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11 pages, 477 KB  
Article
Diagnostic Accuracy of [68Ga]Ga-PSMA-11 PET-CT in Characterising Bone Lesions in Prostate Cancer: A Single-Centre Study
by Aishani Sachdeva, Mona Salem, John Jenkins, Kyle Wong, Gary J. R. Cook and Gurdip Azad
Cancers 2026, 18(7), 1090; https://doi.org/10.3390/cancers18071090 - 27 Mar 2026
Abstract
Background: Precise staging of prostate cancer is vital for treatment planning and prognosis. While [68Ga]Ga-PSMA-11 PET-CT has demonstrated high diagnostic accuracy in detecting metastatic disease, the interpretation of indeterminate or potentially benign PSMA-avid bone lesions remains a clinical challenge in routine [...] Read more.
Background: Precise staging of prostate cancer is vital for treatment planning and prognosis. While [68Ga]Ga-PSMA-11 PET-CT has demonstrated high diagnostic accuracy in detecting metastatic disease, the interpretation of indeterminate or potentially benign PSMA-avid bone lesions remains a clinical challenge in routine practice. Methods: We conducted a retrospective single-centre study involving 214 patients who underwent [68Ga]Ga-PSMA-11 PET-CT between January 2021 and January 2024. Patients with prior known bone metastases or alternative PSMA radiotracers were excluded. Only those with follow-up imaging were included for diagnostic accuracy analysis. Follow-up modalities included PSMA PET-CT, CT, MRI, and bone scintigraphy. Final classification (metastatic or benign) was based on radiological and clinical assessment. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated using follow-up imaging as the reference standard. Lesions classified as indeterminate were analysed separately and excluded from diagnostic performance calculations. Results: Of the 214 included patients, 142 had follow-up imaging. Among 80 patients with bone lesions initially reported as metastatic, 74 (92.5%) were confirmed. Among 28 patients initially reported as having benign bone lesions, 26 (92.9%) remained benign on follow-up. Thirty-four patients with indeterminate lesions were reviewed; four were ultimately metastatic. Excluding indeterminate cases, sensitivity, specificity, PPV, and NPV were 97.4%, 86.7%, 94.9%, and 92.9%, respectively. Diagnostic discordance was primarily associated with benign uptake in the ribs, iliac bones, pubic rami and degenerative changes. Conclusions: [68Ga]Ga-PSMA-11 PET-CT shows excellent sensitivity and positive predictive value for detecting metastatic bone disease in prostate cancer. However, benign lesions may also exhibit uptake, emphasising the importance of integrating imaging results with PSA levels, Gleason scores, and TNM staging. Prospective studies are needed to validate these findings and assess their impact on long-term outcomes. Full article
(This article belongs to the Special Issue PET/CT in Radiation Oncology)
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15 pages, 966 KB  
Article
Omitting Elective Pelvic Nodes Irradiation in High Risk Prostate Cancer: Report on 43 Consecutive Elderly Patients
by Emanuele Chioccola, Mara Caroprese, Christina Amanda Goodyear, Angela Barillaro, Gianluca Valerio, Caterina Oliviero, Mauro Buono, Stefania Clemente, Antonio Farella, Manuel Conson and Roberto Pacelli
J. Pers. Med. 2026, 16(4), 177; https://doi.org/10.3390/jpm16040177 - 24 Mar 2026
Viewed by 30
Abstract
Background: Radiotherapy (RT) combined with androgen deprivation therapy (ADT) is a standard treatment for non-metastatic high-risk (HR) prostate cancer (PC). However, the benefit of elective nodal irradiation (ENI) in clinically node-negative (cN0) patients, although suggested, remains controversial, particularly in the elderly. We [...] Read more.
