Treatment response assessment in mCRPC: is PSMA-PET/CT going to take the lead?

The assessment of response to therapy in prostate cancer (PCa) patients is an ongoing, open issue. Prostate-specific antigen has limitations, especially in advanced metastatic PCa, which often displays intratumor variability in terms of response to therapy. Conventional imaging (i.e. computerized tomography and bone scan) is of limited use for its low sensitivity and specificity. Positron-emission tomography (PET) with prostate-specific membrane antigen (PSMA) demonstrated higher sensitivity and specificity, and novel PSMA-based criteria have been recently proposed for treatment response, with promising results in different scenarios, from chemotherapy to radioligand therapy. PSMA-based criteria have been found to outperform the current RECIST 1.1 and Prostate Cancer Working Group 3 frameworks in describing the behavior of PCa, precisely assessing tumor phenotypes through molecular-imaging-derived parameters. This review critically explores the current evidence about the role of PSMA PET/computed tomography in the assessment of treatment response.

Prostate-specific membrane antigen PET versus [99mTc]Tc-MDP bone scan for diagnosing bone metastasis in prostate cancer: a head-to-head comparative meta-analysis.

Purpose: To evaluate the diagnostic performance of PSMA PET/CT, including [68Ga]Ga-PSMA-11 and [18F]DCFPyL, in comparison with the [99mTc]Tc-MDP bone scan (BS) in identifying bone metastases among prostate cancer patients. Methods: A search was performed in the PubMed and Embase databases to locate pertinent publications from inception to February 12, 2024. The studies included were those that examined the diagnostic effectiveness of PSMA PET/CT (covering [68Ga]Ga-PSMA-11 and [18F]DCFPyL) compared to [99mTc]Tc-MDP BS in identifying bone metastases among prostate cancer patients. The quality of the selected studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) checklist. Results: The meta-analysis included nine articles involving 702 patients. The sensitivity of PSMA PET/CT was higher compared to [99mTc]Tc-MDP BS (0.98 vs. 0.85, P < 0.01), while the specificity of PSMA PET/CT was also higher than [99mTc]Tc-MDP BS (0.97 vs. 0.70,P < 0.01). In subgroup analysis, the sensitivity of [68Ga]Ga-PSMA-11 PET/CT was higher compared to [99mTc]Tc-MDP BS (0.98 vs. 0.86), while the specificity of [68Ga]Ga-PSMA-11 PET/CT was also higher than [99mTc]Tc-MDP BS (0.98 vs. 0.65). Conclusion: Our meta-analysis demonstrates that PSMA PET/CT exhibits superior sensitivity and specificity in comparison with [99mTc]Tc-MDP BS for identifying bone metastases in prostate cancer patients. Further research with head-to-head design is necessary to validate these results and evaluate the clinical effectiveness of these imaging methods. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier PROSPERO CRD42024545112.

PSMA PET/CT patterns of recurrence after mono-brachytherapy in men with low and intermediate prostate cancer and subsequent management.

PURPOSE: Brachytherapy as monotherapy is a recommended treatment option for men with low to intermediate risk prostate cancer. Local recurrence is difficult to identify. This study investigated PSMA PET/CT for recurrence after brachytherapy, as well as their subsequent management when recurrence occurred only within the prostate. METHODS: We performed a retrospective single-center analysis for patients who were treated with brachytherapy as monotherapy for prostate cancer from May 2002 to May 2021 and who underwent a PSMA PET/CT for BCR. We report the findings on PSMA PET/CT, quantitative parameters, as well as the later management of the patients. RESULTS: Forty patients were identified, who underwent PSMA PET/CT to investigate a rising PSA at a median (IQR) of 7 years (3.0-10.8) after initial therapy. Median (IQR) PSA at time of PSMA PET/CT was 6.54 ng/mL (3.9-15.5). On PSMA PET/CT, 20/40 (50%) men had prostate-only recurrence. Of the 20 patients with prostate-only recurrence, 8/20 (40%) had recurrence in a high-dose radiation zone, versus 7/20 (35%) in an under-covered zone. On PSMA PET/CT, recurrence within the prostate had median (IQR) SUVmax 10.4 (5.1-15.7) and volume 2.9 mL (2.0-11.2). Subsequent management of these patients with local recurrence included surveillance followed by ADT (9/20, 45%). For those with surveillance followed by ADT, the mean time before introduction of ADT was 4.1 years (range 1-8 years).

