Search Results (729)

Background/Objectives: Iatrogenic nerve injury is a significant challenge in urologic surgery, with radical prostatectomy posing a high risk due to complex pelvic neural anatomy. Despite advances in robotic-assisted and nerve-sparing techniques, postoperative urinary incontinence and erectile dysfunction remain prevalent, adversely affecting patients’ quality of life and imposing substantial healthcare costs. Methods: A narrative review was conducted using PubMed, MEDLINE, and the Cochrane Library (searches through February 2026) for studies on radical prostatectomy epidemiology, mechanisms of nerve injury, functional outcomes, and economic burden. Emerging intraoperative fluorescence imaging technologies, surgical strategies to mitigate iatrogenic nerve injuries, and the financial costs of post-prostatectomy complications were assessed. Results: Robotic-assisted radical prostatectomy now accounts for >80% of procedures in the United States, and has been associated in observational studies with improved early recovery of erectile function compared with open and laparoscopic approaches. However, the lack of real-time nerve visualization remains a limiting factor. Recent milestones (January 2026) include the Food and Drug Administration Investigational New Drug clearance for the nerve-specific fluorophore LGW16-03 (NerveTrace), which enables real-time identification of sub-millimeter nerve branches, and the 510(k) premarket clearance of Dendrite imaging (November 2025). Conclusions: Enhanced intraoperative nerve discrimination via molecularly targeted imaging has the potential to reduce iatrogenic complications and improve long-term functional and economic outcomes in prostate cancer surgery, although these benefits have yet to be demonstrated in prospective clinical and health-economic studies. Full article

Focal therapy is emerging as an organ-preserving strategy for selected patients with localized prostate cancer, aiming to preserve urinary and sexual function while maintaining acceptable cancer control. However, patient and technology selection remain complex because prostate cancer is often multifocal, clinically significant lesions may be missed by imaging or biopsy, and long-term comparative oncological data are limited. This narrative review summarizes current evidence and consensus recommendations on oncological suitability, histopathological risk features, tumor burden, imaging assessment, anatomical considerations, functional priorities, and follow-up. We also discuss the complementary roles of multiparametric magnetic resonance imaging, prostate-specific membrane antigen positron emission tomography, micro-ultrasound, and artificial intelligence-assisted planning. Finally, we review how tumor location and proximity to critical structures guide selection among high-intensity focused ultrasound, cryotherapy, irreversible electroporation, transurethral ultrasound ablation, laser ablation, and photodynamic therapy. Focal therapy remains promising but requires careful selection, shared decision-making, and structured follow-up. Full article

Background/Objectives: Enzalutamide and abiraterone acetate are commonly used androgen receptor pathway inhibitors in metastatic castration-resistant prostate cancer (mCRPC), including after docetaxel. However, real-world outcomes remain heterogeneous, and simple prognostic markers may help describe this variability. This study aimed to describe survival outcomes with enzalutamide and abiraterone acetate after docetaxel and to explore the prognostic value of a routine clinical-inflammatory risk classification. Methods: This retrospective single-center study included 136 patients with mCRPC treated with enzalutamide or abiraterone acetate after docetaxel. A composite risk classification was defined using four routinely available variables: pan-immune-inflammation value (PIV) > 457.99, time to castration resistance < 12 months, baseline hemoglobin ≤ 12 g/dL, and Gleason score ≥ 8. One point was assigned for each adverse factor, and patients were classified as low, moderate, or high risk. Overall survival (OS) was assessed using Kaplan–Meier estimates and Cox regression. The prognostic score and Cox regression-based nomogram were evaluated as exploratory tools. Results: Of the 136 patients, 8 (5.9%) were classified as low risk, 67 (49.3%) as moderate risk, and 61 (44.9%) as high risk. Median OS was not reached in the low-risk group, compared with 33.84 months in the moderate-risk group and 9.66 months in the high-risk group. In multivariable analysis, high-risk status was independently associated with worse OS (HR = 9.87; 95% CI: 2.38–40.92; p = 0.002). No statistically significant OS difference was observed between enzalutamide and abiraterone acetate in this non-randomized cohort (HR = 1.36; 95% CI: 0.90–2.06; p = 0.142). Conclusions: In this real-world post-docetaxel mCRPC cohort, no statistically significant OS difference was observed between enzalutamide and abiraterone acetate; however, the study was not designed to establish comparative effectiveness or therapeutic equivalence. The exploratory risk classification based on routine clinical and inflammatory variables was associated with distinct survival outcomes. External validation is required before clinical application. Full article