Background: Radiotherapy (RT) combined with androgen deprivation therapy (ADT) is a standard treatment for non-metastatic high-risk (HR) prostate cancer (PC). However, the benefit of elective nodal irradiation (ENI) in clinically node-negative (cN0) patients, although suggested, remains controversial, particularly in the elderly. We report the outcomes of elderly HR PC patients treated with prostate-only RT (PORT) and ADT in a “real-word” setting. Methods: Between 2016 and 2022, 43 consecutive elderly patients (median age 76 years) with HR- or very HR-PC according to NCCN criteria version 1.2026 (cN0, cT3-cT4 and/or ISUP Grade Group 4–5 and/or PSA serum levels at diagnosis ≥ 20 ng/mL) were treated at our institution. All patients were staged with abdominal MRI or CT and bone scan; nineteen patients (44.2%) also underwent 68Ga-PSMA-11 or 18F-fluorocholine PET/CT. All patients received PORT (predominantly moderate hypofractionation, 67.5–70 Gy in 25–28 fractions) and ADT (median duration 24 months). To ensure consistency, all oncological endpoints—Biochemical Failure-Free Survival (BFFS; Phoenix criteria), Disease-Free Survival (DFS), Metastasis-Free Survival (MFS), Prostate Cancer-Specific Survival (PCSS), and Overall Survival (OS)—were calculated from a unified time-zero (initiation of first oncological treatment). DFS was defined as a composite endpoint including biochemical failure, radiological recurrence, or initiation of salvage therapy. Results: at a median follow-up of 60 months, no patient reached the Phoenix threshold, resulting in a 100% 5- and 7-year BFFS. However, 4 patients (9.3%) experienced radiological recurrence detected via PET/CT before reaching the nadir + 2 threshold, yielding an estimated 5-year and 7-year DFS of 94.7% and 71.8%, respectively. The 5- and 7-year MFS was of 97.6% and 88.7%, respectively. Seven deaths occurred, all non-PC related, resulting in a 5-year OS of 86.7% and a Prostate Cancer-Specific Survival of 100%. Gastrointestinal toxicity was notably low (no acute or late G3-G4 events). Conclusions: Our findings suggest that PORT, when combined with long-term ADT and modern staging, provides excellent disease control and a favorable safety profile in elderly HR PC patients. Given the high rate of competing mortality in this population, treatment de-escalation via PORT appears to be a clinically reasonable strategy. These results are hypothesis-generating and warrant validation in prospective randomized trials. Full article
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17 pages, 1057 KB  
Review
Integrating Multiparametric MRI and PSMA PET Imaging in Prostate Cancer: Toward a Unified Diagnostic and Risk-Stratification Paradigm
by Rosa Alba Pugliesi, Roberto Cannella, Karim Ben Mansour, Daniele Di Biagio and Pierpaolo Alongi
Medicina 2026, 62(3), 610; https://doi.org/10.3390/medicina62030610 - 23 Mar 2026
Viewed by 442
Abstract
Prostate cancer represents a highly prevalent malignancy affecting men globally, necessitating precise staging and risk stratification for effective patient management. Multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen positron emission tomography (PSMA PET) have individually revolutionized the diagnosis and management of prostate [...] Read more.
Prostate cancer represents a highly prevalent malignancy affecting men globally, necessitating precise staging and risk stratification for effective patient management. Multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen positron emission tomography (PSMA PET) have individually revolutionized the diagnosis and management of prostate cancer. Recent developments emphasize the integration of these imaging modalities to improve detection capabilities, inform therapeutic interventions, and facilitate personalized management. This narrative article reviews existing literature on the clinical utilization of mpMRI and PSMA PET in prostate cancer. Key areas encompass initial diagnosis, both local and systemic staging, detection of biochemical recurrence, and their influence in treatment strategies. The integration of mpMRI and PSMA PET offers complementary insights, with mpMRI demonstrating superior capability in local tumor characterization and PSMA PET enhancing the detection of nodal and distant metastases. Quantitative imaging biomarkers, including apparent diffusion coefficient (ADC) and standardized uptake values (SUV), have the potential to improve risk stratification and inform personalized treatment strategies. Hybrid imaging techniques may improve diagnostic accuracy and guide decisions regarding surgery, radiotherapy, and systemic treatment. The integration of mpMRI and PSMA PET allows a potentially transformative advancement in the realm of precision imaging for prostate cancer. This integrated approach can improve diagnostic accuracy, better define disease extent, and support personalized management strategies. Full article
(This article belongs to the Special Issue Advances in Use of PET-CT Imaging in Disease Diagnosis)
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17 pages, 1102 KB  
Article
Can Tc-99m-PSMA SPECT/CT Be Used as Accessible Alternative for Diagnosis of Biochemically Recurrent Prostate Cancer? A Prospective Study
by Veljković Miloš, Beatović Slobodanka, Pejčić Tomislav, Bukumirić Zoran, Odalović Strahinja, Grozdić Milojević Isidora, Stojiljković Milica, Petrović Jelena, Ivanovski Ana, Šobić Šaranović Dragana and Artiko Vera
Diagnostics 2026, 16(6), 895; https://doi.org/10.3390/diagnostics16060895 - 18 Mar 2026
Viewed by 195
Abstract
Objective: To evaluate Tc-99m-PSMA SPECT/CT detection of biochemical recurrence (BCR) of prostate cancer across serum PSA levels in patients treated with radical prostatectomy or radiation therapy, to explore clinical/pathologic predictors of scan positivity and metastatic disease, and to assess its potential role as [...] Read more.