Evaluating response to radium-223 using 68Ga-PSMA PET/CT imaging in patients with metastatic castration-resistant prostate cancer.

AIM: Conventional imaging techniques and prostate-specific antigen (PSA) values are not useful to follow-up patients during Radium-223 treatment. The study aimed to evaluate the predictive value of prostate-specific membrane antigen PSMA PET/CT-based response in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving Radium-223 dichloride treatment. MATERIALS AND METHODS: Patients treated with radium-223, having performed two 68Ga-PSMA-11 PET/CT scans (baseline 1 month before treatment initiation and follow-up 2 weeks after the third cycle), were retrospectively evaluated. Visual and quantitative PET image analyses were performed, and patients were dichotomized into progressive (PD) and non-PD according to Response Evaluation Criteria in PSMA­imaging (RECIP1.0) and PSMA-PET Progression criteria (PPP). The primary endpoint was overall survival (OS). Cohen's Kappa (κ) was used to test the agreement between the two criteria. The Cox regression hazard model and Kaplan-Meier method were used for survival analyses. RESULTS: Twenty-eight mCRPC patients were evaluated. Sixteen (43%) and 18 (64%) patients had PD according to RECIP1.0 and PPP, respectively; κ = 0.85 (95% CI 0.65-1.00). After a median follow-up of 16 months (interquartile IQR 9-33), 20 (71%) patients died. Patients with PSMA PD showed a higher risk of death than non-PD according to RECIP1.0 (HR = 2.9; 95% CI 1.14-7.46; p = 0.029) and PPP (HR = 2.8; 95% CI 1.04-7.64; p = 0.042). For both criteria, the median OS was shorter for PD than non-PD (37 vs. 12 months, Log-rank; p < 0.05). The C-index for RECIP1.0 and PPP were almost equal (0.66 and 0.63; respectively). CONCLUSION: This study demonstrated that PSMA-PET/CT imaging is valuable for monitoring radium-223 treatment. Both PSMA PET/CT response criteria (RECIP1.0 and PPP) perform similarly predicting OS at follow-up after three cycles of radium-223. These findings urge further validation in prospective trials.

Unusual Prostate-Specific Membrane Antigen (PSMA) Splenic Uptake in a Patient With Prostate Cancer.

There are many benefits to early detection of prostate cancer, including improved survival rates, less invasive treatment options, and better quality of life. Apart from traditional tests and imaging (including the prostate-specific antigen (PSA) test, digital rectal exam, biopsy, computed tomography (CT), and magnetic resonance imaging (MRI)), an imaging technique called prostate-specific membrane antigen positron emission tomography (PSMA PET) is more specific and sensitive, targeting PSMA expressed by prostate cancer cells on their surface. This case report describes a 62-year-old male with metastatic prostate adenocarcinoma and unusual PSMA uptake in the spleen. Elevated PSA levels and MRI indicated aggressive prostate cancer, confirmed by a Gleason score of 7 from biopsies. A PSMA PET/CT scan showed intense activity in both the prostate and spleen, initially suggesting metastasis. However, further imaging identified the splenic lesion as a benign hemangioma. This case showcases the importance of thorough diagnostic evaluations for distinguishing metastatic disease from benign conditions to ensure accurate diagnosis and appropriate treatment.

Exophthalmos as the initial presentation of metastatic prostate cancer.

Primary metastatic prostate cancer to the orbit is exceedingly rare. Benign lesions, including meningioma, have demonstrated PSMA expression and can be visualized using PSMA-based PET tracers. We report the findings of 18F-PSMA-1007 PET/CT in a 76-year-old man with progressive confusion and long-standing blindness of the left eye. PET/CT scan revealed increased uptake of PSMA in the orbital and temporal region, and other sites throughout the body. Histopathological examination after biopsy of the left orbit showed adenocarcinoma of the prostate. This case substantiates the diverse clinical and radiological presentations of metastatic prostate cancer and underscores the diagnostic significance of targeted biopsy.

Outstanding increase in tumor-to-background ratio over time allows tumor localization by [89Zr]Zr-PSMA-617 PET/CT in early biochemical recurrence of prostate cancer.