Background/Objectives: Clinical studies of prostate cancer treated with radically hypofractionated high-dose-rate brachytherapy (HDR-BT) have reported a significant loss of tumor control that contradicts the standard linear-quadratic (LQ) and low-$\alpha /\beta$-ratio paradigm for prostate cancer. In a previous study by our group, we showed that the linear–quadratic–linear (LQL) model could describe this response, but the underlying biological drivers remained unclear. In this follow-up study, we further investigate whether the interplay between hypoxia and reoxygenation kinetics can explain the poor response to extreme hypofractionation. Methods: We analyzed a large dataset of 3239 patients (44 schedules) using a three-compartment reoxygenation model (the MSK model) that simulates the dynamics of oxic, intermediate, and hypoxic cell populations. Results: The results show that the MSK model achieves an excellent fit to the clinical data ($p>0.99$) while maintaining a biologically plausible low $\alpha /\beta$ ratio (≤8 Gy). The reoxygenation model provided a performance comparable to the LQL model for low-risk prostate cancer and slightly inferior for intermediate-risk. Conclusions: This suggests that the observed reduction in tumor control may not necessarily be a failure of the LQ formalism but, rather, a consequence of oxygen dynamics associated with ultra-hypofractionated schedules. Nonetheless, neither this nor our previous work can provide insight into the driving mechanism and should only be interpreted as showing that both hypotheses are compatible with the clinical data. Full article

Background/Objectives: This study explored whether a multimodal artificial intelligence (MMAI) model integrating digitized histopathology and clinical features can identify prostate cancer patients who may benefit from neoadjuvant hormonal therapy (NHT) and whole-pelvic radiotherapy (WPRT). Methods: This secondary analysis of NRG/RTOG 9413 included NHT-treated patients with digitized biopsy slides and clinical data who were not part of the MMAI model optimization. A previously validated MMAI model estimated long-term risk, and Fine-Gray models evaluated interactions between MMAI-derived scores and the radiation field (WPRT vs. prostate-only RT [PORT]) for biochemical failure (BF), chosen over progression-free survival because of extended follow-up and distant metastasis (DM), with subgroup analyses by predefined MMAI strata. Results: Among 81 eligible patients, the MMAI-by-treatment interaction for BF did not confirm a differential effect (p = 0.30). Therefore, subgroup findings should be interpreted as descriptive and hypothesis-generating. Nevertheless, the magnitude effect of WPRT was numerically greater in the MMAI high-risk subgroup (5-yr: 41% vs. 79%; 10-yr: 47% vs. 79%; aHR 0.35 [0.14–0.86]) than in the low–intermediate group (5-yr: 18% vs. 33%; 10-yr: 44% vs. 57%; aHR 0.66 [0.29–1.48]). Conclusions: Although no statistically significant treatment-by-MMAI interaction was demonstrated, these findings are hypothesis-generating and support further investigation of MMAI approaches for guiding WPRT in NRG/RTOG 0534, 0924, GETUG-01, and POP-RT trials. Full article

Background/Objectives: Lymph node metastasis within the prostatic anterior fat pad (PAFP) is uncommon but may refine nodal staging when pelvic lymph node dissection and PSMA PET/CT are negative. Case Presentation: A 58-year-old man with PSA 59 ng/mL, negative digital rectal examination, and a PI-RADS 5 anterior lesion underwent transperineal MRI/US fusion biopsy, showing an acinar adenocarcinoma (Gleason score 5 + 5 = 10, ISUP grade group 5) confined to anterior cores. 18F-PSMA-1007 PET/CT showed intense intraprostatic uptake (SUVmax 55.2) without nodal or distant disease. Retropubic radical prostatectomy, bilateral extended pelvic lymph node dissection (ePLND), and separate PAFP submission were performed. Final pathology showed a 38 mm bilateral anterior tumor involving 35% of the prostate, focal anterior extraprostatic extension, negative margins, absent seminal vesicle and bladder neck invasion, perineural and lymphovascular invasion, and no cribriform or intraductal carcinoma. All 15 pelvic nodes were negative. One of two PAFP nodes contained a 3 mm PSA-positive metastasis without extranodal extension, resulting in pT3aN1 staging. Postoperative PSA persistence prompted radiotherapy plus androgen deprivation therapy; PSA was 0.01 ng/mL at 6 months. Conclusions: In very-high-risk anterior prostate cancer, separate PAFP evaluation may provide clinically relevant staging information when PSMA PET/CT and pelvic lymph nodes are negative. This case highlights the PAFP as a potential site of occult regional nodal disease. Full article