Objective: To evaluate Tc-99m-PSMA SPECT/CT detection of biochemical recurrence (BCR) of prostate cancer across serum PSA levels in patients treated with radical prostatectomy or radiation therapy, to explore clinical/pathologic predictors of scan positivity and metastatic disease, and to assess its potential role as a pragmatic alternative when PSMA PET/CT is unavailable in resource-limited settings. Materials and Methods: In this prospective single-center study, we included 132 men with biochemical recurrence who underwent Tc-99m-PSMA SPECT/CT between January 2024 and December 2025 after predefined inclusion and exclusion criteria were applied, and they were further stratified by primary treatment (radical prostatectomy or radiation therapy). Patients were followed up for up to 6 months after imaging to verify observed findings (histopathology, confirmatory imaging and PSA response) and a logistic regression was applied to identify predictors of scan positivity and metastatic disease. Results: In men initially treated with radical prostatectomy, detection increased from 38.9% at PSA 0.2 to <2 ng/mL to 63.2% at 2 to <4 ng/mL, 71.4% at 4 to <7 ng/mL, and 90% at PSA ≥ 7 ng/mL (overall 69.1%). In the radiation therapy cohort, detection was 58.3% at PSA 2 to <4 ng/mL, rising to 85.7% at 4 to <7 ng/mL and 96% at PSA ≥ 7 ng/mL (overall 84.3%). In the multivariable analysis, PSA doubling (log2[PSA]) independently predicted scan positivity and metastatic disease in both cohorts, while seminal vesicle invasion independently predicted metastatic spread in the post-prostatectomy group. Conclusions: Tc-99m-PSMA SPECT/CT is a useful tool for detecting prostate cancer BCR, with performance strongly dependent on PSA and higher detection in patients with higher PSA levels. Increasing PSA independently predicted scan positivity and metastatic disease, while seminal vesicle invasion was independently associated with metastatic spread. In settings where PSMA PET/CT is unavailable, Tc-99m-PSMA SPECT/CT may represent a practical alternative, particularly for patients with elevated PSA. Full article
(This article belongs to the Special Issue Diagnostic Imaging of Prostate Cancer)
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3 pages, 778 KB  
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Pretherapeutic 18F-PSMA PET/CT Reveals Incidental Tracheal Epithelial–Myoepithelial Carcinoma
by Farid Gossili, Nelson Fuentes-Martinez and Christian Høyer
Diagnostics 2026, 16(6), 883; https://doi.org/10.3390/diagnostics16060883 - 16 Mar 2026
Viewed by 217
Abstract
A 75-year-old man with newly diagnosed high-risk prostate cancer (cT3bN0M0) underwent 18F-PSMA PET/CT, which demonstrated intense tracer uptake in a left tracheal mass causing near-complete luminal obstruction, raising suspicion of a primary lung malignancy or metastatic disease. Endoscopic debulking was performed due [...] Read more.
A 75-year-old man with newly diagnosed high-risk prostate cancer (cT3bN0M0) underwent 18F-PSMA PET/CT, which demonstrated intense tracer uptake in a left tracheal mass causing near-complete luminal obstruction, raising suspicion of a primary lung malignancy or metastatic disease. Endoscopic debulking was performed due to progressive respiratory symptoms with dyspnea. Histopathology and immunohistochemistry (p63, SMA, CK5/6 positive; PSA, NKX3.1, and AR negative, with downregulated PSMA-expression) established the diagnosis of low-grade epithelial–myoepithelial carcinoma of the trachea. Following debulking, the patient’s symptoms resolved, and a watchful-waiting strategy was adopted for the tracheal tumor, while curative-intent therapy for prostate cancer continued. This case highlights that 18F-PSMA PET/CT may reveal rare, intensely PSMA-avid non-prostatic neoplasms and underscores the importance of recognizing atypical uptake patterns to avoid misinterpretation during prostate cancer staging. Full article
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17 pages, 460 KB  
Review
Nerve-Sparing in High-Risk Prostate Cancer: Advantages and Pitfalls of Current Strategies and Technologies
by Daniele Robesti, Pierluigi Russo, Giuseppe Fallara, Fernando Blank, Massimo Valerio, Ashutosh K. Tewari, Francesco Montorsi, Guillaume Ploussard, Nilesh Patil and Alberto Martini
Cancers 2026, 18(6), 945; https://doi.org/10.3390/cancers18060945 - 13 Mar 2026
Viewed by 387
Abstract
Background and Objective: Positive surgical margins (PSMs) remain a major challenge during radical prostatectomy, particularly in patients with high-risk prostate cancer (HR-PCa), where extracapsular extension, multifocal disease, and aggressive tumor biology substantially increase the likelihood of incomplete resection. In this setting, PSMs [...] Read more.
