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Purpose: TMPRSS2:ERG gene fusion negatively regulates PSMA expression in prostate adenocarcinoma (PCa) cell lines. Therefore, immunohistochemical (IHC) ERG expression, a surrogate for an underlying ERG rearrangement, and PSMA expression patterns in radical prostatectomy (RPE) specimens of primary PCa, including corresponding PSMA-PET scans were investigated., Methods: Two cohorts of RPE samples (total n=148): In cohort #1 (n=62 patients) with available RPE and preoperative [ 68 Ga]Ga-PSMA-11 PET, WHO/ISUP grade groups, IHC-ERG (positive vs. negative) and IHC-PSMA expression (% PSMA-negative tumour area, PSMA %neg ) were correlated with the corresponding SUV max . In the second cohort #2 (n=86 patients) including RPE only, same histopathological parameters were evaluated., Results: Cohort #1: PCa with IHC-ERG expression (35.5%) showed significantly lower IHC-PSMA expression and lower SUV max values on the corresponding PET scans. Eight of 9 PCa with negative PSMA-PET scans had IHC-ERG positivity, and confirmed TMPRSS2::ERG rearrangement. In IHC-PSMA positive PCa, IHC-ERG positivity was significantly associated with lower SUV max values. In cohort #2, findings of higher IHC-PSMA %neg and IHC-ERG expression was confirmed with only 0-10% PSMA %neg tumour areas in IHC-ERG-negative PCa., Conclusion: IHC-ERG expression is significantly associated with more heterogeneous and lower IHC-PSMA tissue expression in two independent RPE cohorts. There is a strong association of ERG positivity in RPE tissue with lower [ 68 Ga]Ga-PSMA-11 uptake on corresponding PET scans. Results may serve as a base for future biomarker development to enable tumour-tailored, individualized imaging approaches., Competing Interests: Declarations. Ethics approval: The study was approved by the local Cantonal Ethics committee (BASEC Nr. 2018–01284, BASEC Nr. 2022-1778). Consent to participate: A general written informed consent for the use of their material and data was signed by all included patients. Consent to publish: Not applicable Competing interests: The authors have no competing interests to declare that are relevant to the content of this article., (© 2024. The Author(s).)

Purpose: To develop and evaluate a lymph node invasion (LNI) prediction model for men staged with [ 68 Ga]Ga-PSMA-11 PET., Methods: A consecutive sample of intermediate to high-risk prostate cancer (PCa) patients undergoing [ 68 Ga]Ga-PSMA-11 PET, extended pelvic lymph node dissection (ePLND), and radical prostatectomy (RP) at two tertiary referral centers were retrospectively identified. The training cohort comprised 173 patients (treated between 2013 and 2017), the validation cohort 90 patients (treated between 2016 and 2019). Three models for LNI prediction were developed and evaluated using cross-validation. Optimal risk-threshold was determined during model development. The best performing model was evaluated and compared to available conventional and multiparametric magnetic resonance imaging (mpMRI)-based prediction models using area under the receiver operating characteristic curves (AUC), calibration plots, and decision curve analysis (DCA)., Results: A combined model including prostate-specific antigen, biopsy Gleason grade group, [ 68 Ga]Ga Ga-PSMA-11 positive volume of the primary tumor, and the assessment of the [ 68 Ga]Ga-PSMA-11 report N-status yielded an AUC of 0.923 (95% CI 0.863-0.984) in the external validation. Using a cutoff of  ≥ 17%, 44 (50%) ePLNDs would be spared and LNI missed in one patient (4.8%). Compared to conventional and MRI-based models, the proposed model showed similar calibration, higher AUC (0.923 (95% CI 0.863-0.984) vs. 0.700 (95% CI 0.548-0.852)-0.824 (95% CI 0.710-0.938)) and higher net benefit at DCA., Conclusions: Our results indicate that information from [ 68 Ga]Ga-PSMA-11 may improve LNI prediction in intermediate to high-risk PCa patients undergoing primary staging especially when combined with clinical parameters. For better LNI prediction, future research should investigate the combination of information from both PSMA PET and mpMRI for LNI prediction in PCa patients before RP., (© 2023. The Author(s).)

