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12 pages, 352 KB  
Article
Patterns and Predictors of Urinary Continence Recovery After Extraperitoneal Single-Port Robot-Assisted Radical Prostatectomy
by Lorenzo Santodirocco, Luca A. Morgantini, Marwan Alkassis, Jinchun Qi and Simone Crivellaro
J. Clin. Med. 2026, 15(7), 2563; https://doi.org/10.3390/jcm15072563 - 27 Mar 2026
Viewed by 155
Abstract
Background/Objectives: Urinary continence recovery after robot-assisted radical prostatectomy (RARP) follows a progressive trajectory that is often simplified into binary outcomes. Modeling continence recovery as an ordered process may better reflect post-operative functional patterns and identify clinically relevant predictors. Methods: We retrospectively [...] Read more.
Background/Objectives: Urinary continence recovery after robot-assisted radical prostatectomy (RARP) follows a progressive trajectory that is often simplified into binary outcomes. Modeling continence recovery as an ordered process may better reflect post-operative functional patterns and identify clinically relevant predictors. Methods: We retrospectively analyzed 180 patients undergoing extraperitoneal single-port RARP. At 6 months, continence recovery was classified into three ordered categories: early continence, late continence, and persistent incontinence. Multivariable ordinal logistic regression was used to identify independent predictors of continence recovery. The primary model included nerve-sparing (NS) status, postoperative complications, age, and prostate volume. Sensitivity analyses were performed by sequentially replacing prostate volume with body mass index, surgical case number, or preoperative prostate-specific antigen (PSA). An interaction between NS and age group was also tested. Results: NS surgery was the factor most strongly associated with favorable continence recovery (p < 0.001), followed by absence of post-operative complications (p = 0.003). Younger age and larger prostate volume were also independently associated with improved continence recovery. Sensitivity analyses confirmed the robustness of the primary model, as replacement of prostate volume with body mass index, surgical case number, or PSA did not improve model performance and did not alter the effect of NS surgery. No significant interaction between NS and age group was observed. Conclusions: Continence recovery after extraperitoneal RARP is primarily associated with NS surgery and an uncomplicated post-operative course, with age and prostate volume providing additional refinement. Modeling continence as an ordinal outcome offers a clinically meaningful framework for evaluating functional recovery after prostatectomy. Full article
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16 pages, 681 KB  
Article
Pathological Tumour Volume Percentage as a Quantitative Biomarker of Biological Aggressiveness in High-Risk Prostate Cancer
by Lorand Tibor Reman, Călin Chibelean, Daniel Porav-Hodade, Árpád-Olivér Vida, Ciprian Todea Moga, Veronica Maria Ghirca, Raul-Dumitru Gherasim, Rares-Florin Vascul, Orsolya-Brigitta Katona, Szabolcs Andre, Edva Anna Frunda and Orsolya Katalin Ilona Martha
Cancers 2026, 18(7), 1069; https://doi.org/10.3390/cancers18071069 - 25 Mar 2026
Viewed by 168
Abstract
Background: Tumour volume percentage (TVP) is considered an important pathological parameter, particularly in prostate cancer, representing the ratio of tumour volume to the total gland, and it can be used to measure the quantity of malignancy. Previous reports have already demonstrated that [...] Read more.