Background and Objective: Positive surgical margins (PSMs) remain a major challenge during radical prostatectomy, particularly in patients with high-risk prostate cancer (HR-PCa), where extracapsular extension, multifocal disease, and aggressive tumor biology substantially increase the likelihood of incomplete resection. In this setting, PSMs are strongly associated with early biochemical recurrence and frequently prompt adjuvant or salvage treatments, potentially exposing patients to overtreatment and added morbidity. Materials and Methods: To review and critically appraise established and emerging intraoperative technologies for surgical margin assessment during radical prostatectomy, with a specific focus on their potential role and relevance in patients with HR-PCa. Evidence Acquisition: A non-systematic literature review was performed using Pubmed, MEDLINE, Web of Science, and Google Scholar, focusing on preoperative, intraoperative ex vivo, and intraoperative in vivo technologies for margin assessment. Emphasis was placed on techniques with potential applicability to HR-PCa, where real-time intraoperative decision-making is particularly consequential. Evidence Synthesis: Preoperative tools, including multiparametric MRI, PSMA-PET imaging, and predictive nomograms, aid surgical planning but show limited sensitivity for microscopic extracapsular extension, especially in high-risk disease. Intraoperative frozen section analysis reduces positive surgical margin rates while enabling selective nerve-sparing (defined as a side-specific, risk-adapted preservation strategy); however, its widespread adoption is constrained by substantial logistical and resource requirements, and robust oncological outcome data in high-risk populations remain limited. Novel ex vivo approaches, such as fluorescence confocal microscopy and specimen-based PSMA PET/CT imaging, offer rapid whole-gland or targeted margin assessment with reduced dependency on dedicated pathology workflows. In parallel, emerging in vivo technologies, particularly PSMA-targeted near-infrared-fluorescence-guided surgery, enable real-time detection of residual tumor and facilitate selective re-resection, representing a biology-driven approach that may be especially suited to HR-PCa. Conclusions: In high-risk prostate cancer, intraoperative margin assessment technologies may extend beyond functional preservation and play a central role in optimizing oncological radicality and multimodal treatment sequencing. While NeuroSAFE remains the reference standard, PSMA-based ex vivo and in vivo technologies are particularly promising in HR-PCa due to their ability to integrate tumor biology into surgical decision-making. Prospective studies focusing on high-risk-specific oncological and patient-reported outcomes are needed before widespread clinical implementation. Full article
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13 pages, 2105 KB  
Article
Repeatability of Semi-Quantitative and Volumetric Features from Artificial-Intelligence-Guided Lesion Segmentation on 18F-DCFPyL PSMA-PET/CT Images: Results from a Test-Retest Cohort
by Md Zobaer Islam, Timothy G. Perk, Amy Weisman, Mark C. Markowski, Kenneth J. Pienta, Young E. Whang, Matthew I. Milowsky, Martin G. Pomper, Nicholas Wisniewski, Ralph A. Bundschuh, Rudolf A. Werner, Michael A. Gorin and Steven P. Rowe
Tomography 2026, 12(3), 38; https://doi.org/10.3390/tomography12030038 - 11 Mar 2026
Viewed by 491
Abstract
Objectives: This study evaluated the test–retest repeatability of semi-quantitative and volumetric features derived from artificial intelligence (AI)-assisted lesion segmentation on 18F-DCFPyL Prostate Specific Membrane Antigen (PSMA)-PET/CT imaging of patients with prostate cancer (PCa). Specifically, we assessed the reliability of maximum, minimum and [...] Read more.
Objectives: This study evaluated the test–retest repeatability of semi-quantitative and volumetric features derived from artificial intelligence (AI)-assisted lesion segmentation on 18F-DCFPyL Prostate Specific Membrane Antigen (PSMA)-PET/CT imaging of patients with prostate cancer (PCa). Specifically, we assessed the reliability of maximum, minimum and total standardized uptake values (SUVmax, SUVmean, SUVtotal) and lesion volume measurements across varying lesion sizes and explored the implications of variability for clinical decision-making. Methods: We analyzed 18F-DCFPyL PSMA-PET/CT images from 22 patients with metastatic PCa. Lesion segmentation was performed using the AI-guided TRAQinform IQ technology, followed by a manual review to eliminate potential false-positive sites of uptake. Lesion-level test–retest repeatability was evaluated using 95% limits of agreement (LOA), intra-class correlation coefficient (ICC), within-subject coefficient of variation (wCOV) and Bland–Altman analysis for SUV and volumetric parameters. Lesions were stratified by size (>1 cm3 and >1.5 cm3) to assess the impact of lesion volume cut-offs on measurement variability. Results: A total of 297 lesions were analyzed, including 191 lesions > 1 cm3 and 161 lesions > 1.5 cm3. Test–retest variability was higher in smaller lesions, with narrower LOA and lower wCOV for larger lesions. SUVmax and SUVmean exhibited lower variability than SUVtotal and lesion volume. The 95% LOA for SUVmax ranged from −33.81% to +38.02% for all lesions, improving to −31.82% to +31.01% for lesions > 1.5 cm3. Similar trends were observed for SUVmean, SUVtotal, and volume. Bland–Altman plots confirmed reduced variability in larger lesions, with no significant systematic bias. Conclusions: The test–retest repeatability of AI-assisted PSMA-PET/CT features varies by feature type, with semi-quantitative features demonstrating improved repeatability relative to volumetric features. Additionally, repeatability is influenced by lesion size, with larger lesions exhibiting greater reliability. These findings highlight the importance of lesion size-dependent thresholds in response assessment and variability-aware feature selection in prognostic models. Current algorithms may be better optimized for larger lesions and higher volumes of disease, with limitations remaining in the robust detection and segmentation of smaller/more subtle lesions. Full article
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15 pages, 4852 KB  
Article
Prostate-Specific Membrane Antigen (PSMA): A Potential Theranostic Biomarker in Breast Cancer
by Alessandra Virga, Flavia Foca, Stefania Cortecchia, Francesca Poli, Paola Caroli, Federica Matteucci, Roberta Maltoni, Massimiliano Mazza, Fabio Nicolini, Paola Ulivi, Giovanni Paganelli, Maurizio Puccetti and Sara Bravaccini
Biomedicines 2026, 14(3), 628; https://doi.org/10.3390/biomedicines14030628 - 11 Mar 2026
Viewed by 326
Abstract
Background: Subtype classification for breast cancer (BC) patients is important for risk-stratification. Unfortunately, this parameter is not always able to discriminate between high- and low-risk diseases. Glutamate Carboxypeptidase-II (GCPII), also known as prostate-specific membrane antigen (PSMA), could be an important biomarker of [...] Read more.
