The additional value of 68Ga-PSMA PET/CT SUVmax in predicting ISUP GG ≥ 2 and ISUP GG ≥ 3 prostate cancer in biopsy.

BACKGROUND: Prebiopsy magnetic resonance imaging (MRI) increases the detection rate of clinically significant prostate cancer (csPCa). Prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA PET/CT) maximum standardized uptake value (SUVmax) of the prostate may offer additional value in predicting the likelihood of csPCa in biopsy. METHODS: A single-center cohort study involving patients with biopsy-proven PCa who underwent both MRI and PSMA PET/CT between 2020 and 2021. Logistic regression models were developed for International Society of Urological Pathology (ISUP) Grade Group (GG) ≥ 2 and GG ≥ 3 using noninvasive prebiopsy parameters: age, (log-)prostate-specific antigen (PSA) density, PI-RADS 5 lesion presence, extraprostatic extension (EPE) on MRI, and SUVmax of the prostate. Models with and without SUVmax were compared using Likelihood ratio tests and area under the curve (AUC). DeLong's test was used to compare the AUCs. RESULTS: The study included 386 patients, with 262 (68%) having ISUP GG ≥ 2 and 180 (47%) having ISUP GG ≥ 3. Including SUVmax significantly improved both models' goodness of fit (p < 0.001). The GG ≥ 2 model had a higher AUC with SUVmax 89.16% (95% confidence interval [CI]: 86.06%-92.26%) than without 87.34% (95% CI: 83.93%-90.76%) (p = 0.026). Similarly, the GG ≥ 3 model had a higher AUC with SUVmax 82.51% (95% CI: 78.41%-86.6%) than without 79.33% (95% CI: 74.84%-83.83%) (p = 0.003). The SUVmax inclusion improved the GG ≥ 3 model's calibration at higher probabilities. CONCLUSION: SUVmax of the prostate on PSMA PET/CT potentially improves diagnostic accuracy in predicting the likelihood of csPCa in prostate biopsy.

Implementation of PSMA PET/CT and alignment of ordering to SNMMI appropriate use criteria in a large network system.

INTRODUCTION: The Society of Nuclear Medicine and Molecular Imaging (SNMMI) provides appropriate use criteria (AUC) for prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) which include guidance on imaging in newly diagnosed prostate cancer and in patients with biochemically recurrent (BCR) disease. This study aims to examine trends in PSMA implementation and the prevalence and outcomes of scans ordered in scenarios deemed rarely appropriate or not meeting SNMMI AUC. METHODS: We retrospectively identified patients who were diagnosed with presumptive National Comprehensive Cancer Network unfavorable intermediate, high, or very high risk prostate cancer, patients who underwent staging for BCR, and all patients staged with PSMA between July 2021 and March 2023. Positivity was validated by adherence to a predetermined reference standard. RESULTS: The frequency of PSMA use increased in initial staging from 24% to 80% and work-up of BCR from 91% to 99% over our study period. In addition, 5% (17/340) of PSMA scans ordered for initial staging did not meet AUC and 3% (15/557) of posttreatment scans were deemed rarely appropriate. Initial staging orders not meeting SNMMI AUC resulted in no positivity (0/17), while rarely appropriate posttreatment scans were falsely positive in 75% (3/4) of cases. Urologists (53%, 17/32) comprised the largest ordering specialty in rarely appropriate use. CONCLUSION: The frequency of PSMA use rose across the study period. A significant minority of patients received PSMA PET/CT in rarely appropriate scenarios yielding no positivity in initial staging and significant false positivity post-therapy. Further education of providers and electronic medical record-based interventions could help limit the rarely appropriate use of PET imaging.

Key learnings from concordant systematic biopsies in prostate-specific membrane antigen positron emission tomography/computed tomography-guided prostate biopsies: Enhancing targeting accuracy.

BACKGROUND: Prostate cancer (PCa) diagnosis and staging have evolved with the advent of 68Ga-Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT). This study investigates the role of complementary systematic biopsies (SB) during PSMA-PET/CT-guided targeted prostate biopsies (PET-TB) for PCa detection, grading, and distribution. We address the uncertainty surrounding the necessity of SB in conjunction with PET-TB. METHODS: We analyzed PCa grading and distribution in 30 men who underwent PET-TB and SB because of contraindication to magnetic resonance imaging or high clinical suspicion of PCa. Tumor distribution was assessed in relation to the PET-highlighted lesions. Standardized reporting schemes, encompassing SUVmax, PRIMARY score, and miTNM classification, were evaluated. RESULTS: 80% of patients were diagnosed with PCa, with 70% classified as clinically significant (csPCa). SB detected more csPCa cases than PET-TB, but the differences were not statistically significant. Discordant results were observed in 25% of cases, where SB outperformed PET-TB. Spatial analysis revealed that tumor-bearing cores from SB were often located in close proximity to the PET-highlighted region. Reporting schemes showed potential for csPCa detection with significantly increased SUVmax in csPCA patients. Subsequent follow-up data underscored the importance of SB in precise PCa grading and staging. CONCLUSIONS: While PET-TB can simplify prostate biopsy and reduce invasiveness by core number, SB cannot be omitted yet due to potential PET-TB targeting errors. Factors such as limited spatial resolution and fusion inaccuracies contribute to the need for SB. Standardization in reporting schemes currently cannot compensate for targeting errors highlighting the need for refinement.

