The impact of short-term non-steroidal androgen antagonist therapy on PSMA expression and tumor cellularity studied with dynamic [68Ga]Ga-PSMA-11 PET/MR in hormone-sensitive prostate cancer patients, a preliminary longitudinal prospective study

Background:Gallium-68-prostate-specific membrane antigen (68Ga-PSMA) positron emission tomography/computed tomography (PET/CT) has recently been shown to be very high accuracy in biopsy-naïve prostate cancer (PCa) detection and can potentially improve the low specificity noted with diffusion-weighted magnetic resonance imaging (DW-MRI), especially in instances of prostate inflammation. We aimed to compare the diagnostic accuracy of DW-MRI and PSMA PET/CT using apparent diffusion coefficient (ADC) and maximum standardized uptake (SUVmax) values in the diagnosis of PCa.Patients and Methods:A retrospective study comparing and analyzing the diagnostic accuracy of prebiopsy DW-MRI and 68Ga-PSMA PET/CTs done in patients with suspected PCa (raised prostate specific antigen [PSA] and/or positive digital rectal examination) from January 2019 to December 2020. The standard of reference was transrectal ultrasound-guided biopsies.Results:Sixty-seven patients were included in the study, mean age: 70 years (range 49–84), mean PSA: 23.2 ng/ml (range 2.97–45.6). Biopsy was positive for PCa in 56% (n = 38) and negative in 43% (n = 29). Of the benign results, benign hyperplasia was noted in 75% (n = 22) and prostatitis in 25% (n = 7). Of the PCa, 55% (n = 21) of were high International Society of Urological Pathology (ISUP) grade (4–5) and 45% (n = 17) low/intermediate ISUP grade (1–3). Overall the sensitivity/specificity/Accuracy for prediction of PCa of MRI using prostate imaging and reporting data system version 2 criteria and PSMA PET/CT using PCa molecular imaging standardized evaluation criteria was 92.1%/65.5%/80.5% and 76.3%/96.5%/85.1% respectively. Mean apparent diffusion co-efficient (mean ADC) value of benign lesions and PCa was 1.135 × 10-3 mm2/s and 0.723 × 10-3 mm2/s, respectively (P = 0.00001). Mean SUVmax and ADC of benign and PCa lesions was 4.01 and 16.4 (P = 0.000246). Mean SUVmax/ADC ratio of benign and malignant lesions was 3.8 × 103 versus 25.21 × 103 (P < 0.000026). Inverse correlation was noted between ADC and SUVmax values (R = −0.609), inverse correlation noted between ADC and Gleason's score (R = −0.198), and positive correlation of SUVmax and SUVmax/ADC with Gleason's score (R = 0.438 and R = 0.448). Receiver operating characteristic curve analysis revealed a SUVmax cutoff 6.03 (sensitivity/specificity - 76%/90%, area under the curve (AUC) - 0.935, Youden index (YI) - 0.66), ADC cutoff of 0.817 × 10−3 mm2/s (sensitivity/specificity – 79%/86%, AUC – 0.890, YI - 0.65), and SUVmax/ADC ratio cutoff of 7.43 × 103 (sensitivity/specificity – 87%/98%, AUC - 0.966, YI - 0.85) for PCa diagnosis.Conclusion:For diagnosis of biopsy-naïve PCas, the combination of diffusion-weighted MRI and PSMA PET/CT (i.e., SUVmax/ADC ratio) shows better diagnostic accuracy than either used alone and the combination of PET and MRI is especially useful when distinguishing cancer from prostatitis.