Background: Subtype classification for breast cancer (BC) patients is important for risk-stratification. Unfortunately, this parameter is not always able to discriminate between high- and low-risk diseases. Glutamate Carboxypeptidase-II (GCPII), also known as prostate-specific membrane antigen (PSMA), could be an important biomarker of aggressiveness, given that it has been reported to be expressed in BC tumor cells and even more in endothelial cells of tumor vessels. Methods: We analyzed 22 Luminal A, 47 Luminal B, 9 HER2-positive (HER2+), and 23 triple-negative (TN) BC to assess whether PSMA, Ki67 expression, and tumor-infiltrating lymphocytes (TILs) were different in BC subtypes. Results: Median PSMA and Ki67 values were significantly higher in TNBC than in Luminal A and B tumors. We saw a correlation between PSMA and Ki67 expression, especially in HER2+ tumors (p = 0.035), while an inverse correlation between PSMA and TILs was observed in Luminal A (p = 0.028). Conclusions: Our results suggest that PSMA could be used as a biomarker in BC, given that it is highly expressed in more aggressive tumors. These findings open the way to a clinical investigation for the possible use of PSMA as a theranostic biomarker in BC patients with PSMA positive PET scan. Full article
(This article belongs to the Section Cancer Biology and Oncology)
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13 pages, 3625 KB  
Article
Reirradiation of Local Recurrences of Prostate Cancer: PROSTARE (PROstate Cancer STereotActic REirradiation) Early Safety Analysis of a Phase 2 Study with a Limited Cohort
by Wojciech Majewski, Aleksandra Napieralska, Marcin Miszczyk, Anna Misiorowska-Gołosz, Marcela Krzempek, Małgorzata Stąpór-Fudzińska, Justyna Rembak-Szynkiewicz and Jerzy Wydmański
Cancers 2026, 18(5), 848; https://doi.org/10.3390/cancers18050848 - 6 Mar 2026
Viewed by 533
Abstract
Objective: This study aims to report the early safety outcomes from an ongoing single-center, non-randomized phase 2 trial on focal salvage stereotactic radiotherapy (s-SBRT) for local prostate cancer recurrence. Materials and methods: This prospective phase 2 study includes patients with local [...] Read more.
Objective: This study aims to report the early safety outcomes from an ongoing single-center, non-randomized phase 2 trial on focal salvage stereotactic radiotherapy (s-SBRT) for local prostate cancer recurrence. Materials and methods: This prospective phase 2 study includes patients with local recurrence after conventional or hypofractionated radiotherapy, ultrahypofractionated radiotherapy, or post-prostatectomy radiotherapy. The present analysis includes an initial subset of 21 out of 55 planned patients. All patients undergo mpMRI and PSMA-PET; biopsy is not required if imaging results are unambiguous. Focal s-SBRT is delivered to the recurrent lesion with a dose of 5 × 6.75 Gy. The primary endpoint is the rate of treatment-related CTCAE v5.0 grade ≥ 3 genitourinary (GU) or gastrointestinal (GI) toxicity. Secondary endpoints include early biochemical response (BR), defined as any PSA decline at 3 months. Results: With a median follow-up of 14 months (range: 4.5–25), one patient (4.8%) experienced both early and persistent late Grade 3 GU toxicity (bladder bleeding). Late Grade 2 GU and GI toxicities occurred in five (23.8%) and one (4.8%) patients, respectively. In exploratory univariable analysis, PTV volume 13 cc was identified as a marginal predictor for increased GU/GI radiation reactions (p < 0.1). Regarding efficacy, all 21 patients (100%) demonstrated an early biochemical response, with 15 patients (71.4%) achieving a PSA reduction of 50%. Conclusions: Focal s-SBRT demonstrates a favorable early safety profile and consistent biochemical response, supporting the preliminary safety of this ongoing study. Full article
(This article belongs to the Special Issue Radiation Therapy in Oncology)
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12 pages, 671 KB  
Article
PSA Zero Radiographic Disease Progression on PSMA PET/CT
by Ahmed M. Mahmoud, Carter Day, Eman E. Ahmed, Mohamed E. Ahmed, Rimki Haloi, Mindie Mahon, Yalda Nikanpour, Daniel S. Childs, Jacob J. Orme, Ayse Tuba Kendi, Geoffrey B. Johnson, Eugene D. Kwon and Jack R. Andrews
Cancers 2026, 18(5), 831; https://doi.org/10.3390/cancers18050831 - 4 Mar 2026
Viewed by 564
Abstract
Background and Objective: Radiographic progression in prostate cancer (PCa) can occur even when prostate-specific antigen (PSA) levels are undetectable. We aimed to determine the frequency and characteristics of radiographic disease progression (rDP) on PSMA PET/CT in patients with undetectable PSA, referred to as [...] Read more.