The prognostic significance of a negative PSMA-PET scan prior to salvage radiotherapy following radical prostatectomy.

AIM: The optimal management for early recurrent prostate cancer following radical prostatectomy (RP) in patients with negative prostate-specific membrane antigen positron-emission tomography (PSMA-PET) scan is an ongoing subject of debate. The aim of this study was to evaluate the outcome of salvage radiotherapy (SRT) in patients with biochemical recurrence with negative PSMA PET finding. METHODS: This retrospective, multicenter (11 centers, 5 countries) analysis included patients who underwent SRT following biochemical recurrence (BR) of PC after RP without evidence of disease on PSMA-PET staging. Biochemical recurrence-free survival (bRFS), metastatic-free survival (MFS) and overall survival (OS) were assessed using Kaplan-Meier method. Multivariable Cox proportional hazards regression assessed predefined predictors of survival outcomes. RESULTS: Three hundred patients were included, 253 (84.3%) received SRT to the prostate bed only, 46 (15.3%) additional elective pelvic nodal irradiation, respectively. Only 41 patients (13.7%) received concomitant androgen deprivation therapy (ADT). Median follow-up after SRT was 33 months (IQR: 20-46 months). Three-year bRFS, MFS, and OS following SRT were 73.9%, 87.8%, and 99.1%, respectively. Three-year bRFS was 77.5% and 48.3% for patients with PSA levels before PSMA-PET ≤ 0.5 ng/ml and > 0.5 ng/ml, respectively. Using univariate analysis, the International Society of Urological Pathology (ISUP) grade > 2 (p = 0.006), metastatic pelvic lymph nodes at surgery (p = 0.032), seminal vesicle involvement (p < 0.001), pre-SRT PSA level of > 0.5 ng/ml (p = 0.004), and lack of concomitant ADT (p = 0.023) were significantly associated with worse bRFS. On multivariate Cox proportional hazards, seminal vesicle infiltration (p = 0.007), ISUP score >2 (p = 0.048), and pre SRT PSA level > 0.5 ng/ml (p = 0.013) remained significantly associated with worse bRFS. CONCLUSION: Favorable bRFS after SRT in patients with BR and negative PSMA-PET following RP was achieved. These data support the usage of early SRT for patients with negative PSMA-PET findings.

Initial [18F]DCFPyL PET/CT in treatment-naïve prostate cancer: correlation with post-ADT PSA outcomes and recurrence.

PURPOSE: Positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) targeting tracers has emerged as a valuable diagnostic tool for prostate cancer (PCa), androgen deprivation therapy (ADT) stands as the cornerstone treatment for advanced PCa, yet forecasting the response to hormonal therapy poses a significant clinical hurdle. METHODS: In a prospective cohort of 86 PCa patients undergoing short-term ADT, this study evaluated the prognostic potential of [18F]DCFPyL PET/CT scans. Comprehensive data encompassing clinical profiles, baseline prostate-specific antigen (PSA) levels, and imaging metrics were assessed. We developed predictive models for assessing decreases in PSA levels (PSA50 and PSA70) based on a combination of PET-related parameters and clinical factors. Kaplan-Meier survival analysis was utilized to ascertain the prognostic value of PET-based metrics. RESULTS: In this study, elevated [18F]DCFPyL uptake within the primary tumor, as indicated by a SUV ≥ 6.78 (p = 0.0024), and a reduction in the tumor volume (TV) of primary PSMA-avid tumor with PSMA-TV < 41.96 cm3 (p = 0.038), as well as an increased burden of metastatic PSMA-avid tumor, with PSMA-TV (PSMA-TV ≥ 71.39 cm3) (p = 0.012) were identified in association with diminished progression-free survival (PFS). PET and clinical parameters demonstrated constrained predictive capacity for PSA50 response as indicated by an area under the curve (AUC) of 0.442. CONCLUSION: Our study revealed that pretreatment [18F]DCFPyL uptake in primary or metastatic tumor sites is prognostically relevant in high-risk PCa patients undergoing ADT. Further research is needed to develop robust predictive models in this multifaceted landscape of PCa management.