Background: Tumour volume percentage (TVP) is considered an important pathological parameter, particularly in prostate cancer, representing the ratio of tumour volume to the total gland, and it can be used to measure the quantity of malignancy. Previous reports have already demonstrated that an elevated tumour volume percentage is associated with unfavourable factors, including extraprostatic extension, positive surgical margins, and lymph node metastasis. The independent value of TVP, especially in high-risk prostate cancer treated by radical prostatectomy, remains an area of active research, despite established prognostic factors such as PSA, ISUP grade, and TNM stage. Materials and Methods: We retrospectively analyzed the records of 159 high-risk prostate cancer patients who underwent open or laparoscopic radical prostatectomy between January 2016 and January 2025 at the Clinic of Urology of Targu Mures. High-risk patients were defined as those with ISUP grade 4–5 or PSA >20 ng/mL or clinical stage ≥T2c or stage cT3–4 and/or lymph node metastasis. Tumour volume percentage was calculated from the final pathology result and was determined as the proportion of prostate cancer volume relative to the total prostate volume. Clinical and pathological features, including PSA, ISUP grade, TNM stage, surgical margin, and lymph node involvement, were reported. To assess TVP as an indicator of tumour aggressiveness, univariate and multivariate regression analyses were performed. A p-value < 0.05 was considered statistically significant. Results: A total of 159 high-risk prostate cancer patients (100%), with a median age of 66 years, who underwent open or laparoscopic radical prostatectomy were included. The median tumour volume percentage was 7.6%, and the median prostate volume was 43.8 cc. On univariate analysis, patients with extraprostatic extension (p < 0.001), positive surgical margins (p = 0.005), a higher ISUP grade (p < 0.001), and lymph node metastasis (p = 0.006) exhibited higher TVP compared to their counterparts. A significant correlation was also observed between TVP and the number of positive biopsy cores (p < 0.001), a higher PSA value (p = 0.005), and a younger age (p = 0.041). Conversely, no correlation was identified between TVP and perioperative factors such as hospital stay, surgery duration, ICU days, type of approach, or positive urine culture. Two regression models on multivariate analyses were performed with TVP as the dependent variable. In the continuous variable model (Adjusted R2 = 0.43, p < 0.001), independent predictors of higher TVP were the number of positive biopsy cores (B = 0.54, p < 0.001), the number of positive lymph nodes (B = 2.59, p < 0.001), and surgical margin dimension (B = 1.19, p < 0.001). Age, PSA, and perioperative variables showed no significant correlation with TVP on multivariate analysis. In the categorical regression model (Adjusted R2 = 0.438), statistical significance was confirmed (F-test, p < 0.001). Independent predictors of increased tumour volume percentage included ISUP grade 5 in the effect-coded model (B = +6.60, 95% CI: 0.96–12.25, p = 0.022), and pathological TNM stage pT4 (B = +24.70, 95% CI: 17.69–31.70, p < 0.001). ROC analysis showed limited-to-moderate discrimination for positive surgical margins (AUC = 0.655; 95% CI 0.565–0.744; p = 0.001) and stronger discrimination for pN1 (AUC = 0.793; 95% CI 0.650–0.936; p = 0.002). The Youden-derived cut-offs were 4.90% for positive surgical margins and 5.77% for lymph-node metastasis. Conclusions: Tumour volume percentage is significantly associated with several adverse pathological features in high-risk prostate cancer. Rather than a standalone biomarker, its association with adverse pathological features underscores its potential role in risk stratification models, and the incorporation into pathology reports and prognostic nomograms may improve clinical decision-making. Full article
(This article belongs to the Section Cancer Biomarkers)
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13 pages, 1449 KB  
Article
Carboxylesterase 2-Engineered Stem Cell Therapy Shows Superior Efficacy over Cytosine Deaminase in Castration-Resistant Prostate Cancer
by Jae Heon Kim, Miho Song, Sang Hun Lee and Yun Seob Song
Biomedicines 2026, 14(3), 681; https://doi.org/10.3390/biomedicines14030681 - 16 Mar 2026
Viewed by 261
Abstract
Purpose: Castration-resistant prostate cancer (CRPC) responds poorly to conventional chemotherapy. We evaluated a cell-based enzyme–prodrug therapy using adipose-derived stem cells (ADSCs) engineered to express cytosine deaminase (CD) or carboxylesterase 2 (CE2), paired with their respective prodrugs 5-fluorocytosine (5-FC) or irinotecan (CPT-11), to [...] Read more.