Objective: This study aims to explore new hematological indicators with differential diagnostic significance for clinically significant prostate cancer (csPCa) by conducting comprehensive hematological tests, and to construct a novel discrimination index (DI) (csPCa-DI) to improve the diagnostic accuracy of csPCa. Methods: A total of 542 patients suspected of prostate cancer who were admitted to Beijing Tsinghua Changgung Hospital from November 2014 to May 2025 were enrolled in this study. All patients underwent complete blood count, coagulation testing, full biochemical analysis, and prostate biopsy. According to the biopsy results, patients were divided into the csPCa group and the non-csPCa group. The differences in hematological indicators between the two groups were compared, and multivariate logistic regression analysis was used to screen independent risk factors for csPCa. Two scoring systems (Fib-PLT Score and Fib-PLT-DD Score) were constructed based on coagulation-related parameters, and a csPCa discrimination index (csPCa-DI) was further established by integrating independent risk factors. The diagnostic efficacy of these scores, csPCa-DI, and traditional PSA-related indicators was evaluated by receiver operating characteristic (ROC) curves. Stratified validation was performed in the PSA gray zone (4–10 ng/mL) population. Results: Multivariate logistic regression identified prostate-specific antigen density (PSAD) (OR = 18.063, 95% CI: 7.125–45.792, p < 0.001), age (OR = 1.062, 95% CI: 1.024–1.102, p = 0.001), and Fib-PLT-DD Score (OR = 0.388, 95% CI: 0.251–0.599, p < 0.001) as independent predictors of csPCa. Based on the regression coefficient (β) weights of the independent predictors, the csPCa-DI was formulated as: csPCa-DI = 2.894 × PSAD + 0.060 × Age − 0.946 × Fib-PLT-DD Score (Fib-PLT-DD Score = 0.672 × Fib + 0.008 × PLT − 0.028 × DD). In the overall cohort, the area under the ROC curve (AUC) of csPCa-DI for diagnosing csPCa was 0.821 (95% CI: 0.773–0.868, p < 0.001), higher than that of total PSA (0.701) and f/t PSA ratio (0.727), and slightly higher than PSAD (0.797). The optimal cut-off value of csPCa-DI in the overall cohort was 1.46 points, with a sensitivity of 87.4% and specificity of 61.8%. In the PSA gray zone population, csPCa-DI exhibited superior diagnostic efficacy with an AUC of 0.736 (95% CI: 0.634–0.838, p < 0.001), significantly higher than total PSA (0.465) and f/t PSA ratio (0.638), and slightly higher than PSAD (0.720). A csPCa-DI cut-off value of 0.92 points in the PSA gray zone achieved a high sensitivity of 96.0% (specificity = 48.0%), effectively reducing missed diagnosis, while the cut-off of 1.46 points balanced sensitivity (68.0%) and specificity (70.7%). Conclusions: The novel csPCa-DI constructed by integrating PSAD, age, and coagulation-derived Fib-PLT-DD Score based on β weights has higher diagnostic efficacy for csPCa than traditional single PSA-related parameters, especially in the PSA gray zone, which can provide a new clinical tool for the screening and differential diagnosis of csPCa. This study also clarifies the correlation between local coagulation abnormalities and csPCa, providing a new perspective for understanding the pathological mechanism of csPCa. Full article

