68Ga-labeled Prostate-specific Membrane Research Articles

The Value of 68Ga-PSMA PET/MRI for Classifying Patients with PI-RADS 3 Lesions on Multiparametric MRI: A Prospective Single-Center Study.

Prostate Imaging Reporting and Data System (PI-RADS) category 3 lesions remain a diagnostic challenge for detecting clinically significant prostate cancer (csPCa). This article evaluates the added value of 68Ga-labeled prostate-specific membrane antigen-11 (68Ga-PSMA) PET/MRI in classifying PI-RADS 3 lesions to avoid unnecessary biopsies. Methods: Sixty biopsy-naïve men with PI-RADS 3 lesions on multiparametric MRI were prospectively enrolled between February 2020 and October 2022. In all, 56 participants underwent 68Ga-PSMA PET/MRI and prostate systematic biopsy. 68Ga-PSMA PET/MRI was independently evaluated and reported by the 5-level PRIMARY score developed within the PRIMARY trial. Receiver-operating-characteristic curve analysis was used to estimate the diagnostic performance. Results: csPCa was detected in 8 of 56 patients (14.3%). The proportion of patients with csPCa and a PRIMARY score of 1, 2, 3, 4, and 5 was 0% (0/12), 0% (0/13), 6.3% (1/16), 38.5% (5/13), and 100% (2/2), respectively. The estimated area under the curve of the PRIMARY score was 0.91 (95% CI, 0.817-0.999). For a PRIMARY score of 4-5 versus a PRIMARY score of 1-3, the sensitivity, specificity, positive predictive value, and negative predictive value were 87.5%, 83.3%, 46.7%, and 97.5%, respectively. With a PRIMARY score of at least 4 to make a biopsy decision in men with PI-RADS 3 lesions, 40 of 48 patients (83.3%) could avoid unnecessary biopsies, at the expense of missing 1 of 8 (12.5%) csPCa cases. Conclusion: 68Ga-PSMA PET/MRI has great potential to classify patients with PI-RADS 3 lesions and help avoid unnecessary biopsies.

Salvage high-dose rate brachytherapy for local recurrence of prostate cancer after radical prostatectomy

Background. The current need for optimization of salvage treatment methods is dictated by the growing expansion of indications for radical prostatectomy in many centers in the developed countries of the world.Aim. To evaluate the effectiveness, toxicity, and technical characteristics of high-dose rate brachytherapy in treatment of local prostate cancer (PCa) recurrences after radical prostatectomy.Materials and methods. Between January 2015 and December 2020, salvage high-dose rate brachytherapy was performed in 17 patients at the Russian Scientific Center of Roentgenology and Radiology for local recurrence of PCa after radical prostatectomy. All patients underwent multiparametric magnetic resonance imaging of the pelvis at the stage of primary diagnosis in order to determine macroscopic tissue component in the prostate bed area. To rule out regional and distant metastases, all patients underwent positron emission tomography with 18F- or 68Ga-labeled prostate-specific membrane antigen. All patients included in the study underwent perineal biopsy of the prostate bed and seminal vesicles.Results. Median follow-up in the treatment group was 35.7 (24–54) months. Overall survival was 100 %. Prostatespecific antigen-specific survival was 88.2 %. There were no local recurrences of PCa in the treatment group. In patients with local PCa recurrence, significant predictors of treatment failure were the presence of clinically extremely high risk of progression at initial diagnosis (p = 0.003), development of biochemical relapse up to 24 months after main treatment (p = 0.001), and increased blood level of prostate-specific antigen above 10 ng/mL during registration of biochemical relapse (p = 0.002).Conclusion. High-dose rate brachytherapy is a safe and effective salvage treatment for local recurrence of PCa after radical prostatectomy. In addition to the brachytherapy technique, the diagnostic stage is also of great importance providing visualization of the exact location of tumor recurrence.

Impact of 68Ga-PSMA PET/CT on Survival and Management in Prostate Cancer.