The association of quantitative PSMA PET parameters with pathologic ISUP grade: an international multicenter analysis.

PURPOSE: To assess if PSMA PET quantitative parameters are associated with pathologic ISUP grade group (GG) and upgrading/downgrading. METHODS: PCa patients undergoing radical prostatectomy with or without pelvic lymph node dissection staged with preoperative PSMA PET at seven referral centres worldwide were evaluated. PSMA PET parameters which included SUVmax, PSMAvolume, and total PSMA accumulation (PSMAtotal) were collected. Multivariable logistic regression evaluated the association between PSMA PET quantified parameters and surgical ISUP GG. Decision-tree analysis was performed to identify discriminative thresholds for all three parameters related to the five ISUP GGs The ROC-derived AUC was used to determine whether the inclusion of PSMA quantified parameters improved the ability of multivariable models to predict ISUP GG ≥ 4. RESULTS: A total of 605 patients were included. Overall, 2%, 37%, 37%, 10% and 13% patients had pathologic ISUP GG1, 2, 3, 4, and 5, respectively. At multivariable analyses, all three parameters SUVmax, PSMAvolume and PSMAtotal were associated with GG ≥ 4 at surgical pathology after accounting for PSA and clinical T stage based on DRE, hospital and radioligand (all p < 0.05). Addition of all three parameters significantly improved the discrimination of clinical models in predicting GG ≥ 4 from 68% (95%CI 63 - 74) to 74% (95%CI 69 - 79) for SUVmax, 72% (95%CI 67 - 76) for PSMAvolume, 74% (70 - 79) for PSMAtotal and 75% (95%CI 71 - 80) when all parameters were included (all p < 0.05). Decision-tree analysis resulted in thresholds that discriminate between GG (SUVmax 0-6.5, 6.5-15, 15-28, > 28, PSMAvol 0-2, 2-9, 9-20 and > 20 and PSMAtotal 0-12, 12-98 and > 98). PSMAvolume was significantly associated with GG upgrading (OR 1.03 95%CI 1.01 - 1.05). In patients with biopsy GG1-3, PSMAvolume ≥ 2 was significantly associated with higher odds for upgrading to ISUP GG ≥ 4, compared to PSMAvolume < 2 (OR 6.36, 95%CI 1.47 - 27.6). CONCLUSION: Quantitative PSMA PET parameters are associated with surgical ISUP GG and upgrading. We propose clinically relevant thresholds of these parameters which can improve in PCa risk stratification in daily clinical practice.

The prognostic role of next-generation imaging-driven upstaging in newly diagnosed prostate cancer patients.

PURPOSE: Phase III evidence showed that next-generation imaging (NGI), such as prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT), provides higher diagnostic accuracy than bone scan and contrast-enhanced computed tomography (conventional imaging, CI) in the primary staging of intermediate-to-high-risk prostate cancer (PCa) patients. However, due to the lack of outcome data, the introduction of NGI in routine clinical practice is still debated. Analysing the oncological outcome of patients upstaged by NGI (though managed according to CI) might shed light on this issue, supporting the design of randomised trials comparing the effects of treatments delivered based on NGI vs. CI. METHODS: We prospectively enrolled a cohort of 100 biopsy-proven intermediate-to-high-risk PCa patients staged with CI and PSMA PET/CT (though managed according to the CI stage), to assess the frequency of the stage migration phenomenon. Stage migration was then assessed as biochemical recurrence-free survival (bRFS) predictor. RESULTS: Three patients were lost at follow-up after imaging. PSMA PET/CT upstaged 26.8% of patients compared to CI, while it downstaged 6.1% of patients. Notably, 50% of patients excluded from surgery due to the presence of bone metastases at CI would have been treated with radical-intent approaches if PSMA PET/CT had guided the treatment choice. After a median follow-up of 6 months of surgically treated patients, 22/83 (26.5%) had biochemical recurrence (BCR). PSMA PET/CT-driven upstaging determined a significant risk increase for BCR (HR:3.41, 95%CI:1.21-9.56, p = 0.019). Including stage migration in a univariable and multivariable model identified PSMA PET/CT-upstaging as an independent predictor of bRFS. CONCLUSIONS: In conclusion, implementing NGI for staging purposes improves the prediction of bRFS. Although phase III evidence is still needed, this advancement suggests that NGI may better identify patients who would benefit from local treatments than those who may achieve better oncological outcomes through systemic treatment.

Prostate-specific membrane antigen radioguided surgery with negative histopathology: an in-depth analysis.