Purpose: Recently, a significant association was shown between novel growth patterns on histopathology of prostate cancer (PCa) and prostate-specific membrane antigen (PSMA) uptake on [ 68 Ga]PSMA-PET. It is the aim of this study to evaluate the association between these growth patterns and ADC (mm 2 /1000 s) values in comparison to [ 68 Ga]PSMA uptake on PET/MRI., Methods: We retrospectively evaluated patients who underwent [ 68 Ga]PSMA PET/MRI for staging or biopsy guidance, followed by radical prostatectomy at our institution between 07/2016 and 01/2020. The dominant lesion per patient was selected based on histopathology and correlated to PET/MRI in a multidisciplinary meeting, and quantified using SUV max for PSMA uptake and ADC mean for diffusion restriction. PCa growth pattern was classified as expansive (EXP) or infiltrative (INF) according to its properties of forming a tumoral mass or infiltrating diffusely between benign glands by two independent pathologists. Furthermore, the corresponding WHO2016 ISUP tumor grade was evaluated. The t test was used to compare means, Pearson's test for categorical correlation, Cohen's kappa test for interrater agreement, and ROC curve to determine the best cutoff., Results: Sixty-two patients were included (mean PSA 11.7 ± 12.5). The interrater agreement between both pathologists was almost perfect with κ = 0.81. While 25 lesions had an EXP-growth with an ADC mean of 0.777 ± 0.109, 37 showed an INF-growth with a significantly higher ADC mean of 1.079 ± 0.262 (p < 0.001). We also observed a significant difference regarding PSMA SUV max for the EXP-growth (19.2 ± 10.9) versus the INF-growth (9.4 ± 6.2, p < 0.001). Within the lesions encompassing the EXP- or the INF-growth, no significant correlation between the ISUP groups and ADC mean could be observed (p = 0.982 and p = 0.861, respectively)., Conclusion: PCa with INF-growth showed significantly lower SUV max and higher ADC mean values compared to PCa with EXP-growth. Within the growth groups, ADC mean values were independent from ISUP grading., (© 2022. The Author(s).)

Purpose: Prostate-specific membrane antigen (PSMA)-targeted PET is increasingly used for staging prostate cancer (PCa) with high accuracy to detect significant PCa (sigPCa). [ 68  Ga]PSMA-11 PET/MRI-guided biopsy showed promising results but also persisting limitation of sampling error, due to impaired image fusion. We aimed to assess the possibility of intraoperative quantification of [ 18 F]PSMA-1007 PET/CT uptake in core biopsies as an instant confirmation for accurate lesion sampling., Methods: In this IRB-approved, prospective, proof-of-concept study, we included five consecutive patients with suspected PCa. All underwent [ 18 F]PSMA-1007 PET/CT scans followed by immediate PET/CT-guided and saturation template biopsy (3.1 ± 0.3 h after PET). The activity in biopsy cores was measured as counts per minute (cpm) in a gamma spectrometer. Pearson's test was used to correlate counts with histopathology (WHO/ISUP), tumor length, and membranous PSMA expression on immunohistochemistry (IHC)., Results: In 43 of 113 needles, PCa was present. The mean cpm was overall significantly higher in needles with PCa (263 ± 396 cpm) compared to needles without PCa (73 ± 44 cpm, p < 0.001). In one patient with moderate PSMA uptake (SUV max 8.7), 13 out of 24 needles had increased counts (100-200 cpm) but only signs of inflammation and PSMA expression in benign glands on IHC. Excluding this case, ROC analysis resulted in an AUC of 0.81, with an optimal cut-off to confirm PCa at 75 cpm (sens/spec of 65.1%/87%). In all 4 patients with PCa, the first or second PSMA PET-guided needle was positive for sigPCa with high counts (156-2079 cpm)., Conclusions: [ 18 F]PSMA-1007 uptake in PCa can be used to confirm accurate lesion sampling of the dominant tumor intraoperatively. This technique could improve confidence in imaging-based biopsy guidance and reduce the need for saturation biopsy., Trial Registration Number: NCT03187990, 15/06/2017., (© 2021. The Author(s).)