68Ga-labeled prostate-specific membrane antigen positron emission tomography-computed tomography (68Ga-PSMA PET/CT) has led to altered treatment plans for prostate cancer (PCa) patients. This study aimed to investigate the impact of 68Ga-PSMA PET/CT on overall survival (OS) and management in PCa. Consecutive 100 patients who had 68Ga-PSMA PET/CT and conventional imaging (CI) were included in this retrospective study. Disease stages and treatment plans according to both CI and 68Ga-PSMA PET/CT were compared. The effect of 68Ga-PSMA PET/CT on OS was assessed. After 68Ga-PSMA PET/CT, the stage changed in 64 patients (64%). By the reason of 68Ga-PSMA PET/CT findings, treatment plans based on CI were changed in 73 patients (73%). According to the ROC analysis, patients with a PSA value below 8 had higher rates of change in staging (p<0.0001) and treatment (p=0.034). Both a PSA below 8 (OR 8.79 95% CI (2.72-28.43), p<0.001), and having a hormone-sensitive disease at the time of imaging (OR 5.6 95% CI (1.35-23.08), p=0.017) were significant independent factors predicting change in staging with 68Ga-PSMA PET/CT. The results of a phi correlation coefficient analysis showed a significant relationship between therapy and changes in staging (ϕ=0.638, p<0.0001). Two-year OS was statistically different in hormone-sensitive patients with and without treatment change (95% vs 81%, p=0.006). 68Ga-PSMA PET/CT has the effect of changing the treatment in 73% of PCa patients. There is a positive correlation between the changes in staging and treatment. Survival of hormone sensitive patients has improved due to treatment changes based on PET/CT findings.

Diagnostic Efficacy of 68Ga-Labeled Prostate-Specific Membrane Antigen and 18F-Labeled Sodium Fluoride PET/CT in Prostate Cancer With Bone Metastasis

Objective To compare the efficiency of 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA-11) and 18F-labeled sodium fluoride (18F-NaF) PET/CT in the diagnosis of bone metastasis in the patients with prostate cancer.Methods The prostate cancer patients suspected of bone metastasis who underwent 68Ga-PSMA-11 PET/CT and 18F-NaF PET/CT from January 2018 to January 2021 were included in this study.The number of lesions,maximum standardized uptake value (SUVmax),and tumor-to-background (T/B) ratio were compared between the two methods.Results 18F-NaF PET/CT detected more metastases than 68Ga-PSMA-11 PET/CT (310 vs.264,P<0.001).The median SUVmax[23.2 (16.4,33.4) vs.4.1 (2.5,5.6)] and median T/B ratio[7.0 (4.9,9.9) vs.6.7 (3.7,9.6)] of 18F-NaF PET/CT were higher than those of 68Ga-PSMA-11 PET/CT (all P<0.001).With the number of lesions as the indicator,the sensitivity,specificity,accuracy,positive predictive value,and negative predictive value of 18F-NaF PET/CT were 100.0%,92.0%,92.0%,98.7%,and 100.0% respectively,and those of 68Ga-PSMA-11 PET/CT were 85.2%,94.0%,79.2%,98.9%,and 50.5%,respectively.Conclusion 18F-NaF PET/CT is superior to 68Ga-PSMA-11 PET/CT in the detection of bone metastases of prostate cancer.

Exploration of 68Ga-labelled prostate-specific membrane antigen-11 PET/CT parameters for identifying PBRM1 status in primary clear cell renal cell carcinoma

To investigate the predictive value of 68Ga-labelled prostate-specific membrane antigen-11 (68Ga-PSMA-11) integrated positron-emission tomography (PET)/computed tomography (CT) in PBRM1-deficient clear cell renal cell carcinoma (ccRCC). A total of 41 patients with ccRCC, were enrolled retrospectively and underwent 68Ga-PSMA-11 PET/CT preoperatively. Radiological parameters, including CT attenuation value and maximum standard uptake value (SUVmax), were derived. Immunohistochemical and multiple immunofluorescences staining were performed to evaluate the PBRM1 status and immune response. The predictive value of imaging factors was analysed using a receiver operator characteristic curve analysis. Univariate and multivariate logistic regression analyses were used to investigate the relationship between clinical and radiological variables and PBRM1 status. A total of 41 patients were included in this study, with 14 patients having PBRM1-deficient status. The tumour diameter on imaging and SUVmax differed significantly in patients with different PBRM1 expression statuses and no difference in CT attenuation was identified. Univariate and multivariate logistic regression analyses showed SUVmax was an obvious predictor for identification of PBRM1-deficient tumours. In addition, PBRM1-deficient tumours tended to be accompanied by greater cytotoxic T-cell infiltration, although most of them were in an exhausted state. 68Ga-PSMA-11 PET/CT could be used to discriminate invasive PBRM1-deficient ccRCC.

Preoperative evaluation of prostate cancer by 68Ga-PMSA positron emission tomography/computed tomography: comparison with magnetic resonance imaging and with histopathological findings.

