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Keywords = recurrent prostate cancer

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28 pages, 845 KiB  
Review
Circulating Tumor DNA in Prostate Cancer: A Dual Perspective on Early Detection and Advanced Disease Management
by Stepan A. Kopytov, Guzel R. Sagitova, Dmitry Y. Guschin, Vera S. Egorova, Andrei V. Zvyagin and Alexey S. Rzhevskiy
Cancers 2025, 17(15), 2589; https://doi.org/10.3390/cancers17152589 - 6 Aug 2025
Abstract
Prostate cancer (PC) remains a leading cause of malignancy in men worldwide, with current diagnostic methods such as prostate-specific antigen (PSA) testing and tissue biopsies facing limitations in specificity, invasiveness, and ability to capture tumor heterogeneity. Liquid biopsy, especially analysis of circulating tumor [...] Read more.
Prostate cancer (PC) remains a leading cause of malignancy in men worldwide, with current diagnostic methods such as prostate-specific antigen (PSA) testing and tissue biopsies facing limitations in specificity, invasiveness, and ability to capture tumor heterogeneity. Liquid biopsy, especially analysis of circulating tumor DNA (ctDNA), has emerged as a transformative tool for non-invasive detection, real-time monitoring, and treatment selection for PC. This review examines the role of ctDNA in both localized and metastatic PCs, focusing on its utility in early detection, risk stratification, therapy selection, and post-treatment monitoring. In localized PC, ctDNA-based biomarkers, including ctDNA fraction, methylation patterns, fragmentation profiles, and mutations, demonstrate promise in improving diagnostic accuracy and predicting disease recurrence. For metastatic PC, ctDNA analysis provides insights into tumor burden, genomic alterations, and resistance mechanisms, enabling immediate assessment of treatment response and guiding therapeutic decisions. Despite challenges such as the low ctDNA abundance in early-stage disease and the need for standardized protocols, advances in sequencing technologies and multimodal approaches enhance the clinical applicability of ctDNA. Integrating ctDNA with imaging and traditional biomarkers offers a pathway to precision oncology, ultimately improving outcomes. This review underscores the potential of ctDNA to redefine PC management while addressing current limitations and future directions for research and clinical implementation. Full article
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14 pages, 1614 KiB  
Article
Adverse Pathology After Radical Prostatectomy in Low- and Intermediate-Risk Prostate Cancer: A Propensity Score-Matched Analysis of Long-Term Health-Related Quality of Life
by Michael Chaloupka, Alexander Buchner, Marc Kidess, Benedikt Ebner, Yannic Volz, Nikolaos Pyrgidis, Stephan Timo Ledderose, Dirk-André Clevert, Julian Marcon, Philipp Weinhold, Christian G. Stief and Maria Apfelbeck
Diagnostics 2025, 15(15), 1969; https://doi.org/10.3390/diagnostics15151969 - 6 Aug 2025
Abstract
Background and Objective: Adverse pathology to high-risk prostate cancer (PCa) after radical prostatectomy (upgrading) poses a threat to risk stratification and treatment planning. The impact on sexual function, urinary continence, and health-related quality of life (HRQOL) remains unclear. Methods: From 2004 [...] Read more.
Background and Objective: Adverse pathology to high-risk prostate cancer (PCa) after radical prostatectomy (upgrading) poses a threat to risk stratification and treatment planning. The impact on sexual function, urinary continence, and health-related quality of life (HRQOL) remains unclear. Methods: From 2004 to 2024, 4189 patients with preop low-/intermediate-risk PCa (Gleason score 6 or 7a, PSA ≤ 20 ng/mL) underwent radical prostatectomy at our department and were analyzed. Primary endpoint was HRQOL, erectile function, and urinary continence. Secondary endpoint was rate of salvage therapies and biochemical-free survival. Propensity score matching was performed using “operative time”, “robot-assisted surgery”, “blood loss”, “nerve-sparing surgery”, “age”, and “BMI” to represent comparable surgical approach. Median follow-up was 39 months (Interquartile-range (IQR) 15–60). Key Findings and Limitations: Patients who were upgraded to high-risk PCa showed a higher rate of postoperative radiotherapy and androgen-deprivation therapy compared to patients who were not upgraded (21% vs. 7%, p < 0.001; 9% vs. 3%, p = 0.002). Five-year biochemical recurrence-free survival was 68% in the upgrading group vs. 84% in the no-upgrading group (p < 0.001). We saw no difference in patient-reported HRQOL, urinary continence, or erectile function. Multivariable analysis showed that postoperative upgrading was a significant risk for not achieving good overall HRQOL (OR: 0.77, 95% CI: 0.61–0.97, p = 0.028) during the follow-up. Conclusions and Clinical Implications: Although postoperative upgrading to high-risk PCa leads to worse oncologic outcomes and higher salvage therapy rates, this study indicates that its impact on health-related quality of life is minimal and should not deter a cautious approach to radical prostatectomy. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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14 pages, 917 KiB  
Article
Deep Learning Treatment Recommendations for Patients Diagnosed with Non-Metastatic Castration-Resistant Prostate Cancer Receiving Androgen Deprivation Treatment
by Chunyang Li, Julia Bohman, Vikas Patil, Richard Mcshinsky, Christina Yong, Zach Burningham, Matthew Samore and Ahmad S. Halwani
BioMedInformatics 2025, 5(3), 42; https://doi.org/10.3390/biomedinformatics5030042 - 4 Aug 2025
Abstract
Background: Prostate cancer (PC) is the second leading cause of cancer-related death in men in the United States. A subset of patients develops non-metastatic, castration-resistant PC (nmCRPC), for which management requires a personalized consideration for appropriate treatment. However, there is no consensus regarding [...] Read more.
