Purpose: the prognostic value of positive surgical margins (PSMs) after radical prostatectomy (RP) remains debated, particularly when distinguishing focal from extensive involvement. Moreover, the interaction between margin status and other adverse pathological features, such as tumour stage, grade, and nodal status, is not fully defined. The study aims to evaluate the impact of focal and extensive PSMs on biochemical recurrence-free survival (BCRFS), stratified by pathological stage, Gleason grade, and nodal involvement. Methods: we retrospectively analyzed 1258 patients who underwent robot-assisted RP between 2017 and 2023, evaluating BCRFS as primary endpoint. Survival was analyzed using Kaplan-Meier and log-rank tests across margin categories (negative, focal, extensive). Analyses were stratified by pT stage (pT2-pT3b), ISUP grade (<3 vs. ≥3), and nodal status (pN0/pNx vs. pN+). Median follow-up was 39 months (IQR 24-62), and 5-year BCRFS was used as the reference endpoint. Results: median age was 68 years and median PSA 6.9 ng/mL. Stage distribution: pT2 56.4%, pT3a 29.8%, pT3b 13.6%; 16.6% were pN+. ISUP grade ≥ 3 was observed in 60.6%. Overall, 20.3% developed biochemical recurrence. In pT2 tumours or primary Gleason pattern 3, focal PSMs showed 5-year BCRFS of 88-90%, very similar to negative margins (91-93%) and clearly better than extensive PSMs (~72%). In pT3 tumours or primary Gleason pattern 4, focal PSMs showed 5-year BCRFS of ~55-60%, similar to extensive PSMs (~40-50%) and significantly worse than negative margins (78% in pT3a and 65% in pT3b, p < 0.01). In N + 5-year BCRFS was similarly poor in negative (~45%), focal (~42%), and extensive margins (~40%, p = 0.455). Conclusions: the prognostic impact of positive surgical margins depends on tumour biology. In organ-confined or ISUP ≤ 2 disease, focal PSMs show recurrence rates similar to negative margins and may be managed with observation. In locally advanced or ISUP ≥ 3 tumours, both focal and extensive PSMs carry a markedly higher risk of biochemical recurrence and might suggest an early intervention. PSMs lose discriminatory value in node-positive patients.

BACKGROUND:Surgery for benign prostatic obstruction (BPO) is often associated with postoperative ejaculatory dysfunction. Traditional techniques like transurethral resection of the prostate (TUR-P) or open prostatectomy (OP) effectively relieve lower urinary tract symptoms (LUTS) but usually compromise antegrade ejaculation. Minimally invasive surgical techniques (MISTs), such as Rezūm® or modified endoscopic surgeries, like the ejaculation-sparing anatomical photoselective vaporization of the prostate (ESa-PVP), were developed to preserve sexual function while ensuring symptom relief. However, few comparative data are available. Our study aims to compare the early functional and sexual outcomes of Rezūm® and ESa-PVP in BPO. METHODS:This prospective, non-randomised study analysed two cohorts of men with LUTS unresponsive to medication or an indwelling catheter, surgically treated at our centre between December 2022 and December 2023. The primary outcome of the study was the assessment of postoperative antegrade ejaculation. Secondary outcomes included LUTS evaluation and surgical complications. Postoperative outcomes were assessed after three months by administering validated questionnaires: International Prostate Symptom Score (IPSS), International Index of Erectile Function-5 (IIEF-5), and Male Sexual Health Questionnaire-Ejaculatory Dysfunction, short form (MSHQ-EjD). RESULTS:A total of 54 patients were evaluated (31 Rezūm, 23 ESa-PVP). After three months, the ESa-PVP showed a better improvement of both IPSS scores (p = 0.009) and patient-perceived quality of life (p = 0.008). No significant differences were found in erectile function (IIEF-5 scores, p = 0.340), while the MSHQ-EjD scores were significantly higher in the Rezūm group (p = 0.001). Ejaculation was maintained in 26 out of 31 (83%) Rezūm patients versus 14 out of 23 (60%) ESa-PVP patients (p = 0.056). CONCLUSIONS:Rezūm® and ESa-PVP are both effective and safe procedures for the treatment of BPO. While the ESa-PVP seems to provide better symptom relief in the short term, Rezūm® showed higher rates of immediate antegrade ejaculation preservation. Personalised counselling is crucial to achieve optimal patient satisfaction.