BackgroundXanthogranulomatous prostatitis (XGP) is a rare disorder of the prostate. It presents as a hard fixed nodule on digital rectal examination (DRE), and may cause obstructive urinary symptoms and elevated serum prostate-specific antigen (PSA) levels, therefore mimicking prostate cancer (PCa) clinically and biochemically. Radiological features of XGP overlap with those of PCa, and the 2 conditions cannot be distinguished by pelvic multiparametric magnetic resonance imaging (mpMRI). 68Ga-labelled prostate-specific membrane antigen (68Ga-PSMA) with positron emission tomography/computed tomography (PET/CT) has shown its potential in the initial diagnosis and staging of PCa; however, the imaging characteristics of XGP on 68Ga-PSMA PET/CT have yet to be reported.Case DescriptionWe report the case of a 56-year-old man who had slowly progressing dysuria for 10 years, which was significantly worse for 1 week, and a PSA level of 49.19 ng/L. Ultrasound revealed a hypoechoic lesion in the left periphery of the prostate, which was hypointense with capsular irregularity on axial T2-weighted imaging (T2WI), hyperintense on the diffusion weighted imaging (DWI), and hypointense on the apparent diffusion coefficient (ADC) maps resulting in a Prostate Imaging-Reporting and Data System (PI-RADS) score of 5. The patient was highly suspected of having high-risk PCa and underwent a 68Ga-PSMA PET/CT for staging. The PET/CT images showed no PSMA uptake in the involved region. Considering that a small proportion of cases of PCa do not express PSMA, a subsequent targeted biopsy was performed, guided by mpMRI. Histopathological examination showed a large number of foamy macrophages in the neutrophile granulocyte infiltrate, and XGP was finally diagnosed. After treatment with antibiotic levofloxacin, the patient’s PSA returned to normal, and his dysuria symptoms had disappeared at the 2-month follow-up.ConclusionsNon-uptake of PSMA in a lesion may still provide information for a diagnosis by exclusion or regular follow-up checks in patients that are highly suspected to have PCa in clinic or on mpMRI.

PEARLS: Is Our Use of Prostate-specific Membrane Antigen Positron Emission Tomography-Computed Tomography Meaningful for Our Patients?

Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Compared with Conventional Imaging for Initial Staging of Treatment-naïve Intermediate- and High-risk Prostate Cancer: A Retrospective Single-center Study

Background: There is increasing interest in using combination immunotherapy in the neoadjuvant setting in prostate cancer, however, endpoints for such studies remain elusive. We have conducted a clinical trial evaluating immunotherapy with ADT in patients with high risk prostate cancer. Patients were assessed for immune responses and changes in endorectal (er) MRI which can be used to assess intraprostatic tumors. Methods: Treatment-naïve high-risk (Gleason 8-10, PSA&amp;gt;20, or stage T3) prostate cancer patients (pts) were randomized to standard ADT+Radiation + an immunotherapy targeting MUC1 (tecemotide, aka L-BLP25) in this trial (NCT01496131). ADT consisted of gonadotropin-releasing hormone therapy. Immunotherapy included low dose (300 mg/m2, maximum 600 mg) pre-treatment cyclophosphamide for regulatory T-cell depletion. erMRI was done at baseline and after 2 months of immunotherapy including multiparametric MRI evaluation of apparent diffusion coefficient (ADC) maps from diffusion-weighted MRI. Monthly peripheral blood assessments analyzed immune cell subsets using flow cytometry and intracellular cytokine (ICC) staining for MUC-1 specific responses. Results: 28 pts with high risk prostate cancer were enrolled (n=14/arm). As expected, PSA declined in all pts 2 months after ADT. erMRI after 2 months of treatment suggested greater improvements in ADC values in pts receiving immunotherapy+ADT vs. ADT alone. Improved ADC on MRI indicates increased intratumoral diffusion and has been associated with decreased tumor density. The improvements in ADC were seen when one dominant tumor per patient was evaluated (p=0.17) but were more pronounced when up to 3 lesions were evaluated per pt (n=44 lesions; p=0.031). Compared to baseline, there were trends to increases in CTLA4+ CD8+ T-cells consistent with immune activation and decreases in myeloid derived suppressor cells (MDSCs) in pts receiving immunotherapy+ADT coinciding with the erMRI changes. These immune findings were not seen in the ADT alone group. 3 of 14 pts had MUC1 specific immune response by ICC. 2 of these patients had the greatest changes in ADC noted on erMRI over a 2-year period. Conclusions: Based on assessments by erMRI, pts who received ADT+immunotherapy had greater improvements in ADC than pts receiving ADT alone. Given that ADC improvements are associated with decreased tumor density, this suggests a possible greater anti-tumor effect of the ADT-immunotherapy combination vs. ADT alone. These findings were associated with trends to increased activated CD8+ T-cells and decreased MDSCs in pts receiving immunotherapy+ADT, with 3/14 pts having MUC1 specific immune responses. Further studies are required to confirm the potential to use ADC on erMRI as a potential (bio)marker of anti-tumor effect of immune combinations including ADT. Citation Format: Ravi A. Madan, Baris Turkbey, Lauren M. Lepone, Renee N. Donahue, Italia Grenga, Samuel Samuel Borofsky, Peter A. Pinto, Deborah Citrin, Aradhana Kaushal, Andra Krauze, Sheri McMahon, Myrna Rauchhorst, Anna Couvillon, Martin H. Falk, S Peter Eggleton, Stephen C. Greco, Peter L. Choyke, William L. Dahut, Jeffrey Schlom, James L. Gulley. Neoadjuvant immunotherapy with androgen deprivation therapy (ADT) prior to radiation in prostate cancer: Impact on multiparametric prostate MRI and immune responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-059. doi:10.1158/1538-7445.AM2017-LB-059

Prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography (PET/CT) is an emerging modality to detect metastatic disease in patients with prostate cancer (PCa). This prospective study aimed to evaluate the role of [68Ga]-PSMA PET/CT in the initial workup of intermediate and high-risk PCa. Twenty-five patients with newly transrectal ultrasound biopsy-proven, untreated intermediate- and high-risk PCa (mean age, 68.5±6.2 years; range 55-83 years) were enrolled in this prospective study between September 2018 and June 2020 and underwent a [68Ga]-PSMA PET/CT examination. All images were analyzed both visually and semiquantitatively by measuring the maximum standardized uptake value (SUVmax) of the primary prostatic tumor and metastatic lesions. The diagnostic sensitivity of [68Ga]-PSMA PET/CT for the diagnosis of PCa was established by histopathology as the reference standard. The associations between SUVmax of the primary tumors and prostate-specific antigen (PSA) levels, Gleason scores (GSs), and metastatic extent of the disease were studied. All patients had a positive [68Ga]-PSMA PET/CT exam. Seventeen patients (58%) showed [68Ga]-PSMA avidity in both prostate lobes and 8 (32%) had unilateral uptake. SUVmax in the primary tumor significantly correlated with serum PSA values (r=0.57, P=0.003). PSMA PET/CT depicted regional lymph node metastases in 32% of patients, distant lymph node metastases in 20%, osseous metastases in 16% and pulmonary metastases in 8% of patients. Sixty percent of PSMA-positive bone metastases and 21.4% of intraprostatic tumoral lesions were missed on the contemporaneous bone scintigraphy and magnetic resonance imaging, respectively. [68Ga]-PSMA PET/CT shows promise as a valuable imaging modality with high diagnostic sensitivity in the setting of intermediate and high-risk PCa. Moreover, the SUVmax of the primary tumor has a positive correlation with PSA levels at the time of the scan.

PurposeTo determine the impact on clinical management of patients with high-risk (HR) prostate cancer at diagnosis and patients with biochemical recurrence (BCR) using a new kit form of 68Ga-prostate-specific membrane antigen (PSMA), namely tris(hydroxypyridinone) (THP)-PSMA, with positron emission tomography-computed tomography (PET-CT).MethodsOne hundred eighteen consecutive patients (50 HR, 68 BCR) had management plans documented at a multidisciplinary meeting before 68Ga-THP-PSMA PET-CT. Patients underwent PET-CT scans 60-min post-injection of 68Ga-THP-PSMA (mean 159 ± 21.2 MBq). Post-scan management plans, Gleason score, prostate-specific antigen (PSA) and PSA doubling time (PSAdt) were recorded.ResultsHR group: 12/50 (24%) patients had management changed (9 inter-modality, 3 intra-modality). Patients with PSA < 20 μg/L had more frequent management changes (9/26, 34.6%) compared with PSA > 20 μg/L (3/24, 12.5%). Gleason scores > 8 were associated with detection of more nodal (4/16, 25% vs 5/31, 16.1%) and bone (2/16, 12.5% vs 2/31, 6.5%) metastases. BCR group: Clinical management changed in 23/68 (34%) patients (17 inter-modality, 6 intra-modality). Forty out of 68 (59%) scans were positive. Positivity rate increased with PSA level (PSA < 0.5 μg/L, 0%; PSA 0.5–1.0 μg/L, 35%; PSA 1.0–5.0 μg/L, 69%; PSA 5.0–10.0 μg/L, 91%), PSAdt of < 6 months (56% vs 45.7%) and Gleason score > 8 (78.9% vs 51.2%).Conclusions68Ga-THP-PSMA PET-CT influences clinical management in significant numbers of patient with HR prostate cancer pre-radical treatment and is associated with PSA. Management change also occurs in patients with BCR and is associated with PSA and Gleason score, despite lower scan positivity rates at low PSA levels < 0.5 μg/L.