Purpose: Prostate-specific membrane antigen (PSMA-) PET has become a promising tool in staging and restaging of prostate carcinoma (PCa). However, specific primary tumour features might impact accuracy of PSMA-PET for PCa detection. We investigated histopathological parameters and immunohistochemical PSMA expression patterns on radical prostatectomy (RPE) specimens and correlated them to the corresponding 68 Ga-PSMA-11-PET examinations., Methods: RPE specimens of 62 patients with preoperative 68 Ga-PSMA-11-PET between 2016 and 2018 were analysed. WHO/ISUP grade groups, growth pattern (expansive vs. infiltrative), tumour area and diameter as well as immunohistochemical PSMA heterogeneity, intensity and negative tumour area (PSMA %neg ) were correlated with spatially corresponding SUV max on 68 Ga-PSMA-11-PET in a multidisciplinary analysis., Results: All tumours showed medium to strong membranous (2-3 +) and weak to strong cytoplasmic (1-3 +) PSMA expression. Heterogeneously expressed PSMA was found in 38 cases (61%). Twenty-five cases (40%) showed at least 5% and up to 80% PSMA %neg . PSMA %neg , infiltrative growth pattern, smaller tumour area and diameter and WHO/ISUP grade group 2 significantly correlated with lower SUV max values. A ROC curve analysis revealed 20% PSMA %neg as an optimal cutoff with the highest sensitivity and specificity (89% and 86%, AUC 0.923) for a negative PSMA-PET scan. A multiple logistic regression model revealed tumoural PSMA %neg (p < 0.01, OR = 9.629) and growth pattern (p = 0.0497, OR = 306.537) as significant predictors for a negative PSMA-PET scan., Conclusions: We describe PSMA %neg , infiltrative growth pattern, smaller tumour size and WHO/ISUP grade group 2 as parameters associated with a lower 68 Ga-PSMA-11 uptake in prostate cancer. These findings can serve as fundament for future biopsy-based biomarker development to enable an individualized, tumour-adapted imaging approach., (© 2021. The Author(s).)

Purpose: Prostate-specific membrane antigen (PSMA) targeted positron emission tomography (PET) imaging significantly improved the detection of recurrent prostate cancer (PCa). However, the value of PSMA PET imaging in patients with advanced hormone-sensitive or hormone-resistant PCa is still largely unknown. The aim of this study was to analyze the detection rate and distribution of lesions using PSMA PET imaging in patients with advanced PCa and ongoing androgen deprivation therapy (ADT)., Methods: A total of 84 patients diagnosed with hormone-sensitive or hormone-resistant PCa who underwent 68 Ga-PSMA-11 PET/magnetic resonance imaging (MRI) or computer tomography (CT) under ongoing ADT were retrospectively analyzed. We assessed the detection of PSMA-positive lesions overall and for three PSA subgroups (0 to < 1 ng/mL, 1 to < 20 ng/mL and > 20 ng/mL). In addition, PSMA-positive findings were stratified by localization (prostatic fossa, pelvic, para-aortic, mediastinal/supraclavicular and axillary lymph nodes, bone lesions and visceral lesions) and hormone status (hormone-sensitive vs. hormone-resistant). Furthermore, we assessed how many patients would be classified as having oligometastatic disease (≤ 3 lesions) and theoretically qualify for metastasis-directed radiotherapy (MDRT) in a personalized patient management., Results: We detected PSMA-positive lesions in 94.0% (79 of 84) of all patients. In the three PSA subgroups detection rates of 85.2% (0 to < 1 ng/mL, n = 27), 97.3% (1 to < 20 ng/mL, n = 37) and 100% (> 20 ng/mL, n = 20) were observed, respectively. PSMA-positive visceral metastases were observed only in patients with a PSA > 1 ng/mL. Detection of PSMA-positive lesions did not significantly differ between patients with hormone-sensitive and hormone-resistant PCa. Oligometastatic PCa was detected in 19 of 84 patients (22.6%). Almost all patients, 94.7% (n = 18) would have been eligible for MDRT., Conclusions: In this study, we observed an overall very high detection rate of 94% using PSMA PET imaging in patients with advanced PCa and ongoing ADT. Even in a majority of patients with very low PSA values < 1 ng/ml PSMA-positive lesions were found., (© 2021. The Author(s).)

