Search Results (158)

We investigated the clinical significance of positive surgical margins (PSMs) in index tumors following radical prostatectomy (RP), with particular attention to the tumor’s zonal origin. Among 1148 patients with localized prostate cancer who underwent RPs, 973 were included after excluding those who received perioperative therapy or had incomplete data. Index tumors were categorized by zonal origin: transition zone, peripheral zone, or central zone (CZ). Overall, PSMs were observed in 26.4% of index tumors. Although CZ index tumors were relatively uncommon (6.5%), they exhibited the highest PSM rate (42.9%) and showed the most aggressive pathological features. The 5-year biochemical recurrence (BCR)-free survival rate was significantly lower in patients with PSMs in index tumors than in those with negative surgical margins (45.6% vs. 86.8%, p < 0.0001). Notably, patients with PSMs in CZ index tumors had the worst outcomes, with a 5-year BCR-free survival rate of 22.0%. Multivariate analysis identified PSMs in index tumors as an independent predictor of BCR (HR: 3.4; 95% CI: 2.5–4.5), with a similar trend observed in early recurrence. These findings highlight the prognostic significance of PSMs in index tumors during RP, especially in CZ tumors, and emphasize the importance of securing local control in these cases. Full article

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

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

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

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

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

Background: This retrospective study evaluated and compared oncological outcomes in patients with localized prostate cancer treated either by laparoscopic radical prostatectomy (LRP) or by external beam radiotherapy (EBRT) combined with androgen deprivation therapy (ADT). The primary aim was to identify predictors of biochemical recurrence (BCR) and to assess recurrence-free survival. Subjects and methods: A total of 107 patients diagnosed with localized prostate cancer and treated between 2016 and 2023 were included in the analysis. Of these, 61 patients underwent LRP, and 46 patients received EBRT+ADT. The median follow-up period was 60 months for the LRP group (IQR 24–72) and 66 months for the EBRT group (IQR 49.5–72). Biochemical recurrence (BCR) was defined as a PSA level > 0.2 ng/mL after LRP or an increase > 2 ng/mL above nadir following EBRT. Kaplan–Meier survival curves, log-rank tests, Pearson’s chi-square, and Cox regression models were used to evaluate outcomes and identify predictors of recurrence, with significance set at p < 0.05. Results: Biochemical recurrence occurred in 21 (34.4%) of LRP patients and 10 (21.7%) of EBRT patients. The five-year BCR-free survival was 40 (65.6%) patients in the LRP group and 33 (71.7%) for EBRT, with a trend toward improved outcomes in the EBRT group that approached statistical significance (log-rank p = 0.089). Median time to recurrence was 30 months for LRP (IQR 12.75–60) and 48 months for EBRT (IQR 30–60). Predictive analysis revealed that in the LRP group, higher ISUP grade at biopsy (p = 0.001), advanced pathological stage (p < 0.001), positive surgical margins (p < 0.001), and intermediate initial PSA levels (10–20 ng/mL; p = 0.080) were associated with increased risk of BCR. No independent predictors of recurrence were identified in the EBRT group. Conclusions: Both LRP and EBRT+ADT provide effective cancer control with similar five-year BCR-free survival. However, LRP was associated with a higher recurrence rate, particularly among patients with intermediate-risk features such as iPSA 10–20 ng/mL, high ISUP grade, advanced pathological stage, or positive surgical margins. These findings highlight the need for risk-adapted follow-up and timely salvage treatment in high-risk LRP patients to improve long-term outcomes. Full article

Accurate preoperative prediction of biochemical recurrence (BCR) in prostate cancer (PCa) is essential for treatment optimization, and demands an explicit focus on tumor microenvironment (TME). To address this, we developed MRMS-CNNFormer, an innovative framework integrating 2D multi-region (intratumoral, peritumoral, and periprostatic) and multi-sequence magnetic resonance imaging (MRI) images (T2-weighted imaging with fat suppression (T2WI-FS) and diffusion-weighted imaging (DWI)) with clinical characteristics. The framework utilizes a CNN-based encoder for imaging feature extraction, followed by a transformer-based encoder for multi-modal feature integration, and ultimately employs a fully connected (FC) layer for final BCR prediction. In this multi-center study (46 BCR-positive cases, 186 BCR-negative cases), patients from centers A and B were allocated to training (n = 146) and validation (n = 36) sets, while center C patients (n = 50) formed the external test set. The multi-region MRI-based model demonstrated superior performance (AUC, 0.825; 95% CI, 0.808–0.852) compared to single-region models. The integration of clinical data further enhanced the model’s predictive capability (AUC 0.835; 95% CI, 0.818–0.869), significantly outperforming the clinical model alone (AUC 0.612; 95% CI, 0.574–0.646). MRMS-CNNFormer provides a robust, non-invasive approach for BCR prediction, offering valuable insights for personalized treatment planning and clinical decision making in PCa management. Full article