Background: Prostate cancer (PC) is the second leading cause of cancer-related death in men in the United States. A subset of patients develops non-metastatic, castration-resistant PC (nmCRPC), for which management requires a personalized consideration for appropriate treatment. However, there is no consensus regarding when to switch from androgen deprivation therapy (ADT) to more aggressive treatments like abiraterone or enzalutamide. Methods: We analyzed 5037 nmCRPC patients and employed a Weibull Time to Event Recurrent Neural Network to identify patients who would benefit from switching from ADT to abiraterone/enzalutamide. We evaluated this model using differential treatment benefits measured by the Kaplan–Meier estimation and milestone probabilities. Results: The model achieved an area under the curve of 0.738 (standard deviation (SD): 0.057) for patients treated with abiraterone/enzalutamide and 0.693 (SD: 0.02) for patients exclusively treated with ADT at the 2-year milestone. The model recommended 14% of ADT patients switch to abiraterone/enzalutamide. Analysis showed a statistically significant absolute improvement using model-recommended treatments in progression-free survival (PFS) of 0.24 (95% confidence interval (CI): 0.23–0.24) at the 2-year milestone (PFS rate increasing from 0.50 to 0.74) with a hazard ratio of 0.44 (95% CI: 0.39–0.50). Conclusions: Our model successfully identified nmCRPC patients who would benefit from switching to abiraterone/enzalutamide, demonstrating potential outcome improvements. Full article
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15 pages, 19662 KiB  
Review
Partial Cystectomy for Muscle-Invasive Bladder Cancer
by Peter S. Palencia, Nethusan Sivanesan, Syed Rahman, Fady Ghali, David Hesse, John Colberg, Ashwin Sridhar, John D. Kelly, Byron H. Lee, Ashish M. Kamat and Wei-Shen Tan
Cancers 2025, 17(15), 2562; https://doi.org/10.3390/cancers17152562 - 3 Aug 2025
Viewed by 219
Abstract
Partial cystectomy is a surgical bladder-sparing option for selected patients with muscle-invasive bladder cancer (MIBC), urachal adenocarcinoma and diverticular bladder tumors. Partial cystectomy hold several advantages. It allows for definite pathology and accurate staging while avoiding side effects from radiation therapy and preserves [...] Read more.
Partial cystectomy is a surgical bladder-sparing option for selected patients with muscle-invasive bladder cancer (MIBC), urachal adenocarcinoma and diverticular bladder tumors. Partial cystectomy hold several advantages. It allows for definite pathology and accurate staging while avoiding side effects from radiation therapy and preserves the option for salvage radical therapy (radical cystectomy or radical radiotherapy). Patients should have a CT urogram, prostatic urethral biopsy and mapping biopsies or blue light cystoscopy to rule out multifocal disease or CIS. Small solitary MIBC patients without carcinoma in situ in an area of the bladder where resection can be performed with negative margin would be the ideal candidates for partial cystectomy. Neoadjuvant systemic therapy is recommended for patients undergoing partial cystectomy. Partial cystectomy can be performed either by open or robotic approaches. When compared to radical cystectomy, partial cystectomy affords a lower complication rate and length of stay and better quality of life. Recurrence-free survival, cancer-specific survival and overall survival at 5 years is 39–67%, 62–84% and 45–70%, respectively. Following partial cystectomy, patients should have three monthly cystoscopy and urinary cytology for the first 24 months followed by 6-monthly cystoscopy for year 3 and 4 and then yearly for life. Cross-sectional imaging should be performed every 3–6 months for the first 2–3 years and then annually for 5 years. Full article
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12 pages, 1472 KiB  
Article
Furosemide Reduces Radionuclide Activity in the Bladder in 18F-PSMA-1007-PET/CT: A Single-Center Retrospective Intra-Individual Comparative Study
by Martin A. Cahenzli, Andreas S. Kreusch, Philipp Huber, Marco Dressler, Janusch P. Blautzik and Gregor Sommer
Diagnostics 2025, 15(15), 1931; https://doi.org/10.3390/diagnostics15151931 - 31 Jul 2025
Viewed by 165
Abstract
Background/Objectives: 18F-PSMA-1007 is one of the more widely used radioligands in prostate cancer imaging with PET/CT. Its major advantage lies in the low urinary tracer activity due to primarily hepatobiliary clearance, but unexpectedly high tracer accumulation in the bladder can occur, [...] Read more.
