Prostate-specific Membrane Antigen Positron Emission Research Articles

68Ga-PSMA PET CT/MRI in the initial diagnosis and staging of prostate cancer: A review

Prostate-specific membrane antigen-positron emission tomography (PSMA-PET) imaging has demonstrated potential in addressing prostate cancer (PCa) diagnostic difficulties. According to current guidelines, gallium-68 (68Ga)-PSMA-PET is used as an adjunct to traditional imaging modalities in patients with primary PCa. The purpose of this review, conducted using Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, is to give an overview of studies that have examined the role of 68Ga-PSMA in the initial diagnosis of PCa, its performance in TNM staging, its correlation with prostate-specific antigen (PSA) levels, targeted biopsies, and the International Society of Urological Pathology (ISUP) scores using computed tomography (CT) or magnetic resonance imaging (MRI). The findings demonstrate that, in addition to MRI alone, combining 68Ga-PSMA-PET with MRI-targeted biopsy improves the initial identification of clinically significant prostate cancer (csPCa), particularly for ambiguous prostate imaging-reporting and data system (PI-RADS) three lesions. 68Ga-PSMA-PET/CT is useful when MRI results for csPCa are uncertain, but consistent techniques are required. Regarding risk assessment and therapy planning, 68Ga-PSMA-PET has a strong correlation with both PSA levels and ISUP scores. It accurately detects primary PCa lesions, making it suitable for high-risk patients. In 68Ga-PSMA-PET, higher maximum standardized uptake value (SUVmax) readings are linked to more aggressive illness. For N and M staging, 68Ga-PSMA-PET/CT is more sensitive and specific than conventional imaging; however, for T-staging, multiparametric MRI (mpMRI) provides better accuracy. 68Ga-PSMA-PET/MRI shows improved accuracy for primary PCa detection compared to mpMRI alone. Challenges include the lack of standardized SUVmax cutoff values. 68Ga-PSMA-PET is useful for the initial diagnosis and staging of PCa, complementing MRI, although further research is needed to standardize imaging techniques and interpretations.

A Pilot Study of PSMA PET/CT and MRI Fusion for Prostate Cancer: Software to Replace PET/MRI Hardware.

Introduction: Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT), in combination with magnetic resonance imaging (MRI), may enhance the diagnosis and staging of prostate cancer. Image fusion of separately acquired PET/CT and MRI images serve to facilitate clinical integration and treatment planning. This study aimed to investigate different PSMA PET/CT and MRI image fusion workflows for prostate cancer visualisation. Methods: Eighteen patients with prostate cancer who underwent PSMA PET/CT and MRI prior to radical prostatectomy were retrospectively selected. Alignment of the prostate was performed between PET/CT and MRI via three techniques: semi-automatic rigid, automatic rigid, and automatic non-rigid. Image fusion accuracy was evaluated through boundary and volume agreement, quantified by the Dice Similarity Coefficient (DSC), 95% Hausdorff Distance (HD), and Mean Surface Distance (MSD), with comparison against reconstructed histopathology slices. Results: Image fusion using all techniques resulted in clear lesion visualisation from PSMA PET/CT overlay and anatomical detail afforded by the MRI base and was consistent with histopathology tumour location. Image fusion accuracy was within the recommended range based on a DSC of 0.8-0.9. The automatic non-rigid registration method had the highest volume agreement (DSC: 0.96 ± <0.01) and boundary agreement (HD: 1.17 ± 0.35 mm) when compared to automatic rigid (DSC 0.88 ± 0.02, HD 3.18 ± 0.29 mm) and semi-automatic rigid (DSC 0.80 ± 0.06, HD 5.25 ± 1.68 mm). Conclusions: Image fusion of clinically obtained PET/CT and MRI is feasible and clinically acceptable for use in prostate cancer diagnosis and surgical management. While the best accuracy was observed with the automatic non-rigid technique, which requires further validation, image fusion with clinically accessible methods (semi-automatic rigid) may currently aid patient education, pre-operative planning, and intra-operative guidance.