BACKGROUND:International Society of Uro-Pathology (ISUP) grade group 2 prostate cancer (GG2 PCa) with suspicion of extraprostatic extension (EPE) on preoperative multiparametric MRI (mpMRI) presents a paradox: an histologically favorable intermediate-risk tumor with aggressive imaging features. We aimed to characterize this population, and identify predictors of pathological upgrading, downstaging, and oncological outcomes after robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS:We analyzed data from 150 patients across 8 European centers with MRI-targeted biopsy-confirmed GG2 PCa and mpMRI-suspected EPE (icT3a), stratified by EPE score, who underwent RARP between 2019 and 2024. Primary endpoint was predictors of pathological upgrading (GG ≥ 3); secondary endpoints included downstaging (pT2), surgical margins, and biochemical recurrence (BCR)-free survival. RESULTS:Patients were divided by EPE score: low (1-2, n = 87) and high (3, n = 38). Pathological upgrading occurred in 36% (55/150), including 10% to GG 4-5. High EPE score was the only significant predictor. Conversely, 46% (69/150) were downstaged to pT2, with low EPE score as main predictor. Positive surgical margins were observed in 30% (45/150). At a median follow-up of 28 months (IQR 17-43), 5-year BCR-free survival was 67% (95% CI 53-85). Posterior/apical EPE on MRI and cT3a stage were linked to higher BCR risk. CONCLUSIONS:GG2 PCa with mpMRI-suspected EPE is heterogeneous, showing risks of both upgrading and organ-confined disease. EPE score was the main predictor of both. Despite imaging suspicion, RARP outcomes remained favorable.

BACKGROUND AND OBJECTIVE:There has been debate for decades whether transperineal prostate biopsy (TP-Bx) or transrectal biopsy (TR-Bx) is the optimal route. Randomized controlled trials (RCTs) conducted in the contemporary era provide new evidence for reassessment of the comparative infectious risks and diagnostic performance, particularly relevant given rising antibiotic resistance and evolving prostate cancer (PC) diagnostic paradigms. Our aim was to compare infectious complications, detection of clinically significant PC (csPC), and other biopsy-related outcomes between TP-Bx and TR-Bx in men with suspected PC undergoing biopsy in the multiparametric magnetic resonance imaging (mpMRI) era. METHODS:A systematic literature search (MEDLINE, Embase, CINAHL, Cochrane CENTRAL, and ClinicalTrials.gov) was conducted on April 1, 2025 in accordance with PRISMA guidelines. RCTs comparing TP-Bx and TR-Bx published after 2010 were included. Data were independently extracted by two reviewers using a standardized protocol (PROSPERO CRD42024522857). Risk of bias was assessed using the updated Cochrane tool. We performed a Bayesian random-effects meta-analysis, using models specifically suited for few-study settings and rare events. Sensitivity analyses were performed. The primary outcome was the infectious complication rate. Secondary outcomes included detection of csPC and non-clinically significant PC (ncsPC), urinary retention, bleeding, and patient-reported pain. KEY FINDINGS AND LIMITATIONS:Five RCTs involving 3072 men were included (1547 TP-Bx, 1525 TR-Bx). The vast majority were Bx-naïve and underwent mpMRI-targeted Bx. TP-Bx was associated with lower risk of infectious complications (pooled odds ratio [pOR] 0.38, 95% credible interval [CrI] 0.11-0.90), despite no antibiotic prophylaxis in this arm. Results also suggest a lower risk of bleeding requiring intervention with TP-Bx (pOR 0.54, 95% CrI 0.23-1.14), although the estimates were imprecise. There was no evidence of a difference in detection of csPC (pOR 1.01, 95% CrI 0.65-1.51) or ncsPC (pOR 1.12, 95% CrI 0.63-2.18), or in acute urinary retention (pOR 0.66, 95% CrI 0.26-1.58). Two studies assessing pain reported higher post-Bx pain scores for TP-Bx, and two studies reported slightly longer operating times, although these differences were of uncertain clinical relevance. CONCLUSIONS AND CLINICAL IMPLICATIONS:TP-Bx offers lower infection rates with no antibiotic prophylaxis needed and equivalent PC detection in comparison to TR-Bx, despite minimal increases in discomfort and procedure time. When feasible, TP-Bx should be considered the preferred Bx approach.