Purpose: Ultrasound-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 68 Ga-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., Methods: Prospective, 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., Results: SigPCa 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., Conclusion: PSMA-PET/MRI has a high accuracy for detecting sigPCa and is a promising tool to select patients with suspicion of PCa for biopsy., Trial Registration: This 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 )., (© 2021. The Author(s).)

Background: Positron emission tomography (PET) targeting the prostate-specific membrane antigen (PSMA) has superior sensitivity over conventional imaging (CI) to stage prostate cancer (PCa) and therefore is increasingly used in staging to stratify patients before radical therapy. Whether this improved diagnostic accuracy translates into improved outcome after radical prostatectomy (RPE) has not yet been shown. Therefore, the aim of this study was to compare the oncological outcome after RPE between patients that underwent preoperative staging with CI or PSMA-PET for intermediate and high-risk PCa., Methods: We retrospectively selected all patients that underwent RPE for intermediate- or high-risk PCa at our institution before PSMA-PET introduction (between March 2014 and September 2016) and compared the oncologic outcome of patients staged with PSMA-PET (between October 2016 and October 2018). Oncological pre-surgical risk parameters (age, PSA, D'Amico score, biopsy-ISUP, and cT stage) were compared between the groups. Oncological outcome was determined as PSA persistence, nerve-sparing rate, and surgical margin status. Wilcoxon rank-sum, Fisher's, and chi-square tests where used for statistical testing., Results: One hundred five patients were included, 53 in the CI group and 52 in the PSMA-group. Patients in the PSMA group had higher ISUP grade (p < 0.001) and D'Amico score (p < 0.05). The rate of free surgical margins and PSA persistence after RPE was 64% and 17% for the CI and 77% and 6% for the PSMA group (p = 0.15 and 0.13, respectively). Subgroup analysis with high-risk patients revealed PSA persistence in 7% (3/44) in the PSMA group and 25% (7/28) in the CI group (p = 0.04). Limitations include the retrospective design and choline-PET for some patients in the CI group., Conclusion: Immediate outcome after RPE was not worse in the PSMA group compared with the CI group, despite a higher-risk cohort. In a comparison of only high-risk patients, PSMA-PET staging was associated with a significantly lower rate of postsurgical PSA persistence.

Therapy response assessment is a critical step in cancer management, leading clinicians to optimize the use of therapeutic options during the course of the disease. Imaging is a pivotal biomarker for therapy response evaluation in oncology and has gained wider use through the development of reproducible data-based guidelines, of which the Response Evaluation Criteria in Solid Tumors is the most successful example. Disease-specific criteria have also been proposed, and the Prostate Cancer Working Group 3 criteria are the mainstay for prostate cancer (PC). However, conventional imaging evaluation in metastatic PC has several limitations, including (a) the inability to detect small-volume disease, (b) the high prevalence of bone (nonmeasurable) lesions at imaging, and (c) the established role of serum prostate-specific antigen (PSA) levels as the biomarker of choice for response assessment and disease progression. In addition, there are an increasing number of newer treatment options with various effects on imaging features. Prostate-specific membrane antigen (PSMA) PET has improved patient selection for newer treatments, such as metastasis-directed therapy (MDT) or radionuclide therapy. The role of PSMA PET in response assessment for many metastatic PC therapeutic options (MDT, androgen deprivation therapy, chemotherapy, radionuclide therapy, and immunotherapy) is an evolving issue, with emerging data showing good correlation with PSA levels and clinical outcome. However, there are specific implications of each therapy (especially androgen deprivation therapy and immunotherapy) on PSMA expression by PC cells, leading to potential pitfalls and inaccuracies that must be known by radiologists. Despite some limitations, PSMA PET is addressing gaps left by conventional imaging methods (eg, CT and bone scanning) and nonimaging biomarkers (PSA levels) in metastatic PC therapy response assessment, a role that can be improved with advances like refinement of interpretation criteria and whole-body tumor burden quantification. © RSNA, 2020See discussion on this article by Barwick and Castellucci.