The Added Value of Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography to Magnetic Resonance Imaging for Local Staging of Prostate Cancer in Patients Undergoing Radical Prostatectomy

Background and objectiveThe role of prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET)/computed tomography (CT) in addition to magnetic resonance imaging (MRI) for local staging of prostate cancer (PC) has been poorly addressed so far. Our aim was to assess the diagnostic accuracy of PSMA PET/CT and MRI, alone and combined, for detection of extraprostatic extension (EPE) and seminal vesicle invasion (SVI) in PC. MethodsWe conducted a multicenter retrospective study evaluating patients undergoing PSMA PET/CT and MRI before radical prostatectomy. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC) for detection of EPE and SVI were calculated for MRI and PSMA PET/CT alone and combined. Key findings and limitationsWe included 550 patients, of whom 2%, had low-risk, 43% had intermediate-risk, and 55% had high-risk PC. Overall, 52% of patients had EPE and 21% had SVI at histopathology. Patient-based comparison of MRI versus PSMA PET/CT for detection of EPE revealed sensitivity of 60% versus 41% (p < 0.001), specificity of 77% versus 83% (p = 0.075), PPV of 75% versus 73% (p = 0.6), NPV of 64% versus 56% (p < 0.001), and AUC of 69% versus 62% (p = 0.01). Combining the modalities increased the sensitivity (73%; p < 0.001) and NPV (69%; p < 0.001) and decreased the specificity (67%; p < 0.001) and PPV (71%; p = 0.01) over MRI alone. Patient-based comparison of MRI versus PSMA PET/CT for detection of SVI revealed sensitivity of 36% versus 44% (p = 0.2), specificity of 96% versus 96% (p > 0.99), PPV of 71% versus 75% (p = 0.6), NPV of 85% versus 87% (p = 0.2), and AUC of 66% versus 70% (p = 0.2). Combining the modalities increased the sensitivity (60%; p < 0.001), NPV (90%; p < 0.001), and AUC (76%; p < 0.001) and decreased the specificity (92%; p < 0.001) over MRI alone. Limitations include the retrospective nature of the study, selection of higher-risk cases for PSMA PET/CT, and lack of central review. Conclusions and clinical implicationsPSMA PET/CT has lower sensitivity for EPE detection in comparison to MRI. However, addition of PSMA PET information to MRI improved the sensitivity for EPE and SVI detection. Thus, the two modalities should be combined to guide treatment selection. Patient summaryCombining MRI (magnetic resonance imaging) scans with another type of imaging called PSMA PET/CT (prostate-specific membrane antigen positron emission tomography/computed tomography) for patients with prostate cancer leads to better identification of cancer growth outside the prostate in comparison to MRI alone. This could potentially improve the choice of prostate cancer treatment.

Prostate-Specific Membrane Antigen (PSMA) PET/CT in the Detection and Diagnosis of Hepatocellular Carcinoma (HCC): A Systematic Review and Meta-Analysis.

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is widely used in prostate cancer. Recent studies indicate hepatocellular carcinoma (HCC) demonstrates PSMA PET uptake. The diagnostic accuracy of PSMA PET for HCC is not known. We conducted a systematic review and meta-analysis of studies assessing 68Ga-PSMA-11 in HCC. Nine studies were included, with 196 patients and a total of 491 HCC lesions. Per-patient analysis yielded a pooled sensitivity of 89.8% (95% CI 78.5-95.5). Specificity was poorly reported, with insufficient data. When per-lesion level analysis was performed on seven studies, the pooled sensitivity was 94.5% (95% CI 82.9-98.4), and specificity was again poorly reported with insufficient data. Among the three studies with adequate data for full per-lesion meta-analysis, 115 lesions in 41 patients demonstrated sensitivity of 97.1% (95% CI 87.8-99.4), while specificity was 42.2% (95% CI 0.3-99.4). Two studies provided sufficient data for meta-analysis on a per-patient level (n = 50 patients), demonstrating a sensitivity of 92.5% (95% CI 64.0-98.9) and specificity of 72.4% (95% CI 1.3-99.8). PSMA PET demonstrates a high sensitivity for HCC and shows promise as an imaging modality for diagnosis and staging of HCC. However, the existing literature does not provide enough data to confidently evaluate its specificity and, therefore, accuracy. Further prospective studies are necessary, with a focus on the accurate reporting of benign lesions and inclusion of patients with an intermediate probability of HCC.

Better Oncological Outcomes After Prostate-specific Membrane Antigen Positron Emission Tomography–guided Salvage Radiotherapy Following Prostatectomy