BackgroundPrognostic models are crucial for prostate cancer (PCa) treatment decision making at the time of diagnosis, particularly for distinguishing active surveillance (AS) candidates from those requiring curative treatment. While several models exist, their ability to predict metastatic disease—the primary driver of PCa mortality—remains underexplored.MethodsWe analysed the Turin Prostate Cancer Prognostication cohort, which includes 891 unselected PCa patients diagnosed between 2008 and 2013 in Turin, Italy. Three widely used prognostic models—D’Amico, CAPRA, and MSKCC—were updated and compared based on optimism-corrected discrimination and overall prediction error for metastatic PCa (mPCa) within five years of diagnosis, accounting for competing risks. Overall survival was also assessed. Additionally, we investigated whether replacing standard AS eligibility criteria with nomogram-based risk thresholds could better identify patients at low risk of metastasis, maximizing AS uptake while minimising metastatic risk.ResultsThe MSKCC nomogram (optimism-corrected AUCt: 0.81; scaled Brier score: 0.15) outperforming the CAPRA score (AUCt: 0.77; Brier score: 0.11) and the D’Amico classification (AUCt 0.64; Brier score: 0.03) in predicting mPCa. The same ranking was observed for overall mortality prediction. When 95th percentile of MSKCC’s predicted probabilities among patients selected for six different AS protocols was used as a threshold, the proportion of potentially eligible patients increased from 7.8% when UCSF criterion was used to 57.0% without substantially increasing metastatic risk (observed 5-year risk: 1.7%).ConclusionsThe MSKCC nomogram outperformed other models in predicting mPCa and overall mortality. Implementing risk-based AS eligibility thresholds derived from MSKCC could enhance patient selection while facilitating shared decision-making between patients and clinicians.

BACKGROUND:Three-dimensional (3D) virtual models are increasingly used to support minimally invasive partial nephrectomy (PN), but their clinical value remains uncertain. We assessed whether 3D guidance improves perioperative, oncological, and early functional outcomes and evaluated its cost. METHODS:We retrospectively analyzed 159 patients who underwent laparoscopic or robot-assisted PN between 2022 and 2024. Propensity score matching generated two comparable groups (35 patients each) treated with or without 3D virtual model guidance, according to age, PADUA score, and surgical approach. Perioperative, pathological, early oncological, and early functional outcomes were compared using non-parametric tests. RESULTS:Although matching improved comparability, some residual imbalance remained. The 3D group had longer operative times (median 200 vs 170 min; p=0.008). No significant differences were found in clamping strategy, warm ischemia time, estimated blood loss, hospital stay, pathological stage, surgical margins, postoperative complications, or early recurrence. Changes in haemoglobin, serum creatinine, and estimated glomerular filtration rate from baseline to discharge were similar between groups. Each 3D virtual model cost €800. CONCLUSIONS:In this propensity score-matched cohort, 3D virtual model guidance during minimally invasive PN was associated with longer operative time, added cost, and no measurable benefit in perioperative, oncological, or early functional outcomes.

Background and Objective: Conventional imaging with pelvic magnetic resonance imaging (MRI) and abdominopelvic computed tomography (CT) is still used for staging of prostate cancer (PCa), particularly when molecular imaging is unavailable. mpMRI is currently recommended before prostate biopsy. We evaluated the agreement between MRI and CT for nodal and distant staging, their diagnostic accuracy against surgical nodal staging, and the real-world clinical utility of CT when pelvic MRI is already available. Methods: Among consecutive prostate biopsies, we retrieved patients with unfavorable intermediate- or high-risk PCa who underwent both pelvic MRI and abdominopelvic CT (and bone scan). Agreement for nodal staging was assessed using Cohen’s κ. Diagnostic performance was evaluated in patients undergoing radical prostatectomy with pelvic lymph node dissection, using final pathology as the reference standard. The clinical yield of CT was assessed post hoc, considering nodal or metastatic reclassification or urgent non-PCa-related findings. Key Findings and Limitations: We included 323 consecutive patients. MRI and CT identified cN1 disease in 6.8% and 8.1% of cases, respectively, and showed moderate agreement for pelvic nodal staging (κ = 0.51), with higher agreement in non-surgical patients. Both modalities demonstrated very low sensitivity for nodal metastases (≤ 20%) compared with pathology, with area under the curve (AUC) < 0.60. In the subgroup of patients with also molecular imaging available (n = 82) PSMA PET/CT showed superior performance (AUC = 0.86). MRI and CT (plus bone scan) showed moderate agreement for distant metastasis (κ = 0.56). CT provided clinically relevant information not detectable in mpMRI in 14.1% of patients (number needed to scan = 7). Limitations include the retrospective design and lack of centralized imaging review. Intervention: Imaging strategies were evaluated observationally. Conclusions and Clinical Implications: Pelvic MRI and CT show moderate agreement for nodal staging but poor diagnostic accuracy. Although the incremental value of CT beyond pelvic MRI is limited, it may still contribute to change management when PSMA PET/CT is unavailable.