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) using prostate-specific membrane antigen (PSMA)-targeted radiotracers labeled with zirconium-89 (89Zr; half-life ~ 78.41 h) showed promise in localizing biochemical recurrence of prostate cancer (BCR) in pilot studies. METHODS: Retrospective analysis of 38 consecutive men with BCR (median [minimum-maximum] prostate-specific antigen 0.52 (0.12-2.50 ng/mL) undergoing [89Zr]Zr-PSMA-617 PET/CT post-negative [68Ga]Ga-PSMA-11 PET/CT. PET/CT acquisition 1-h, 24-h, and 48-h post-injection of a median (minimum-maximum) [89Zr]Zr-PSMA-617 tracer activity of 123 (84-166) MBq. RESULTS: [89Zr]Zr-PSMA-617 PET/CT detected altogether 57 lesions: 18 local recurrences, 33 lymph node metastases, 6 bone metastases in 30/38 men with BCR (78%) and prior negative conventional PSMA PET/CT. Lesion uptake significantly increased from 1-h to 24-h and, in a majority of cases, from 24-h to 48-h. Tumor-to-background ratios significantly increased over time, with absolute increases of 100 or more. No side effects were noted. After [89Zr]Zr-PSMA-617 PET/CT-based treatment, prostate-specific antigen concentration decreased in all patients, becoming undetectable in a third of patients. LIMITATIONS: retrospective, single center design; infrequent histopathological and imaging verification. CONCLUSION: This large series provides further evidence that [89Zr]Zr-PSMA-617 PET/CT is a beneficial imaging modality to localize early BCR. A remarkable increase in tumor-to-background ratio over time allows localization of tumor unidentified on conventional PSMA PET/CT.

Case report: positive pitfalls of PSMA PET/CT: diagnostic challenges in degenerative bone lesions including MODIC type 1.

Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is an imaging technique that has demonstrated high sensitivity and specificity in detecting prostate cancer and its metastasis, especially in the bones. This case describes a 60-year-old man who presented for increased prostate-specific antigen (PSA) level and underwent [68Ga]gallium-PSMA-11 PET/CT imaging for better disease assessment. 68Ga-PSMA-11 PET/CT revealed numerous radiotracer-positive lesions in both prostate lobes with associated sclerotic lesions on L4 and L5, but only L5 showed increased radiotracer avidity raising the possibility of metastasis. Magnetic Resonance Imaging (MRI) raises the possibility of aggressive MODIC type 1 lesion vs. infectious/inflammatory process. A biopsy of the radiotracer avid area was performed and showed no evidence of metastasis. The final diagnosis was aggressive MODIC type 1, in keeping with the false positive result of 68Ga-PSMA-11 PET/CT. This example demonstrates the possible limitations of 68Ga-PSMA-11 PET/CT, particularly in detecting bone metastases, and emphasizes the need for cautious interpretation and additional study to improve its diagnostic accuracy. Understanding and resolving these limitations is critical for increasing the accuracy of PSMA PET/CT in prostate cancer management.

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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

PSMA PET/CT imaging and its application to prostate cancer treatment.

Recognition of the importance of prostate-specific membrane antigen (PSMA) PET/CT in the diagnosis of prostate cancer has steadily increased following the publication of extensive data on its diagnostic accuracy and impact on patient management over the past decade. Several recent clinical trials and investigations regarding PSMA PET/CT have been ongoing in our country, and this examination is expected to become increasingly widespread in the future. This review explains the characteristics of PSMA PET/CT, its diagnostic capabilities and superiority over other modalities, the three proposed PSMA PET/CT interpretation criteria (the European Association of Nuclear Medicine [EANM], the Prostate Cancer Molecular Imaging Standardized Evaluation [PROMISE], and the PSMA Reporting and Data System [PSMA-RADS]), and the application of PSMA PET/CT to prostate cancer treatment (improvement of local control, irradiation of oligometastases, and salvage radiotherapy), incorporating actual clinical images and the latest findings.

Survey of Clinical Protocols for the Use of 177Lu-PSMA-617 in the United States.

Although guidelines for the use of 177Lu-PSMA-617 published by various organizations are important, they do not include all the essential, practical points necessary for a complete institutional protocol. Therefore, a brief survey was performed to assess key components of the 177Lu-PSMA-617 protocol before, during, and after delivery of therapy. This survey demonstrated the wide variability in many aspects of institutional protocols regarding determination of eligibility for and administration of 177Lu-PSMA-617 therapy. The real-world protocol details provided here from a variety of institutions may help new and established theranostic programs.

Association of Declining Prostate-specific Antigen Levels with Clinical Outcomes in Patients with Metastatic Castration-resistant Prostate Cancer Receiving [177Lu]Lu-PSMA-617 in the Phase 3 VISION Trial.