To evaluate the accuracy of preoperative positron emission tomography/computed tomography with 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA PET/CT) for staging prostate cancer and compare it with magnetic resonance imaging (MRI) using histopathology of surgical specimens as the gold standard. In this retrospective study, 65 patients with prostate cancer were analyzed. The accuracy of 68Ga-PSMA PET/CT for tumor detection was 95%, and that of MRI was 91%. There was no difference between 68Ga-PSMA PET/CT and MRI regarding localization of the lesion. The sensitivity of 68Ga-PSMA PET/CT for detecting extraprostatic extension was quite low (14%). For detection of seminal vesicle invasion, 68Ga-PSMA PET/CT showed a sensitivity of 57% and accuracy of 91%. There was a moderate correlation between the maximum standardized uptake value (SUVmax) and the serum level of prostate-specific antigen (p < 0.01; ρ = 0.368) and between the SUVmax and the International Society of Urological Pathology (ISUP) grade (p < 0.01; ρ = 0.513). 68Ga-PSMA PET/CT is a promising tool for detecting and evaluating the primary tumor, which can alter the staging and management of the disease.

Performance of 68Ga-labeled prostate-specific membrane antigen ligand positron emission tomography/computed tomography in the diagnosis of primary prostate cancer: a systematic review and meta-analysis.

To explore the feasibility of 68Ga-PSMA PET/CT in diagnosing primary prostate cancer. Embase, PubMed and Cochrane Library databases were searched for studies published before July 2020. The studies that used 68Ga-PSMA PET/CT for detecting primary prostate cancer, and pathological biopsy as the reference standard were included. The selecting process used preferred reporting items for systematic reviews and meta-analyses (PRISMA). The quality of enrolled studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. According to our search strategy, 9 studies were included for analysis. A total of 547 patients with primary prostate cancer and 443 lesion segments that underwent 68Ga-PSMA PET/CT scans were included and their pathological biopsies were compared. The results of these studies showed some differences. For instance, the lowest sensitivity of 68Ga-PSMA PET/CT in diagnosing primary prostate cancer was 67%, while the highest sensitivity recorded was 97%. Compared with conventional imaging examinations, 68Ga-PSMA PET/CT had higher sensitivity and specificity in detecting primary prostate cancer. At present, most of the studies that used 68Ga-PSMA PET/CT for detecting prostate cancer are retrospective studies. Based on its advantage of high detection rate, the use of 68Ga-PSMA PET/CT in the detection of primary prostate cancer is worthy of promotion.

68Ga-PSMA-I&T PET/CT for assessment of tumor burden in primary lesions of treatmentnaïve prostate cancer

To investigate the value of 68Ga-labeled prostate specific membrane antigen (PSMA) PET/CT for assessing tumor load in primary lesions for risk stratification and predicting metastasis of newly diagnosed prostate cancer (PCa). We retrospectively analyzed the data of 36 patients (mean age 71.3 ± 8.6 years, range 56 to 89 years) with newly diagnosed PCa undergoing 68Ga-PSMA-I&T PET/CT from June 2018 to July 2019. SUVmax and SUVmean of the primary lesions were measured, and the primary PSMA tumor volume (PSMA-TV) and total lesion PSMA (TL-PSMA) were automatically measured and calculated in all the patients. The correlations of primary SUVmax, PSMA-TV, and TL-PSMA with PSA and Gleason score (GS) were analyzed, and SUVmax, PSMA-TV and TL-PSMA of the primary lesions were compared among different PCa subgroups. SUVmax, PSMA-TV and TL-PSMA of the primary lesions were all correlated with PSA and GS (P < 0.05). PCa subgroup analysis showed that SUVmax, PSMA-TV and TL-PSMA were all significantly higher in patients with PSA >20 ng/mL than in those with PSA ≤20 ng/mL (P < 0.001), and were higher in patients with a GS ≥8 than in those with a GS ≤7 (P < 0.001). PSMA-TV and TL-PSMA were significantly higher in patients with tumor metastasis than in those without metastasis (P < 0.001), while SUVmax did not differ significantly with tumor metastasis. SUVmax (P=0.002), PSMA-TV (P < 0.001), and TL-PSMA (P < 0.001) were all significantly higher in high-risk group than in low-to moderate-risk group. PSMA-TV and TL-PSMA of 68Ga-PSMA-I&T PET/CT have potential value in predicting risk stratification and metastasis of newly diagnosed PCa.