Background/Objectives: 18F-PSMA-1007 is one of the more widely used radioligands in prostate cancer imaging with PET/CT. Its major advantage lies in the low urinary tracer activity due to primarily hepatobiliary clearance, but unexpectedly high tracer accumulation in the bladder can occur, potentially hindering assessment of lesions near the prostate bed. This study assesses the impact of furosemide on 18F-PSMA-1007 tracer accumulation in the bladder. Methods: In this single-center, retrospective, intra-individual comparative analysis, 18 patients undergoing two consecutive 18F-PSMA-1007 PET/CT scans for biochemical relapse (BCR) or persistence (BCP)—one with and one without prior furosemide administration—were included. Images were acquired 60 min post-injection of 250 MBq of tracer activity. Standardized Uptake Values (SUVmax, SUVpeak, SUVmean) were measured in the bladder and in tissues with physiological uptake by three readers. Differences were analyzed using Wilcoxon signed-rank tests. The inter-reader agreement was assessed using intraclass correlation coefficient. Results: Furosemide significantly decreased bladder SUVmax, SUVpeak, and SUVmean (all p < 0.001). Mean bladder SUVmax decreased from 13.20 ± 10.40 to 3.92 ± 3.47, SUVpeak from 10.94 ± 8.02 to 3.47 ± 3.13, and SUVmean from 8.74 ± 6.66 to 2.81 ± 2.56, representing a large effect size (r ≈ 0.55). Physiological tracer uptake in most organs was not significantly influenced by furosemide (all p > 0.05). Conclusions: Despite the predominantly hepatobiliary clearance of 18F-PSMA-1007, furosemide-induced forced diuresis leads to a significant reduction in tracer activity in the bladder, which in clinical practice could help in early detection of tumor recurrence. Full article
(This article belongs to the Special Issue Research Update on Nuclear Medicine)
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5 pages, 476 KiB  
Correction
Correction: Cloître et al. Spatial Distribution of Recurrence and Long-Term Toxicity Following Dose Escalation to the Dominant Intra-Prostatic Nodule for Intermediate–High-Risk Prostate Cancer: Insights from a Phase I/II Study. Cancers 2024, 16, 2097
by Minna Cloître, Sofian Benkhaled, Sarah Boughdad, Niklaus Schaefer, John O. Prior, Michele Zeverino, Dominik Berthold, Thomas Tawadros, Jean-Yves Meuwly, Paul Martel, Chantal Rohner, Leonie Heym, Frederic Duclos, Véronique Vallet, Massimo Valerio, Jean Bourhis and Fernanda G. Herrera
Cancers 2025, 17(15), 2496; https://doi.org/10.3390/cancers17152496 - 29 Jul 2025
Viewed by 114
Abstract
In the original publication [...] Full article
13 pages, 2372 KiB  
Article
PTEN and ERG Biomarkers as Predictors of Biochemical Recurrence Risk in Patients Undergoing Radical Prostatectomy
by Mihnea Bogdan Borz, Bogdan Fetica, Maximilian Cosma Gliga, Tamas-Csaba Sipos, Bogdan Adrian Buhas and Vlad Horia Schitcu
Diseases 2025, 13(8), 235; https://doi.org/10.3390/diseases13080235 - 24 Jul 2025
Viewed by 297
Abstract
Background/Objectives: Prostate cancer (PCa) remains a major global health issue, associated with significant mortality and morbidity. Despite advances in diagnosis and treatment, predicting biochemical recurrence (BCR) after radical prostatectomy remains challenging, highlighting the need for reliable biomarkers to guide prognosis and therapy. [...] Read more.