PURPOSE: To identify reasons for negative histopathology of specimens from prostate-specific membrane antigen (PSMA) radioguided surgery (PSMA-RGS) in recurrent prostate cancer (PCa) after prostatectomy. METHODS: Of 302 patients who underwent PSMA-RGS, 17 (5.6%) demonstrated a negative histopathology. Preoperative data, PSMA PET, PSMA SPECT, and follow-up information were analyzed retrospectively to differentiate true/false positive (TP/FP) from true/false negative (TN/FN) lesions. RESULTS: The median prostate-specific antigen at PET was 0.4 ng/ml (interquartile range [IQR] 0.3-1.2). Twenty-five index lesions (median short axis 7 mm, IQR 5-8; median long-axis 12 mm, IQR 8-17) had a median SUVmax of 4 (IQR 2.6-6; median PSMA expression score 1, IQR 1-1). Six lesions were TP, twelve were FP, one was TN, and six remained unclear. All TP lesions were in the prostatic fossa or adjacent to the internal iliac arteries. Three suspected local recurrences were FP. All FP lymph nodes were located at the distal external iliac arteries or outside the pelvis. A low PSMA-expressing TN node was identified next to a common iliac artery. Unclear lesions were located next to the external iliac arteries or outside the pelvis. CONCLUSION: In most cases with a negative histopathology from PSMA-RGS, lesions were FP on PSMA PET. Unspecific uptake should be considered in low PSMA-expressing lymph nodes at the distal external iliac arteries or outside the pelvis, especially if no PSMA-positive lymph nodes closer to the prostatic fossa are evident. Rarely, true positive metastases were missed by surgery or histopathology.

Whole pelvis vs. hemi pelvis elective nodal radiotherapy in patients with PSMA-positive nodal recurrence after radical prostatectomy - a retrospective multi-institutional propensity score analysis.

PURPOSE: Despite growing evidence for bilateral pelvic radiotherapy (whole pelvis RT, WPRT) there is almost no data on unilateral RT (hemi pelvis RT, HPRT) in patients with nodal recurrent prostate cancer after prostatectomy. Nevertheless, in clinical practice HPRT is sometimes used with the intention to reduce side effects compared to WPRT. Prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA-PET/CT) is currently the best imaging modality in this clinical situation. This analysis compares PSMA-PET/CT based WPRT and HPRT. METHODS: A propensity score matching was performed in a multi-institutional retrospective dataset of 273 patients treated with pelvic RT due to nodal recurrence (214 WPRT, 59 HPRT). In total, 102 patients (51 in each group) were included in the final analysis. Biochemical recurrence-free survival (BRFS) defined as prostate specific antigen (PSA) < post-RT nadir + 0.2ng/ml, metastasis-free survival (MFS) and nodal recurrence-free survival (NRFS) were calculated using the Kaplan-Meier method and compared using the log rank test. RESULTS: Median follow-up was 29 months. After propensity matching, both groups were mostly well balanced. However, in the WPRT group there were still significantly more patients with additional local recurrences and biochemical persistence after prostatectomy. There were no significant differences between both groups in BRFS (p = .97), MFS (p = .43) and NRFS (p = .43). After two years, BRFS, MFS and NRFS were 61%, 86% and 88% in the WPRT group and 57%, 90% and 82% in the HPRT group, respectively. Application of a boost to lymph node metastases, a higher RT dose to the lymphatic pathways (> 50 Gy EQD2α/ß=1.5 Gy) and concomitant androgen deprivation therapy (ADT) were significantly associated with longer BRFS in uni- and multivariate analysis. CONCLUSIONS: Overall, this analysis presents the outcome of HPRT in nodal recurrent prostate cancer patients and shows that it can result in a similar oncologic outcome compared to WPRT. Nevertheless, patients in the WPRT may have been at a higher risk for progression due to some persistent imbalances between the groups. Therefore, further research should prospectively evaluate which subgroups of patients are suitable for HPRT and if HPRT leads to a clinically significant reduction in toxicity.

Prediction of clinically significant prostate cancer by [68 Ga]Ga-PSMA-11 PET/CT: a potential tool for selecting patients for active surveillance.