Purpose: Castration-resistant prostate cancer (CRPC) responds poorly to conventional chemotherapy. We evaluated a cell-based enzyme–prodrug therapy using adipose-derived stem cells (ADSCs) engineered to express cytosine deaminase (CD) or carboxylesterase 2 (CE2), paired with their respective prodrugs 5-fluorocytosine (5-FC) or irinotecan (CPT-11), to compare their antitumor efficacy. Materials and Methods: Human telomerase reverse transcriptase (hTERT)-immortalized ADSCs were transduced with CD or CE2, and transgene expression and stem cell phenotype were confirmed. CD expression was verified at the transcript level and by functional 5-FC-to-5-fluorouracil (5-FU) conversion, whereas CE2 expression was verified by transcript analysis and immunoblotting. Tumor tropism toward PC3 prostate cancer cells was tested using migration assays and analysis of chemoattractant ligand/receptor expression. Prodrug-induced self-killing and bystander tumor cell killing were assessed through viability assays and co-culture with PC3 cells. For the CE2/CPT-11 system, SN-38 was not directly quantified; functional activity was inferred from prodrug-dependent cytotoxicity and in vivo efficacy. In vivo efficacy was evaluated in nude mice with PC3 tumors treated systemically with engineered ADSCs plus prodrug. Results: CD- and CE2-expressing ADSCs were successfully established and retained mesenchymal stem cell (MSC) characteristics. Both cell types exhibited significant migration toward PC3 cells. The CE2/CPT-11 system produced stronger prodrug-mediated cytotoxicity than CD/5-FC, with CE2-modified ADSCs showing higher sensitivity to CPT-11 and inducing greater apoptosis in co-cultured PC3 cells. In vivo, both treatments suppressed tumor growth, but CE2/CPT-11 achieved greater inhibition (tumor volume ~26% of control vs. ~32% for CD/5-FC at day 14). No overt clinical toxicity was observed based on body weight and daily clinical monitoring; however, hematology/serum chemistry were not assessed. Conclusions: Engineered ADSCs home to CRPC tumors and enable local prodrug activation, producing significant antitumor effects. Within the constraints of our in vitro assays and subcutaneous xenograft model, CE2/CPT-11 demonstrated stronger efficacy outcomes than CD/5-FC. Mechanistic attribution to intratumoral SN-38 exposure should be confirmed by direct metabolite measurements in future studies. Full article
(This article belongs to the Section Cancer Biology and Oncology)
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21 pages, 4219 KB  
Article
3D-StyleGAN2-ADA: Volumetric Synthesis of Realistic Prostate T2W MRI
by Claudia Giardina and Verónica Vilaplana
J. Imaging 2026, 12(3), 130; https://doi.org/10.3390/jimaging12030130 - 14 Mar 2026
Viewed by 234
Abstract
This work investigates the extension of StyleGAN2-ADA to three-dimensional prostate T2-weighted (T2W) MRI generation. The architecture is adapted to operate on 3D anisotropic volumes, enabling stable training at a clinically relevant resolution of 256×256×24, where a baseline 3D-StyleGAN [...] Read more.
This work investigates the extension of StyleGAN2-ADA to three-dimensional prostate T2-weighted (T2W) MRI generation. The architecture is adapted to operate on 3D anisotropic volumes, enabling stable training at a clinically relevant resolution of 256×256×24, where a baseline 3D-StyleGAN fails to converge. Quantitative evaluation using Fréchet Inception Distance (FID), Kernel Inception Distance (KID), and generative Precision–Recall metrics demonstrates substantial improvements over a 3D-StyleGAN baseline. Specifically, FID decreased from 114.2 to 27.3, while generative Precision increased from 0.22 to 0.82, indicating markedly improved fidelity and alignment with the real data distribution. Beyond generative metrics, the synthetic volumes were evaluated through radiomic feature analysis and downstream prostate segmentation. Synthetic data augmentation resulted in segmentation performance comparable to real-data training, supporting that volumetric generation preserves anatomically relevant structures, while multivariate radiomic analyses showed strong global feature alignment between real and synthetic volumes. These findings indicate that a 3D extension of StyleGAN2-ADA enables stable high-resolution volumetric prostate MRI synthesis while preserving anatomically coherent structure and global radiomic characteristics. Full article
(This article belongs to the Topic Machine Learning and Deep Learning in Medical Imaging)
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16 pages, 3583 KB  
Article
Fibrosis of Periprostatic Adipose Tissue: A Potential Marker of Prostate Cancer Aggressiveness
by Yiling Jin, Jinyue Hu, Gang Wang, Yu Zhang, Zhiming Bai, Mengxing Huang and Jing Chen
Cancers 2026, 18(6), 949; https://doi.org/10.3390/cancers18060949 - 14 Mar 2026
Viewed by 346
Abstract
Background: Periprostatic adipose tissue (PPAT) fibrosis is a histological feature potentially linked to prostate cancer (PCa) aggressiveness, though its role is not fully understood. This study investigates the correlation between PPAT fibrosis and PCa aggressiveness and develops a radiomics model based on [...] Read more.