Urethra Sparing With Target Motion Mitigation in Dose-Escalated Extreme Hypofractionated Prostate Cancer Radiotherapy: 7-Year Results From a Phase II Study.

PurposeTo explore whether the rectal distension-mediated technique, harnessing human physiology to achieve intrafractional prostate motion mitigation, enables urethra sparing by inverse dose painting, thus promoting dose escalation with extreme hypofractionated stereotactic ablative radiotherapy (SABR) in prostate cancer.Materials and MethodsBetween June 2013 and December 2018, 444 patients received 5 × 9 Gy SABR over 5 consecutive days. Rectal distension-mediated SABR was employed via insertion of a 150-cm3 air-inflated endorectal balloon. A Foley catheter loaded with 3 beacon transponders was used for urethra visualization and online tracking. MRI-based planning using Volumetric Modulated Arc Therapy - Image Guided Radiotherapy (VMAT-IGRT) with inverse dose painting was employed in delivering the planning target volume (PTV) dose and in sculpting exposure of organs at risk (OARs). A 2-mm margin was used for PTV expansion, reduced to 0 mm at the interface with critical OARs. All plans fulfilled Dmean ≥45 Gy. Target motion ≥2 mm/5 s motions mandated treatment interruption and target realignment prior to completion of the planned dose delivery.ResultsPatient compliance to the rectal distension-mediated immobilization protocol was excellent, achieving reproducible daily prostate localization at a patient-specific retropubic niche. Online tracking recorded ≤1-mm intrafractional target deviations in 95% of treatment sessions, while target realignment in ≥2-mm deviations enabled treatment completion as scheduled in all cases. The cumulative incidence rates of late grade ≥2 genitourinary (GU) and gastrointestinal (GI) toxicities were 5.3% and 1.1%, respectively. The favorable toxicity profile was corroborated by patient-reported quality of life (QOL) outcomes. Median prostate-specific antigen (PSA) nadir by 5 years was 0.19 ng/ml. The cumulative incidence rate of biochemical failure using the Phoenix definition was 2%, 16.6%, and 27.2% for the combined low/favorable–intermediate, unfavorable intermediate, and high-risk categories, respectively. Patients with a PSA failure underwent a 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA) scan showing a 20.2% cumulative incidence of intraprostatic relapses in biopsy International Society of Urological Pathology (ISUP) grade ≥3.ConclusionThe rectal distension-mediated technique is feasible and well tolerated. Dose escalation to 45 Gy with urethra-sparing results in excellent toxicity profiles and PSA relapse rates similar to those reported by other dose-escalated regimens. The existence of intraprostatic recurrences in patients with high-risk features confirms the notion of a high α/β ratio in these phenotypes resulting in diminished effectiveness with hypofractionated dose escalation.

Stereotactic Radiotherapy for Lesions Detected via 68Ga-Prostate-specific Membrane Antigen and 18F-Fluorodexyglucose Positron Emission Tomography/Computed Tomography in Patients with Nonmetastatic Prostate Cancer with Early Prostate-specific Antigen Progression on Androgen Deprivation Therapy: A Prospective Single-center Study

BackgroundDual-tracer positron emission tomography/computed tomography (PET/CT) with a 68Ga-labelled prostate-specific membrane antigen (PSMA) ligand and 18F-fluorodeoxyglucose (FDG) improves detection of metastatic heterogeneity and burden in patients with nonmetastatic prostate cancer (nmPCa). However, there is limited prospective evidence regarding its impact on the efficacy of stereotactic body radiotherapy (SBRT). ObjectiveTo evaluate metastasis-free survival (MFS) and toxicity after SBRT to dual-tracer PET/CT-detected metastases in patients with nmPCa and early prostate-specific antigen (PSA) progression on androgen deprivation therapy (ADT; PSA ≤2 ng/ml). Design, setting, and participantsPatients were prospectively screened using dual-tracer PET/CT between April 2019 and October 2020. SBRT was recommended for patients with five or fewer nonvisceral metastases (SBRT group). Patients without detectable metastases (N−/M− group) and those who refused SBRT (ADT group) continued to receive ADT. Patients were followed with conventional imaging. InterventionSBRT to each PET/CT-detected metastasis. Outcome measurements and statistical analysisKaplan-Meier methods were used to determine MFS. Toxicity was evaluated using Common Terminology Criteria for Adverse Event v4.0. Results and limitationsSeventy-four consecutive patients were screened. The median PSA and PSA doubling time were 0.59 ng/ml and 4.56 mo, respectively. Overall, 54 patients had metastases and 17 had PSMA-/FDG+ disease. Seven patients were excluded from the MFS analysis, including two with a history of abiraterone treatment and five with more than five metastases. The median follow-up was 21.4 mo. The ADT group had shorter MFS than the SBRT group (11.0 mo vs not reached; hazard ratio [HR] 4.69, 95% confidence interval [CI] 2.92–25.0; p < 0.001) and the N−/M− group (11.0 mo vs not reached; HR 8.78, 95% CI 4.04–40.30; p < 0.001). There was no significant difference in median MFS between the SBRT group and the N−/M− group (p = 0.261). A PSA response >90% was achieved by 86% of patients in the SBRT group. There were no grade ≥3 adverse events after SBRT. The nonrandomized design is the major study limitation. ConclusionsDual-tracer PET/CT-guided SBRT delivered superior local control rates in comparison to ADT alone and had minimal toxicity. Patient summaryWe investigated metastasis-targeted radiotherapy for patients with up to five prostate cancer metastases detected with two different radioisotope scans. Our results show that this approach yields promising metastasis-free survival and low toxicity.