PURPOSE: In our study, our aim was to investigate the role of [68 Ga]Ga-PSMA-11 PET /CT imaging in the diagnosis of clinically significant prostate cancer (csPCa) (ISUP GG 2 and higher) in patients initially diagnosed with ISUP GG 1 and 2 after prostate biopsy. MATERIALS AND METHODS: We retrospectively reviewed 147 patient records in whom [68 Ga]Ga-PSMA-11 PET/CT imaging was performed preoperatively. All patients were initially diagnosed with ISUP GG 1 and 2 PCa by biopsy. Final pathology reports were obtained after radical prostatectomy. The [68 Ga]Ga-PSMA-11 PET/CT images were evaluated to determine the PRIMARY score. Patients' mpMRI-PIRADS scores were also recorded when available and analyzed in correlation with the pathology results. RESULTS: For the 114 patients scored using PRIMARY, 19 out of 37 patients with scores of 1 and 2 (51%) were diagnosed with csPCa. Of the 77 patients with PRIMARY scores between 3 and 5, 64 (83%) had csPCa. Notably, every patient with a PRIMARY score of 5 had csPCa. PRIMARY scoring had a sensitivity of 77% and specificity of 58%, with a positive predictive value of 83%. A moderate correlation was observed between PRIMARY scores and ISUP GG (Rho = 0.54, p < 0.001). In contrast, the PIRADS score displayed a sensitivity and specificity of 86% and 25% respectively, with a positive predictive value of 68%. No substantial correlation was found between PIRADS and ISUP GG. Statistical analysis revealed a significant correlation between PRIMARY and ISUP GG (p < 0.001), but not between PIRADS and ISUP GG (p = 0.281). Comparatively, PRIMARY scoring was significantly more reliable than PIRADS scoring in identifying csPCa. CONCLUSION: [68 Ga]Ga-PSMA-11 PET/CT imaging is promising for distinguishing high-risk prostate cancer patients from those apt for active surveillance, potentially aiding in the identification of csPCa.

Added Value of [18F]PSMA-1007 PET/CT and PET/MRI in Patients With Biochemically Recurrent Prostate Cancer: Impact on Detection Rates and Clinical Management.

BACKGROUND: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) can change management in a large fraction of patients with biochemically recurrent prostate cancer (BCR). PURPOSE: To investigate the added value of PET to MRI and CT for this patient group, and to explore whether the choice of the PET paired modality (PET/MRI vs. PET/CT) impacts detection rates and clinical management. STUDY TYPE: Retrospective. SUBJECTS: 41 patients with BCR (median age [range]: 68 [55-78]). FIELD STRENGTH/SEQUENCE: 3T, including T1-weighted gradient echo (GRE), T2-weighted turbo spin echo (TSE) and dynamic contrast-enhanced GRE sequences, diffusion-weighted echo-planar imaging, and a T1-weighted TSE spine sequence. In addition to MRI, [18F]PSMA-1007 PET and low-dose CT were acquired on the same day. ASSESSMENT: Images were reported using a five-point Likert scale by two teams each consisting of a radiologist and a nuclear medicine physician. The radiologist performed a reading using CT and MRI data and a joint reading between radiologist and nuclear medicine physician was performed using MRI, CT, and PET from either PET/MRI or PET/CT. Findings were presented to an oncologist to create intended treatment plans. Intrareader and interreader agreement analysis was performed. STATISTICAL TESTS: McNemar test, Cohen's κ, and intraclass correlation coefficients. A P-value <0.05 was considered significant. RESULTS: 7 patients had positive findings on MRI and CT, 22 patients on joint reading with PET/CT, and 18 patients joint reading with PET/MRI. For overall positivity, interreader agreement was poor for MR and CT (κ = 0.36) and almost perfect with addition of PET (PET/CT κ = 0.85, PET/MRI κ = 0.85). The addition of PET from PET/CT and PET/MRI changed intended treatment in 20 and 18 patients, respectively. Between joint readings, intended treatment was different for eight patients. DATA CONCLUSION: The addition of [18F]PSMA-1007 PET/MRI or PET/CT to MRI and CT may increase detection rates, could reduce interreader variability, and may change intended treatment in half of patients with BCR. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.

Prostate-specific membrane antigen positron emission tomography in addition to multiparametric magnetic resonance imaging and biopsies to select prostate cancer patients for focal therapy.

OBJECTIVE: To evaluate the additional value of prostate-specific membrane antigen positron emission tomography (PSMA-PET) to conventional diagnostic tools to select patients for hemi-ablative focal therapy (FT). PATIENTS AND METHODS: We performed a retrospective analysis on a multicentre cohort (private and institutional) of 138 patients who underwent multiparametric magnetic resonance imaging (mpMRI), PSMA-PET, and systematic biopsies prior to radical prostatectomy between January 2011 and July 2021. Patients were eligible when they met the consensus criteria for FT: PSA <15 ng/mL, clinical/radiological T stage ≤T2b, and International Society of Urological Pathology (ISUP) grade 2-3. Clinically significant prostate cancer (csPCa) was defined as ISUP grade ≥2, extracapsular extension >0.5 mm or seminal vesicle involvement at final histopathology. The diagnostic accuracy of mpMRI, systematic biopsies and PSMA-PET for csPCa (separate and combined) was calculated within a four-quadrant prostate model by receiver-operating characteristic and 2 × 2 contingency analysis. Additionally, we assessed whether the diagnostic tools correctly identified patients suitable for hemi-ablative FT. RESULTS: In total 552 prostate quadrants were analysed and 272 (49%) contained csPCa on final histopathology. The area under the curve, sensitivity, specificity, positive predictive value and negative predictive value for csPCa were 0.79, 75%, 83%, 81% and 77%, respectively, for combined mpMRI and systematic biopsies, and improved after addition of PSMA-PET to 0.84, 87%, 80%, 81% and 86%, respectively (P < 0.001). On final histopathology 46/138 patients (33%) were not suitable for hemi-ablative FT. Addition of PSMA-PET correctly identified 26/46 (57%) non-suitable patients and resulted in 4/138 (3%) false-positive exclusions. CONCLUSIONS: Addition of PSMA-PET to the conventional work-up by mpMRI and systematic biopsies could improve selection for hemi-ablative FT and guide exclusion of patients for whom whole-gland treatments might be a more suitable treatment option.