Background: Periprostatic adipose tissue (PPAT) fibrosis is a histological feature potentially linked to prostate cancer (PCa) aggressiveness, though its role is not fully understood. This study investigates the correlation between PPAT fibrosis and PCa aggressiveness and develops a radiomics model based on PPAT MRI features for non-invasive prediction. Methods: This retrospective study included 51 patients who underwent radical prostatectomy. PPAT samples were collected, stained with Sirius Red and quantitatively evaluated for fibrosis using 12 indices via 3D reconstruction with Imaris software. Patients were stratified by cancer aggressiveness based on Grade Groups. Radiomic features were extracted from T1-weighted MRIs of the PPAT. An XGBoost model was developed to predict aggressiveness using these features. Results: Significant correlations were found between multiple PPAT fibrosis indices and PCa aggressiveness (p < 0.05), with more aggressive tumors showing increased fiber complexity. PPAT fibrosis was also significantly associated with primary tumor location in the peripheral zone (p < 0.05). Conversely, PPAT volume showed no significant correlation with aggressiveness (p = 0.616). The radiomics model based on PPAT features achieved an AUC of 0.86 in predicting cancer aggressiveness. Conclusions: PPAT fibrosis is a promising marker of PCa aggressiveness, superior to PPAT volume. The significant link with tumor location provides new insights into the tumor microenvironment (TME). MRI-based radiomics of PPAT offers a potential non-invasive method for assessing fibrosis and aggressiveness, aiding in early diagnosis and personalized treatment. Full article
(This article belongs to the Section Clinical Research of Cancer)
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29 pages, 567 KB  
Review
Current Applications and Future Directions of Artificial Intelligence in Prostate Cancer Diagnosis: A Narrative Review
by Cong-Yi Zhu, Rui Qu, Yi Dai and Luo Yang
Curr. Oncol. 2026, 33(3), 166; https://doi.org/10.3390/curroncol33030166 - 13 Mar 2026
Viewed by 402
Abstract
Prostate cancer (PCa) remains a major global health challenge, yet conventional diagnostic methods are often limited by suboptimal accuracy and efficiency. Artificial intelligence (AI) has emerged as a rapidly developing technology capable of integrating multi-source data to enhance clinical decision-making. This narrative review [...] Read more.
Prostate cancer (PCa) remains a major global health challenge, yet conventional diagnostic methods are often limited by suboptimal accuracy and efficiency. Artificial intelligence (AI) has emerged as a rapidly developing technology capable of integrating multi-source data to enhance clinical decision-making. This narrative review synthesizes current evidence regarding AI applications across key diagnostic domains, including medical imaging, digital pathology, liquid biopsy, and multi-omics integration. Findings indicate that AI models for magnetic resonance imaging (MRI) can improve risk stratification and may reduce unnecessary biopsies in some cohorts, particularly when evaluated alongside structured radiology assessment and clinical variables. In digital pathology, deep learning algorithms have shown high agreement with expert genitourinary pathologists for automated Gleason grading in controlled and externally validated settings, with potential to reduce reporting time for high-volume workflows. Additionally, AI-powered liquid biopsy models may support non-invasive risk stratification, particularly for patients with prostate-specific antigen (PSA) levels in the diagnostic gray zone, while multi-omics integration is being investigated to enhance personalized assessment. Despite advances, challenges regarding data heterogeneity, algorithm interpretability, and workflow integration persist. Future research should prioritize multimodal data fusion, explainable AI development, robust calibration and decision-analytic evaluation, and large-scale prospective validation to standardize protocols and fully realize the potential of AI in precision prostate cancer care. Full article
(This article belongs to the Collection New Insights into Prostate Cancer Diagnosis and Treatment)
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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 531
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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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 542
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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14 pages, 585 KB  
Article
Impact of Hydrogel Spacer Insertion on Radiation Dose to Erectile Structures and Longitudinal Sexual Function in Prostate Cancer Patients
by Eyael Zeru, Ziwei Feng, Liang Dong, Ning Meng, Yike Guo, Yi Luo, Yin Zhang, Holly Schuh and Kai Ding
Cancers 2026, 18(5), 814; https://doi.org/10.3390/cancers18050814 - 3 Mar 2026
Viewed by 446
Abstract
Background: Erectile dysfunction is a common late effect of prostate radiotherapy. Hydrogel spacers aim to reduce radiation exposure to nearby structures by increasing the distance between the prostate and surrounding tissues, potentially preserving sexual function. Methods: In this retrospective cohort study of 117 [...] Read more.