Background/Objectives: Prostate cancer (PCa) remains a major global health issue, associated with significant mortality and morbidity. Despite advances in diagnosis and treatment, predicting biochemical recurrence (BCR) after radical prostatectomy remains challenging, highlighting the need for reliable biomarkers to guide prognosis and therapy. The study aimed to evaluate the prognostic significance of the PTEN and ERG biomarkers in predicting BCR and tumor progression in PCa patients who underwent radical prostatectomy. Methods: This study consisted of a cohort of 91 patients with localized PCa who underwent radical prostatectomy between 2016 and 2022. From this cohort, 77 patients were selected for final analysis. Tissue microarrays (TMAs) were constructed from paraffin blocks, and immunohistochemical (IHC) staining for PTEN and ERG was performed using specific antibodies on the Ventana BenchMark ULTRA system (Roche Diagnostics, Indianapolis, IN, USA). Stained sections were evaluated and correlated with clinical and pathological data. Results: PTEN expression showed a significant negative correlation with BCR (r = −0.301, p = 0.014), indicating that reduced PTEN expression is associated with increased recurrence risk. PTEN was not significantly linked to PSA levels, tumor stage, or lymph node involvement. ERG expression correlated positively with advanced pathological tumor stage (r = 0.315, p = 0.005) but was not associated with BCR or other clinical parameters. Conclusions: PTEN appears to be a valuable prognostic marker for recurrence in PCa, while ERG may indicate tumor progression. These findings support the potential integration of PTEN and ERG into clinical practice to enhance risk stratification and personalized treatment, warranting further validation in larger patient cohorts. Full article
(This article belongs to the Section Oncology)
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14 pages, 2043 KiB  
Article
Synergistic Efficacy of WST11-VTP and P-Selectin-Targeted Nanotherapy in a Preclinical Prostate Cancer Model
by Lucas Nogueira, Ricardo Alvim, Hanan Baker, Karan Nagar, Jasmine Thomas, Laura Alvim, Kwanghee Kim, Daniel A. Heller, Augusto Reis, Avigdor Scherz and Jonathan Coleman
Cancers 2025, 17(14), 2361; https://doi.org/10.3390/cancers17142361 - 16 Jul 2025
Viewed by 296
Abstract
Objective: Radical therapies are associated with significant morbidity in patients with localized prostate cancer (PCa). While advances in nuclear magnetic resonance techniques have enabled the development of focal ablation procedures that can selectively destroy tumors, preserve the gland and surrounding structures, and minimize [...] Read more.
Objective: Radical therapies are associated with significant morbidity in patients with localized prostate cancer (PCa). While advances in nuclear magnetic resonance techniques have enabled the development of focal ablation procedures that can selectively destroy tumors, preserve the gland and surrounding structures, and minimize side effects, existing vascular-targeted photodynamic therapy (VTP) and nanodrug therapies often face limitations, such as recurrence and insufficient drug concentration at the tumor site. This study investigated a novel approach that combines VTP with systemic treatment using drug-loaded nanoparticles in a murine model, demonstrating substantial advancements beyond current monotherapies. Methods: SCID (severe combined immunodeficiency) mice were engrafted with androgen-sensitive prostate tumor cells (LNCaP-AR) and treated with a combination of VTP and two different drugs linked to fucoidan nanoparticles (Enzalutamide and Paclitaxel). Experiments were performed using different cohorts: the evaluation of oncological effect, the administration time and concentration of systemic therapy, a comparison of efficacy between VTP and radiotherapy, and the induction of the abscopal effect in untreated synchronous tumors. Results: The groups that received combination therapy showed better tumor control. After eight weeks, the recurrence-free survival rates were 87.5%, 62.5%, and 50% in the VTP + N-PAC, VTP + N-ENZ, and VTP monotherapy groups, respectively (p < 0.05). There was a significant difference in the intra-tumoral concentration of nanodrugs between the groups with combined treatment and monotherapy. After two weeks, the monotherapy groups showed almost total elimination of the drugs, whereas in the combined therapy groups, this concentration remained high, starting to decrease after three weeks (p < 0.05). Treatment with nanodrugs associated with VTP showed superior oncological benefits compared to radiotherapy alone or in combination with other therapies. The abscopal effect on synchronous tumors was not demonstrated with VTP alone or in combination with nanodrugs. Conclusions: Combining vascular photodynamic therapy with nanodrugs was highly effective in treating a prostate tumor model, leading to increased survival and a reduced risk of tumor recurrence. This approach significantly advances beyond existing VTP and nanodrug therapies by improving tumor control, ensuring sustained intra-tumoral drug concentration, and yielding superior oncological outcomes. Our results suggest that this therapy is a potential treatment option for prostate tumors treated with VTP in future clinical trials. Full article
(This article belongs to the Special Issue Advancements in Molecular Research of Prostate Cancer)
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9 pages, 1484 KiB  
Article
In-Bore MRI-Guided Ureteral Stent Placement During Prostate Cancer Cryoablation—A Case Series
by Sydney Whalen, David Woodrum, Scott Thompson, Dan Adamo, Derek Lomas and Lance Mynderse
Diagnostics 2025, 15(14), 1781; https://doi.org/10.3390/diagnostics15141781 - 15 Jul 2025
Viewed by 314
Abstract
Introduction: Ureteral stents are widely used in the specialty of urology to preserve renal function and provide ureteral patency in cases of urolithiasis, strictures, malignancy, and trauma. This paper presents a novel application of prophylactic ureteral stents deployed under MRI-guidance for ureteral [...] Read more.
