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To develop and validate a novel Comorbidity score for Robotic Surgery (CRS) in predicting severe complications after robot-assisted radical prostatectomy (RARP). Furthermore, we investigated the impact of the surgical platform (Multi-Port - MP vs Single-Port - SP) according to this score. We included 2085 ("development cohort") and 595 ("validation cohort") patients undergoing RARP at two tertiary referral centers between 2014 and March 2024 in a retrospective study. Statistical analyses included validation of the Charlson Comorbidity Index (CCI) to predict 30-day severe complications (Clavien-Dindo ≥ 3a), development and external validation of CRS using calibration plots and decision curve analysis. Lastly, locally weighted scatterplot smoothing (LOWESS) analysis was used to graphically explore the impact of the robotic platform according to novel CRS. CCI exhibited limited predictive ability for severe complications (60% in the validation cohort). In multivariable logistic regression analyses testing the correlation between each condition included in CCI and severe complications, diabetes and myocardial infarction resulted as independent predictors (OR 1.75 [95%CI 1.05-2.82]; OR 1.92 [95%CI 1.26-2.88]) and were subsequently fitted into a multivariable logistic model including age, previous abdominal surgery and obesity (BMI > 30). The resulting predictive model demonstrated superior discrimination and clinical net benefit in predicting severe complications compared to CCI (AUC 64 vs 60%). At LOWESS analysis, SP platform was associated with lower risk of severe complications as CRS increased compared to MP system. The validated CRS showed better accuracy compared to CCI in predicting severe complications after RARP. Additionally, the use of SP robotic platform may reduce the risk of severe complications in highly comorbid patients according to CRS., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Objectives: To test the performance of ex vivo fluorescence confocal microscopy (FCM; Vivascope 2500M-G4), as compared to intra-operative frozen section (IFS) analysis, to evaluate surgical margins during robot-assisted radical prostatectomy (RARP), with final pathology as the reference standard., Methods: Overall, 54 margins in 45 patients treated with RARP were analysed with: (1) ex vivo FCM; (2) IFS analysis; and (3) final pathology. FCM margins were evaluated by two different pathologists (experienced [M.I.: 10 years] vs highly experienced [G.R.: >30 years]) as strongly negative, probably negative, doubtful, probably positive, or strongly positive. First, inter-observer agreement (Cohen's κ) between pathologists was tested. Second, we reported the sensitivity, specificity, positive predictive (PPV) and negative predictive value (NPV) of ex vivo FCM. Finally, agreement between ex vivo FCM and IFS analysis (Cohen's κ) was reported. For all analyses, four combinations of FCM results were evaluated., Results: At ex vivo FCM, the inter-observer agreement between pathologists ranged from moderate (κ = 0.74) to almost perfect (κ = 0.90), according to the four categories of results. Indeed, at ex vivo FCM, the highly experienced pathologist reached the best balance between sensitivity (70.5%) specificity (91.8%), PPV (80.0%) and NPV (87.1%). Conversely, on IFS analysis, the sensitivity, specificity, PPV and NPV were, respectively, 88.2% vs 100% vs 100% vs 94.8%. The agreement between the ex vivo FCM and IFS analyses ranged from moderate (κ = 0.62) to strong (κ = 0.86), according to the four categories of results., Conclusion: Evaluation of prostate margins at ex vivo FCM appears to be feasible and reliable. The agreement between readers encourages its widespread use in daily practice. Nevertheless, as of today, the performance of FCM seems to be sub-par when compared to the established standard of care (IFS analysis)., (© 2024 BJU International.)

Abstract: The study aimed to test if Briganti's 2012 nomogram could be associated with the risk of prostate cancer (PCa) progression in European Association of Urology (EAU) intermediate-risk patients treated with robotic surgery. From January 2013 to December 2021, 527 consecutive patients belonging to the EAU intermediate-risk class were selected. Briganti's 2012 nomogram, which predicts the risk of pelvic lymph node invasion (PLNI), was assessed as a continuous and dichotomous variable that categorized up to the median of 3.0%. Disease progression defined as biochemical recurrence and/or metastatic progression was evaluated by Cox proportional hazards (univariate and multivariate analysis). After a median follow-up of 95.0 months (95% confidence interval [CI]: 78.5-111.4), PCa progression occurred in 108 (20.5%) patients who were more likely to present with an unfavorable nomogram risk score, independently by the occurrence of unfavorable pathology including tumor upgrading and upstaging as well as PLNI. Accordingly, as Briganti's 2012 risk score increased, patients were more likely to experience disease progression (hazard ratio [HR] = 1.060; 95% CI: 1.021-1.100; P = 0.002); moreover, it also remained significant when dichotomized above a risk score of 3.0% (HR = 2.052; 95% CI: 1.298-3.243; P < 0.0001) after adjustment for clinical factors. In the studied risk population, PCa progression was independently predicted by Briganti's 2012 nomogram. Specifically, we found that patients were more likely to experience disease progression as their risk score increased. Because of the significant association between risk score and tumor behavior, the nomogram can further stratify intermediate-risk PCa patients, who represent a heterogeneous risk category for which different treatment paradigms exist., (Copyright © 2024 Copyright: ©The Author(s)(2024).)