Background/Objectives: Metabolic syndrome is a prevalent global health concern characterized by central obesity, insulin resistance, hypertension, and dyslipidemia. Growing evidence suggests that metabolic dysregulation may influence prostate cancer risk and disease behavior; however, findings across studies remain inconsistent. This systematic review aimed to evaluate the association between metabolic syndrome and prostate cancer risk, clinicopathologic characteristics, and disease outcomes. Methods: A systematic literature search was conducted in PubMed/MEDLINE from database inception through the final search update on 10 January 2026, with supplementary searches of Google Scholar, Wiley Online Library, the Clinical Oncology journal collection, and reference lists. Observational studies assessing the relationship between metabolic syndrome and prostate cancer outcomes were eligible for inclusion. Two reviewers independently screened titles and abstracts, followed by full text review to determine eligibility. Discrepancies were resolved through consensus. Risk of bias was assessed using design-specific tools, including the Newcastle–Ottawa Scale, Cochrane Risk of Bias 2 tool, and Joanna Briggs Institute checklist. Findings were synthesized narratively because of heterogeneity in study design, metabolic syndrome definitions, populations, outcomes, and effect estimates. Results: A total of 1304 records were identified across all databases. After duplicate assessment, records underwent title and abstract screening, followed by full text assessment. Twenty-four studies, ranging from small clinic-based cohorts to large population-based cohorts exceeding 5 million participants, met the inclusion criteria and were included in the qualitative synthesis. Most studies were cohort or case–control designs conducted in North America, Europe, and Asia. Overall, evidence for a uniform association between composite metabolic syndrome and prostate cancer incidence was inconsistent. Associations appeared more suggestive for clinically significant, high-grade, or adverse pathological features, although findings varied by study design, metabolic syndrome definition, detection context, and adjustment level. Several studies suggested that individual components of metabolic syndrome, particularly obesity and insulin resistance, may be key drivers of these associations. Conclusions: Available evidence suggests a heterogeneous relationship between metabolic syndrome, related metabolic abnormalities, and prostate cancer outcomes. Evidence for a uniform association with overall prostate cancer incidence was inconsistent, whereas signals were more frequently reported for clinically significant, high-grade, or adverse pathological features. However, these findings should be interpreted cautiously because of observational study designs, heterogeneous MetS definitions, detection context, and variable adjustment. Further well-designed prospective studies are needed to clarify temporality, causal pathways, and the contributions of individual metabolic components. Full article

Introduction: Lymph nodes (LN) in the anterior periprostatic fat (APPF) may harbour metastatic disease in patients with Prostate Cancer (PCa). We investigated the incidence and significance of LN in APPF tissue removed during robotic and laparoscopic radical prostatectomy (RP). Patients and Methods: We retrospectively analysed RP performed by a single surgeon from 2013 to 2023. A total of 670 patients underwent RP, with 407 procedures conducted laparoscopically and 263 robotically. Histological results were available for 509 patients, who were examined for the presence of LN and any evidence of metastatic involvement. Results: LN were detected in the periprostatic fat of eighty patients; however, only twelve had lymph node metastasis. Seven of the twelve patients presented with prostate-specific antigen (PSA) levels greater than 10 ng/mL. All LN-positive patients had a Gleason score of seven or higher. On MRI, all patients had a PIRADS score of four or higher, and eleven were staged at T3 or higher. Additionally, all twelve patients had a Briganti score exceeding twenty. Conclusions: Our series indicates that the APPF contains LN that can harbour metastatic disease. Patients can have LN involved in APPF without the involvement of pelvic LN. Therefore, our study suggests that routine excision of APPF should be considered for appropriate LN staging and to avoid missing any metastasis, and that scoring systems like Briganti should be used to help identify this high-risk group. Full article