Very Low Prostate PET/CT PSMA Uptake May Be Misleading in Staging Radical Prostatectomy Candidates.

Purpose: to evaluate a unique subpopulation of radical prostatectomy (RP) candidates with “negative” prostate 68Ga-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET) computed tomography (CT) imaging scans and to characterize the clinical implications of misleading findings. Materials and Methods: This case-control retrospective study compared the final histological outcomes of patients with “negative” pre-RP PSMA PET/CT prostate scans (with a prostate maximal standardized uptake value [SUVmax] below the physiologic uptake) to those with an “intense” prostatic tracer uptake (with a SUVmax above the physiologic uptake). The patients underwent an RP between March 2015 and July 2019 in five academic centers. Data on the demographics, comorbidities, prostate-specific antigen (PSA) and rectal exam findings, prior biopsies, imaging results, biopsies, and RP histology results were collected. Results: Ninety-seven of the 392 patients who underwent an RP had PSMA PET/CT imaging preoperatively. Fifty-two (54%) had a “negative” uptake (in the study group), and 45 (46%) had a “positive” uptake (in the control group). Only the lesion size and SUVmax values on the PSMA PET/CT differed between the groups preoperatively. On the histological analysis, only the ISUP score, seminal vesicles invasion, T stage, and positive margin rates differed between the groups (p < 0.05), while 50 (96%) study group patients harbored clinically significant disease (ISUP ≥ 2), with an extra-prostatic disease in 24 (46%), perineural invasion in 35 (67%), and positive lymph nodes in 4 (8%). Conclusions: Disease aggressiveness generally correlated with an intense PSMA uptake on the preoperative PSMA PET/CT, but a subpopulation of patients with clinically significant cancer and aggressive characteristics showed a deceptively weak PSMA uptake. These data raise a concern about the unqualified application of PSMA PET/CT for staging RP candidates.

Multicenter External Validation of a Nomogram for Predicting Positive Prostate-specific Membrane Antigen/Positron Emission Tomography Scan in Patients with Prostate Cancer Recurrence

BackgroundA nomogram has recently been developed to predict 68Ga-labeled prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)/computed tomography (PSMA-PET) results in recurrent prostate cancer (PCa) patients. ObjectiveTo perform external validation of the original nomogram in a multicentric setting. Design, setting, and participantsA total of 1639 patients who underwent PSMA-PET for prostate-specific antigen (PSA) relapse after radical therapy were retrospectively included from six high-volume PET centers. The external cohort was stratified according to clinical setting categories: group 1: first-time biochemical recurrence (n = 774); group 2: PSA relapse after salvage therapy (n = 499); group-3: biochemical persistence after radical prostatectomy (n = 210); and group-4: advanced-stage PCa before second-line systemic therapies (n = 124). InterventionPSMA-PET in recurrent PCa. Outcome measurements and statistical analysisPSMA-PET detection rate was assessed in the overall population and in each subgroup. A multivariable logistic regression model was produced to evaluate the predictors of a positive scan. The performance characteristics of the model were assessed by quantifying the predictive accuracy (PA) according to model calibration. The Youden’s index was used to find the best nomogram’s cutoff. Decision curve analysis (DCA) was implemented to quantify the nomogram’s clinical net benefit. Results and limitationsIn the external cohort, the overall detection rate was 53.8% versus 51.2% in the original population. At multivariate analysis, International Society of Urological Pathology grade group, PSA, PSA doubling time, and clinical setting were independent predictors of a positive scan (all p ≤ 0.02). The PA of the nomogram was identical to the original model (82.0%); the model showed an optimal calibration curve. The best nomogram’s cutoff was 55%. In the DCA, the nomogram revealed clinical net benefit when the threshold nomogram probabilities were ≥20%. The retrospective design is a major limitation. ConclusionsThe original nomogram exhibited excellent characteristics on external validation. The incidence of a false negative scan can be reduced if PSMA-PET is performed when the predicted probability is ≥20%. Patient summaryA nomogram has been developed to predict prostate-specific membrane antigen/positron emission tomography (PSMA-PET) results for recurrent prostate cancer (PCa). The nomogram represents an easy tool in the decision-making process of recurrent PCa.