Background: Prostate cancer (PCa) is a highly heterogeneous disease, making tailored treatment approaches challenging. Magnetic resonance imaging (MRI), notably diffusion-weighted imaging (DWI) and the derived Apparent Diffusion Coefficient (ADC) maps, plays a crucial role in PCa characterization. In this context, radiomics is a very promising approach able to disclose insights from MRI data. However, the sensitivity of radiomic features to MRI settings, encompassing DWI protocols and multicenter variations, requires the development of robust and generalizable models., Purpose: To develop a comprehensive radiomics framework for noninvasive PCa characterization using ADC maps, focusing on identifying reliable imaging biomarkers against intra- and inter-institution variations., Materials and Methods: Two patient cohorts, including an internal cohort (118 PCa patients) used for both training (75%) and hold-out testing (25%), and an external cohort (50 PCa patients) for independent testing, were employed in the study. DWI images were acquired with three different DWI protocols on two different MRI scanners: two DWI protocols acquired on a 1.5-T scanner for the internal cohort, and one DWI protocol acquired on a 3-T scanner for the external cohort. One hundred and seven radiomics features (i.e., shape, first order, texture) were extracted from ADC maps of the whole prostate gland. To address variations in DWI protocols and multicenter variability, a dedicated pipeline, including two-way ANOVA, sequential-feature-selection (SFS), and ComBat features harmonization was implemented. Mann-Whitney U-tests (α = 0.05) were performed to find statistically significant features dividing patients with different tumor characteristics in terms of Gleason score (GS) and T-stage. Support-Vector-Machine models were then developed to predict GS and T-stage, and the performance was assessed through the area under the curve (AUC) of receiver-operating-characteristic curves., Results: Downstream of ANOVA, two subsets of 38 and 41 features stable against DWI protocol were identified for GS and T-stage, respectively. Among these, SFS revealed the most predictive features, yielding an AUC of 0.75 (GS) and 0.70 (T-stage) in the hold-out test. Employing ComBat harmonization improved the external-test performance of the GS model, raising AUC from 0.72 to 0.78., Conclusion: By incorporating stable features with a harmonization procedure and validating the model on an external dataset, model robustness, and generalizability were assessed, highlighting the potential of ADC and radiomics for PCa characterization., (© 2024 The Author(s). Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Background and Objective: Robotic surgery has contributed greatly to the shift from traditional surgery to minimally invasive surgery. Urology is the major field of application of robotic surgery. Several urological procedures, especially radical prostatectomy, benefit from the use of robotic surgery., Methods: Non-systematic research of the literature was performed using "Robot-assisted radical prostatectomy" and "Robotic platforms" as keywords to understand the actual situation and the future perspectives of this technology in prostate cancer treatment., Key Content and Findings: The robotic platform landscape is constantly evolving. DaVinci has always been the mainstay in this field, particularly after the advent of the new single port platforms. New platforms are emerging, providing an alternative option to the well-known DaVinci system. Since in literature, few studies compare the use of different robotic platforms, their application in urological procedures is not yet widely used, for both oncological and non-oncological procedures. Furthermore, artificial intelligence begins to play a role in this landscape and could be useful for future developments. So further studies are warranted to give a full comprehension of the whole scenario., Conclusions: This review aims to analyze the current state of the use of robotic platforms in urology, particularly in radical prostatectomy, and to understand the evolution.