BACKGROUND AND OBJECTIVE: The prognostic value of declining prostate-specific antigen (PSA) levels is under investigation in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) receiving PSMA-targeted radioligand therapy with [177Lu]Lu-PSMA-617 (177Lu-PSMA-617). This post hoc analysis of the phase 3 VISION trial aimed to evaluate associations between PSA decline and clinical and patient-reported outcomes in patients receiving 177Lu-PSMA-617. METHODS: Of 831 enrolled patients with PSMA-positive progressive mCRPC treated previously with one or more androgen receptor pathway inhibitors and one to two taxanes, 551 were randomised to 177Lu-PSMA-617 plus protocol-permitted standard of care (SoC). Radiographic progression-free survival, overall survival, radiographic objective response rate, and patient-reported health-related quality of life (HRQoL) and pain were analysed in subgroups of patients categorised by the magnitude of unconfirmed PSA decline from baseline. KEY FINDINGS AND LIMITATIONS: Patients randomised to 177Lu-PSMA-617 with the best PSA declines of ≥0-<50% (96/551 [17%]), ≥50-<90% (152/551 [28%]), and ≥90% (83/551 [15%]) up to and including week 12 had 61%, 72%, and 88% reduced risks of radiographic disease progression or death, and 51%, 70%, and 87% reduced risks of death, respectively, versus those with increased PSA levels (160/551 [29%]), based on hazard ratios in a multivariate Cox proportional hazard model. In patients with greater PSA declines, radiographic responses were more frequent and median time to worsening in HRQoL and pain scores were longer. CONCLUSIONS AND CLINICAL IMPLICATIONS: The magnitude of PSA decline was associated with improvement in clinical and patient-reported outcomes in patients with mCRPC receiving 177Lu-PSMA-617 plus SoC in VISION. PSA decline therefore appears to have a prognostic value during 177Lu-PSMA-617 treatment in this population.

Searching for Protein Off-Targets of Prostate-Specific Membrane Antigen-Targeting Radioligands in the Salivary Glands.

Background: Prostate specific membrane antigen (PSMA)-targeted radioligand therapies represent a highly effective treatment for metastatic prostate cancer. However, high and sustain uptake of PSMA-ligands in the salivary glands led to dose limiting dry mouth (xerostomia), especially with α-emitters. The expression of PSMA and histologic analysis couldn't directly explain the toxicity, suggesting a potential off-target mediator for uptake. In this study, we set out to search for possible off-target non-PSMA protein(s) in the salivary glands. Methods: A machine-learning based quantitative structure activity relationship (QSAR) model was built for seeking the possible off-target(s). The resulting target candidates from the model prediction were subjected to further analysis for salivary protein expression and structural homology at key regions required for PSMA-ligand binding. Furthermore, cellular binding assays were performed utilizing multiple cell lines with high expression of the candidate proteins and low expression of PSMA. Finally, PSMA knockout (PSMA-/-) mice were scanned by small animal PET/MR using [68Ga]Ga-PSMA-11 for in-vivo validation. Results: The screening of the trained QSAR model did not yield a solid off-target protein, which was corroborated in part by cellular binding assays. Imaging using PSMA-/- mice further demonstrated markedly reduced PSMA-radioligand uptake in the salivary glands. Conclusion: Uptake of the PSMA-targeted radioligands in the salivary glands remains primarily PSMA-mediated. Further investigations are needed to illustrate a seemingly different process of uptake and retention in the salivary glands than that in prostate cancer.

Comparative Performance of 68Ga-PSMA-11 PET/CT and Conventional Imaging in the Primary Staging of High-Risk Prostate Cancer Patients Who Are Candidates for Radical Prostatectomy.

This prospective study aimed to (1) compare the diagnostic performance of 68Ga-PSMA-11 PET/CT with respect to conventional imaging (computed tomography (CT) and bone scintigraphy (BS)) in the primary staging of high-risk prostate cancer (PCa) patients and (2) validate PSMA-PET/CT accuracy in pelvic nodal staging in comparison with postoperative histopathology and assess PSMA-PET/CT's impact on patient management. Sixty castration-sensitive high-risk (ISUP 4-5 and/or PSA > 20 ng/mL and/or cT3) PCa patients eligible for radical prostatectomy were enrolled (median PSA 10.10 [IQR: 6.22-17.95] ng/mL). PSMA-PET/CT, compared with CT, identified nodal (N) and/or distant metastases (M1) in 56.7% (34/60) vs. 13.3% (8/60) (p < 0.001) of patients: N + 45% vs. 13.3% (p < 0.001), M1a 11.7% vs. 1.7% (p = 0.03), M1b 23.3% vs. 1.7% (p < 0.001). Compared with BS, PSMA-PET/CT localized unknown skeletal metastases in 15% (9/60) of cases, with no false negative findings. Overall, PSMA-PET/CT led to a TNM upstaging in 45.0% (27/60) of cases, with no evidence of downstaging, resulting in a change in management in up to 28.8% (17/59) of patients. Compared with histopathology data (n = 32 patients), the per-patient accuracy of PSMA-PET/TC for detecting pelvic nodal metastases was 90.6%. Overall, the above evidence supports the use of PSMA-PET/CT in the diagnostic workup of high-risk prostate cancer staging.