Assessment of volumetric parameters derived from 68Ga-PSMA PET/CT in prostate cancer patients with biochemical recurrence: an institutional experience.

The aim of this study was to evaluate the relationship between volumetric parameters calculated using semiautomatic quantification of lesions detected in 68Ga-labeled prostate-specific membrane antigen PET-computed tomography (68Ga-PSMA PET/CT) and clinical characteristics in prostate cancer (PCa) patients with biochemical recurrence. A total of 85 consecutive PCa patients with biochemical recurrence who underwent 68Ga-PSMA PET/CT at our institution from January 2019 to March 2020 were retrospectively assessed. 68Ga-PSMA PET/CT-derived volumetric parameters, including whole-body PSMA tumor volume (wbPSMA-TV) and whole-body total lesion PSMA (wbTL-PSMA), as well as the established maximum and mean standardized uptake value (SUVmax and SUVmean), were calculated for each patient. All PET-derived parameters were analyzed for correlation with prostate-specific antigen (PSA) levels and for association with Gleason scores. Eighty-five patients with a mean age of 68.9 ± 7.8 years (range, 47-83 years) and a mean PSA level of 40.9 ± 92.1 ng/ml (range, 0.2-533.2 ng/ml) were analyzed. Volumetric parameters, that is, wbPSMA-TV and wbTL-PSMA, demonstrated a statistically significant correlation with PSA levels (r = 0.403 and r = 0.556, respectively, all at P < 0.001) and only the means of wbTL-PSMA were significantly different between the Gleason score groups (P < 0.05). The results of our study indicate that 68Ga-PSMA PET/CT might be a valuable tool for the detection and follow-up of recurrence in PCa patients. 68Ga-PSMA PET/CT-derived quantitative volumetric parameters demonstrated a highly significant correlation with changes in PSA levels. Larger prospective studies are needed to help reveal the full potential of parameters such as PSMA-TV and TL-PSMA derived from PET imaging with 68Ga-PSMA.

68Ga-PSMA-PET screening and transponder-guided salvage radiotherapy to the prostate bed alone for biochemical recurrence following prostatectomy: interim outcomes of a phase II trial

PurposeTo evaluate outcomes for men with biochemically recurrent prostate cancer who were selected for transponder-guided salvage radiotherapy (SRT) to the prostate bed alone by 68Ga-labelled prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-PET).MethodsThis is a single-arm, prospective study of men with a prostate-specific antigen (PSA) level rising to 0.1–2.5 ng/mL following radical prostatectomy. Patients were staged with 68Ga-PSMA-PET and those with a negative finding, or a positive finding localised to the prostate bed, continued to SRT only to the prostate bed alone with real-time target-tracking using electromagnetic transponders. The primary endpoint was freedom from biochemical relapse (FFBR, PSA > 0.2 ng/mL from the post-radiotherapy nadir). Secondary endpoints were time to biochemical relapse, toxicity and patient-reported quality of life (QoL).ResultsNinety-two patients (median PSA of 0.18 ng/ml, IQR 0.12–0.36), were screened with 68Ga-PSMA-PET and metastatic disease was found in 20 (21.7%) patients. Sixty-nine of 72 non-metastatic patients elected to proceed with SRT. At the interim (3-year) analysis, 32 (46.4%) patients (95% CI 34.3–58.8%) were FFBR. The median time to biochemical relapse was 16.1 months. The rate of FFBR was 82.4% for ISUP grade-group 2 patients. Rates of grade 2 or higher gastrointestinal and genitourinary toxicity were 0% and 15.2%, respectively. General health and disease-specific QoL remained stable.ConclusionPre-SRT 68Ga-PSMA-PET scans detect metastatic disease in a proportion of patients at low PSA levels but fail to improve FFBR. Transponder-guided SRT to the prostate bed alone is associated with a favourable toxicity profile and preserved QoL.Trial registration numberACTRN12615001183572, 03/11/2015, retrospectively registered.