Background: This study aims to prospectively compare the outcomes of robot-assisted radical prostatectomy (RARP) performed using the Hugo RAS and da Vinci Xi systems, focusing on the postoperative course, pathological findings, and health-related quality of life., Methods: The COMPAR-P trial, a prospective post-market study (clinical-trials.org NCT05766163), commenced in March 2023, enrolling patients for RARP performed with either da Vinci or Hugo RAS without selection criteria for up to 50 consecutive cases per system. Two experienced console surgeons performed the procedures according to a standardized technique. The study evaluated differences between da Vinci and Hugo RAS regarding the postoperative course, pathology findings, 30-day PSA value, functional metrics, and health-related quality of life using SF-36 and University of California Los Angeles Prostate Cancer Index questionnaires., Results: Fifty patients underwent DV-RARP and H-RARP each. Postoperative complications, pathological data, and quality of life metrics did not significantly differ between the groups. Noteworthy limitations include the comparison between the first 50 H-RARP and last 50 DV-RARP cases, as well as the potential influence of surgeons' specialized expertise on the generalizability of findings., Conclusions: This prospective study of 100 unselected patients undergoing RARP with either da Vinci or Hugo RAS systems reveals comparable outcomes in postoperative course, pathology, functional metrics, and health-related quality of life. However, further research with larger sample sizes, longer follow-up periods, and diverse surgical expertise is essential to validate these findings and better understand the implications for clinical practice.

Unspecific bone uptake (UBU) related to [ 18 F]PSMA-1007 PET/CT imaging represents a clinical challenge. We aimed to assess whether a combination of clinical, biochemical, and imaging parameters could predict skeletal metastases in patients with [ 18 F]PSMA-1007 bone focal uptake, aiding in result interpretation. Methods: We retrospectively analyzed [ 18 F]PSMA-1007 PET/CT performed in hormone-sensitive prostate cancer (PCa) patients at 3 tertiary-level cancer centers. A fourth center was involved in performing an external validation. For each, a volume of interest was drawn using a threshold method to extract SUV max , SUV mean , PSMA tumor volume, and total lesion PSMA. The same volume of interest was applied to CT images to calculate the mean Hounsfield units (HU mean ) and maximum Hounsfield units. Clinical and laboratory data were collected from electronic medical records. A composite reference standard, including follow-up histopathology, biochemistry, and imaging data, was used to distinguish between PCa bone metastases and UBU. PET readers with less ( n = 2) or more ( n = 2) experience, masked to the reference standard, were asked to visually rate a subset of focal bone uptake ( n = 178) as PCa metastases or not. Results: In total, 448 bone [ 18 F]PSMA-1007 focal uptake specimens were identified in 267 PCa patients. Of the 448 uptake samples, 188 (41.9%) corresponded to PCa metastases. Ongoing androgen deprivation therapy at PET/CT ( P < 0.001) with determination of SUV max ( P < 0.001) and HU mean ( P < 0.001) independently predicted bone metastases. A composite prediction score, the bone uptake metastatic probability (BUMP) score, achieving an area under the receiver-operating-characteristic curve (AUC) of 0.87, was validated through a 10-fold internal and external validation ( n = 89 bone uptake, 51% metastatic; AUC, 0.92). The BUMP score's AUC was significantly higher than that of HU mean (AUC, 0.62) and remained high among lesions with HU mean in the first tertile (AUC, 0.80). A decision-curve analysis showed a higher net benefit with the score. Compared with the visual assessment, the BUMP score provided added value in terms of specificity in less-experienced PET readers (88% vs. 54%, P < 0.001). Conclusion: The BUMP score accurately distinguished UBU from bone metastases in PCa patients with [ 18 F]PSMA-1007 focal bone uptake at PET imaging, offering additional value compared with the simple assessment of the osteoblastic CT correlate. Its use could help clinicians interpret imaging results, particularly those with less experience, potentially reducing the risk of patient overstaging., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective: To test the ability of high-performance machine learning (ML) models employing clinical, radiological, and radiomic variables to improve non-invasive prediction