BackgroundBiochemical recurrence after radiotherapy is common and clinically challenging in prostate cancer (PCa), as accurate restaging is required to identify patients eligible for local salvage therapy and distinguish them from those requiring systemic or metastasis-directed treatment. This review evaluates the diagnostic value of multiparametric MRI (mpMRI) and prostate-specific membrane antigen–targeted PET/CT (PSMA-targeted PET/CT) for restaging radiorecurrent prostate cancer.MethodsA narrative review was conducted using PubMed and Scopus. Original English-language studies published within the last 10 years were included if they reported the diagnostic performance of mpMRI, PSMA-targeted PET/CT, or combined imaging in patients with suspected radiorecurrent prostate cancer, using histopathology as the reference standard. Evidence was synthesized with particular attention to intraprostatic recurrence, extraprostatic disease, and imaging performance after brachytherapy.ResultsTen studies (4 prospective and 6 retrospective) met the inclusion criteria. mpMRI demonstrated heterogeneous sensitivity for intraprostatic recurrence with moderate-to-high specificity (64–87%), and frequently underestimated multifocal disease, particularly in the post-brachytherapy setting. PSMA-targeted PET/CT showed high sensitivity for intraprostatic recurrence (up to ~89%) and superior detection of nodal and distant metastases, although very small or low–PSMA-expressing intraprostatic lesions may remain undetected. The combination of mpMRI and PSMA-targeted PET/CT provided the highest diagnostic confidence: concordant findings achieved a positive predictive value of 97.6%, supporting improved patient selection for salvage treatment strategies.ConclusionsmpMRI and PSMA-targeted PET/CT provide complementary diagnostic information rather than being interchangeable modalities. A multimodal imaging approach improves restaging accuracy in radiorecurrent prostate cancer and may better guide biopsy targeting and selection of candidates for salvage therapy. Nevertheless, histological confirmation remains mandatory before local salvage treatment.

Introduction:The advent of prostate-specific membrane antigen - positron emission tomography (PSMA-PET) imaging influences prostate cancer (PCa) salvage radiotherapy (SRT) decision-making, especially in biochemical recurrence (BCR) with low PSA. This study evaluates the impact of PSMA-PET on recurrent post-prostatectomy patients treated with radiotherapy (RT) ± hormonal therapy (HT). Materials and methods:In a prospective, observational study (2016-2020), 103 hormone-sensitive post-prostatectomy pN0-pNx PCa patients with proven BCR were analyzed. PSMA-positive patients received tailored treatments based on lesion sites, ranging from prostate bed (P-bed) SRT abort, metastases-directed therapy, to systemic therapy. PSMA-negative patients were mainly treated with SRT. Primary objectives included PSMA-based management changes and biochemical progression-free survival (bPFS) comparison. Results:PSMA-PET was positive in 28.1% (29/103) at a median PSA of 0.5 ng/mL. The most common relapse sites were bones and pelvic lymph nodes. Among positive PSMA-PET patients, the P-bed abort rate was 58.6% (17/29 patients). Excluding patients with PSMA-positive uptake solely in the P-bed (7 patients), the rate of P-bed abort was 77.3% (17/22 patients). Management was altered in 75.8% of PSMA-positive and 21.3% overall. Most PSMA-positive lesions were managed with SBRT, either as a standalone treatment or within combined-modality approaches: SBRT was delivered to 50% of nodal recurrences (including both N1 and M1a cases) and to 100% of bone lesions. At 5 years, bPFS was 66.8% in PSMA-negative patients (undergoing SRT+/-HT) vs. 26.7% in PSMA-positive patients (any treatment). Conclusion:PSMA-PET led to management changes in nearly one-third of post-prostatectomy recurrent PCa, notably affecting RT strategies and systemic therapy. Emerging evidence suggests that treatment intensification based on PSMA-PET findings may improve patient outcomes compared to de-intensified approaches. The impact on outcomes awaits validation from ongoing prospective randomized trials.

Proton pump inhibitors (PPIs) are widely prescribed drugs that have been associated with increased prostate cancer (PCa) cell proliferation in vitro and worse oncological outcomes in vivo. However, data on their influence on PSA levels in the general population are lacking. We extracted individual participant data from the 2001–2010 cycles of the National Health and Nutrition Examination Survey (NHANES), in which PSA levels were measured in all male participants aged 40 years or older. The association of PPI use with total PSA levels and free/total PSA ratio was evaluated through multivariable linear regression analyses, adjusted for potential confounders. A total of 7366 subjects were included (median age: 53 years; median serum PSA: 0.9 ng/mL), of whom 746 were receiving PPI treatment at the time of the study. After adjustment for potential confounders, ongoing PPI use was associated with lower total PSA levels (-0.24 ng/mL, 95