Diagnostic performance of 68Ga-PSMA-11 PET/MRI-guided biopsy in patients with suspected prostate cancer: a prospective single-center study

PurposeUltrasound-guided biopsy (US biopsy) with 10–12 cores has a suboptimal sensitivity for clinically significant prostate cancer (sigPCa). If US biopsy is negative, magnetic resonance imaging (MRI)–guided biopsy is recommended, despite a low specificity for lesions with score 3–5 on Prostate Imaging Reporting and Data System (PIRADS). Screening and biopsy guidance using an imaging modality with high accuracy could reduce the number of unnecessary biopsies, reducing side effects. The aim of this study was to assess the performance of positron emission tomography/MRI with 68Ga-labeled prostate-specific membrane antigen (PSMA-PET/MRI) to detect and localize primary sigPCa (ISUP grade group 3 and/or cancer core length ≥ 6 mm) and guide biopsy.MethodsProspective, open-label, single-center, non-randomized, diagnostic accuracy study including patients with suspected PCa by elevation of prostate-specific antigen (PSA) level and a suspicious lesion (PIRADS ≥3) on multiparametric MRI (mpMRI). Forty-two patients underwent PSMA-PET/MRI followed by both PSMA-PET/MRI-guided and section-based saturation template biopsy between May 2017 and February 2019. Primary outcome was the accuracy of PSMA-PET/MRI for biopsy guidance using section-based saturation template biopsy as the reference standard.ResultsSigPCa was found in 62% of the patients. Patient-based sensitivity, specificity, negative and positive predictive value, and accuracy for sigPCa were 96%, 81%, 93%, 89%, and 90%, respectively. One patient had PSMA-negative sigPCa. Eight of nine false-positive lesions corresponded to cancer on prostatectomy and one in six false-negative lesions was negative on prostatectomy.ConclusionPSMA-PET/MRI has a high accuracy for detecting sigPCa and is a promising tool to select patients with suspicion of PCa for biopsy.Trial registrationThis trial was retrospectively registered under the name “Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) Guided Biopsy in Men with Elevated PSA” (NCT03187990) on 06/15/2017 (https://clinicaltrials.gov/ct2/show/NCT03187990).

Establishment and prospective validation of an SUVmax cutoff value to discriminate clinically significant prostate cancer from benign prostate diseases in patients with suspected prostate cancer by 68Ga-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.

The frequency of thyroid incidental findings and risk of malignancy detected by 68Ga-labeled prostate-specific membrane antigen PET/CT in prostate cancer.

Gallium-68-prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) has become a well-established imaging method for the evaluation of patients with prostate cancer. However, several cases have revealed PSMA uptake in a large variety of conditions other than prostate cancer. Prostate-specific membrane antigen uptake in thyroid cancer has also been reported. The aim of the present study was to systematically investigate the prevalence and clinical significance of thyroid incidental findings in patients undergoing 68Ga-PSMA PET/CT. We retrospectively identified all patients referred for 68Ga-PSMA PET/CT at the Department of Nuclear Medicine, Aalborg University Hospital, Denmark between May 2015 and May 2019. Patients with increased PSMA uptake in the thyroid gland were included in the analysis. Follow-up included imaging, biochemical, and/or histopathological collected over six months. A total of 341 patients were included. Increased 68Ga-PSMA uptake in the thyroid gland was observed in 13 patients (4%). Focal uptake was observed in seven patients, diffuse uptake in five patients and mixed focal and diffuse uptake in one patient. Malignancy was verified in two patients (2/13 patients, 15%), both patients with focal PSMA uptake. Gallium-68-PSMA thyroid incidental findings are rare in prostate cancer patients. However, cases of focal PSMA uptake in the thyroid gland should be further investigated, as these findings may represent metastatic or primary malignancy of the thyroid gland.

A comparison between 68Ga-labeled prostate-specific membrane antigen-PET/CT and multiparametric MRI for excluding regional metastases prior to radical prostatectomy.