Background: Prostate cancer remains a major cause of cancer-related morbidity and mortality among men worldwide. Limited access to oncology services contributes to late presentation, delayed diagnosis, and treatment. This study describes the clinicopathological profile of prostate cancer and identifies factors associated with disease severity at presentation in an Eastern Cape population. Methods: A retrospective cross-sectional study was conducted among men diagnosed with prostate cancer at a tertiary hospital between 2014 and 2024. Demographic, clinical, and pathological data were extracted. Descriptive analyses were performed, and multivariable logistic regression was used to identify independent predictors of advanced disease. Results: The study included 202 patients with a mean age of 67.2 years. Thirty-four (16.8%) reported a family history of prostate cancer, and 62.4% had never undergone PSA screening before diagnosis. Elevated PSA levels were common (60.4%), and more than half of patients presented with advanced disease (54.5%). High-risk and very high-risk disease were identified in 44.1% and 21.3% of patients, respectively. Lack of prior PSA screening was independently associated with high-risk disease (aOR 2.4, 95% CI 1.1–5.0), advanced stage at presentation (aOR 2.4, 95% CI 1.2–4.8), and PSA > 20 ng/mL. Conclusions: There is a high burden of late-stage, high-risk prostate cancer at presentation. These findings highlight ongoing challenges in early detection and emphasize the need for improved awareness, screening, and referral pathways to improve outcomes. Full article

Prostate cancer (PCa) remains a major global health concern, with a subset of patients progressing to aggressive disease despite advances in diagnosis and treatment. Epithelial–mesenchymal transition (EMT) plays a pivotal role in tumor invasion, metastasis, and immune evasion; however, its cellular heterogeneity and clinical relevance in PCa remain incompletely understood. We analyzed single-cell transcriptomic data to characterize EMT dynamics in malignant epithelial cells. Malignant cells were identified based on aberrant copy number variation patterns, and EMT activity was quantified using AUCell. Gene expression profiling and gene set enrichment analysis identified key EMT-associated genes. By integrating bulk transcriptomic data with LASSO regression analysis, we identified five pivotal genes and constructed an EMT infiltration scoring model. The model demonstrated robust predictive performance in an external Gene Expression Omnibus validation cohort and effectively predicted early biochemical recurrence. Further analyses revealed significant associations between EMT scores, clinicopathological features, immune cell infiltration, genomic instability, and tumor immune dysfunction and exclusion scores. Pathway enrichment analysis highlighted distinct molecular characteristics between high- and low-score groups. Additionally, molecular docking using AutoDock identified potential targeted therapeutic agents for key EMT genes. Overall, this study systematically delineates EMT heterogeneity at the single-cell level and establishes a robust EMT infiltration model for prognostic prediction and therapeutic guidance in PCa, providing novel insights for precision risk stratification and individualized treatment strategies. Full article

Background/Objectives: Prostate cancer (PCa) remains a prevalent malignancy among men, often complicated by recurrence and unfavorable clinical outcomes. Consequently, precise risk stratification and timely clinical intervention are paramount. Initially, we delineated distinct expression profiles of histone modification regulators via unsupervised clustering, identifying PCa subtypes with divergent survival probabilities and biological phenotypes. Subsequently, we sought to develop a prognostic gene signature, derived from the transcriptomic variations among these regulator-defined subtypes, to predict outcomes in PCa patients following radical prostatectomy (RP). Methods: Clinical and transcriptomic data from PCa cohorts were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) repositories for comprehensive analysis. Subtypes driven by histone modification regulators were established using unsupervised consensus clustering, followed by in-depth characterization of their molecular features and associated pathways. A risk-scoring model was then developed to evaluate its prognostic efficacy in this patient population. Results: Stratification based on histone modification regulators yielded four distinct PCa subtypes exhibiting heterogeneous survival outcomes, functional pathways, and genomic mutational landscapes. Following rigorous feature selection, a 21-gene risk signature (HIS_score)—comprising MXD3, CCDC28B, COL11A2, SLC39A5, GPT, DNASE1L2, PIF1, KRTAP5-9, TTLL10, KRTAP5-1, KRTAP5-10, HAGHL, MSLNL, AMH, NKAIN4, CCDC114, SLC9A3, SULT1E1, ALB, SLC6A14, and RPE65—was constructed. Survival analyses demonstrated that patients assigned to the high HIS_score cohort experienced significantly worse clinical outcomes compared to their low-score counterparts. Furthermore, we integrated this signature into a novel clinical nomogram to facilitate individualized prognostic assessments. Conclusions: Derived from transcriptomic disparities between extreme epigenetic subtypes, the HIS_score and its associated nomogram serve as robust prognostic instruments. These tools effectively encapsulate the downstream transcriptional sequelae of histone modification dysregulation, offering clinicians a valuable framework to accurately predict post-RP outcomes and expedite the formulation of personalized therapeutic strategies. Full article