Objectives: We aimed to develop and evaluate a novel computer-aided detection (CADe) approach for identifying small metastatic biochemically recurrent (BCR) prostate cancer (PCa) lesions on PSMA-PET images, utilizing multi-angle Maximum Intensity Projections (MA-MIPs) and state-of-the-art (SOTA) object detection algorithms. Methods: We fine-tuned and evaluated 16 SOTA object detection algorithms (selected across four main categories of model types) applied to MA-MIPs as extracted from rotated 3D PSMA-PET volumes. Predicted 2D bounding boxes were back-projected to the original 3D space using the Ordered Subset Expectation Maximization (OSEM) algorithm. A fine-tuned Medical Segment-Anything Model (MedSAM) was then also used to segment the identified lesions within the bounding boxes. Results: The proposed method achieved a high detection performance for this difficult task, with the FreeAnchor model reaching an F1-score of 0.69 and a recall of 0.74. It outperformed several 3D methods in efficiency while maintaining comparable accuracy. Strong recall rates were observed for clinically relevant areas, such as local relapses (0.82) and bone metastases (0.80). Conclusion: Our fully automated CADe tool shows promise in assisting physicians as a “second reader” for detecting small metastatic BCR PCa lesions on PSMA-PET images. By leveraging the strength and computational efficiency of 2D models while preserving 3D spatial information of the PSMA-PET volume, the proposed approach has the potential to improve detectability and reduce workload in cancer diagnosis and management. Full article

Emerging imaging-guided technologies, such as prostate-specific membrane antigen radioguided surgery (PSMA-RGS) and augmented reality (AR), could enhance the precision and efficacy of robot-assisted prostate cancer (PCa) surgical approaches, maximizing the surgeons’ ability to remove all cancer sites and thus patients’ outcomes. Sentinel node biopsy (SNB) represents an imaging-guided technique that could enhance nodal staging accuracy by leveraging lymphatic mapping with tracers. PSMA-RGS uses radiolabeled tracers with the aim to improve intraoperative lymph node metastases (LNMs) detection. Several studies demonstrated its feasibility and safety, with promising accuracy in nodal staging during robot-assisted radical prostatectomy (RARP) and in recurrence setting during salvage lymph node dissection (sLND) in patients who experience biochemical recurrence (BCR) after primary treatment and have positive PSMA positron emission tomography (PET). Near-infrared PSMA tracers, such as OTL78 and IS-002, have shown potential in intraoperative fluorescence-guided surgery, improving positive surgical margins (PSMs) and LNMs identification. Finally, augmented reality (AR), which integrates preoperative imaging (e.g., multiparametric magnetic resonance imaging [mpMRI] of the prostate and computed tomography [CT]) onto the surgical field, can provide a real-time visualization of anatomical structures through the creation of three-dimensional (3D) models. These technologies may assist surgeons during intraoperative procedures, thus optimizing the balance between oncological control and functional outcomes. However, challenges remain in standardizing these tools and assessing their impact on long-term PCa control. Overall, these advancements represent a paradigm shift toward personalized and precise surgical approaches, emphasizing the integration of innovative strategies to improve outcomes of PCa patients. Full article