A systematic review on artificial intelligence evaluating PSMA PET scan for intraprostatic cancer.

OBJECTIVES: To assess artificial intelligence (AI) ability to evaluate intraprostatic prostate cancer (PCa) on prostate-specific membrane antigen positron emission tomography (PSMA PET) scans prior to active treatment (radiotherapy or prostatectomy). MATERIALS AND METHODS: This systematic review was registered on the International Prospective Register of Systematic Reviews (PROSPERO identifier: CRD42023438706). A search was performed on Medline, Embase, Web of Science, and Engineering Village with the following terms: 'artificial intelligence', 'prostate cancer', and 'PSMA PET'. All articles published up to February 2024 were considered. Studies were included if patients underwent PSMA PET scan to evaluate intraprostatic lesions prior to active treatment. The two authors independently evaluated titles, abstracts, and full text. The Prediction model Risk Of Bias Assessment Tool (PROBAST) was used. RESULTS: Our search yield 948 articles, of which 14 were eligible for inclusion. Eight studies met the primary endpoint of differentiating high-grade PCa. Differentiating between International Society of Urological Pathology (ISUP) Grade Group (GG) ≥3 PCa had an accuracy between 0.671 to 0.992, sensitivity of 0.91, specificity of 0.35. Differentiating ISUP GG ≥4 PCa had an accuracy between 0.83 and 0.88, sensitivity was 0.89, specificity was 0.87. AI could identify non-PSMA-avid lesions with an accuracy of 0.87, specificity of 0.85, and specificity of 0.89. Three studies demonstrated ability of AI to detect extraprostatic extensions with an area under curve between 0.70 and 0.77. Lastly, AI can automate segmentation of intraprostatic lesion and measurement of gross tumour volume. CONCLUSION: Although the current state of AI differentiating high-grade PCa is promising, it remains experimental and not ready for routine clinical application. Benefits of using AI to assess intraprostatic lesions on PSMA PET scans include: local staging, identifying otherwise radiologically occult lesions, standardisation and expedite reporting of PSMA PET scans. Larger, prospective, multicentre studies are needed.

Intra-individual comparison of prostate-specific membrane antigen positron emission tomography/computed tomography versus bone scan in detecting skeletal metastasis at prostate cancer diagnosis.

OBJECTIVES: To compare the diagnostic performance and radiological staging impact of 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) compared to 99 Tc whole-body bone scan (WBBS) for the detection of skeletal metastasis in the primary staging of prostate cancer (PCa). PATIENTS AND METHODS: A prospective institutional database was retrospectively examined for patients who underwent both PSMA PET and WBBS within a 1 week interval for PCa primary staging. Lesions were categorised as 'negative', 'equivocal', or 'definite' based on nuclear medicine physician interpretation. Metastatic burden was characterised for each imaging modality according to three groups: (i) local disease (no skeletal metastases), (ii) oligometastatic disease (three or fewer skeletal metastases), or (iii) polymetastatic disease (more than three skeletal metastases). RESULTS: There were 667 patients included. The median (interquartile range) prostate-specific antigen level was 9.2 (6.2-16) ng/mL and 60% of patients were high risk according to a modified D'Amico risk classification. The overall distribution of skeletal metastasis detection changed across the two scans overall (P = 0.003), being maintained within high-risk (P = 0.030) and low-risk (P = 0.018) groups. PSMA PET/CT identified more definite skeletal metastases compared to WBBS overall (10.3% vs 7.3%), and according to risk grouping (high: 12% vs 9%, intermediate: 4% vs 1%). Upstaging was more common with PSMA PET/CT than WBBS (P = 0.001). The maximum standardised uptake value (SUVmax ) of the primary tumour was associated with upstaging of skeletal metastases on PSMA PET/CT (P = 0.025), while age was associated with upstaging on WBBS (P = 0.021). The SUVmax of the primary tumour and metastases were both higher according to extent of metastatic disease (P = 0.001 and P < 0.001, respectively). CONCLUSIONS: More skeletal metastases were detected with PSMA PET/CT than WBBS, resulting in a higher upstaging rate mostly in high-risk patients. The SUVmax of the primary tumour and metastases was associated with upstaging.