Volumetric Modulated Arc Therapy for High-Risk and Very High-Risk Locoregional Prostate Cancer in the Modern Era: Real-World Experience from an Asian Cohort.

This study retrospectively evaluates the clinical outcomes of definitive volumetric modulated arc therapy (VMAT) for high-risk or very high-risk locoregional prostate cancer patients from an Asian institution. Consecutive patients who received VMAT (76 Gy in 38 fractions) between January 2017 and June 2022 were included. Whole pelvic radiotherapy (WPRT) (46 Gy in 23 fractions) was employed for clinically node-negative disease (cN0) and a Roach estimated risk of ≥15%, as well as simultaneous integrated boost (SIB) of 55-57.5 Gy to node-positive (cN1) disease. The primary endpoint was biochemical relapse-free survival (BRFS). Secondary endpoints included radiographic relapse-free survival (RRFS), metastasis-free survival (MFS) and prostate cancer-specific survival (PCSS). A total of 209 patients were identified. After a median follow-up of 47.5 months, the 4-year actuarial BRFS, RRFS, MFS and PCSS were 85.2%, 96.8%, 96.8% and 100%, respectively. The incidence of late grade ≥ 2 genitourinary (GU) and gastrointestinal (GI) toxicity were 15.8% and 11.0%, respectively. No significant difference in cancer outcomes or toxicity was observed between WPRT and prostate-only radiotherapy for cN0 patients. SIB to the involved nodes did not result in increased toxicity. International Society of Urological Pathology (ISUP) group 5 and cN1 stage were associated with worse RRFS (p < 0.05). PSMA PET-CT compared to conventional imaging staging was associated with better BRFS in patients with ISUP grade group 5 (p = 0.039). Five-year local experience demonstrates excellent clinical outcomes. PSMA PET-CT staging for high-grade disease and tailored pelvic irradiation based on nodal risk should be considered to maximize clinical benefit.

From Oncogenesis to Theranostics: The Transformative Role of PSMA in Prostate Cancer.

Prostate cancer, a leading cause of cancer-related mortality among men, is characterized by complex genetic and epigenetic alterations, dysregulation of oncogenic pathways, and a dynamic tumor microenvironment. Advances in molecular diagnostics and targeted therapies have significantly transformed the management of this disease. Prostate-specific membrane antigen (PSMA) has emerged as a critical biomarker, enhancing the precision of prostate cancer diagnosis and treatment. Theranostics, which integrates PSMA-targeted imaging with radioligand therapies, has shown remarkable efficacy in detecting and treating advanced prostate cancer. By leveraging the dual capabilities of PSMA-based diagnostics and therapeutic agents, theranostics offers a personalized approach that improves patient outcomes. This comprehensive review explores the latest developments in PSMA-targeted theranostics and their impact on the future of prostate cancer management, highlighting key clinical trials and emerging therapeutic strategies.

Developmental Therapeutics in Metastatic Prostate Cancer: New Targets and New Strategies.

There is an unmet need to develop new treatments for metastatic prostate cancer. With the development of targeted radioligand therapies, bispecific T cell engagers, antibody-drug conjugates and chimeric antigen receptor T cell (CAR T) therapies, tumor-associated cell surface antigens have emerged as new therapeutic targets in metastatic prostate cancer. Ongoing and completed clinical trials targeting prostate-specific membrane antigen (PSMA), six transmembrane epithelial antigens of the prostate 1 (STEAP1), kallikrein-related peptidase 2 (KLK2), prostate stem cell antigen (PSCA), and delta-like protein 3 (DLL3) in metastatic prostate cancer were reviewed. Strategies for sequential or combinational therapy were discussed.

Potential application of [18F]AlF-PSMA-11 PET/CT in radioiodine refractory thyroid carcinoma.