Background: Despite numerous studies assessing LCs in urological surgical oncology, high-quality evidence and a fully structured curriculum are missing. We aimed to systematically search and review the available literature on the LCs of robot-assisted surgery in urological cancers. Methods: Medline was systematically searched up to December 2024 to retrieve studies following the Preferred Reporting Items reporting on LC in robot-assisted radical prostatectomy (RARP), robot-assisted radical cystectomy (RARC), robot-assisted radical and partial nephrectomy (RARN, RAPN), and robot-assisted radical nephroureterectomy (RANU). The results of the last five years were then compared to those of the previous years. Results: In total, 82 studies were identified, 47 of which were for prostatectomy, 9 of which were for the last 5 years. Eighteen studies referred to partial-nephrectomy, seven over the previous 5 years. Finally, 16 studies referred to radical cystectomy, 7 over the previous five years. For radical prostatectomy, LC was based on operative time (OT), estimated blood loss (EBL), length of hospital stays, complication rate, positive surgical margin (PSM), biochemical recurrence (BCR), continence, and potency with ranges of 100–400, 90–290, 200, 15–250, 50–300, 30–250, 200–500 and 200–300 cases, respectively. For partial nephrectomy, the LC was based on OT, EBL, length of hospital stay, complication rate, warm ischemia time (WIT), and trifecta, with unclear ranges for the first three categories and 20–50, 26–140, and 50–77 cases, respectively, for the rest. Finally, for radical cystectomy, the LC was based on OT, EBL, length of hospital stay, complication rate, PSM, and lymph node yield, with ranges 20–75, 88, 40–198, 16–100, no difference, and 30–50 cases, respectively. We could not identify any study assessing the LCs in RARN and RANU. Conclusions: Robot-assisted surgery does not have a standard definition of LC regardless of the type of operation, which causes heterogeneity between the studies. Nevertheless, LCs appear to be steep and continuous. Training curriculums are essential to optimize outcomes and prepare new surgeons. Full article

Background/Objectives: Prostate-specific antigen (PSA) persistence, defined as a postoperative PSA level ≥ 0.1 ng/mL measured within 4–8 weeks after radical prostatectomy (RP), predicts biochemical recurrence (BCR) and adverse oncological outcomes. The influence of nerve-sparing (NS) surgical techniques on PSA persistence remains debated, especially among patients with high-risk pathological features. This study aimed to evaluate the impact of NS techniques on PSA persistence following robot-assisted radical prostatectomy (RARP), considering tumor characteristics, surgical parameters, and patient-specific factors. Methods: A retrospective cohort analysis was performed on 779 patients who underwent RARP at a single institution between January 2002 and December 2015. The inclusion criteria consisted of histologically confirmed prostate cancer with available preoperative and postoperative data, including PSA measurements taken 4–8 weeks after surgery. PSA persistence served as the primary outcome. Statistical analyses included descriptive statistics, univariate and multivariable logistic regression models to identify predictors of PSA persistence, and Spearman’s correlation along with the Kruskal–Wallis H test to evaluate associations. Results: Of the 779 patients included, 55% underwent NS surgery (51% unilateral, 49% bilateral). The mean preoperative PSA was 11.85 ng/mL (SD: 7.63), while the mean postoperative PSA was 0.70 ng/mL (SD: 4.42). An elevated postoperative PSA was associated with a larger tumor size (r = 0.1285, p < 0.001), advanced pathological stages (χ² = 45.10, p = 3.79 × 10⁻⁹), and higher Gleason scores (χ² = 24.74, p = 1.57 × 10⁻⁴). NS surgery correlated with a lower postoperative PSA (mean: 0.20 ng/mL) compared to non-NS procedures (mean: 0.65 ng/mL), with slight differences between unilateral (mean: 0.30 ng/mL) and bilateral (mean: 0.35 ng/mL) NS approaches. Multivariable regression analysis identified advanced pathological stage (coefficient = 1.16, p = 0.04) as an independent predictor of PSA persistence, while NS techniques had no significant independent effect (coefficient = −0.01, p = 0.99). Conclusions: Nerve-sparing surgical techniques do not independently predict PSA persistence after RARP when adjusting for tumor-related factors and confounders. Advanced pathological stage, particularly stage pT3b, primarily determines PSA persistence. These findings highlight the necessity of personalized surgical planning informed by preoperative imaging and patient-centered decision making to optimize oncological and functional outcomes. Full article