of the pathological status of prostate cancer (PCa) in a large, single-institution cohort., Methods: Patients who underwent multiparametric MRI and prostatectomy in our institution in 2015-2018 were considered; a total of 949 patients were included. Gradient-boosted decision tree models were separately trained using clinical features alone and in combination with radiological reporting and/or prostate radiomic features to predict pathological T, pathological N, ISUP score, and their change from preclinical assessment. Model behavior was analyzed in terms of performance, feature importance, Shapley additive explanation (SHAP) values, and mean absolute error (MAE). The best model was compared against a naïve model mimicking clinical workflow., Results: The model including all variables was the best performing (AUC values ranging from 0.73 to 0.96 for the six endpoints). Radiomic features brought a small yet measurable boost in performance, with the SHAP values indicating that their contribution can be critical to successful prediction of endpoints for individual patients. MAEs were lower for low-risk patients, suggesting that the models find them easier to classify. The best model outperformed (p ≤ 0.0001) clinical baseline, resulting in significantly fewer false negative predictions and overall was less prone to under-staging., Conclusions: Our results highlight the potential benefit of integrative ML models for pathological status prediction in PCa. Additional studies regarding clinical integration of such models can provide valuable information for personalizing therapy offering a tool to improve non-invasive prediction of pathological status., Clinical Relevance Statement: The best machine learning model was less prone to under-staging of the disease. The improved accuracy of our pathological prediction models could constitute an asset to the clinical workflow by providing clinicians with accurate pathological predictions prior to treatment., Key Points: • Currently, the most common strategies for pre-surgical stratification of prostate cancer (PCa) patients have shown to have suboptimal performances. • The addition of radiological features to the clinical features gave a considerable boost in model performance. Our best model outperforms the naïve model, avoiding under-staging and resulting in a critical advantage in the clinic. •Machine learning models incorporating clinical, radiological, and radiomics features significantly improved accuracy of pathological prediction in prostate cancer, possibly constituting an asset to the clinical workflow., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Purpose: Prostate-Specific Membrane Antigen (PSMA)-targeted Positron Emission Tomography (PET) has revolutionised prostate cancer (PCa) diagnosis and treatment, offering superior diagnostic accuracy over traditional methods and enabling theragnostic applications. However, a significant diagnostic challenge has emerged with identifying unspecific bone uptakes (UBUs), which could lead to over-staging and inappropriate treatment decisions if misinterpreted. This systematic review explores the phenomenon of UBUs in PCa patients undergoing PSMA-PET imaging., Methods: Studies assessing the prevalence, topographical distribution, and potential clinical implications of UBUs were selected according to the Preferred Reporting Items for a Systematic Review and Meta-Analysis (PRISMA) method and evaluated with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool., Results: The percentage of PCa patients with UBUs on PSMA-PET scans ranged from 0 to 71.7%, depending on the radiopharmaceutical used, with [ 18 F]PSMA-1007 showing the highest incidence. The ribs are the primary site of UBUs across all PSMA-targeted radiopharmaceuticals. The spine is the second most frequent UBU site for [ 68 Ga]Ga-PSMA-11, [ 18 F]DCFPyL, [ 18 F]rhPSMA-7, while the pelvic girdle represents the second most frequent site for [ 18 F]PSMA-1007. The average maximum Standardized Uptake Value (SUV max ) of UBUs varied from 3.4 to 7.7 and was generally lower than that of bone metastases., Conclusions: Our findings underscore the need for heightened awareness and precise interpretation of UBUs to avoid potential over-staging and subsequent inappropriate treatment decisions. Considering the radiopharmaceutical used, PET-derived semiquantitative parameters, the topographical distribution of UBUs, and accurately evaluating the pre-test probability based on clinical and laboratory parameters may aid nuclear medicine physicians in interpreting PSMA-PET findings., (© 2024. The Author(s).)