Comparison of Ga-PSMA PET MRI with mpMRI in localization and regional staging of prostate cancer.

PURPOSE: To compare diagnostic accuracy in localization and detection of extraprostatic extension (EPE), seminal vesicle invasion (SVI), lymph node involvement (LNI) between PSMA PET MRI and multiparametric MRI (mpMRI) in carcinoma prostate. METHODS: We did a prospective study of consecutive men with biopsy-proven prostate cancer who underwent radical prostatectomy between July'2020 and Dec'2021 at our institution. Patients underwent PSMA PET MRI imaging. MpMRI findings were inferred separately by another radiologist who was blinded to the PSMA PET findings. PIRADS > 2 and any standardized uptake value (SUV) were considered positive. Findings were mapped to a 30-region anatomical grid and compared with pathology. The uro-pathologist also marked the presence of the tumor onto the same anatomical grid. The presence of EPE, SVI, and LVI was noted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The significance in difference: McNemar test. SUVmax and Gleason score: Kruskal-Wallis test. RESULTS: Seventy-five men (mean age 65) with an average PSA of 21.5 ng/ml were included. The sensitivity of PSMA PET MRI for localization was higher [63.6 vs 41.9] (p < 0.001) while specificity was similar [81.5 vs 83.2] (p 0.103). The former had a higher sensitivity to detect SVI [85.7 vs 57.10] (p = 0.03). No difference in the detection of EPE or LNI was noted. SUVmax > 7 was associated with high-risk disease (Gleason score >/= 7). LIMITATIONS: non-randomized nature, higher risk population. CONCLUSION: Ga-PSMA PET MRI improved the localization of prostate cancer and better detection of SVI. Further studies are required. It can act as a single-stop investigation for the primary staging of prostate cancer.

The role of PSMA PET/CT in predicting downgrading in patients with Gleason score 4+4 prostate cancer in prostate biopsy.

BACKGROUND: To investigate the predictable parameters associated with downgrading in patients with a Gleason score (GS) 8 (4+4) in prostate biopsy after radical prostatectomy. METHODS: We retrospectively analyzed 62 patients with a GS of 4+4 on prostate biopsy who underwent robotic radical prostatectomy between 2017 and 2022. RESULTS: 38 of 62 (61.2%) were downgraded. In multivariable logistic regression model, Ga-68 prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) SUV max was independent predictor of downgrading (OR 0.904; p = 0.011) and a Logistic Regression model was constructed using the following formula: Y = 1.465-0.95 (PSMA PET/CT SUV max). The model using this variable correctly predicted the downgrading in 72.6% of patients. The AUC for PSMA PET/CT SUV max was 0.709 the cut off being 8.8. A subgroup analysis was performed in 37 patients who had no other European Association of Urology (EAU) high risk features. 25 out of 37 (67.5%) were downgraded, and 21 of these 25 had organ confined disease. Low PSMA SUV max (<8.1) and percentage of GS 4+4 biopsy cores to cancer bearing cores (45.0%) were independently associated with downgrading to GS 7. CONCLUSION: PSMA PET/CT can be used to predict downgrading in patients with GS 4+4 PCa. Patients with GS 4+4 disease, but no other EAU high risk features, low percentage of GS 4+4 biopsy cores to cancer bearing cores, and a low PSMA PET/CT SUV max are associated with a high likelihood of the cancer reclassification to intermediate risk group.

A PSMA PET/CT-based risk model for prediction of concordance between targeted biopsy and combined biopsy in detecting prostate cancer.