A circulating tumor DNA (ctDNA) assay is an emerging non-invasive diagnostic approach providing real-time insights into the heterogeneous tumor molecular landscape of advanced prostate cancer, overcoming the limitations of traditional tissue biopsies and PSA. Detection methods include droplet digital PCR, next-generation sequencing, and new epigenomic and fragmentomic strategies (investigational) designed to improve sensitivity in cases of low ctDNA shedding. While ctDNA’s role in localized prostate cancer is limited, it offers significant prognostic value in metastatic cases, where high ctDNA levels correlate with shorter survival. Additionally, longitudinal ctDNA monitoring can predict treatment response and identify emerging resistance mechanisms, including androgen receptor alterations associated with androgen receptor pathway inhibitor therapy and BRCA reversion mutations linked to PARP inhibitors. Importantly, liquid biopsy enables genomic characterization to inform treatment decision-making, particularly in clinical scenarios where tissue biopsy is challenging, such as bone-only disease. However, the widespread clinical implementation of ctDNA analysis is hindered by several analytical challenges, including low sensitivity in localized disease and low disease burden, and the risk of false positives due to clonal hematopoiesis. Furthermore, greater efforts are required to standardize pre-analytical workflows and post-analytical data interpretation and reporting across institutions. This review aims to summarize the evolving role of cfDNA technologies in localized and advanced prostate cancer, highlighting their prognostic and predictive value and their role in uncovering mechanisms of treatment resistance. Full article

The diagnostic field of prostate cancer (PCa) has undergone a significant evolution with the widespread integration of multiparametric magnetic resonance imaging (mpMRI) and mpMRI-targeted biopsies (TBx). This approach has been shown to improve the detection of clinically significant prostate cancer (csPCa) while reducing the overdiagnosis of low-risk disease. However, a conceptual and clinical challenge, which can be referred to as the “Precision Paradox,” has emerged. By directing biopsy cores almost exclusively into the most suspicious MRI lesions, clinicians may inadvertently overrepresent the biological significance of a limited high-grade component. This can lead to grade migration and pathological downgrading at the time of radical prostatectomy (RP). Although downgrading does not automatically equate to clinical overtreatment, it introduces prognostic uncertainty that complicates risk stratification for active surveillance (AS) and focal therapy. This conceptual commentary provides a critical perspective on this diagnostic issue. We synthesize recent meta-analyses to evaluate the true rates of grade mismatch associated with TBx and combined biopsy approaches. Furthermore, we discuss the spatial limitations of biopsy sampling, the pathological mechanisms driving grade discordance, and the clinical relevance of minor high-grade components such as cribriform architecture. Finally, we highlight the role of multi-omics and validated genomic biomarkers in risk models, ultimately fostering improved shared decision-making in the modern mpMRI era. Full article

Prostate cancer (PCa) is one of the most common malignancies in men and remains a major cause of cancer-related death worldwide. Radiotherapy is a well-established treatment modality for PCa, offering clinical outcomes comparable to surgical approaches. In recent years, stereotactic body radiotherapy (SBRT), characterized by the delivery of high radiation doses in a limited number of fractions, has been increasingly adopted as a standard approach in the treatment of prostate cancer, due to its favorable efficacy and toxicity profile. CyberKnife (CK) is one of the most commonly used hypofractionated radiotherapy techniques. This preliminary study aimed to evaluate and compare the radiation dose delivery and treatment time of CK-based SBRT using two different collimation systems: the multileaf collimator (MLC) and the IRIS variable aperture collimator, a dynamic device that adjusts its opening to simulate different circular field sizes. A total of 19 patients with low-to-intermediate-risk PCa were selected and treated at the Radiation Oncology Department of the National Cancer Institute IRCCS Fondazione G. Pascale in Naples between January 2024 and January 2025. For each patient, two treatment plans were generated—one with the IRIS collimator and one with the MLC. The results demonstrated that the use of the MLC significantly reduced treatment time while maintaining dosimetric quality comparable to IRIS-based plans. These findings support the clinical benefit of MLC implementation in prostate SBRT with the CK system. Full article