Background: Erectile dysfunction is a common late effect of prostate radiotherapy. Hydrogel spacers aim to reduce radiation exposure to nearby structures by increasing the distance between the prostate and surrounding tissues, potentially preserving sexual function. Methods: In this retrospective cohort study of 117 prostate cancer patients who received hydrogel spacers, we compared pre- and post-insertion radiation dose and anatomical positioning of erectile structures using paired t-tests. Longitudinal sexual function, assessed via EPIC scores, was modeled using linear mixed-effects regression with natural splines (df = 3), incorporating random intercepts and slopes to account for within-subject variability. Results: Spacer insertion significantly reduced radiation dose to the left and right neurovascular bundles (mean reductions: 1.66 Gy, 95% CI: 1.32–2.00; and 1.64 Gy, 95% CI: 1.28–2.01, respectively; p < 0.01) and the right perineal artery (1.33 Gy, 95% CI: 0.57–2.09; p < 0.01). No significant dose changes were observed for the penile bulb or left perineal artery, nor in anatomical distances. However, spatial displacement was confirmed by significant overlap and integrated volume changes. Longitudinal modeling showed a significant decline in sexual function between 12 and ≥36 months post-treatment (Spline 2: β = –12.72, 95% CI: −18.52–−6.92 and Spline 3: β = –6.68, 95% CI: −10.96–−2.40; p < 0.01). Conclusions: Hydrogel spacer insertion was associated with significant reductions in radiation dose to erectile structures, most notably the neurovascular bundles and the right perineal artery. However, longitudinal analyses revealed no corresponding preservation of sexual function. These findings suggest that while hydrogel spacers effectively reduce radiation exposure to key anatomical structures, their clinical benefit for maintaining erectile function remains uncertain. Full article
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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 315
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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17 pages, 2814 KB  
Article
Reproducibility of MRI Radiomics Measurements in Men with Prostate Cancer Undergoing Active Surveillance
by Himanshu Sharma, Haitham Al-Mubarak, Juan Lloret Del Hoyo, Ghadi Abboud, Octavia Bane, Mickael Tordjman, Mira M. Liu, Vinayak Wagaskar, Ashutosh Tewari, Bachir Taouli and Sara Lewis
Cancers 2026, 18(5), 778; https://doi.org/10.3390/cancers18050778 - 28 Feb 2026
Viewed by 377
Abstract
Background: MRI-based radiomics has shown promise in men with prostate cancer (PCa); however, successful clinical implementation is contingent upon on reproducible measurements. Purpose: We assessed the reproducibility of radiomics features extracted from bi-parametric prostate MRI (bpMRI) in prostate lesions and non-tumoral [...] Read more.
Background: MRI-based radiomics has shown promise in men with prostate cancer (PCa); however, successful clinical implementation is contingent upon on reproducible measurements. Purpose: We assessed the reproducibility of radiomics features extracted from bi-parametric prostate MRI (bpMRI) in prostate lesions and non-tumoral prostate tissue in men with PCa undergoing active surveillance (AS). Methods: This retrospective study included 47 men with biopsy-proven PCa undergoing AS (mean 68.9 ± 8.2 years, mean PSA density [PSAD] 0.08 ± 0.03 ng/mL/mL) who underwent two bpMRI approximately 12 months apart (range, 10–14 months; December 2018 to April 2020). The reproducibility of radiomics measurements was assessed using the same MRI platform (3T Skyra, Siemens Healthineers; inter-platform) (n = 37), different MRI vendors (Skyra, Siemens Healthineers; 3T Discovery MR750, GE Healthcare; inter-platform) (n = 10), and between observers (n = 10). Shape/1st-/2nd-order radiomics features were extracted from regions of interest on axial T2-weighted (T2-WI), diffusion-weighted imaging (DWI, b1600), and apparent diffusion coefficient (ADC) maps on prostate lesions, non-tumoral peripheral zones (PZs), and transition zones (TZs) using software. Reproducibility was evaluated by calculating the intraclass correlation coefficient (ICC) and coefficient of variation (CV). Associations of clinical variables and prostate volume were assessed. Results: PCa diagnoses included Gleason grade groups 1 (n = 46) and 2 (n = 1)]. Thirty-seven lesions (mean size 0.9 ± 0.4 cm) in 31 patients had PI-RADS v2.1 scores of 2 (n = 3)/3 (n = 12)/4 (n = 21)/5 (n = 1); 16 patients