Introduction: Ureteral stents are widely used in the specialty of urology to preserve renal function and provide ureteral patency in cases of urolithiasis, strictures, malignancy, and trauma. This paper presents a novel application of prophylactic ureteral stents deployed under MRI-guidance for ureteral protection in the setting of in-bore salvage cryoablation therapy for recurrent and metastatic prostate cancer. This is the first known case series of ureteral stent placement using near real-time MRI. Materials and Methods: A retrospective chart review was performed for all patients who underwent MRI-guided ureteral stent placement prior to in-bore cryoablation therapy from 2021 to 2022. Each case was managed by an interdisciplinary team of urologists and interventional radiologists. Preoperative and postoperative data were collected for descriptive analysis. Physics safety testing was conducted on the cystoscope and viewing apparatus prior to its implementation for stent deployment. Results: A total of seven males, mean age 73.4 years (range 65–81), underwent successful prophylactic, cystoscopic MRI-guided ureteral stent placement prior to cryoablation therapy of their prostate cancer. No intraoperative complications occurred. A Grade 2 postoperative complication of pyelonephritis and gross hematuria following stent removal occurred in one case. The majority of patients were discharged the same day as their procedure. Conclusions: This case series demonstrates the feasibility of in-bore cystoscopic aided MRI guidance for ureteral stent placement. Ureteral stents can be used to increase the safety margin of complex cryoablation treatments close to the ureter. Furthermore, by following the meticulous MRI safety protocols established by MRI facility safety design guidelines, MRI conditional tools can aid therapy in the burgeoning interventional MRI space. Full article
(This article belongs to the Special Issue Challenges in Urology: From the Diagnosis to the Management)
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18 pages, 1760 KiB  
Article
Integrating 68Ga-PSMA-11 PET/CT with Clinical Risk Factors for Enhanced Prostate Cancer Progression Prediction
by Joanna M. Wybranska, Lorenz Pieper, Christian Wybranski, Philipp Genseke, Jan Wuestemann, Julian Varghese, Michael C. Kreissl and Jakub Mitura
Cancers 2025, 17(14), 2285; https://doi.org/10.3390/cancers17142285 - 9 Jul 2025
Viewed by 441
Abstract
Background/Objectives: This study evaluates whether combining 68Ga-PSMA-11-PET/CT derived imaging biomarkers with clinical risk factors improves the prediction of early biochemical recurrence (eBCR) or clinical progress in patients with high-risk prostate cancer (PCa) after primary treatment, using machine learning (ML) models. Methods: We [...] Read more.