Prostate-specific membrane antigen (PSMA) targeted PET has a high detection rate for biochemical recurrence (BCR) of prostate cancer (PCa). Nevertheless, even at high prostate-specific antigen (PSA) levels (> 3 ng/ml), a relevant number of PSMA-PET scans are negative, mainly due to PSMA-negative PCa. Our objective was to investigate whether PSMA-expression patterns of the primary tumour on immunohistochemistry (IHC) are associated with PSMA-PET detection rate of recurrent PCa. Methods: Retrospective institutional review board approved single-centre analysis of patients who had undergone 68 Ga-PSMA-11-PET for BCR after radical prostatectomy (RPE) between 04/2016 and 07/2019, with tumour specimens available for PSMA-IHC. Clinical information (age, PSA-level, ongoing androgen deprivation therapy (ADT), Gleason score) and PSMA-IHC of the primary tumour were collected and their relationship to results from PSMA-PET (positive/negative) was investigated using a multiple logistic regression analysis. Results: 120 PSMA-PET scans in 74 patients were available for this analysis. Overall detection rate was 62% (74/120 scans), with a mean PSA value at scan time of 0.99 ng/ml (IQR 0.32-4.27). Of the clinical factors, only PSA-level and ADT were associated with PSMA-PET positivity. The percentage of PSMA-negative tumour area on IHC (PSMA %neg ) had a significant association to PSMA-PET negativity (OR = 2.88, p < 0.001), while membranous PSMA-expression showed no association ( p = 0.73). The positive predictive value of PSMA %neg ≥ 50% for a negative PSMA-PET was 85% (13/11) and for a PSMA %neg of 80% or more, 100% (9/9). Conclusions: PSMA-negative tumour area on IHC exhibited the strongest association with negative PSMA-PET scans, beside PSA-level and ADT. Even at very high PSA levels, PSMA-PET scans were negative in most of the patients with PSMA %neg ≥ 50%., Competing Interests: Competing Interests: IAB has received research grants and speaker honorarium from GE Healthcare, research grants from Swiss Life and speaker honorarium from Bayer Health Care and Astellas Pharma AG. MM received speaker fees from GE Healthcare. TH holds an advisory function for MSD and Bayer. Authors DAF, JHR, UJM, BK, JM, LH, DE, and NJR declare no conflict of interest. The Department of Nuclear Medicine holds an institutional Research Contract with GE Healthcare. The authors thank the Sick legat and the Iten-Kohaut foundation for their financial support., (© The author(s).)

Background: Accurate staging is of major importance to determine the optimal treatment modality for patients with prostate cancer. Positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) is a promising technique that outperformed conventional imaging in the detection of nodal and distant metastases in previous studies. However, it is still unclear whether the superior sensitivity and specificity also translate into improved patient management. The aim of this study was to assess the performance of 68 Ga-PSMA-11 PET for staging of intermediate and high-risk prostate cancer and its potential impact on disease management., Methods: In this retrospective analysis, 116 patients who underwent 68 Ga-PSMA-11 PET/CT or MRI scans for staging of their intermediate or high-risk prostate cancer between April 2016 and May 2018 were included. The potential impact of 68 Ga-PSMA-11 PET staging on patient management was assessed within a simulated multidisciplinary tumour board where hypothetical treatment decisions based on clinical information and conventional imaging alone was determined. This treatment decision was compared with the treatment recommendation based on clinical information and 68 Ga-PSMA-11 PET imaging., Results: The primary tumour was positive on 68 Ga-PSMA-11 PET in 113 patients (97%). Nodal metastases were detected in 28 patients (24%) and bone metastases in 14 patients (12%). Compared with clinical staging and conventional imaging, 68 Ga-PSMA-11 PET resulted in new information in 42 of 116 patients (36%). In 32 of 116 patients (27%), this information would most likely have changed the management into a different therapy modality (15 patients, 13%) or adjusted treatment details (e.g. modification of radiotherapy field or lymph node dissection template; 17 patients, 14%)., Conclusion: Information from 68 Ga-PSMA-11 PET staging has the potential to change the management in more than a fourth of the patients who underwent PET staging for their intermediate to high-risk prostate cancer. Whether these more personalized 68 Ga-PSMA-11 PET-based treatment decisions will improve patient outcome needs further investigation.

