.01). Thirty-two patients (13.6%) had metastatic disease. They tended to be older (68.4 vs 65.1 yr, p = 0.023), and have higher prostate-specific antigen (PSA; median PSA 9.6 vs 6.2ng/ml, p < 0.001) and abnormal prostate on digital rectal examination (78.2% vs 44.1%, p < 0.001). Multiparametric MRI had superior diagnostic accuracy to PSMA-PET/CT for detecting PCa, though the difference is not significant in case of csPCa detection. A combination of mpMRI and PSMA-PET/CT showed improved sensitivity and NPV. PSMA-PET/CT could be considered for diagnostic use in patients unable to have mpMRI or those with concerning clinical features but negative mpMRI. In this trial, we compared the ability of 18F-labelled prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) with that of multiparametric magnetic resonance imaging (mpMRI) to diagnose prostate cancer by biopsy in a prostate-specific antigen screening population. We found that MRI was superior to PSMA to diagnose prostate cancer, though there was no difference in ability to diagnose clinically significant prostate cancer. PSMA-PET/CT could be considered for diagnostic use in patients unable to have mpMRI or those with concerning clinical features but negative mpMRI. Combining MRI with PSMA-PET increases the negative predictive value over MRI alone and may help men avoid invasive prostate biopsy.

Wong LM ，Sutherland T ，Perry E ，Tran V ，Spelman T ，Corcoran N ，Lawrentschuk N ，Woo H ，Lenaghan D ，Buchan N ，Bax K ，Symons J ，Saeed Goolam A ，Chalasani V ，Hegarty J ，Thomas L ，Christov A ，Ng M ，Khanani H ，Lee SF ，Taubman K ，Tarlinton L ... -  《European Urology Oncology》

Prospective Evaluation of (68)Ga-labeled Prostate-specific Membrane Antigen Ligand Positron Emission Tomography/Computed Tomography in Primary Prostate Cancer Diagnosis.

Positron emission tomography (PET)/computed tomography (CT) with 68Ga-labeled prostate-specific membrane antigen ligand (68Ga-PSMA) may represent the most promising alternative to multiparametric magnetic resonance imaging (mpMRI) for prostate cancer (PCa) diagnosis. To test the diagnostic performance of 68Ga-PSMA PET/CT in this clinical context. From January 2017 to December 2018 we prospectively enrolled 97 patients with persistently elevated prostate-specific antigen and/or Prostate Health Index score, negative digital rectal examination, and previous negative biopsy. We also included patients with either negative mpMRI or contraindications to or positive mpMRI but previous negative biopsy. Patients underwent 68Ga-PSMA PET/CT with additional pelvic reconstruction. The primary endpoint of the study was the diagnostic performance of 68Ga-PSMA PET/CT in detecting malignant lesions and clinically significant PCa (Gleason score [GS] ≥7). 68Ga-PSMA PET/transrectal ultrasound fusion biopsy was performed in 64 of 97 patients (66%) for 114 regions of interest (ROIs). Forty patients (41%) had already undergone mpMRI with either a negative result for PCa (n = 15; 22 ROIs) or a positive mpMRI result but a previous negative biopsy. According to pathology, 23 patients (36%) had evidence of PCa: eight (16 ROIs) with GS 6, 13 (21 ROIs) with GS 7 (3 + 4 or 4 + 3), one (2 ROIs) with GS 8, and one (2 ROIs) with GS 10. Clinically significant PCa was identified in four patients with previous negative mpMRI (25%). PET/CT demonstrated PCa in seven patients (14 ROIs) with previous positive mpMRI and negative biopsy. The median maximum standardized uptake value (SUVmax) and median SUV ratio were significantly higher for PCa lesions than for benign lesions (p <  0.001). Optimal cutoff points obtained for SUVmax (>5.4) and SUV ratio (>2.2) could identify clinically significant PCa with accuracy of 81% and 90%, respectively. In our cohort of patients with high suspicion of cancer,68Ga-PSMA PET/CT was capable of detecting malignancy and accurately identifying clinically relevant PCa. Positron emission tomography/computed tomography with a 68Ga-labeled ligand for prostate-specific membrane antigen is capable of detecting prostate cancer in patients with a high suspicion of cancer and a previous negative biopsy.

Lopci E ，Lughezzani G ，Castello A ，Saita A ，Colombo P ，Hurle R ，Peschechera R ，Benetti A ，Zandegiacomo S ，Pasini L ，Casale P ，Pietro D ，Bevilacqua G ，Balzarini L ，Buffi NM ，Guazzoni G ，Lazzeri M ... -  《European Urology Focus》

(68)Ga-PSMA PET/CT-based multivariate model for highly accurate and noninvasive diagnosis of clinically significant prostate cancer in the PSA gray zone.

The prostate-specific antigen (PSA) has been widely used in screening and early diagnosis of prostate cancer (PCa). However, in the PSA grey zone of 4-10 ng/ml, the sensitivity and specificity for diagnosing PCa are limited, resulting in considerable number of unnecessary and invasive prostate biopsies, which may lead to potential overdiagnosis and overtreatment. We aimed to predict clinically significant PCa (CSPCa) by combining the maximal standardized uptake value (SUVmax) based on 68Ga‑PSMA PET/CT and clinical indicators in men with gray zone PSA levels. 81 patients with suspected PCa based on increased serum total PSA (TPSA) levels of 4 - 10 ng/mL who underwent transrectal ultrasound/magnetic resonance imaging (MRI)/PET fusion-guided biopsy were enrolled. Among them, patients confirmed by histopathology were divided into the CSPCa group and the non-CSPCa group, and data on PSA concentration, prostate volume (PV), PSA density (PSAD), free PSA (FPSA)/TPSA, Prostate Imaging-Reporting and Data System version 2.1 (PI-RADS v2.1) score, 68Ga-PSMA PET/CT imaging evaluation results and SUVmax were compared. Multivariate logistic regression analysis was performed to identify the independent predictors for CSPCa, thereby establishing a predictive model based on SUVmax that was evaluated by analyzing the receiver operating characteristic (ROC) curve and decision curve analysis. Compared to non-CSPCa, CSPCa patients had smaller PVs (median, 31.40 mL), lower FPSA/TPSA (median, 0.12), larger PSADs (median, 0.21 ng/mL2) and higher PI-RADS scores (P < 0.05). The prediction model comprising 68Ga-PSMA PET/CT maximal standardized uptake value, PV and FPSA/TPSA had the highest AUC of 0.927 compared with that of other predictors alone (AUCs of 0.585 for PSA, 0.652 for mpMRI and 0.850 for 68Ga-PSMA PET/CT). The diagnostic sensitivity and specificity of the prediction model were 86.21% and 86.54%, respectively. Given the low diagnostic accuracy of regular PSA tests, a new prediction model based on the 68Ga-PSMA PET/CT SUVmax, PV and FPSA/TPSA was developed and validated, and this model could provide a more satisfactory predictive accuracy for CSPCa. This study provides a noninvasive prediction model with high accuracy for the diagnosis of CSPCa in the PSA gray zone, thus may be better avoiding unnecessary biopsy procedures.

Yang J ，Li J ，Xiao L ，Zhou M ，Fang Z ，Cai Y ，Tang Y ，Hu S ... -  《-》

More advantages in detecting bone and soft tissue metastases from prostate cancer using (18)F-PSMA PET/CT.

Pianou NK ，Stavrou PZ ，Vlontzou E ，Rondogianni P ，Exarhos DN ，Datseris IE ... -  《Hellenic Journal of Nuclear Medicine》