Diffusion-weighted magnetic resonance imaging (DW-MRI) and 2-deoxy-2-[18F]fluoro-D-glucose-positron emission tomography/computed tomography (PET/CT) is increasingly recognized as important for assessing tumor malignancy in oncology. Apparent diffusion coefficient (ADC) and standardized uptake value (SUV) are negatively correlated in some types of cancer based on tumor aggressiveness. To evaluate relationships between ADC of magnetic resonance imaging and SUV of PET/CT in pancreatic adenocarcinomas. Twenty-nine patients histopathologically diagnosed with pancreatic adenocarcinomas were evaluated. ADC maps were generated from 3 T-MRI using b values (b = 0, 800 s/mm(2)). PET/CT was performed 60 min after intravenous injection of FDG (3.7 MBq/kg). The margins of tumors on DW-MRI and PET/CT were assessed to measure ADC and SUV of tumor appropriately. For tumors considered well-marginated, minimal and mean ADC as well as maximal and mean SUV were measured. The correlation of ADC and SUV were statistically evaluated and survival period stratified on ADC and SUV also evaluated. Twenty-two tumors on DW-MRI and 25 on PET/CT were deemed well-marginated. Minimal ADC was significantly and negatively correlated with maximal and mean SUV (r = -0.61, P = 0.0040; r = -0.66, P = 0.0015), and mean ADC also showed significantly and negatively correlation with maximal and mean SUV (r = -0.50, P = 0.024; r = -0.54, P = 0.012). There was no significant difference on overall survival stratified on ADC and SUV. ADC and SUV were significantly correlated in pancreatic adenocarcinomas, although no significant findings were observed in overall survival.

Objective The objective of this study was to evaluate the clinical utility of gallium-68 [ 68 Ga] prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) with rising prostate-specific antigen (PSA) levels in prostate cancer diagnosis. Methods This is a retrospective, single-center, observational cross-sectional study, which is provided after ethics committee clearance, from May 2, 2022 to June 25, 2022. Study includes sample size of 50 patients with prostate adenocarcinoma with varying PSA levels and Gleason score of 6 to 9 who underwent [ 68 Ga] PSMA PET/CT scan. The patients included in this study underwent PET/CT scan on uMI550 (United Imaging Healthcare, Shanghai, China). Results All patients were divided into three groups based on PSA levels in ng/mL as: PSA ≤ 0.2 (8%), 0.2 < PSA ≤ 1 (10%), 1 < PSA ≤ 3 (8%), 3 < PSA ≤ 10 (18%), and PSA > 10 (56%). Among 50 scans, at least one PSMA avid lesion was visualized in 41 scans (78.9%). These scans were considered positive and included in this study, rest of the scans had insignificant PSMA uptake and were considered negative. [ 68 Ga] PSMA PET/CT detection rates were 75.0, 20.0, 50.0, 88.90, and 89.3% in patients with PSA ≤ 0.2, 0.2 < PSA ≤ 1, 1 < PSA ≤ 3, 3 < PSA ≤ 10, and PSA > 10, respectively. In addition to prostate bed, lesions were also visualized in lymph nodes (32%), liver (2%), skeleton (28%), and thorax (6%). Considering lesions in the prostate bed a significant direct correlation was detected between maximal standardized uptake value (SUVmax) and PSA value ( p = 0.03). Discussion PSMA PET/CT has been demonstrated to be an effective method for identifying both low-grade Gleason score tumors and low PSA levels. The study provides support for the use of [ 68 Ga] PSMA PET/CT in conjunction with PSA levels for the evaluation of prostate cancer, including local recurrence and distant metastases. Conclusion The findings of this study indicate that PSMA PET/CT is an effective method for diagnosing prostate cancer, as it allows for the detection of high SUVmax values in pathological tissues. Furthermore, high sensitivity and detection rates are noted with PSMA PET/CT scan even in cases where PSA levels were low. Therefore, this study demonstrates that [ 68 Ga] PSMA PET/CT is beneficial for the early detection of prostate cancer and the prediction of treatment outcomes.

Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) can detect low-volume, nonlocalized (ie, regional or metastatic) prostate cancer that was occult on conventional imaging. However, the long-term clinical implications of PSMA PET/CT upstaging remain unclear. To evaluate the prognostic significance of a nomogram that models an individual's risk of nonlocalized upstaging on PSMA PET/CT and to compare its performance with existing risk-stratification tools. This cohort study included patients diagnosed with high-risk or very high-risk prostate cancer (ie, prostate-specific antigen [PSA] level >20 ng/mL, Gleason score 8-10, and/or clinical stage T3-T4, without evidence of nodal or metastatic disease by conventional workup) from April 1995 to August 2018. This multinational study was conducted at 15 centers. Data were analyzed from December 2020 to March 2021. Curative-intent radical prostatectomy (RP), external beam radiotherapy (EBRT), or EBRT plus brachytherapy (BT), with or without androgen deprivation therapy. PSMA upstage probability was calculated from a nomogram using the biopsy Gleason score, percentage positive systematic biopsy cores, clinical T category, and PSA level. Biochemical recurrence (BCR), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall survival (OS) were analyzed using Fine-Gray and Cox regressions. Model performance was quantified with the concordance (C) index. Of 5275 patients, the median (IQR) age was 66 (60-72) years; 2883 (55%) were treated with RP, 1669 (32%) with EBRT, and 723 (14%) with EBRT plus BT; median (IQR) PSA level was 10.5 (5.9-23.2) ng/mL; 3987 (76%) had Gleason grade 8 to 10 disease; and 750 (14%) had stage T3 to T4 disease. Median (IQR) follow-up was 5.1 (3.1-7.9) years; 1221 (23%) were followed up for at least 8 years. Overall, 1895 (36%) had BCR, 851 (16%) developed DM, and 242 (5%) died of prostate cancer. PSMA upstage probability was significantly prognostic of all clinical end points, with 8-year C indices of 0.63 (95% CI, 0.61-0.65) for BCR, 0.69 (95% CI, 0.66-0.71) for DM, 0.71 (95% CI, 0.67-0.75) for PCSM, and 0.60 (95% CI, 0.57-0.62) for PCSM (P < .001). The PSMA nomogram outperformed existing risk-stratification tools, except for similar performance to Staging Collaboration for Cancer of the Prostate (STAR-CAP) for PCSM (eg, DM: PSMA, 0.69 [95% CI, 0.66-0.71] vs STAR-CAP, 0.65 [95% CI, 0.62-0.68]; P < .001; Memorial Sloan Kettering Cancer Center nomogram, 0.57 [95% CI, 0.54-0.60]; P < .001; Cancer of the Prostate Risk Assessment groups, 0.53 [95% CI, 0.51-0.56]; P < .001). Results were validated in secondary cohorts from the Surveillance, Epidemiology, and End Results database and the National Cancer Database. These findings suggest that PSMA upstage probability is associated with long-term, clinically meaningful end points. Furthermore, PSMA upstaging had superior risk discrimination compared with existing tools. Formerly occult, PSMA PET/CT-detectable nonlocalized disease may be the main driver of outcomes in high-risk patients.

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.

Background and objectivesThe association between prostate-specific antigen (PSA) level and probability of metastatic disease on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has not yet been established in patients with newly diagnosed prostate cancer (PCa). Our objective was to assess the probability of metastatic disease within different PSA ranges using PSMA PET/CT for initial staging of PCa, and to identify both the anatomical distribution and the predictors of metastases on PSMA PET/CT. MethodsIn total, 2193 patients with newly diagnosed PCa were retrospectively studied. PSMA PET/CT was performed for staging purposes between January 2017 and May 2022. The proportion of patients with PSMA-avid metastases, stratified by PSA level, was studied. A vast majority of patients in whom at least one high-risk prognostic factor was present underwent PSMA PET/CT. A multivariable logistic regression analysis was performed to identify the predictors of metastases on PSMA PET/CT using clinical, biochemical, radiological, and pathological variables. Key findings and limitationsThe median PSA level at PSMA PET/CT was 14.1 ng/ml. Any metastatic disease (miN1-M1a-c) was observed in 34.7% (763/2193) of all patients and distant metastases (miM1a-c) in 25.4% (557/2193) of patients. The presence of any metastatic disease increased with PSA levels, being 15.4% in men with PSA levels <10 ng/ml and 87.5% in men with PSA levels >100 ng/ml. The multivariable logistic regression analysis found significant associations between the presence of any metastatic disease and PSA subgroups, clinical tumor stage ≥T2, grade group >3, and radiological tumor stage ≥T3b. Conclusions and clinical implicationsThis is the first large epidemiological study in patients with PCa demonstrating the association between PSA subgroups and metastatic disease on modern imaging PSMA PET/CT. Data from this study can be used to counsel patients on the probability of metastatic disease at the time of PSA screening and to provide guidance on existing guidelines. Patient summaryThe prostate-specific antigen level could be used to assess the risk of metastases on prostate-specific membrane antigen positron (PSMA) emission tomography/computed tomography (PET/CT). This knowledge is valuable for selecting patients who will benefit most from metastatic screening with PSMA PET/CT.