Background and objectiveUp to 50% of patients with prostate cancer experience prostate-specific antigen (PSA) relapse following primary radical prostatectomy (RP). Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is increasingly being used for staging after RP owing to its high detection rate. Our aim was to compare outcomes for patients who received salvage radiotherapy (sRT) with versus without PSMA PET guidance. MethodsIn this observational case-control study, the control group consisted of 344 patients from the SAKK09/10 trial (sRT without PSMA PET guidance from 2011 to 2014). The treatment group consisted of 1548 patients from a retrospective multicenter cohort (PSMA PET-guided sRT from July 2013 to 2020). Data were collected up to November 2023. Patients with pN1 status at RP, initial cM1 status, cM1 status on PET, or PSA >0.5 ng/ml were excluded. Patients with detectable PSA after RP who were treated with sRT were eligible. We assessed 3-yr biochemical recurrence-free survival (BRFS) and metastasis-free survival (MFS). Key findings and limitationsThe study population of 717 patients comprised a control group (n = 255) with median follow-up of 75 mo and a PSMA PET group (n = 462) with median follow-up of 31 mo. In the PSMA PET cohort, 103 patients (22.3%) had PSMA-positive pelvic lymph nodes (PLNs), 85 (18.4%) received androgen deprivation therapy (ADT), and 104 (22.5%) underwent PLN irradiation. The BRFS rate at 3 yr was 71% (95% confidence interval [CI] 64–78%) for the control group and 77% (95% CI 72–82%) for the PSMA PET group. The PSMA PET group had favorable BRFS at 18–24 mo after sRT (hazard ratio 0.32, 95% CI 0.0.14–0.75; p = 0.01) and a lower rate of lymph node relapse after sRT (standardized mean difference 0.603). The MFS rate at 3 yr was 89.2% (95% CI 84.6–94.1%) for the control group and 91.2% (95% CI 88.1–94.4%) for the PSMA PET group. Conclusions and clinical implicationsOur results suggest a moderate improvement in short-term BRFS if PSMA PET is used to guide sRT. One possible reason is individualized PLN coverage facilitated by PET. MFS was not improved by PSMA PET guidance for sRT. Patients’ summaryFor patients who experience recurrence of prostate cancer after surgical removal of their prostate, salvage radiotherapy (sRT) is a further treatment option. We found that a type of scan called PSMA PET (prostate-specific membrane antigen positron emission tomography) to identify recurrence and guide sRT can improve recurrence-free survival because of better targeting of pelvic lymph nodes that may contain cancer cells.

P104 Concordance between response on prostate-specific membrane antigen positron emission tomography/computed tomography and biochemical response in patients with metastatic hormone-sensitive prostate cancer starting on androgen deprivation therapy plus apalutamide or abiraterone acetate

P104 Concordance between response on prostate-specific membrane antigen positron emission tomography/computed tomography and biochemical response in patients with metastatic hormone-sensitive prostate cancer starting on androgen deprivation therapy plus apalutamide or abiraterone acetate

P105 Prostate-specific membrane antigen positron emission tomography/computed tomography maximum standardized uptake values as a predictor for development of castration resistant prostate cancer in patients with biochemical recurrence after radical prostatectomy

P105 Prostate-specific membrane antigen positron emission tomography/computed tomography maximum standardized uptake values as a predictor for development of castration resistant prostate cancer in patients with biochemical recurrence after radical prostatectomy

O06 Prostate-specific membrane antigen positron emission tomography before meeting the Phoenix criteria for biochemical recurrent prostate cancer after radiotherapy: Earlier detection of recurrences

O06 Prostate-specific membrane antigen positron emission tomography before meeting the Phoenix criteria for biochemical recurrent prostate cancer after radiotherapy: Earlier detection of recurrences

Tubarial salivary glands show a low relative contribution to functional salivary gland tissue mass.

In 2021, the tubarial salivary glands (TSGs) were newly identified on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) as macroscopic glands in the nasopharyngeal wall. However, the relative contribution of the TSGs to the total salivary gland function, and consequently on the development of xerostomia after external beam radiotherapy (EBRT) or PSMA-targeted radionuclide therapy (RNT) is not known. Therefore, we aimed to determine the presence of the TSGs and to quantify uptake in the TSGs on PSMA PET. Qualitative and quantitative analyses were performed on 68Ga-PSMA-11 PET/CT scans of 100 patients with prostate cancer. The mean and maximum standardized uptake value (SUVmean and SUVmax) in the TSGs were measured and compared to the parotid, submandibular and sublingual salivary glands (PSGs, SMSGs and SLSGs, respectively). Furthermore, proportional function of the TSGs was compared to the PSGs, SMSGs and SLSGs based on the total organ PSMA (TO-PSMA). The TSGs were visible on 95% of the 68Ga-PSMA-11 PET/CT scans. The normalized median SUVmean and SUVmax was significantly higher for the PSGs (p < 0.001) and SMSGs (p < 0.001) compared to the TSGs, but not for the SLSGs (p = 0.242 and p = 0.300, respectively). The normalized median TO-PSMA was significantly higher for the PSGs (p < 0.001) and SMSGs (p < 0.001), and significant lower for the SLSGs (p < 0.001) compared the TSGs. The SUVmean, SUVmax and TO-PSMA of the TSGs were most comparable to the SLSGs. However, the measured PSMA uptake may be disproportional towards the saliva production. Therefore, future studies should focus on the relation between PSMA uptake and salivary function before and after PSMA therapy.