Positron-emission tomography (PET) with prostate-specific membrane antigen (PSMA) has been increasingly used to image prostate cancer in the last decade. In the staging setting several studies have already been published suggesting PSMA PET can be a valuable tool. They, however, did not translate into recommendations by guidelines. Both PSMA PET/computed tomography (CT) and PET/magnetic resonance imaging have been investigated in the staging setting, showing higher detection rate of prostate cancer lesions over the conventional imaging work-up and some studies already showed an impact on disease management. The aim of this review is to provide an overview of the existing published data regarding PSMA PET for staging prostate cancer, with emphasis on PET/magnetic resonance imaging. Despite the fact that PSMA is a relatively new tool and not officially recommended for staging yet, there are >50 original studies in the literature assessing PSMA PET performance in the staging setting of prostate cancer, and some meta-analyses.

Introduction: Radical prostatectomy with extended pelvic lymph node dissection (ePLND) is a curative treatment option for patients with clinically significant localised prostate cancer. The decision to perform an ePLND can be challenging because the overall incidence of lymph node metastasis is relatively low and ePLND is not free of complications. Using current clinical nomograms to identify patients with nodal involvement, approximately 75-85% of ePLNDs performed are negative. The aim of this study was to assess the added value of 68 Ga-PSMA-11 PET in predicting lymph node metastasis in men with intermediate- or high-risk prostate cancer., Methods: 68 Ga-PSMA-11 PET scans of 60 patients undergoing radical prostatectomy with ePLND were reviewed for qualitative (visual) assessment of suspicious nodes and assessment of quantitative parameters of the primary tumour in the prostate (SUV max , total activity (PSMA total ) and PSMA positive volume (PSMA vol )). Ability of quantitative PET parameters to predict nodal metastasis was assessed with receiver operating characteristics (ROC) analysis. A multivariable logistic regression model combining PSA, Gleason score, visual nodal status on PET and primary tumour PSMA total was built. Net benefit at each risk threshold was compared with five nomograms: MSKCC nomogram, Yale formula, Roach formula, Winter nomogram and Partin tables (2016)., Results: Overall, pathology of ePLND specimens revealed 31 pelvic metastatic lymph nodes in 12 patients. 68 Ga-PSMA-11 PET visual analysis correctly detected suspicious nodes in 7 patients, yielding a sensitivity of 58% and a specificity of 98%. The area under the ROC curve for primary tumour SUV max was 0.70, for PSMA total 0.76 and for PSMA vol 0.75. The optimal cut-off for nodal involvement was PSMA total > 49.1. The PET model including PSA, Gleason score and quantitative PET parameters had a persistently higher net benefit compared with all clinical nomograms., Conclusion: Our model combining PSA, Gleason score and visual lymph node analysis on 68 Ga-PSMA-11 PET with PSMA total of the primary tumour showed a tendency to improve patient selection for ePLND over the currently used clinical nomograms. Although this result has to be validated, 68 Ga-PSMA-11 PET showed the potential to reduce unnecessary surgical procedures in patients with intermediate- or high-risk prostate cancer.