DETECTION OF MICROMETASTATIC PROSTATE CANCER CELLS IN THE LYMPH NODES BY REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION IS PREDICTIVE OF BIOCHEMICAL RECURRENCE IN PATHOLOGICAL STAGE T2 PROSTATE CANCER.

Prostate-specific membrane antigen (PSMA) positron emission tomography/computer tomography (PET/CT) in prostate cancer patients with biochemical failure(BCF) showslimited sensitivity when the prostate-specific antigen(PSA) <0.5 ng/mL. The development of digital PET/CT has greatly improved smaller lesion detection. This study's goal was to compare the performance and clinical value of PSMA-targeted piflufolastat PET/CT for prostate cancer BCF with digital versus analog PET/CT. In this retrospective study, all piflufolastat PET/CT scans in subjects with PSA ≤ 3.0 ng/mL who were referred for prostate cancer BCF were included. The performance characteristics of 171 analog PET/CT studies in 155 subjects from May 2017 to January 2020 and 106 digital PET/CT studies in 103 subjects from February 2020 to December 2020 were compared. Lesions were considered malignant if they did not match the known physiological distribution of piflufolastat and did not represent uptake in benign lesions. PSMA PET/CT studies were considered positive if at least one malignant lesion was detected and negative if none were detected. Digital piflufolastat PET/CT outperformed analog piflufolastat PET/CT in subjects with PSA < 0.5 ng/mL with a positivity rate of 69% versus 37%, respectively. In patients with PSA ≥ 0.5 ng/mL, both technologies performed similarly. There was no statistically significant difference between the number or size of piflufolastat-avid lesions detected per PET/CT study. In prostate cancer patients with BCF and PSA < 0.5 ng/mL, digital piflufolastat PET/CT has a higher detection rate of malignant lesions than analog piflufolastat PET/CT.

The current study endeavored to closely compare the detection rate of 68-Gallium labelled prostate-specific membrane antigen ([68Ga]Ga-PSMA) versus [18F]Fluorocholine in men with prostate cancer (PC), to investigate the benefits and pitfalls of each modality in the setting of various patient characteristics. We retrospectively analyzed 29 biopsy-proven PC patients in two categories, staging and restaging, who underwent both scans within a maximum of 30 days of each other. Variables including patient demographics, prostate specific antigen (PSA) level, Gleason score, clinical course, and following treatments were recorded. The number and location of suspicious lesions as well as uptake values were noted. A total of 148 suspicious lesions were detected, of which 70.9% (105/148) were concordantly visualized in both imaging modalities. [68Ga]Ga-PSMA positron emission tomography/computed tomography (PET/CT) revealed a higher number of metastatic lesions per patients (91% vs 78%). The mean of maximum standardized uptake value (SUV max) in concordant lesions was significantly higher in [68Ga]Ga-PSMA compared to [18F]Fluorocholine PET/CT (14.6 ± 8.44 vs. 6.9 ± 3.4, p = 0.001). Discordant lesions were detected by both modalities, but more frequently by [68Ga]Ga-PSMA PET/CT (20.3% in [68Ga]Ga-PSMA versus 8.8% by [18F]Fluorocholine PET/CT). In patients with PSA levels below 1.0 ng/mL and <2.0 ng/mL, [18F]Fluorocholine PET/CT detection rate was half (57% and 55%, respectively) that of [68Ga]Ga-PSMA PET/CT. Tumor, nodes and metastases (TNM) staging, and subsequently patient management, was only influenced in 4/29 patients (14%), particularly by [68Ga]Ga-PSMA PET/CT with PSA values under 0.5 ng/mL. [68Ga]Ga-PSMA PET/CT revealed superior diagnostic performance to [18F]Fluorocholine PET/CT in staging and restaging of PC patients, especially in cases with low PSA levels. However, in a few hormone resistant high-risk PC patients, [18F]Fluorocholine PET/CT may improve overall diagnostic accuracy.