Staging Accuracy and Prognostic Value of Prostate-Specific Membrane Antigen PET/CT Strongly Depends on Lymph Node Tumor Burden.

Objectives: To explore the factors affecting the lymph node metastasis (LNM) detection performance of prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) and to evaluate its prognostic value for biochemical recurrence after radical prostatectomy (RP). Methods: Patients who had intermediate- or high-risk prostate cancer and underwent robot-assisted (RA)RP between 2017 and 2021 were included. Initial lymph node staging was carried out using PSMA PET/CT. Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values were calculated. A cut-off value for LNM tumor deposit size that maximizes specificity was investigated and a post hoc specificity analysis was carried out. In survival analysis for biochemical progression-free survival (bPFS) after RP, Kaplan-Meier curves of molecular imaging (mi)N0 and miN1 patients were compared using the log-rank test and separate Cox regression models were developed to reveal the significance of PSMA PET/CT staging in pre- and post-surgery settings. Results: In 583 patients with a prevalence of pathology-proven LNM of 27.4%, overall sensitivity, specificity, PPV, and NPV of PSMA PET/CT per patient were 26.3% [95%CI 18.9-35.5], 93.9% [95%CI 84.9-100], 61.8% [95%CI 44.5-83.5], and 77.1% [95%CI 69.7-85.1], respectively. PSMA PET/CT showed a better sensitivity as LNM tumor deposit size increased (p = 0.003 OR 2.4 [95%CI 1.3-4.4]) and a better specificity in pT3-4 tumors (96.1%) versus pT2 (91.1%, p = 0.024 OR 2.7 [95%CI 1.1-6.3]). After adjustment according to 5.5 mm LNM tumor deposit size, which showed the best discriminative performance (AUC: 0.905 [95%CI 0.804-1.000, p < 0.001]), overall sensitivity tripled (90.2%, p < 0.001). The 1-year bPFS was 56.0% and 83.3% for miN1 and miN0 patients, respectively (p < 0.001). Whereas miN0pN1 was not, miN1pN1 disease was independently associated with decreased bPFS (HR:2.1 95%CI 1.3-3.4, p < 0.001). Conclusions: PSMA PET/CT has a lymph node tumor burden-dependent and cohort-driven diagnostic ability but consequently a strong independent prognostic value for predicting biochemical recurrence after RARP.

Long-Term Outcomes of Prostate-Specific Membrane Antigen–PET Imaging of Recurrent Prostate Cancer

Although prostate-specific membrane antigen positron emission tomography (PSMA-PET) has shown improved sensitivity and specificity compared with conventional imaging for the detection of biochemical recurrent (BCR) prostate cancer, the long-term outcomes of a widespread shift in imaging are unknown. To estimate long-term outcomes of integrating PSMA-PET into the staging pathway for recurrent prostate cancer. This decision analytic modeling study simulated outcomes for patients with BCR following initial definitive local therapy. Inputs used were from the literature and a retrospective cohort study conducted at 2 institutions. The base case analysis assumed modest benefits of earlier detection and treatment, and scenario analyses considered prostate-specific antigen (PSA) level at imaging and different outcomes of earlier vs delayed treatment. The analysis was performed between April 1, 2023, and May 1, 2024. (1) Immediate PSMA-PET imaging, (2) conventional imaging (computed tomography and bone scan [CTBS]) followed by PSMA-PET if CTBS findings were negative or equivocal, and (3) CTBS alone. The main outcomes were detection of metastases, deaths from prostate cancer, and life-years and quality-adjusted life-years (QALYs) gained. The model estimated that per 1000 simulated patients with BCR (assumed median age, 66 years), PSMA-PET is expected to diagnose 611 (95% uncertainty interval [UI], 565-656) patients with metastasis compared with 630 (95% UI, 586-675) patients diagnosed using CTBS followed by PSMA-PET and 297 (95% UI, 202-410) patients diagnosed using CTBS alone. Moreover, the estimated number of prostate cancer deaths was 512 (95% UI, 472-552 deaths) with PSMA-PET, 520 (95% UI, 480-559 deaths) with CTBS followed by PSMA-PET, and 587 (95% UI, 538-632 deaths) with CTBS alone. Imaging with PSMA-PET yielded the highest number of QALYs, which were 824 (95% UI, 698-885) higher than CTBS. These results differed by PSA level at the time of testing, with the highest incremental life-years and QALYs and lowest number of deaths from prostate cancer among patients with PSA levels of at least 5.0 ng/mL. Finally, the estimates were sensitive to the expected benefit of initiating therapy for recurrent prostate cancer earlier in the disease course. The results of this decision-analytic model suggest that upfront PSMA-PET imaging for the evaluation of BCR is expected to be associated with reduced cancer mortality and gains in life-years and QALYs compared with the conventional imaging strategy, assuming modest benefits of earlier detection and treatment.