Background: There is a strong clinical need to fill the gap of identifying clinically significant prostate cancer (csPCa) in men with prostate-specific antigen (PSA) gray zone values. Promising, but not definitive results have been obtained using PSA derivatives such as prostate health index (PHI) and PHI density (PHID) and the percentage (-2)proPSA/free PSA (%p2PSA/fPSA). Thus, this study aimed to compare the diagnostic value of PHI, PHID, %proPSA/fPSA, and (-2)proPSA/freePSA density (-2pPSA/fPSAD) for csPCa in the patients with PSA within 2-10 ng/mL., Methods: Serum samples and clinicopathological features were prospectively collected from 142 patients who underwent robot-assisted radical prostatectomy  between September 2021 and December 2023. According to the inclusion criteria, the patients with total PSA  within 2 and 10 ng/mL and negative or suspicious digital rectal examination  were enrolled. We used two different classifications for csPCa: 1) patients with Gleason score (GS) ≥ 7(4 + 3) and 2) patients with GS ≥ 7(3 + 4). The receiver operating characteristic curves and the area under the curve (AUC) values were used to assess the diagnostic performance., Results: Of the 142 men included, 116 (82%) patients were diagnosed with csPCa as GS ≥ 3 + 4 and 107 (75%) defined as csPCa as GS ≥ 7(4 + 3), respectively. We found that p2PSA/fPSA, p2PSA/fPSAD, PHI, and PHID were significantly higher in csPCa classified as GS ≥ 7(3 + 4) as well as GS ≥ 7(4 + 3), with p-values 0.027, 0.054, 0.0016, and 0.0027, respectively. AUCs of the analyzed variables were higher when used to predict csPCa as GS ≥ 6 compared to csPCa as GS ≥7(4 + 3), with an AUC equal, respectively, to 0.679 (95% CI: 0.571-0.786), 0.685 (95% CI: 0.571-0.799), 0.737 (95% CI: 0.639-0.836), and 0.736 (95% CI: 0.630-0.841) in the first subgroup and with an AUC equal, respectively, to 0.653 (95% CI: 0.552-0.754), 0.665 (95% CI: 0.560-0.770), 0.668 (95% CI: 0.568-0.769), and 0.670 (95% CI: 0.567-0.773) in the second, respectively. Both PHID and p2PSA/fPSAD allowed improvement in the diagnostic accuracy with respect to PHI and p2PSA/fPSA ratio, however the differences were not statistically significant (p = 0.409, 0.180 for csPCa as G ≥ Gleason grade (GG) 2 and 0.558 and 0.087 for csPCa as G ≥ GG3, respectively). We found that PHI, PHID, p2PSA/fPSA ratio, and p2PSA/fPSAD showed higher sensitivity, specificity, and positive predictive value when used to predict csPCa as GG ≥ 2, whereas negative predictive value of all four parameters was higher when used to predict GG ≥ 3., Conclusions: In men with a PSA level between 2 and 10 ng/mL, PHI and PHID, p2PSA/fPSA, and p2PSA/fPSAD showed good diagnostic performance for postoperative csPCa. However, PHID and p2PSA/fPSAD had a small advantage over PHI which needs to be further investigated for the reduction of unnecessary surgical interventions. This finding suggests that it could be a promising biomarker for making the treatment-decision strategy., (© 2024 Wiley Periodicals LLC.)

Purpose: Our study aimed to assess the oncological outcomes of sentinel node dissection during radical prostatectomy according to nodal location in comparison to extended pelvic lymph node dissection., Materials and Methods: Prospectively collected data of clinically node-negative patients who underwent prostatectomy and extended lymph node dissection with or without sentinel node from January 2013 to January 2023 were retrospectively analyzed. The primary end point was to assess oncological outcomes on the whole population. Kaplan-Meier curves were used to depict biochemical and clinical recurrence-free survival. Multivariable Cox regression models assessed the impact of nodal location on single-photon emission computed tomography on oncological outcomes. Adjustment for case mix included: pathological T stage, ISUP (International Society of Urological Pathology) grade group, initial PSA, nodal burden, age at surgery, and surgical margin status. Secondarily, a propensity score match was performed according to age at surgery, PSA, biopsy ISUP, clinical T stage, and Briganti risk of nodal invasion. Survival and regression analyses were also performed in the matched population., Results: Of the patients, 55.8% had at least 1 sentinel node outside of lymph node dissection template at single-photon emission computed tomography/CT. Log-rank test showed comparable 36-month biochemical ( P = .3) and clinical recurrence-free survival ( P = .6) among patients with sentinel node inside template, outside template, or extended pelvic lymph node dissection alone. At Cox regression, sentinel node location outside template was associated with lower hazard of metastases (HR 0.62; P = .04) in the overall cohort, while in the matched cohort benefits were observed only for biochemical recurrence (HR 0.57; P = .001)., Conclusions: Wider nodal resection boundaries outside the "classic" template, driven by sentinel node procedure, have a positive impact on oncological outcomes in selected patient.