Background/Objectives: This study evaluates whether combining 68Ga-PSMA-11-PET/CT derived imaging biomarkers with clinical risk factors improves the prediction of early biochemical recurrence (eBCR) or clinical progress in patients with high-risk prostate cancer (PCa) after primary treatment, using machine learning (ML) models. Methods: We analyzed data from 93 high-risk PCa patients who underwent 68Ga-PSMA-11 PET/CT and received primary treatment at a single center. Two predictive models were developed: a logistic regression (LR) model and an ML derived probabilistic graphical model (PGM) based on a naïve Bayes framework. Both models were compared against each other and against the CAPRA risk score. The models’ input variables were selected based on statistical analysis and domain expertise including a literature review and expert input. A decision tree was derived from the PGM to translate its probabilistic reasoning into a transparent classifier. Results: The five key input variables were as follows: binarized CAPRA score, maximal intraprostatic PSMA uptake intensity (SUVmax), presence of bone metastases, nodal involvement at common iliac bifurcation, and seminal vesicle infiltration. The PGM achieved superior predictive performance with a balanced accuracy of 0.73, sensitivity of 0.60, and specificity of 0.86, substantially outperforming both the LR (balanced accuracy: 0.50, sensitivity: 0.00, specificity: 1.00) and CAPRA (balanced accuracy: 0.59, sensitivity: 0.20, specificity: 0.99). The decision tree provided an explainable classifier with CAPRA as a primary branch node, followed by SUVmax and specific PET-detected tumor sites. Conclusions: Integrating 68Ga-PSMA-11 imaging biomarkers with clinical parameters, such as CAPRA, significantly improves models to predict progression in patients with high-risk PCa undergoing primary treatment. The PGM offers superior balanced accuracy and enables risk stratification that may guide personalized treatment decisions. Full article
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11 pages, 209 KiB  
Review
Treatment Intensification Prior to Radical Prostatectomy for Clinically Localized Prostate Cancer
by Carlos Jesus Perez Kerkvliet, Joon Yau Leong, Rasheed A. M. Thompson, Kevin Kayvan Zarrabi, William Kevin Kelly, Costas Lallas, Leonard Gomella and Mihir Shah
Cancers 2025, 17(13), 2258; https://doi.org/10.3390/cancers17132258 - 7 Jul 2025
Viewed by 503
Abstract
Current guidelines recommend either radical prostatectomy (RP) or radiation with androgen deprivation therapy (ADT) for unfavorable intermediate- or high-risk prostate cancer. There has been emerging interest in the potential benefits of neoadjuvant ADT prior to RP for this population. Past trials indicate neoadjuvant [...] Read more.
Current guidelines recommend either radical prostatectomy (RP) or radiation with androgen deprivation therapy (ADT) for unfavorable intermediate- or high-risk prostate cancer. There has been emerging interest in the potential benefits of neoadjuvant ADT prior to RP for this population. Past trials indicate neoadjuvant ADT may be associated with reduced surgical complexity, pathologic downstaging, decreased positive margins, and decreased rates of nodal positivity, although they have not shown benefits for cancer progression and survival. Accordingly, neoadjuvant ADT is currently not recommended for surgical patients. Conversely, ADT is a mainstay of treatment in metastatic disease, and interest remains in expanding its use towards patients with clinically localized disease. There are several ongoing trials of second-generation androgen blockers such as enzalutamide, darolutamide, radiopharmaceuticals, and poly (ADP-ribose) polymerase (PARP) inhibitors to explore long-term cancer-specific survival benefits with neoadjuvant use. In this narrative review, we provide a comprehensive overview of the recent literature and ongoing efforts to incorporate neoadjuvant therapy for clinically localized prostate cancer patients who are at high-risk of recurrence after prostatectomy. Full article
(This article belongs to the Section Cancer Therapy)
17 pages, 1787 KiB  
Article
Tumor Segmentation on PSMA PET/CT Predicts Survival in Biochemical Recurrence of Prostate Cancer: A Retrospective Study Using [68Ga]Ga-PSMA-11 and [18F]-PSMA-1007
by Ken Kudura, Yves Schaulin, Arnoud J. Templeton, Tobias Zellweger, Wolfgang Harms, Raphael Georis, Michael C. Kreissl and Robert Foerster
Cancers 2025, 17(13), 2249; https://doi.org/10.3390/cancers17132249 - 4 Jul 2025
Viewed by 604
Abstract
Background: PSMA PET/CT imaging has become a cornerstone in the management of prostate cancer, particularly in the setting of biochemical recurrence (BCR). While semi-quantitative parameters such as SUVmean have been evaluated as prognostic biomarkers in metastatic castration-resistant prostate cancer (mCRPC), particularly after [...] Read more.