Phase 2 trial of PSMA PET CT versus planar bone scan and CT in prostate cancer patients progressing while on androgen deprivation therapy

For prostate cancer patients who experience biochemical progression during androgen deprivation therapy (ADT), prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) has not been prospectively compared to planar bone scan plus CT. This was a single-arm, head-to-head, prospective phase II trial (NCT04928820) designed to enroll 102 men with prostate cancer who experienced biochemical progression (rising prostate-specific antigen [PSA] ≥ 1 ng/mL) during ADT. All patients received 68Ga-PSMA-11 PET/CT and 99mTc-MDP planar bone scans. Each scan was interpreted by three central independent readers. The primary endpoint was the per-patient bone metastasis detection rate of PSMA PET/CT versus planar bone scan and CT. Secondary endpoints compared the number of bone metastases detected per patient and the inter-reader agreement of each imaging modality. Twenty-two men were enrolled between July 2021 and June 2022. Due to slow accrual following approval of PSMA PET radiotracers in the U.S. and a lack of a statistical signal between the two imaging modalities on interim analysis, this trial was closed early on October 2022. Median PSA was 8.5 ng/mL (interquartile range: 1.6–77.6). There was 100% agreement between the two scans. Six patients (27%) had negative findings and 16 patients (73%) had positive findings on both scans. PSMA PET/CT and bone scan plus CT detected an equal number of bone lesions for 14 patients (64%), PSMA PET/CT detected more bone lesions for six patients (27%), and bone scan plus CT detected more bone lesions for two patients (9.1%) (p = 0.092). The inter-reader agreement rates of PSMA PET/CT and bone scan plus CT were 96% and 82%, respectively (p = 0.25). In men with biochemical progression during ADT, 68Ga-PSMA-11 PET/CT and 99mTc-MDP planar bone scan plus CT had identical bone metastasis detection rates. Bone scan plus CT can continue to serve as a cost-effective and readily accessible restaging modality in patients with biochemical progression. ClinicalTrials.gov NCT04928820. Registered 16/06/2021.

Prognostic Role of PSMA-Targeted Imaging in Metastatic Castration-Resistant Prostate Cancer: An Overview.

Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has gained a primary role in prostate cancer (PCa) imaging, overcoming conventional imaging and prostate-specific antigen (PSA) serum levels, and has recently emerged as a promising technique for monitoring therapy response in metastatic castration-resistant prostate cancer (mCRPC) patients treated with novel hormonal therapy, taxanes, and radioligand therapy (RLT). In this review, we aim to provide an overview of the most relevant aspects under study and future prospects related to the prognostic role of PSMA PET/CT in mCRPC. A systematic literature search was performed in the following databases: MEDLINE, PubMed, and EMBASE databases. The study focused exclusively on English-language studies, excluding papers not pertinent to the topic. PSMA PET imaging offers a higher sensitivity and specificity than conventional imaging and provides accurate staging and efficient diagnosis of distant metastases. The data presented herein highlight the usefulness of PET in risk stratification, with a prognostic potential that can have a significant impact on clinical practice. Several prospective trials are ongoing and will shortly provide more evidence supporting the prognostic potential of PET PSMA data in this clinical scenario. Current evidence proves the prognostic role of PSMA PET/CT in different settings, with raising relevance also in the context of mCRPC.

Advanced Imaging for Localized Prostate Cancer

Background/Objectives: Prostate cancer is a prevalent malignancy often presenting without early symptoms. Advanced imaging technologies have revolutionized its diagnosis and management. This review discusses the principles, benefits, and clinical applications of multiparametric magnetic resonance imaging (mpMRI), micro-ultrasound (microUS), and prostate-specific membrane antigen positron emission tomography–computed tomography (PSMA PET/CT) in localized prostate cancer. Methods: We conducted a comprehensive literature review of recent studies and guidelines on mpMRI, microUS, and PSMA PET/CT in prostate cancer diagnosis, focusing on their applications in biopsy-naïve patients, those with previous negative biopsies, and patients under active surveillance. Results: MpMRI has demonstrated high sensitivity and negative predictive value in detecting clinically significant prostate cancer (csPCa). MicroUS, a newer technology, has shown promising results in early studies, with sensitivity and specificity comparable to mpMRI. PSMA PET/CT has emerged as a highly sensitive and specific imaging modality, particularly valuable for staging and detecting metastatic disease. All three technologies have been incorporated into urologic practice for prostate cancer diagnosis and management, with each offering unique advantages in different clinical scenarios. Conclusions: Advanced imaging techniques, including mpMRI, microUS, and PSMA PET/CT, have significantly improved the accuracy of prostate cancer diagnosis, staging, and management. These technologies enable more precise targeting of suspicious lesions during biopsy and therapy planning. However, further research, especially randomized controlled trials, is needed to fully establish the optimal use and inclusion of these imaging modalities in various stages of prostate cancer care.