High-intensity focused ultrasound (HIFU) is a promising new modality for the treatment of localized prostate cancer (PCa). Follow-up of patients is recommended with biopsies and multiparametric MRI (mpMRI). However, mpMRI in the postinterventional setting is often false-negative. It was our aim to investigate if the new tracer targeting the prostate-specific membrane antigen ( 68 Ga-PSMA-11) could be used to localize recurrent disease with PET/MR in patients with discrepant findings between mpMRI and template biopsies. Methods: Interim analysis was performed of the first 10 patients scanned between September 2016 and May 2018 with positive template biopsy and negative mpMRI after HIFU from an ongoing clinical trial (NCT02265159). All patients underwent 68 Ga-PSMA-11 PET/MRI within 3 mo. Four prostatic quadrants were defined, and for every quadrant suspicion for recurrence was rated on a 5-point Likert scale from definitely no recurrence (1) to highly suspected of recurrence (5), with 4 used as a cutoff for suspected disease based on PET/MRI by a masked reader. 68 Ga-PSMA-11 uptake of suspected lesions and background areas was measured with the SUV max The apparent diffusion coefficient values of lesions and background were given for each segment. PET/MRI scans were compared with the template biopsy results, including corresponding Gleason scores (GS), number of positive cores, and tumor length. Results: The quadrant-based sensitivity, specificity, and positive and negative predictive values for PET/MRI were 55%, 100%, 100%, and 85%, respectively. Patient-based PET/MRI was negative in 4 cases with GS 3 + 4 and a tumor length between 0.1 and 3 mm. All tumor lesions with GS 4 + 3 or higher were detected on PET/MRI. Conclusion: Our preliminary results indicate that 68 Ga-PSMA-11-PET/MR has the potential to localize PCa recurrence after HIFU occult on mpMRI., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein expressed in the cytosol of normal prostate tissue and highly overexpressed on the membrane of prostate cancer, therefore increasingly used to image prostate cancer. We report a case of a 65-year-old man with two focal PSMA-positive areas on a Ga-PSMA-11 PET/MR, one corresponding to a prostate carcinoma (Gleason score 4 + 3) and another region without any evidence of malignancy, but with corresponding high PSMA-expression on immunohistochemistry.

Purpose: The fast-increasing use of positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) ligand for the imaging of prostate cancer (PCA) biochemical recurrence has led to a rapid change in treatment concepts. Since the superiority of 68 Ga-PSMA-11 PET in detecting recurrent PCA is well established, the aim of our study was to assess its effect on management and outcome in all patients imaged during the first year after its introduction into clinical routine., Methods: Of 327 patients imaged, 223 were referred for recurrent PCA and gave written informed consent for further analysis of their data for this retrospective consecutive cohort analysis. Twenty patients were lost to further follow-up. The rate of detection of recurrence by 68 Ga-PSMA-11 PET was based on the clinical reports. Management before the availability of PET diagnostic information was assessed according to guidelines (therapy option without 68 Ga-PSMA-11 PET). In the 203 patients with follow-up 6 months after 68 Ga-PSMA-11 PET, the therapies effectively implemented as well as follow-up PSA levels were evaluated, with a PSA value of <0.2 ng/ml representing a complete response and a decrease in PSA value of at least 50% from baseline representing a partial response., Results: 68 Ga-PSMA-11 PET was positive and identified recurrence in 166 of the 223 patients (74%), with a detection rate of 50% for recurrent disease at low PSA values of <0.5 ng/ml. 68 Ga-PSMA-11 PET led to a change in management in 122 of the 203 patients (60%). A substantial increase in the use of metastasis-targeted treatment and a reduction in the use of systemic treatment were observed, with 59 of the 203 patients (29%) undergoing targeted radiotherapy (RTXa) only, and 20 patients (10%) undergoing RTXa with hormonal therapy as the two most frequently selected therapy options. The proportion of patients in whom systemic therapy was selected decreased from 60% (133 of 223 patients) to 34% (70 of 203 patients) on the basis of the information provided by the 68 Ga-PSMA-11 PET scan. PSMA PET-directed metastasis-targeted treatment led to a complete response after 6 months in 45% of patients., Conclusion: The high rate of recurrence detection by PSMA PET was confirmed and PSMA PET led to a change in management in 60% of patients. Focal therapy for PSMA-positive lesions is a promising approach with complete responses in 45% of patients.