Background and Objective: Radiographic progression in prostate cancer (PCa) can occur even when prostate-specific antigen (PSA) levels are undetectable. We aimed to determine the frequency and characteristics of radiographic disease progression (rDP) on PSMA PET/CT in patients with undetectable PSA, referred to as PSA zero rDP. Methods: We analyzed the Mayo Clinic PSMA PET Prostate Cancer Registry to identify patients with rDP on PSMA PET/CT despite undetectable PSA levels. Disease progression was confirmed via biopsy or treatment response. The cohort included patients with non-metastatic and metastatic hormone-sensitive disease, as well as those with castration-resistant prostate cancer at the time of imaging. Overall survival (OS) was estimated using the Kaplan–Meier method. Group comparisons were performed with the log-rank test. Univariate Cox regression was used to identify factors associated with poor OS. Key findings and Limitations: Among 2141 patients imaged between 2021 and 2023, 257 (12%) had PSA zero rDP. Sixty-one percent had initially localized disease; 39% had de novo metastatic disease. Median (IQR) time from diagnosis to PSA zero rDP was 51.9 (18.4–115.5) months. A total of 184 patients (72%) progressed to castration-resistant PCa. Sites of rDP included bone (57%), visceral (15%), lymph node (18%), and local recurrence (10%). During median follow-up of 8.1 (3.5–11.9) months, 5% of patients died. Only visceral metastases were significantly associated with poorer OS (p < 0.0001). Conclusions and Clinical Implications: Prostate cancer patients frequently develop metastatic disease with undetectable PSA values. Our findings suggest the use of periodic advanced imaging techniques, irrespective of PSA value, for more prompt detection and early management of disease progress. Full article
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11 pages, 1001 KB  
Article
Cost Analysis of PSMA-PET in the PROSPET-BX Trial
by Egesta Lopci, Cesare Saitta, Alberto Saita, Elena Vanni, Alessandro Santandrea, Luca Disconzi, Vittorio Fasulo, Nicolò Buffi, Massimo Lazzeri and Giovanni Lughezzani
Cancers 2026, 18(5), 806; https://doi.org/10.3390/cancers18050806 - 2 Mar 2026
Viewed by 458
Abstract
Background: The PROSPET-BX trial compared [68Ga]PSMA-11 PET/CT (PSMA-PET) with multiparametric MRI (mpMRI) in parallel in men with suspicion of prostate cancer (PCa) after at least one previously negative biopsy (ClinicalTrials.gov: NCT05297162; GR-2018-12366240). In this study, we performed the cost analysis of [...] Read more.
Background: The PROSPET-BX trial compared [68Ga]PSMA-11 PET/CT (PSMA-PET) with multiparametric MRI (mpMRI) in parallel in men with suspicion of prostate cancer (PCa) after at least one previously negative biopsy (ClinicalTrials.gov: NCT05297162; GR-2018-12366240). In this study, we performed the cost analysis of the two imaging modalities with respect to the detection of clinically significant PCa (csPCa). Methods: We analyzed the data from patients enrolled in the trial who met the inclusion criteria. For the cost analysis, we identified six competing triage strategies, each defined as a binary decision rule for referral to prostate biopsy: (1) biopsy-all; (2) elevated PSA-density (PSAD; biopsy if PSAD > 0.15 ng/mL/cc; (3) mpMRI positive (PIRADS 3–5); (4) PSMA-PET positive (PRIMARY 3–5); (5) mpMRI or PSMA-PET positive; (6) PSAD and mpMRI. For each strategy, we yielded sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for csPCa. Direct hospital costs were modeled from a provider perspective, incorporating testing and procedural costs. Unit costs (in EUR) were sourced from our institutional accounting records. Pairwise cost-effectiveness comparisons were performed using incremental cost-effectiveness ratio (ICER) and incremental net benefit (INB). Results: Among the six triage strategies evaluated, the “biopsy-all” approach achieved perfect sensitivity, whereas the PSAD + mpMRI pathway was the most parsimonious strategy but missed 14 csPCa cases (53.8%). The combined “mpMRI or PSMA-PET” strategy maximized detection (22 cPCa, missing only 4) at an intermediate cost (EUR 81.991 total; EUR 3.727 per csPCa). The pairwise comparison of each strategy with mpMRI alone showed for the mpMRI or PSMA-PET pathway a low ICER (~EUR 2.900/extra csPCa), with consistently positive and increasing INB across higher WTP (willingness-to-pay). Therefore, this combination provided the most favorable cost-effectiveness profile, balancing detection, efficiency, and cost. Conclusions: To the best of our knowledge, this is the first cost analysis study to compare different strategies incorporating PSMA-PET in the re-biopsy setting, demonstrating that the combined “mpMRI or PSMA-PET” pathway is the most cost-effective diagnostic pathway for csPCa detection. Full article
(This article belongs to the Special Issue Cancer Treatment: Present and Future of Radioligand Therapy)
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16 pages, 3412 KB  
Article
CT Radiomics Models Did Not Outperform Experts in Predicting [68Ga]Ga-PSMA-PET Positivity in Prostate Cancer Lymph Node Staging
by Thula Cannon Walter-Rittel, Boris Gorodetski, Alexander Hartenstein, Julian Rogasch, Imke Schatka, Holger Amthauer, Marcus Makowski, Charlie Alexander Hamm and Tobias Penzkofer
Curr. Oncol. 2026, 33(3), 146; https://doi.org/10.3390/curroncol33030146 - 2 Mar 2026
Viewed by 286
Abstract
Background: The use of [68Ga]Ga-PSMA-PET/CT for prostate cancer (PCa) staging is limited by cost and availability. This study evaluates whether radiomic features from contrast-enhanced (CE) CT can predict PSMA-positive lymph nodes (LNs) as a surrogate for metastasis. Methods: A [...] Read more.