Using a novel PSMA-PET and PSA-based model to enhance the diagnostic accuracy for clinically significant prostate cancer and avoid unnecessary biopsy in men with PI-RADS ≤ 3 MRI.

The diagnostic evaluation of men with suspected prostate cancer (PCa) yet inconclusive MRI (PI-RADS ≤ 3) presents a common clinical challenge. [68Ga]Ga-labelled prostate-specific membrane antigen ([68Ga]Ga-PSMA) positron emission tomography/computed tomography (PET/CT) has shown promise in identifying clinically significant PCa (csPCa). We aim to establish a diagnostic model incorporating PSMA-PET to enhance the diagnostic process of csPCa in PI-RADS ≤ 3 men. This study retrospective included 151 men with clinical suspicion of PCa and PI-RADS ≤ 3 MRI. All men underwent [68Ga]Ga-PSMA PET/CT scans and ultrasound/MRI/PET fusion-guided biopsies. csPCa was defined as Grade Group ≥ 2. PRIMARY-scores from PSMA-PET scans were evaluated. A diagnostic model incorporating PSMA-PET and prostate-specific antigen (PSA)-derived parameters was developed. The discriminative performance and clinical utility were compared with conventional methods. Internal validation was conducted using a fivefold cross-validation with 1000 iterations. In this PI-RADS ≤ 3 cohort, areas-under-the-curve (AUCs) for detecting csPCa were 0.796 (95%CI, 0.738-0.853), 0.851 (95%CI, 0.783-0.918) and 0.806 (95%CI, 0.742-0.870) for PRIMARY-score, SUVmax and routine clinical PSMA-PET assessment, respectively. The diagnostic model comprising PRIMARY-score, SUVmax and serum free PSA/total PSA (fPSA/tPSA) achieved a significantly higher AUC of 0.906 (95%CI, 0.851-0.961) compared to strategies based on PRIMARY-score or SUVmax (P < 0.05) and markedly superior to conventional strategies typically based on PSA density (P < 0.001). The average fivefold cross-validated AUC with 1000 iterations was 0.878 (95%CI, 0.820-0.954). Theoretically, using a threshold of 21.6%, the model could have prevented 78% of unnecessary biopsies while missing only 7.8% of csPCa cases in this cohort. A novel diagnostic model incorporating PSMA-PET derived metrics-PRIMARY-score and SUVmax-along with serum fPSA/tPSA, has been developed and validated. The integrated model may assist clinical decision-making with enhanced diagnostic accuracy over the individual conventional metrics. It has great potential to reduce unnecessary biopsies for men with PI-RADS ≤ 3 MRI results and warrants further prospective and external evaluations.

Prognostic value of PSMA PET in predicting long-term biochemical control following curative intent treatment for prostate cancer.

The aim of this study is to investigate the prognostic value of 68Ga-labelled prostate-specific membrane antigen (PSMA) positron emission tomography (PET) metrics in predicting long-term biochemical failure-free survival (BFFS) following curative intent treatment for prostate cancer. We completed a prospective study that followed men who had PSMA PET for staging of newly diagnosed prostate cancer between 2015 and 2017 who went on to have curative intent treatment with radiotherapy (RT) or radical prostatectomy (RP). PSMA PET CT imaging was reported and the intraprostatic maximum standardised uptake value (SUVmax) was recorded. The primary outcome was BFFS. Statistical analysis included descriptive statistics, Cox proportional hazards (PH) models, Kaplan-Meier survival analysis and a regression tree structured method. A total of 183 men were included in the analysis with a median age of 66 years and the majority of patients (55.2%) had ISUP grade 1-3 disease. All patients had PSMA PET staging prior to curative intent treatment with RP (66.1%) or external beam radiotherapy (33.9%). PSMA-avid pelvic nodes were present in 26 patients but were not associated with worse biochemical control. A PSMA SUVmax of the prostate primary greater than the median (>5.6) was associated with a lower BFFS (HR: 4.4, 95% CI 1.42-3.72, P = 0.01). A multivariate Cox model incorporating initial biopsy grade, age and PSMA SUVmax showed that PSMA SUVmax was an independent predictor of BFFS. The RT-structured method identified an optimal threshold of 6.8 for PSMA SUVmax, above which patients with ISUP 1-3 disease had a significantly worse BFFS. PSMA SUVmax is a strong predictor of BFFS in patients with non-metastatic prostate cancer who underwent curative intent treatment. Patients with low-risk disease on biopsy (ISUP 1-3) but high PSMA SUVmax may have biochemical failure risk analogous to higher-risk disease (ISUP 4-5). These findings allow for further risk stratification and prognosis of patients with newly diagnosed prostate cancer planned for definitive treatment.