To compare the ability of 68Ga -PSMA PET/CT (PSMA PET/CT) and multiparametric MRI (mpMRI) to exclude lymph node invasion (LNI) in patients who undergo radical prostatectomy (RP). A multicenter cohort of patients who underwent PSMA PET/CT and pelvic mpMRI prior to RP with pelvic lymph node dissection (PLND) was analyzed. Increased Ga68-PSMA uptake on PET/CT and enlarged (> 10mm) or abnormal lymph nodes on mpMRI were considered positive findings. The final surgical pathology served as the standard of reference. The negative predictive value (NPV) was calculated for each modality separately, as well as the combined value. Included were 89 patients with D'Amico intermediate (45%) or high-risk (55%) prostate cancer. The median number of extracted LN was 9 (IQR 6-14). LNI was found in 12 (13.5%) patients. The NPV of mpMRI, PSMA PET/CT, and the two tests combined were 87%, 89%, and 90%, in the entire cohort, 95%, 97%, and 97% in patients with intermediate-risk disease, and 80%, 82%, and 83% in patients with high-risk disease, respectively. The median diameter of LN missed by both imaging and the median intranodal tumor diameter was 5.5 (IQR 3-10) mm and 1 (IQR 1-3) mm, respectively. PSMA PET/CT and mpMRI demonstrated similar performance in excluding pelvic LNI with NPV of approximately 90%. The combination of both tests does not improve NPV significantly. Therefore, even in the era of advanced imaging, PLND is still recommended for accurate staging, especially in the high-risk population.

68Ga-PSMA PET/MRI for the diagnosis of primary and biochemically recurrent prostate cancer: A meta-analysis

PurposeOur meta-analysis aimed to evaluate the diagnostic performance of 68Ga-labelled prostate-specific membrane antigen ligand positron emission tomography/magnetic resonance imaging (68Ga-PSMA PET/MRI) in patients with primary and biochemically recurrent prostate cancer (PCa). MethodsWe searched for relevant articles in PubMed, EMBASE, the Cochrane Library and Web of Science until September 12, 2019. Studies regarding the diagnostic performance of68Ga-PSMA PET/MRI in detecting primary PCa and biochemical recurrence (BCR) after definitive treatment were included. The quality of each study was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. The pooled sensitivity and specificity of PET/MRI in identifying primary PCa and the pooled detection rate of PET/MRI for BCR were calculated using a random-effects model. ResultsA total of 13 studies with 707 patients were included in the analysis, and the pooled sensitivity and specificity of PET/MRI in detecting primary PCa were 0.83 (95 % CI, 0.73–0.90) and 0.81 (95 % CI, 0.61–0.93), respectively. In the pooled analysis of BCR, the pooled detection rate was 76 % (95 % CI, 72 %–79 %). For four levels of PSA (0−0.2 ng/mL, 0.2−1 ng/mL, 1−2 ng/mL and more than 2 ng/mL), the pooled detection rates were 38 %, 67 %, 74 %, and 95 %, respectively. There was no distinct publication bias, but there was significant study heterogeneity. Conclusions68Ga-PSMA PET/MRI is likely an effective imaging method in the diagnosis of primary PCa. In addition, the diagnostic accuracy of 68Ga-PSMA PET/MRI in patients with BCR was also high, positively correlating with PSA levels.

Impact of the 68Ga Prostate-Specific Membrane Antigen (68Ga-PSMA) PET/CT on the Management of Prostate Cancer

This review discusses the efficiency and sensitivity of 68Ga-labelled prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) imaging in comparison to other radiotracers and imaging techniques. It also conveys its impact on the treatment or management of prostate cancer patients. PSMA, observed in almost all prostate cancer cells, is used for staging and treatment, due to its high multiplication in this cancer when compared to normal tissues. PSMA PET/magnetic resonance imaging (MRI) has applications in the management of prostate cancer. Though PSMA PET/MRI has yielded preliminary results, it is still studied as an imaging biomarker for tumor responses. PSMA-PET/CT is known for its highly sensitive resolution, as it lights up only the parts harboring prostate cancer or tumor cells and not any other kind of lesion. Therefore, 68Ga-PSMA-PET imaging is chosen over other variants of 68Ga-PSMA-11, such as 177Lu-PSMA or 225Ac-PSMA, and it is used for its greater ability to detect metastatic sites in patients with biochemical recurrence and low serum prostate-specific antigens values. The efficacy of 68Ga-PSMA PET/CT also allows for estimation of oligometastases, as it supports the design of therapeutic trials in measuring long-term effects in patients. Finally, 68Ga-PSMA PET/CT is effective in identifying recurrence localization and, hence, permits the ability to choose the best therapeutic strategy as early as possible.