Objective: Evaluate the detection rates of systematic, targeted and combined cores at biopsy according to tumor positions in biopsy-naïve patients., Material and Methods: A retrospective analysis of a single-center patient cohort (n = 501) that underwent transrectal prostate biopsy between January 2017 and December 2019 was performed. Multi-parametric MRI was executed as a prebiopsy investigation. Biopsy protocol included, for each patient, 12 systematic cores plus 3 to 5 targeted cores per lesion identified at the mpMRI. Pearson and McNemar chi-squared tests were used for statistical analysis to compare tumor location-related detection rates of systematic, targeted and combined (systematic + targeted) cores at biopsy., Results: Median age of patients was 70 years (IQR 62-72), with a median PSA of 8.5 ng/ml (IQR 5.7-15.6). Positive biopsies were obtained in 67.7% of cases. Overall, targeted cores obtained higher detection rates compared to systematic cores (54.3% vs. 43.1%, p < 0.0001). Differences in detection rates were, however, higher for tumors located at the apex (61.1% vs. 26.3%, p < 0.05) and anteriorly (44.4% vs. 19.3%, p < 0.05). Targeted cores similarly obtained higher detection rates in the posterior zone of the prostate gland for clinically significant prostate cancer. A poor agreement was reported between targeted and systematic cores for the apex and anterior zone of the prostate with, respectively κ = 0.028 and κ = -0.018., Conclusion: A combined approach of targeted and systematic biopsy delivers the highest detection rate in prostate cancer (PCa). The location of the tumor could however greatly influence overall detection rates, indicating the possibility to omit (as for the base or posterior zone of the gland) or add (as for the apex or anterior zone of the gland) further targeted cores., (© 2024 Wiley Periodicals LLC.)

Background: Stereotactic body radiation therapy (SBRT) is an effective metastasis-directed therapy for managing oligometastatic prostate cancer patients. However, it lacks reliable biomarkers for risk stratification. Circulating Tumor Cells (CTC) show promise as minimally invasive prognostic indicators. This study evaluates the prognostic value of CTC in oligorecurrent hormone-sensitive prostate cancer (orHSPC)., Methods: orHSPC patients with 1-3 nodal and/or bone metastases undergoing SBRT were enrolled (N = 35), with a median follow-up time of 42.1 months. CTC levels were measured at baseline (T0), 1 month (T1), and 3 months (T2) post-SBRT using a novel metabolism-based assay. These levels were correlated with clinical outcomes through Cox-regression and Kaplan-Meier analyses., Results: Median CTC counts were 5 at T0, 8 at T1, and 5 at T2 with no significant variation over time. Multivariate analysis identified high (≥5/7.5 mL) T0 CTC counts (HR 2.9, 95% CI 1.3-6.5, p = 0.01, median DPFS 29.7 vs. 14.0 months) and having more than one metastasis (HR 3.9, 95% CI 1.8-8.6, p < 0.005, median DPFS 34.1 vs. 10.7 months) as independent predictors of distant progression-free survival (DPFS). CTC assessment successfully stratified patients with a single metastasis (HR 3.4, 95% CI 1.1-10.2, p = 0.03, median DPFS 42.1 vs. 16.7 months), but not those with more than one metastasis. Additionally, a combined score based on CTC levels and the number of metastases effectively stratified patients., Conclusion: The study demonstrates that hypermetabolic CTC could enhance risk stratification in orHSPC patients undergoing SBRT, particularly in patients with limited metastatic burden, potentially identifying patients with indolent disease who are suitable for tailored SBRT interventions., (© 2024 The Author(s). The Prostate published by Wiley Periodicals LLC.)

Purpose: We sought to investigate predictors of unfavorable tumor upgrading in very favorable intermediate-risk (IR) prostate cancer (PCa) patients treated with robot-assisted radical prostatectomy, in addition to evaluate how it may affect the risk of disease progression., Methods: A very favorable subset of IR PCa patients presenting with prostate-specific antigen (PSA) < 10 ng/mL, percentage of biopsy positive cores (BPC) < 50%, and either International Society of Urological Pathology (ISUP) grade group 1 and clinical stage T2b or ISUP grade group 2 and clinical stage T1c-2b was identified. Unfavorable pathology at radical prostatectomy was defined as the presence of ISUP grade group > 2 (unfavorable tumor upgrading), extracapsular extension (ECE), and seminal vesicle invasion (SVI). Disease progression was defined as the event of biochemical recurrence and/or local recurrence and/or distant metastases. Associations were evaluated by Cox regression and logistic regression analyses., Results: Overall, 210 patients were identified between January 2013 and October 2020. Unfavorable tumor upgrading was detected in 71 (33.8%) cases, and adverse tumor stage, including ECE