Biochemical recurrence (BCR) occurs in 20–50% of patients with localized prostate cancer (PC) after radical prostatectomy (RP). Conventional imaging often fails to detect early local or systemic recurrences at low PSA levels. Positron emission tomography/computed tomography (PET/CT) with 18F-DCFPyL PSMA offers improved sensitivity and specificity for detecting recurrent disease. This study evaluates the diagnostic capability of 18F-DCFPyL PET/CT in early BCR of PC following RP and its impact on therapeutic decision-making and clinical management. Methods: In a prospective study, 85 patients with BCR (PSA 0.2–2.0 ng/mL) and negative conventional imaging underwent 18F-DCFPyL PET/CT. Detection rates (DRs) were analyzed against clinical variables, including PSA levels and PSA doubling time (DT-PSA). Lesions were classified into local recurrence, lymph node involvement, bone, and visceral disease. Therapeutic decisions were adjusted based on PET/CT findings. Results: 18F-DCFPyL PET/CT identified lesions in 53% of patients, with DRs of 31.3%, 60%, and 77.8% for PSA levels <0.5, 0.5–1, and >1 ng/mL, respectively. DRs were significantly associated with shorter DT-PSAs (<6 months: 61.5%). The lesions detected included 22.2% local recurrences, 51.1% lymph node disease, 20% bone, and 6.7% visceral involvement. ROC analysis determined optimal PSA and DT-PSA cutoffs of 0.55 ng/mL and 9.2 months, respectively. Therapeutic strategies were modified in 84.4% of PET-positive cases. Conclusions: 18F-DCFPyL PET/CT demonstrates high sensitivity for detecting recurrent PC at low PSA levels, significantly impacting therapeutic decisions and optimizing clinical management. These findings support its integration into guidelines for managing early BCR of PC. Full article

Background/Objectives: The effectiveness of robot-assisted radical prostatectomy (RARP) with extended pelvic lymph node dissection (ePLND) in improving oncological outcomes for patients with high- or very-high-risk prostate cancer (HR/VHR-PCa) remains a subject of debate. This study aimed to compare the efficacy of neoadjuvant chemohormonal therapy (NCHT) and ePLND in reducing biochemical recurrence (BCR) in patients with HR/VHR-PCa undergoing RARP. Methods: This retrospective, multicenter cohort study included 1182 patients with HR/VHR-PCa who underwent RARP at six Japanese institutions. Patients were stratified into three groups: those who received NCHT followed by RARP without ePLND (Group 1), those who received neoadjuvant hormonal therapy (NHT) followed by RARP with ePLND (Group 2), and those who underwent RARP with ePLND (Group 3). The primary endpoint was the rate of BCR, while the secondary endpoint was biochemical recurrence-free survival (BRFS) following RARP. Results: Of the 1182 patients, 154 patients were included in Group 1, 97 patients were included in Group 2, and 470 patients were included in Group 3. By the end of the follow-up period, 243 patients (33.8%) had experienced BCR, 27 (3.7%) had progressed to castration-resistant prostate cancer, and 5 (0.7%) had died from PCa. Over a median follow-up period of 41.4 months, BCR occurred in 16.5% of patients in Group 1, 36.1% of patients in Group 2, and 38.9% in Group 3 (p < 0.001). The 3-year BRFS rate was 63.6% in Group 1, 53.1% in Group 2, and 63.9% in Group 3. Conclusions: The findings of this study indicate that NCHT in patients with HR/VHR-PCa undergoing RARP without ePLND may reduce the risk of postoperative BCR compared to those undergoing RARP with ePLND. Full article

Background: Gleason score (GS) 10 prostate cancer (PC) is a highly aggressive localized disease. Despite advances in treating high-risk PC, the clinical outcomes and molecular underpinnings of GS 10 remain unclear. This study aimed to determine whether GS 10 PC has distinct clinical outcomes from other “high-risk” cancers (i.e., Gleason 8–9) and identify genomic alterations driving its aggressive phenotype. Methods: A retrospective review of The Cancer Genome Atlas database identified patients with GS 8–10 PC who underwent radical prostatectomy. Clinical factors were compared between GS 10 and GS 8–9 cohorts. Time to biochemical recurrence (BCR) was analyzed using Kaplan–Meier and Cox regression. RNA sequencing identified differentially expressed genes, and protein–protein interaction networks identified hub genes. Results: Of 192 patients, 13 (6.8%) had GS 10 PC. After median follow-up of 37.87 months, GS 10 status was associated with significantly lower time to BCR (AHR, 2.67; 95% CI, 1.18–6.02; p = 0.018) compared to GS 8–9. Multiple genes (e.g., RAD54L, FAAH, AATK, MAST2) showed higher alteration frequencies, and high expression of RAD54L, MAST2, and CCHCR1 correlated with shorter disease-free survival. Six overlapping hub genes (CD8A, CDC20, E2F1, IL10, TNF, VCAM1) were overexpressed in GS 10 tumors, reflecting key pathways in tumor progression. Conclusions: GS 10 PC confers inferior time to BCR and displays a distinct genomic landscape compared to GS 8–9 disease, highlighting the need for biomarker-driven therapeutic strategies. Further studies are needed to validate these genomic targets and improve management for this very high-risk population. Full article