Background: The use of [68Ga]Ga-PSMA-PET/CT for prostate cancer (PCa) staging is limited by cost and availability. This study evaluates whether radiomic features from contrast-enhanced (CE) CT can predict PSMA-positive lymph nodes (LNs) as a surrogate for metastasis. Methods: A retrospective study of 447 patients included 2537 segmented LNs (425 PET-positive, 2112 PET-negative). Two uroradiologists assessed 417 LNs on CE-CT using a four-point Likert scale. Radiomic features were extracted, selected using four algorithms, and analyzed with six model-building methods. Model performance was compared to radiologist ratings. Results: Radiomic models achieved an accuracy of 0.77–0.85, sensitivity of 0.85–0.91, and specificity of 0.74–0.85. Compared to radiologists, models had higher NPV (0.97–0.98 vs. 0.96) and sensitivity (0.85–0.91 vs. 0.76), but radiologists had superior accuracy (0.95 vs. 0.77–0.85) and specificity (0.97–0.98 vs. 0.74–0.85). In a subanalysis of LNs rated as probably benign or malignant, expert radiologists outperformed the algorithm with greater specificity and PPV (p < 0.005). A density threshold of >27 HU predicted PSMA-positive LNs with 0.79 accuracy, 0.87 sensitivity, and 0.78 specificity. Conclusions: While radiomics did not outperform expert radiologists, the single first-order parameter CT density >27 HU was predictive of PSMA-positive LNs. Clinical Relevance Statement: Radiomic models did not outperform expert uroradiologists. However, in high-volume or resource-limited settings lacking access to [68Ga]Ga-PSMA-PET/CT, they may help improve LN assessment in PCa patients with CT alone. Full article
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29 pages, 847 KB  
Review
Focusing on Prostate-Specific Membrane Antigen in Precision Diagnosis and Treatment of Prostate Cancer
by Xinyi Ren, Lingling Zhang, Ran An, Hongchen Song, Mingjun Shi and Zhenchang Wang
Biomedicines 2026, 14(2), 482; https://doi.org/10.3390/biomedicines14020482 - 22 Feb 2026
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Abstract
Prostate cancer (PCa) is the most common malignant tumor of the male genitourinary system, and its incidence and mortality have shown a marked global increase in recent years. Prostate-specific membrane antigen (PSMA), a type II transmembrane glycoprotein highly expressed in PCa cells, has [...] Read more.
Prostate cancer (PCa) is the most common malignant tumor of the male genitourinary system, and its incidence and mortality have shown a marked global increase in recent years. Prostate-specific membrane antigen (PSMA), a type II transmembrane glycoprotein highly expressed in PCa cells, has emerged as a vital molecular target in the field of PCa precision diagnosis and therapy. In recent years, significant advances have been achieved in PSMA-based molecular imaging, radioligand therapy, and the development of novel targeted drugs. This review aims to summarize and critically discuss recent advances in PSMA-targeted molecular imaging, radioligand therapy, and emerging therapeutic strategies, highlighting their roles in precision diagnosis and personalized treatment of PCa. PSMA positron emission tomography/computed tomography (PET/CT) imaging using radionuclides such as 68Ga and 18F has markedly improved the accuracy of primary tumor staging, localization of recurrent lesions, and therapeutic response assessment. Radioligand therapies, such as 177Lu-PSMA-617 and 225Ac-PSMA-617, have prolonged survival and demonstrated symptomatic benefits in multiple clinical trials, and are now applied in early disease stages, including chemotherapy-naïve and hormone-sensitive settings. Meanwhile, PSMA-targeted antibodies and antibody–drug conjugates (PSMA-ADCs), as well as bispecific T-cell engagers (BiTEs) and chimeric antigen receptor T-cell (CAR-T) therapies, are constantly being optimized and show promising clinical potential. Furthermore, PSMA-targeted nanoplatforms enable precise delivery of chemotherapeutic agents, photosensitizers, or imaging probes, achieving integrated diagnosis and therapy with multimodal imaging guidance, and offering new strategies for individualized treatment. Taken together, the evidence summarized in this review highlights PSMA as a pivotal molecular target supporting precision diagnosis and personalized treatment across the continuum of prostate cancer management. Full article
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16 pages, 12912 KB  
Review
Contemporary Evidence for Optimization of Robotic Radical Prostatectomy Outcomes Using Advanced Imaging Techniques
by Gary K. Shahinyan and David S. Finley
J. Clin. Med. 2026, 15(4), 1631; https://doi.org/10.3390/jcm15041631 - 21 Feb 2026
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Abstract
Background/Objectives: Robotic-assisted radical prostatectomy (RARP) is a standard treatment for localized and locally advanced prostate cancer; however, optimizing oncologic control while preserving urinary continence and erectile function remains challenging. Advances in preoperative imaging, molecular diagnostics, artificial intelligence (AI), and intraoperative assessment have the [...] Read more.