Prostate-specific Membrane Antigen Positron Emission Tomography Before Reaching the Phoenix Criteria for Biochemical Recurrence of Prostate Cancer After Radiotherapy: Earlier Detection of Recurrences

Background and objectiveBiochemical recurrence (BCR) of prostate cancer (PCa) after curative radiotherapy (RT) is defined according to the Phoenix criteria, which is a prostate-specific antigen (PSA) rise of ≥2.0 ng/ml above the PSA nadir. Prostate-specific membrane antigen (PSMA)-based positron emission tomography/computed tomography (PET/CT) can identify PCa recurrences at very low PSA values. Our aim was to investigate the detection rate and extent of PCa recurrences using PSMA PET/CT after curative RT among patients with a PSA rise of ≥2.0 ng/ml above the nadir (Phoenix positive, Ph+) and patients not reaching this threshold (Phoenix negative, Ph−) and to compare therapeutic management and clinical outcomes in terms of time to androgen deprivation therapy (ADT) and castration-resistance PCa (CRPC), as well as overall survival. MethodsWe conducted a retrospective analysis of the Prostate Cancer Network Amsterdam (2015–2023) cohort of 568 patients who received curative-intent RT for PCa. Data on PSMA PET/CT outcomes, therapeutic management, and clinical follow-up were collected, including (re)initiation of ADT, progression to CRPC, and survival. Results were compared between groups using logistic regression and survival analyses. Key findings and limitationsThe study cohort comprised 222 patients (39.1%) classified as Ph− and 346 (60.9%) classified as Ph+. PSMA-avid lesions were detected in 170 Ph− patients (76.6%) and 322 (93.1%) Ph+ patients. In these groups, 75.9% of Ph− patients and 45.0% of Ph+ patients were eligible for local salvage therapy (odds ratio [OR 3.84]; p < 0.001). Distant metastases were less frequent in the Ph− group (n = 37, 21.8%) than in the Ph+ group (n = 157, 48.8%; OR 0.29; p < 0.001). Survival analyses revealed longer times to ADT (re)initiation and progression to CRPC, as well as lower overall mortality, in the Ph− group (log-rank p < 0.001). The retrospective study design is the main limitation. Conclusions and clinical implicationsFor patients with PCa recurrence, PSMA PET/CT can detect this recurrence in the majority of cases not meeting the Phoenix criteria for BCR. Early imaging detects recurrences at a less advanced disease stage, allowing potential salvage treatments. In addition, early PSMA PET/CT is associated with longer times to ADT (re)initiation and progression to CRPC, as well as longer overall survival. These positive clinical implications warrant confirmation of our results in prospective studies to reduce potential leadtime bias. Patient summaryWe investigated early use of a special type of scan called PSMA PET (prostate-specific membrane antigen positron emission tomography) in patients with suspicion of recurrence of their prostate cancer after radiotherapy. Early scans can detect recurrence before the cancer progresses to a more advanced stage.

Head-to-head comparison of GA-68 PSMA PET/CT and multiparametric MRI findings with postoperative results in preoperative locoregional staging and localization of prostate cancer.

Accurate staging of prostate cancer (PCa) is essential for determining the appropriate treatment and predicting outcomes. This study is comparing the effectiveness of Gallium-68 Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography (Ga-68 PSMA PET/CT) and multiparametric MRI (mpMRI) in preoperative locoregional staging and localizing PCa. A retrospective analysis was conducted on 78 patients who underwent both mpMRI and Ga-68 PSMA PET/CT scans before surgery. The imaging was reviewed by radiologists and nuclear medicine specialists and compared with the final histopathology, which was reviewed by an experienced uropathologist. mpMRI demonstrated higher sensitivity in detecting extraprostatic extension (EPE) and bladder neck invasion (BNI) compared to Ga-68 PSMA PET/CT (83% vs. 44% and 29% vs. 17%, respectively). Conversely, Ga-68 PSMA PET/CT showed higher sensitivity in detecting seminal vesicle invasion (SVI) and lymph node metastasis (LNM) (75% vs. 55% and 50% vs. 30%, respectively). When both methods were combined, sensitivity increased in detecting both EPE and SVI. The index tumor localization in mpMRI and Ga-68 PSMA PET/CT was found to be in complete agreement with histopathological findings at 36.4% and 41.8%, respectively. When both imaging methods were combined, the agreement with histopathology in predicting index tumor localization reached 72.1%. Both mpMRI and Ga-68 PSMA PET/CT provide valuable and complementary information for tumor localization and locoregional staging. While mpMRI showed higher sensitivity in detecting EPE, Ga-68 PSMA PET/CT demonstrated superior performance in detecting LNM and SVI. The combined use of these imaging modalities enhance accuracy of index tumor localizations.