Background: PSMA PET/CT imaging has become a cornerstone in the management of prostate cancer, particularly in the setting of biochemical recurrence (BCR). While semi-quantitative parameters such as SUVmean have been evaluated as prognostic biomarkers in metastatic castration-resistant prostate cancer (mCRPC), particularly after the VISION trial, the prognostic role of volumetric measures such as Total Molecular Volume (TMV) remain largely unexplored, especially in earlier stages of the disease such as in biochemical recurrence following primary treatment. Methods: This retrospective monocentric study included 84 patients with BCR who underwent PSMA PET/CT imaging between 2020 and 2021 using either [68Ga]Ga-PSMA-11(Ga-PSMA) or [18F]-PSMA-1007 (F-PSMA) as tracers. Total tumor burden was assessed through manual 3D segmentation to derive whole-body Total Molecular Volume (wb TMV) and Total Lesion PSMA (wb TL-PSMA). Clinical and imaging variables were correlated with overall survival (OS) and progression-free survival (PFS) using Cox regression models. Kaplan–Meier analyses were performed based on wb TMV and thresholds determined by the Youden index. Results: A PSMA PET/CT correlation for BCR was identified in 69% of patients, with comparable detection rates between tracers (Ga-PSMA 67% vs. F-PSMA 63%, p = 0.7). A higher wb TMV was significantly associated with worse OS (HR 2.20, p < 0.001) and PFS (HR 2.01, p < 0.001) in univariable analyses. In multivariable models, log2(wb TMV) remained an independent prognostic factor for PFS (HR 1.78, p = 0.005). Patients with log2(wb TMV) > 2.87 exhibited significantly poorer survival outcomes. A PSA at diagnosis > 17 ng/mL also predicted shorter PFS. Conclusions: Tumor segmentation from PSMA PET/CT imaging provides powerful prognostic information in patients with biochemical recurrence of prostate cancer, independently of the tracer used. The wb TMV represents a promising volumetric biomarker for future risk stratification and therapeutic decision-making, particularly in earlier stages of prostate cancer progression, where predictive imaging biomarkers remain largely undefined. Full article
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13 pages, 1799 KiB  
Article
Proposal for an Expanded “R” Classification: Impact of Positive Surgical Margin Length on Biochemical Recurrence After Robotic Radical Prostatectomy
by Alper Kerem Aksoy, Ahmet Tahra, Resul Sobay, Ali Kumcu, İlkay Tosun, Uğur Boylu and Eyüp Veli Küçük
J. Clin. Med. 2025, 14(12), 4310; https://doi.org/10.3390/jcm14124310 - 17 Jun 2025
Viewed by 439
Abstract
Objectives: In this study, the effect of positive surgical margin (PSM) length on predicting postoperative biochemical recurrence (BCR) after radical prostatectomy was evaluated, and based on the findings, an additional R subclassification to the TNM-R system was proposed. Methods: We retrospectively [...] Read more.
Objectives: In this study, the effect of positive surgical margin (PSM) length on predicting postoperative biochemical recurrence (BCR) after radical prostatectomy was evaluated, and based on the findings, an additional R subclassification to the TNM-R system was proposed. Methods: We retrospectively analyzed patients who underwent robot-assisted radical prostatectomy between 30 July 2008 and 31 December 2019. Only patients with PSM were included. Those with negative margins, those receiving neoadjuvant/adjuvant hormone therapy, or those with prior pelvic radiotherapy were excluded. A total of 353 pathology specimens were re-evaluated by a uropathologist, and the PSM length was quantitatively measured. BCR was defined as a PSA level of ≥0.2 ng/mL in two consecutive measurements. Results: The median follow-up time of the patients was 49.5 ± 33.4 months. BCR occurred in 27.1% (n = 96) of patients. A PSM cut-off length of 3.5 mm was identified for predicting BCR (p < 0.001). Among patients with PSM < 3.5 mm, 9.8% experienced BCR, while 54.3% of those with PSM ≥ 3.5 mm did. A PSM length ≥ 3.5 mm was associated with a higher risk of recurrence (OR: 1.249, 95% CI: 1.160–1.345, p < 0.001). In multivariate logistic regression analysis, PSM length remained an independent prognostic factor for BCR (p < 0.001). Conclusions: Quantitative measurement of PSM length serves as an independent predictor of BCR following radical prostatectomy. We propose subclassifying R1 margins into R1a (<3.5 mm) and R1b (≥3.5 mm), which may enhance prognostic accuracy in pathological reporting. Full article
(This article belongs to the Special Issue Prostate Cancer: Diagnosis, Clinical Management and Prognosis)
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17 pages, 2685 KiB  
Review
SIU-ICUD: Management of Lymph Node–Positive Prostate Cancer
by Haitham Shaheen, Mack Roach and Eman Essam Elsemary
Soc. Int. Urol. J. 2025, 6(3), 46; https://doi.org/10.3390/siuj6030046 - 13 Jun 2025
Cited by 1 | Viewed by 775
Abstract
Background/Objectives: The management of localized prostate cancer with regional lymph node involvement (N1M0) presents significant clinical challenges. While once considered indicative of systemic disease, improved imaging and evolving treatment paradigms have redefined node-positive disease as potentially curable. This systematic review aims to [...] Read more.