PURPOSE: This study is to investigate the diagnostic value of 68Ga-PSMA-11 in improving the concordance between mpMRI-TB and combined biopsy (CB) in detecting PCa. METHODS: 115 consecutive men with 68Ga-PSMA-11 PET/CT prior to prostate biopsy were included for analysis. PSMA intensity, quantified as maximum standard uptake value (SUVmax), minimum apparent diffusion coefficient (ADCmin) and other clinical characteristics were evaluated relative to biopsy concordance using univariate and multivariate logistic regression analyses. A prediction model was developed based on the identified parameters, and a dynamic online diagnostic nomogram was constructed, with its discrimination evaluated through the area under the ROC curve (AUC) and consistency assessed using calibration plots. To assess its clinical applicability, a decision curve analysis (DCA) was performed, while internal validation was conducted using bootstrapping methods. RESULTS: Concordance between mpMRI-TB and CB occurred in 76.5% (88/115) of the patients. Multivariate logistic regression analyses performed that SUVmax (OR= 0.952; 95% CI 0.917-0.988; P= 0.010) and ADCmin (OR= 1.006; 95% CI 1.003-1.010; P= 0.001) were independent risk factors for biopsy concordance. The developed model showed a sensitivity, specificity, accuracy and AUC of 0.67, 0.78, 0.81 and 0.78 in the full sample. The calibration curve demonstrated that the nomogram's predicted outcomes closely resembled the ideal curve, indicating consistency between predicted and actual outcomes. Furthermore, the decision curve analysis (DCA) highlighted the clinical net benefit achievable across various risk thresholds. These findings were reinforced by internal validation. CONCLUSIONS: The developed prediction model based on SUVmax and ADCmin showed practical value in guiding the optimization of prostate biopsy pattern. Lower SUVmax and Higher ADCmin values are associated with greater confidence in implementing mono-TB and safely avoiding SB, effectively balancing benefits and risks.

Distinguishing spheno-orbital metastatic prostate cancer mimicking a meningioma using novel 18F-PSMA PET/CT imaging.

A 78-year-old man presented with acute-onset left temporal pain, eyelid swelling, and double vision. Computed tomography (CT) demonstrated a left sphenoid wing mass with extra-osseous intra-orbital and intracranial extension, thought to be a typical sphenoid wing meningioma by the primary team. The patient was admitted for an urgent craniotomy, which was planned for the following day. However, upon consultation with ophthalmic plastic surgery, concern was raised for an alternative diagnosis given the atypical timeline, inflammatory changes, and uncharacteristic imaging findings of mixed lytic and sclerotic bony changes without hyperostosis on CT and extensive peri-lesional dural thickening and enhancement on magnetic resonance imaging. A serum prostate-specific antigen was elevated to 206 ng/mL. Subsequent positron emission tomography (PET)/CT using 18F-fluorodeoxyglucose radiotracer was negative for metastatic disease. A prostate-specific membrane antigen (PSMA) PET/CT was then obtained and demonstrated extensive metastases. An orbital biopsy revealed poorly differentiated prostatic adenocarcinoma. The significant incongruence between the standard PET/CT and PSMA PET/CT highlights the value of this novel advanced radiographic modality in narrowing the differential diagnosis and determining the extent of disease. Findings of widespread metastasis on the PSMA PET/CT ultimately helped to avoid a large, morbid neurosurgical intervention in this patient, allowing for a minimally invasive orbital biopsy to characterize the tumor for therapeutic targeting.

Metastatic PSMA avid prostate tumour with penile uptake; a rare metastatic site on PET-CT.

Prostate carcinoma is the most common malignancy in males and the second most common cause of mortality. Initially, metastatic prostate cancers tend to involve bones, but these tumours can involve any system. Gallium-68 prostate specific membrane antigen (PSMA) positron emission computed tomography (PET-CT) scan is indicated in prostate cancer patients if PSA levels are raised, and CT and bone scans are inconclusive. Metastatic penile involvement is a rare phenomenon. We present a case of prostate cancer with foci of PSMA uptake in the penile region. .

Advances in radiology and pathology of prostate cancer: a review for the pathologist.

Multiparametric magnetic resonance imaging (mpMRI) has improved systematic prostate biopsy procedures in the diagnosis of clinically significant prostate cancer (csPCa) by reducing the number of unnecessary biopsies; numerous level one evidence studies have confirmed the accuracy of MRI-targeted biopsy, but, still today, systematic prostate biopsy is recommended to reduce the 15-20% false negative rate of mpMRI. New advanced imaging has been proposed to detect suspicious lesions and perform targeted biopsies especially when mpMRI cannot be performed. Transrectal ultrasound (TRUS) modalities are emerging as methods with greater sensitivity and specificity for the detection of PCa compared to the traditional TRUS; these techniques include elastography and contrast-enhanced ultrasound, as well as improved B-mode and Doppler techniques. These modalities can be combined to define a novel ultrasound approach: multiparametric ultrasound (mpUS). More recently, micro-ultrasound (MicroUS) and prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) have demonstrated to be sensitive for the detection of primary prostatic lesions resulting highly correlated with the aggressiveness of the primary prostatic tumor. In parallel, artificial intelligence is advancing and is set out to deeply change both radiology and pathology. In this study we address the role, advantages and shortcomings of novel imaging techniques for Pca, and discuss future directions including the applications of artificial intelligence-based techniques to imaging as well as histology. The significance of these findings for the practicing pathologist is discussed.