Prediction of Lesion-Based Treatment Response after Two Cycles of Lu-177 Prostate Specific Membrane Antigen Treatment in Metastatic Castration-Resistant Prostate Cancer Using Machine Learning

Introduction: Lutetium-177 (Lu-177) prostate-specific membrane antigen (PSMA) therapy is a radionuclide treatment that prolongs overall survival in metastatic castration-resistant prostate cancer (MCRPC). We aimed to predict lesion-based treatment response after Lu-177 PSMA treatment using machine learning with texture analysis data obtained from pretreatment Gallium-68 (Ga-68) PSMA positron emission tomography/computed tomography (PET/CT). Methods: Eighty-three progressed, and 91 nonprogressed malignant foci on pretreatment Ga-68 PSMA PET/CT of 9 patients were used for analysis. Malignant foci with at least a 30% increase in Ga-68 PSMA uptake after two cycles of treatment were considered progressed lesions. All other changes in Ga-68 PSMA uptake of the lesions were considered nonprogressed lesions. The classifiers tried to predict progressed lesions. Results: Logistic regression, Naive Bayes, and k-nearest neighbors’ area under the ROC curve (AUC) values in detecting progressed lesions in the training group were 0.956, 0.942, and 0.950, respectively, and their accuracy was 87%, 85%, and 89%, respectively. The AUC values of the classifiers in the testing group were 0.937, 0.954, and 0.867, respectively, and their accuracy was 85%, 88%, and 79%, respectively. Conclusion: Using machine learning with texture analysis data obtained from pretreatment Ga-68 PSMA PET/CT in MCRPC predicted lesion-based treatment response after two cycles of Lu-177 PSMA treatment.

A Machine Learning Approach for Predicting Biochemical Outcome After PSMA-PET-Guided Salvage Radiotherapy in Recurrent Prostate Cancer After Radical Prostatectomy: Retrospective Study.

Salvage radiation therapy (sRT) is often the sole curative option in patients with biochemical recurrence after radical prostatectomy. After sRT, we developed and validated a nomogram to predict freedom from biochemical failure. This study aims to evaluate prostate-specific membrane antigen-positron emission tomography (PSMA-PET)-based sRT efficacy for postprostatectomy prostate-specific antigen (PSA) persistence or recurrence. Objectives include developing a random survival forest (RSF) model for predicting biochemical failure, comparing it with a Cox model, and assessing predictive accuracy over time. Multinational cohort data will validate the model's performance, aiming to improve clinical management of recurrent prostate cancer. This multicenter retrospective study collected data from 13 medical facilities across 5 countries: Germany, Cyprus, Australia, Italy, and Switzerland. A total of 1029 patients who underwent sRT following PSMA-PET-based assessment for PSA persistence or recurrence were included. Patients were treated between July 2013 and June 2020, with clinical decisions guided by PSMA-PET results and contemporary standards. The primary end point was freedom from biochemical failure, defined as 2 consecutive PSA rises >0.2 ng/mL after treatment. Data were divided into training (708 patients), testing (271 patients), and external validation (50 patients) sets for machine learning algorithm development and validation. RSF models were used, with 1000 trees per model, optimizing predictive performance using the Harrell concordance index and Brier score. Statistical analysis used R Statistical Software (R Foundation for Statistical Computing), and ethical approval was obtained from participating institutions. Baseline characteristics of 1029 patients undergoing sRT PSMA-PET-based assessment were analyzed. The median age at sRT was 70 (IQR 64-74) years. PSMA-PET scans revealed local recurrences in 43.9% (430/979) and nodal recurrences in 27.2% (266/979) of patients. Treatment included dose-escalated sRT to pelvic lymphatics in 35.6% (349/979) of cases. The external outlier validation set showed distinct features, including higher rates of positive lymph nodes (47/50, 94% vs 266/979, 27.2% in the learning cohort) and lower delivered sRT doses (<66 Gy in 57/979, 5.8% vs 46/50, 92% of patients; P<.001). The RSF model, validated internally and externally, demonstrated robust predictive performance (Harrell C-index range: 0.54-0.91) across training and validation datasets, outperforming a previously published nomogram. The developed RSF model demonstrates enhanced predictive accuracy, potentially improving patient outcomes and assisting clinicians in making treatment decisions.