Background/Objectives: The management of localized prostate cancer with regional lymph node involvement (N1M0) presents significant clinical challenges. While once considered indicative of systemic disease, improved imaging and evolving treatment paradigms have redefined node-positive disease as potentially curable. This systematic review aims to assess current evidence regarding treatment modalities and outcomes for patients with localized N1M0 prostate cancer. Methods: A systematic review was conducted to identify studies evaluating therapeutic strategies for N1M0 prostate cancer. Eligible studies included randomized controlled trials, retrospective analyses, and consensus guidelines. Treatment approaches reviewed included radical prostatectomy (RP) with pelvic lymph node dissection (PLND), whole pelvic radiotherapy (WPRT), prostate-only radiotherapy (PORT), androgen deprivation therapy (ADT), and metastasis-directed therapy (MDT), including stereotactic body radiotherapy (SBRT). Key outcomes included overall survival (OS), biochemical recurrence-free survival (bRFS), disease-free survival (DFS), and treatment-related toxicity. Results: Multimodal approaches—particularly the combination of ADT with WPRT or adjuvant radiotherapy following RP—were associated with improved survival outcomes. Patients with limited nodal burden and undetectable postoperative prostate-specific antigen (PSA) levels derived the most benefit. The use of prostate-specific antigen membrane positron-emission tomography/computed tomography (PSMA PET/CT) enhanced detection and guided MDT in oligorecurrent disease. SBRT, simultaneous integrated boost (SIB), and hypofractionated regimens demonstrated promising efficacy with acceptable toxicity profiles. Conclusions: Node-positive localized prostate cancer is optimally managed with individualized, multidisciplinary strategies. Combining systemic and locoregional treatments improves outcomes in selected patients. Ongoing prospective studies are warranted to refine patient selection, optimize treatment sequencing, and integrate novel imaging and systemic agents. Full article
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9 pages, 278 KiB  
Review
SIU-ICUD: Prevention of Lethal Prostate Cancer via Modifiable Heart-Healthy Lifestyle Changes, Metrics, and Repurposed Medications
by Mark A. Moyad, Raj V. Tiwari, Daniel A. Galvão, Dennis R. Taaffe and Robert U. Newton
Soc. Int. Urol. J. 2025, 6(3), 40; https://doi.org/10.3390/siuj6030040 - 7 Jun 2025
Cited by 1 | Viewed by 1707
Abstract
Background/Objectives: Primary prevention, germline, familial, or other pre- or post-diagnostic and standard treatment-elevated progression or recurrence risk and mitigating adverse events from systemic treatment are all clinical opportunities to reduce the risk of lethal prostate cancer. This review attempted to provide a [...] Read more.
Background/Objectives: Primary prevention, germline, familial, or other pre- or post-diagnostic and standard treatment-elevated progression or recurrence risk and mitigating adverse events from systemic treatment are all clinical opportunities to reduce the risk of lethal prostate cancer. This review attempted to provide a practical and realistic consensus via an international committee of experts who, in general, harbor career-long experience in this discipline. Methods: A PubMed review primarily utilizing the latest meta-analyses, systematic reviews, and methodologically robust epidemiologic recent data adjusting for multiple confounding variables was conducted. The goal of this committee was to highlight tangible options for clinicians and patients. Results: Behavioral patterns and metrics known to reduce cardiovascular morbidity, mortality, and all-cause mortality (premature death) appear to prevent numerous lethal common cancers, including prostate cancer. This practical approach allows for the greatest probability of patient success since cardiovascular disease (CVD) is the primary cause of death in men with and without prostate cancer, and a notable source of morbidity and mortality in men with advanced disease due to systemic conventional treatment as well as the inflammatory contribution of cancer itself. Heart-healthy dietary patterns, exercise, healthy weight/waist circumference, eliminating tobacco, minimizing alcohol exposure, and other behaviors to reduce the risk of CVD should be prioritized. CVD-preventive medications, including aspirin, GLP-1 agonists, metformin, statins, etc., should receive attention to improve compliance for those that already qualify for these agents and to increase the probability of enhancing the quality and quantity of life. Dietary supplements do not have favorable data currently to espouse their utilization to prevent lethal prostate cancer but may have an ancillary role in mitigating some adverse effects of treatment. Conclusions: Remarkably, heart-healthy lifestyle changes, metrics, and promising repurposed medications known to reduce cardiovascular events, promote longevity, and improve mental health could simultaneously prevent lethal prostate cancer. This serendipitous association provides clinicians and their patients a higher probability of success, regardless of their prostate cancer pathway or circumstance. Full article
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