Purpose: TMPRSS2:ERG gene fusion negatively regulates PSMA expression in prostate adenocarcinoma (PCa) cell lines. Therefore, immunohistochemical (IHC) ERG expression, a surrogate for an underlying ERG rearrangement, and PSMA expression patterns in radical prostatectomy (RPE) specimens of primary PCa, including corresponding PSMA-PET scans were investigated. Methods: Two cohorts of RPE samples (total n=148): In cohort #1 (n=62 patients) with available RPE and preoperative [68Ga]Ga-PSMA-11 PET, WHO/ISUP grade groups, IHC-ERG (positive vs. negative) and IHC-PSMA expression (% PSMA-negative tumour area, PSMA%neg) were correlated with the corresponding SUVmax. In the second cohort #2 (n=86 patients) including RPE only, same histopathological parameters were evaluated. Results: Cohort #1: PCa with IHC-ERG expression (35.5%) showed significantly lower IHC-PSMA expression and lower SUVmax values on the corresponding PET scans. Eight of 9 PCa with negative PSMA-PET scans had IHC-ERG positivity, and confirmed TMPRSS2::ERG rearrangement. In IHC-PSMA positive PCa, IHC-ERG positivity was significantly associated with lower SUVmax values. In cohort #2, findings of higher IHC-PSMA%neg and IHC-ERG expression was confirmed with only 0-10% PSMA%neg tumour areas in IHC-ERG-negative PCa. Conclusion: IHC-ERG expression is significantly associated with more heterogeneous and lower IHC-PSMA tissue expression in two independent RPE cohorts. There is a strong association of ERG positivity in RPE tissue with lower [68Ga]Ga-PSMA-11 uptake on corresponding PET scans. Results may serve as a base for future biomarker development to enable tumour-tailored, individualized imaging approaches. [ABSTRACT FROM AUTHOR]

Purpose: Prostate-specific membrane antigen (PSMA-) PET has become a promising tool in staging and restaging of prostate carcinoma (PCa). However, specific primary tumour features might impact accuracy of PSMA-PET for PCa detection. We investigated histopathological parameters and immunohistochemical PSMA expression patterns on radical prostatectomy (RPE) specimens and correlated them to the corresponding 68Ga-PSMA-11-PET examinations. Methods: RPE specimens of 62 patients with preoperative 68Ga-PSMA-11-PET between 2016 and 2018 were analysed. WHO/ISUP grade groups, growth pattern (expansive vs. infiltrative), tumour area and diameter as well as immunohistochemical PSMA heterogeneity, intensity and negative tumour area (PSMA%neg) were correlated with spatially corresponding SUVmax on 68Ga-PSMA-11-PET in a multidisciplinary analysis. Results: All tumours showed medium to strong membranous (2–3 +) and weak to strong cytoplasmic (1–3 +) PSMA expression. Heterogeneously expressed PSMA was found in 38 cases (61%). Twenty-five cases (40%) showed at least 5% and up to 80% PSMA%neg. PSMA%neg, infiltrative growth pattern, smaller tumour area and diameter and WHO/ISUP grade group 2 significantly correlated with lower SUVmax values. A ROC curve analysis revealed 20% PSMA%neg as an optimal cutoff with the highest sensitivity and specificity (89% and 86%, AUC 0.923) for a negative PSMA-PET scan. A multiple logistic regression model revealed tumoural PSMA%neg (p < 0.01, OR = 9.629) and growth pattern (p = 0.0497, OR = 306.537) as significant predictors for a negative PSMA-PET scan. Conclusions: We describe PSMA%neg, infiltrative growth pattern, smaller tumour size and WHO/ISUP grade group 2 as parameters associated with a lower 68Ga-PSMA-11 uptake in prostate cancer. These findings can serve as fundament for future biopsy-based biomarker development to enable an individualized, tumour-adapted imaging approach. [ABSTRACT FROM AUTHOR]