BACKGROUND: Patients diagnosed with radioiodine refractory (RAI-R) thyroid carcinoma (TC) have a significantly worse prognosis than patients with radiosensitive TC. These refractory malignancies are often dedifferentiated, hindering the effectiveness of iodine-based imaging. Additionally, the role of metabolic imaging using [18F]FDG PET/CT is also limited in these cases, making adequate staging of RAI-R TC challenging. Recent case series have shown promising results regarding the role of the prostate-specific membrane antigen (PSMA) in TC. In this study we explored the value of [18F]AlF-PSMA-11 PET/CT in RAI-R TC. METHODS: In this phase II study, lesions detected on [18F]AlF-PSMA-11 PET were compared to findings from [18F]FDG PET/CT. Additionally, the serologic soluble prostate-specific membrane antigen (sPSMA) was measured using ELISA. PSMA-expression on tumor tissue in any available resection specimens was analysed with an immunostainer. RESULTS: Eight patients were included, with a total of 39 identified lesions based on PET imaging. [18F]AlF-PSMA-11 PET identified 30 of 39 lesions, and [18F]FDG PET identified 33 lesions, leading to a detection rate of 76.9% and 84.6%, respectively. Interestingly, while nine lesions were solely visualized on [18F]FDG, six were uniquely seen on [18F]AlF-PSMA-11 PET. While sPSMA was immeasurable in all female patients, no correlation was found between sPSMA in male patients and disease-related factors. In five out of eight patients immunohistology showed PSMA expression on the primary tumor. CONCLUSIONS: Although not all lesions could be visualized, [18F]PSMA-11 PET identified multiple lesions imperceptible on [18F]FDG PET. These results display the potential additional diagnostic role of PSMA-targeted imaging in patients with RAI-R TC. Trial registration number No. EudraCT 2021-000456-19.

A novel assessment of whole-mount Gleason grading in prostate cancer to identify candidates for radical prostatectomy: a machine learning-based multiomics study.

Purpose: This study aims to assess whole-mount Gleason grading (GG) in prostate cancer (PCa) accurately using a multiomics machine learning (ML) model and to compare its performance with biopsy-proven GG (bxGG) assessment. Materials and Methods: A total of 146 patients with PCa recruited in a pilot study of a prospective clinical trial (NCT02659527) were retrospectively included in the side study, all of whom underwent 68Ga-PSMA-11 integrated positron emission tomography (PET) / magnetic resonance (MR) before radical prostatectomy (RP) between May 2014 and April 2020. To establish a multiomics ML model, we quantified PET radiomics features, pathway-level genomics features from whole exome sequencing, and pathomics features derived from immunohistochemical staining of 11 biomarkers. Based on the multiomics dataset, five ML models were established and validated using 100-fold Monte Carlo cross-validation. Results: Among five ML models, the random forest (RF) model performed best in terms of the area under the curve (AUC). Compared to bxGG assessment alone, the RF model was superior in terms of AUC (0.87 vs 0.75), specificity (0.72 vs 0.61), positive predictive value (0.79 vs 0.75), and accuracy (0.78 vs 0.77) and showed slightly decreased sensitivity (0.83 vs 0.89) and negative predictive value (0.80 vs 0.81). Among the feature categories, bxGG was identified as the most important feature, followed by pathomics, clinical, radiomics and genomics features. The three important individual features were bxGG, PSA staining and one intensity-related radiomics feature. Conclusion: The findings demonstrate a superior assessment of the developed multiomics-based ML model in whole-mount GG compared to the current clinical baseline of bxGG. This enables personalized patient management by identifying high-risk PCa patients for RP.

Unveiling the role of PSMA5 in glioma progression and prognosis.

Glioma is the most aggressive intracranial malignancy and is associated with poor survival rates and limited quality of life, impairing neuropsychological function and cognitive competence in survivors. The Proteasome Subunit Alpha Type-5 (PSMA5) is a multicatalytic proteinase complex that has been linked with tumor progression but is rarely reported in glioma. This study investigates the expression pattern, prognostic characteristics, and potential biological functions of PSMA5 in glioma. PSMA5 was significantly overexpressed in 28 types of cancer when compared to normal tissue. Furthermore, elevated levels of PSMA5 were observed in patients with wild-type isocitrate dehydrogenase 1 and exhibited a positive correlation with tumor grade. It was also found to be a standalone predictor of outcomes in glioma patients. Additionally, inhibiting PSMA5-induced cell cycle arrest may provide a therapeutic option for glioma.