demonstrated diffuse PI-RADS 2 changes. Lesion radiomics features from T2-WI yielded a high proportion of good/moderate ICCs (intra-platform, 77.8%; inter-platform, 56.5%), whereas most DWI/ADC features yielded poor reproducibility. Similar results were observed for non-tumoral PZ/TZ. Intra-platform CVs were lowest for T2-WI lesion features (13.6%) and background PZ/TZ (<13.3%), while DWI/ADC exceeded 20%. Inter-platform CVs were lowest for lesions on T2-WI and were <18% for DWI/ADC; all background PZ/TZ CVs were < 16.4%. Inter-observer analyses showed good/moderate ICCs across all sequences and regions (57.4–92.6%). The distribution of ICC and CV values did not differ between intra- and inter-platform analyses (p > 0.05). Higher reproducibility (ICC > 0.5) was associated with larger prostate volume (intra-platform diagnostic odds ratio [DOR] = 2.58, 95% confidence interval [95%CI], 1.35–3.80, p = 0.01; inter-platform DOR = 3.48, 95%CI 1.79–5.17, p = 0.01) and older age (inter-platform DOR = 5.30, 95%CI 3.75–6.85, p < 0.01). Conclusions: Radiomics measurements from T2-WI demonstrated better intra-/inter-platform reproducibility than DWI/ADC for prostate lesions and non-tumoral tissue. Patient factors (larger prostate volumes and older age) influence radiomics stability. The optimization of diffusion-based radiomics features is needed to improve reproducibility given the essential role of DWI in prostate MRI. Full article
(This article belongs to the Section Methods and Technologies Development)
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11 pages, 1395 KB  
Article
Prostate–Rectum Spacing from Apex to Base and Its Impact on Organs-At-Risk Dosimetry in Prostate Cancer SBRT
by Victor C. Ng, Jill Steele and Edward Soffen
Radiation 2026, 6(1), 8; https://doi.org/10.3390/radiation6010008 - 24 Feb 2026
Viewed by 434
Abstract
Stereotactic body radiation therapy (SBRT) for localized prostate cancer delivers high doses per fraction, making dose constraints for the rectum and other organs at risk critical during treatment planning. This study evaluated the association between prostate–rectum separation, achieved with a biodegradable balloon rectal [...] Read more.
Stereotactic body radiation therapy (SBRT) for localized prostate cancer delivers high doses per fraction, making dose constraints for the rectum and other organs at risk critical during treatment planning. This study evaluated the association between prostate–rectum separation, achieved with a biodegradable balloon rectal spacer at different anatomical levels, and corresponding organ-at-risk dose patterns. Thirty-three patients underwent transperineal balloon spacer implantation followed by SBRT to 36.25 Gy in five fractions. Prostate–rectum separation at the apex, mid-gland, and base were measured on CT and/or MRI and categorized as <10 mm, 10–14 mm, or ≥14 mm. Rectal dose–volume parameters and mean doses to the rectum, bladder, and penile bulb were assessed using linear regression analyses and group comparisons at 14 mm separation. Mean prostate–rectum separation was 16.6 mm overall, with minimal high-dose rectal exposure observed. Increasing separation was associated with reduced rectal dose–volume parameters at the apex and mid-gland, while greater base separation corresponded primarily to lower bladder mean dose. Increased apical separation was also associated with reduced penile bulb mean dose. No acute gastrointestinal toxicity was observed, and genitourinary toxicity was limited to low-grade events. These findings indicate that prostate–rectum separation varies by anatomical level and is associated with distinct organ-at-risk dose relationships in prostate SBRT. Full article
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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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24 pages, 11841 KB  
Article
Harnessing Folate-Mediated PSMA Targeting for Precision Therapy: An Intelligent Liposomal Nanoplatform Against Prostate Cancer
by Youlong Hai, Jiayi Ma, Xuehao Yu, Kun Zheng, Yu Huang, Kai Ni and Xiaoyong Hu
Pharmaceutics 2026, 18(2), 244; https://doi.org/10.3390/pharmaceutics18020244 - 15 Feb 2026
Viewed by 1140
Abstract
Background: Prostate cancer is a leading malignancy among males, and conventional chemotherapy is often limited by insufficient tumor selectivity and systemic toxicity. Prostate-specific membrane antigen (PSMA), which is highly expressed on prostate cancer cells, represents a promising target for precision drug delivery. In [...] Read more.