Background/Objectives: Robotic-assisted radical prostatectomy (RARP) is a standard treatment for localized and locally advanced prostate cancer; however, optimizing oncologic control while preserving urinary continence and erectile function remains challenging. Advances in preoperative imaging, molecular diagnostics, artificial intelligence (AI), and intraoperative assessment have the potential to refine surgical planning and execution. This review summarizes contemporary evidence on advanced imaging and intraoperative technologies used to optimize RARP outcomes. Methods: A narrative literature review was conducted of English-language studies published between 2015 and 2025 using PubMed/MEDLINE, Scopus, and Google Scholar. Studies evaluating multi-parametric and bi-parametric MRI, prostate-specific membrane antigen-based positron emission tomography/computed tomography (PSMA PET/CT), AI-assisted tumor modeling, and intraoperative histologic or molecular imaging techniques in the context of robotic-assisted radical prostatectomy were included. Evidence from randomized controlled trials, prospective and retrospective studies, technical feasibility reports, and expert consensus statements was reviewed. Results: MRI remains central to anatomic mapping and local staging but consistently underestimates true tumor extent, with implications for margin control. AI-assisted platforms improve tumor contouring accuracy and may meaningfully influence surgical decision-making. PSMA-based imaging enhances detection of extra-prostatic extension and nodal disease and shows early promise for ex vivo and intraoperative guidance. Intraoperative margin assessment techniques are supported by randomized evidence demonstrating improved functional outcomes without compromising short-term oncologic safety and emerging digital histologic technologies offer scalable alternatives for real-time margin evaluation. Conclusions: Integration of advanced anatomic, molecular, and intraoperative imaging technologies represents an evolving multimodal paradigm in RARP. Combined use of MRI, PSMA-based imaging, AI-assisted modeling, and rapid histologic assessment may enable more precise, individualized surgery that balances oncologic control with functional preservation. Further validation is required to define optimal implementation in routine clinical practice. Full article
(This article belongs to the Special Issue Prostatectomy: Clinical Updates and Perspectives)
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13 pages, 3719 KB  
Article
Prediction of Metastasis-Free Survival in Patients with Localized Prostate Adenocarcinoma Using Delta Radiomics from Pre-Treatment PSMA-PET/CT Scans and Dosiomics
by Apurva Singh, William Silva Mendes, Sang-Bo Oh, Ozan Cem Guler, Aysenur Elmali, Birhan Demirhan, Amit Sawant, Phuoc Tran, Cem Onal and Lei Ren
Cancers 2026, 18(4), 677; https://doi.org/10.3390/cancers18040677 - 19 Feb 2026
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Abstract
Purpose: To develop prognostic models integrating delta radiomics from prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) and dosiomics with clinical variables to predict metastasis-free survival (MFS) in patients with localized prostate adenocarcinoma treated with androgen deprivation therapy and external-beam radiotherapy. Materials/Methods: Delta-radiomics [...] Read more.
Purpose: To develop prognostic models integrating delta radiomics from prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) and dosiomics with clinical variables to predict metastasis-free survival (MFS) in patients with localized prostate adenocarcinoma treated with androgen deprivation therapy and external-beam radiotherapy. Materials/Methods: Delta-radiomics analysis included 43 patients. Radiomics features were extracted from the primary tumor on pre- and post-treatment PSMA-PET/CT, and delta features were calculated as relative changes. Eight high-variance features were selected and combined with clinical variables (age, Gleason score, initial PSA, and a binary variable, indicating the occurrence of PSA relapse). Data was split 70:30 with training-set imbalance correction. Predictors that were significant in univariate Cox regression (p < 0.05) were entered into multivariate Cox models, and five-year MFS was classified using a quadratic support vector machine. Dosiomics analysis included 48 patients. Dosiomics features were extracted from the planning target volume receiving 86 Gy and combined with pre-treatment radiomics and clinical variables using the same framework. Results: For delta radiomics, Model 1 (delta radiomics + pre-treatment radiomics + clinical) achieved the best performance (test c-score 0.58; AUC 0.70), exceeding Model 2 (pre-treatment radiomics + clinical; c-score 0.56; AUC 0.65) and Model 3 (clinical only; c-score 0.51; AUC 0.56). For dosiomics, Model 1 showed the highest performance (test c-score 0.56; AUC 0.67) compared with Model 2 (c-score 0.55; AUC 0.62) and Model 3 (c-score 0.50; AUC 0.54). Conclusions: Integrating delta radiomics or dosiomics with pre-treatment imaging and clinical variables improves MFS prediction and supports their role as non-invasive biomarkers for individualized radiotherapy in localized prostate cancer. Full article
(This article belongs to the Special Issue Advances in Imaging Techniques of Molecular Oncology (2nd Edition))
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