Background: Prostate cancer is a leading malignancy among males, and conventional chemotherapy is often limited by insufficient tumor selectivity and systemic toxicity. Prostate-specific membrane antigen (PSMA), which is highly expressed on prostate cancer cells, represents a promising target for precision drug delivery. In this study, we developed a folate-modified, PSMA-targeting nanoliposome loaded with docetaxel (DFL) to enhance tumor specificity and therapeutic efficacy. Methods: DFL was prepared using a thin-film hydration–sonication method and characterized through physicochemical analyses. Cellular uptake and cytotoxicity were evaluated in PSMA-high LNCaP cells, with PSMA knockdown used to assess target-dependent internalization. Antitumor efficacy was examined with a microfluidic system and LNCaP xenograft nude mice, and safety was evaluated by measuring hepatic and renal biomarkers and performing histopathological analysis of major organs. Results: DFL demonstrated favorable physicochemical properties and significantly enhanced cellular uptake and cytotoxicity in LNCaP cells relative to control formulations. PSMA knockdown markedly attenuated cellular sensitivity to DFL, confirming PSMA-dependent internalization. A 3D microfluidic perfusion platform further corroborated robust and selective DFL uptake under dynamic flow conditions, thereby strengthening the translational relevance of the targeting effect beyond static cultures. In vivo, DFL substantially inhibited tumor progression in LNCaP xenograft models, reducing both tumor volume and weight by more than 50%. TUNEL assays showed increased apoptosis, and immunohistochemistry revealed reduced Ki-67 expression with concomitant upregulation of Caspase-3. No significant alterations in hepatic or renal biomarkers were observed, and histopathological evaluation demonstrated no treatment-associated lesions in major organs. Conclusions: A folate-modified, PSMA-targeting docetaxel nanoliposome was successfully developed, demonstrating enhanced tumor-specific drug delivery and improved antitumor activity with favorable biocompatibility in preclinical models. DFL represents a promising nanomedicine strategy for the precision chemotherapy of prostate cancer. Full article
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12 pages, 708 KB  
Article
Impact of Androgen Deprivation Therapy on Lower Urinary Tract Symptoms in Patients with Prostate Cancer
by Tae Young Park, Sung Ryul Shim and Chang Hee Kim
Medicina 2026, 62(2), 359; https://doi.org/10.3390/medicina62020359 - 11 Feb 2026
Viewed by 520
Abstract
Background and Objectives: The increasing number of patients with prostate cancer receiving long-term androgen deprivation therapy (ADT) underscores the importance of maintaining quality of life during treatment. Lower urinary tract symptoms (LUTS), influenced by prostate size, represent significant determinants of quality of [...] Read more.
Background and Objectives: The increasing number of patients with prostate cancer receiving long-term androgen deprivation therapy (ADT) underscores the importance of maintaining quality of life during treatment. Lower urinary tract symptoms (LUTS), influenced by prostate size, represent significant determinants of quality of life in this population. This study aimed to investigate the impact of ADT on LUTS in patients with prostate cancer, particularly focusing on how ADT, which reduces prostate volume (PV), affects quality of life, and to identify factors influencing changes in LUTS. Materials and Methods: The study included 104 patients with prostate cancer undergoing ADT. Changes in the International Prostate Symptom Score (IPSS), PV, maximal uroflow rate (Qmax), post-void residual urine volume (RU), and prostate-specific antigen (PSA) levels were compared before treatment initiation and at 12 and 24 weeks after treatment. Association between these variables and patient age, body mass index (BMI), Gleason score (GS), and T stage were also assessed. Results: After 12 and 24 weeks of ADT, prostate size decreased by 16.69 cm3 (32.03%) and 25.36 cm3 (48.68%), respectively, with PSA levels decreasing by 7.63 ng/mL and 22.03 ng/mL. Qmax improved by 3.19 mL/s and 5.57 mL/s, and RU decreased by 42.31 mL and 60.68 mL, respectively (p < 0.001). The IPSS decreased by 13.09 and 14.69 points at 12 and 24 weeks, respectively (p < 0.001). Notably, patients with moderate-to-severe LUTS (baseline IPSS ≥ 8) showed a significantly greater reduction in IPSS (p < 0.001). Additionally, patient age and PSA levels were significantly associated with changes in Qmax (p < 0.001). Conclusions: ADT demonstrated a positive effect on LUTS improvement in patients with prostate cancer, particularly among those with moderate-to-severe LUTS, elevated PSA levels, or older age. Full article
(This article belongs to the Section Urology & Nephrology)
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