or SVI in 18 (8.6%) and 11 (5.2%) patients, respectively. Median (interquartile range) follow-up was 38.5 (16-61) months. PCa progression occurred in 24 (11.4%) patients. Very favorable IR PCa patients with unfavorable tumor upgrading at final pathology showed a persistent risk of disease progression, which hold significance after adjustment for all factors (Hazard Ratio [HR]: 5.95, 95% Confidence Interval [CI]: 1.97-17.92, p = 0.002) of which PSA was an independent predictor (HR: 1.52, 95% CI 1.12-2.08, p = 0.008). Moreover, these subjects were more likely to belong to the biopsy ISUP grade group 2., Conclusions: Very favorable IR PCa patients hiding unfavorable tumor upgrading were more likely to experience disease progression. Unfavorable tumor upgrading involved about one-third of cases and was less likely to occur in patients presenting with biopsy ISUP grade group 1. Tumor misclassification is an issue to discuss, when counseling this subset of patients for active surveillance because of the risk of delayed active treatment., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: To investigate the potential prognostic impact of Briganti's 2012 nomogram in EAU intermediate-risk patients presenting with an unfavorable tumor grade and treated with robot-assisted radical prostatectomy, eventually associated with extended pelvic lymph node dissection., Materials and Methods: From January 2013 to December 2021, the study included 179 EAU intermediate-risk patients presenting with an unfavorable tumor grade (ISUP 3), eventually associated with a PSA of 10-20 ng/ml and/or cT-2b. Briganti's 2012 nomogram was assessed as both a continuous and dichotomous variable, categorized according to the median (risk score ⩾7% vs <7%). Disease progression, defined as biochemical recurrence and/or metastatic progression, was evaluated using Cox proportional hazards in both univariate and multivariate analyses., Results: Disease progression occurred in 43 (24%) patients after a median (95% CI) follow-up of 78 (65.7-88.4) months. The nomogram risk score predicted disease progression, evaluated both as a continuous variable (hazard ratio, HR = 1.064; 95% CI: 1.035-1.093; p  < 0.0001) and as a categorical variable (HR = 3.399; 95% CI: 1.740-6.638; p  < 0.0001). This association was confirmed in multivariate analysis, where hazard ratios remained consistent even after adjusting for clinical and pathological factors., Conclusions: In EAU intermediate-risk PCa cases presenting with an unfavorable tumor grade and treated surgically, Briganti's 2012 nomogram was associated with disease progression after surgery. Consequently, as the nomogram risk score increased, patients were more likely to experience PCa progression, facilitating the stratification of the patient population into distinct prognostic subgroups., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Metastasis-directed therapy (MDT) has been tested in clinical trials as a treatment option for oligorecurrent prostate cancer (PCa). However, there is an ongoing debate regarding the impact of using different imaging techniques interchangeably for defining lesions and guiding MDT within clinical trials. Methods: We retrospectively identified oligorecurrent PCa patients who had 5 or fewer nodal, bone, or visceral metastases detected by choline or prostate-specific membrane antigen (PSMA) PET/CT and who underwent MDT stereotactic body radiotherapy with or without systemic therapy in 8 tertiary-level cancer centers. Imaging-guided MDT was assessed as progression-free survival (PFS), time to systemic treatment change due to polymetastatic conversion (PFS2), and overall survival predictor. Propensity score matching was performed to account for clinical differences between groups. Results: Of 402 patients, 232 (57.7%) and 170 (42.3%) underwent MDT guided by [ 18 F]fluorocholine and PSMA PET/CT, respectively. After propensity score matching, patients treated with PSMA PET/CT-guided MDT demonstrated longer PFS (hazard ratio [HR], 0.49 [95% CI, 0.36-0.67]; P < 0.0001), PFS2 (HR, 0.42 [95% CI, 0.28-0.63]; P < 0.0001), and overall survival (HR, 0.39 [95% CI, 0.15-0.99]; P < 0.05) than those treated with choline PET/CT-guided MDT. Additionally, we matched patients who underwent [ 68 Ga]Ga-PSMA-11 versus [ 18 F]F-PSMA-1007 PET/CT, observing longer PFS and PFS2 in the former subgroup (PFS: HR, 0.51 [95% CI, 0.26-1.00]; P < 0.05; PFS2: HR, 0.24 [95% CI, 0.09-0.60]; P < 0.05). Conclusion: Diverse imaging methods may influence outcomes in oligorecurrent PCa patients undergoing MDT. However, prospective, head-to-head studies, ideally incorporating a randomized design, are necessary to provide definitive evidence and facilitate the practical application of these findings., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Objectives: The aims of this study are to develop and validate a clinical decision support system based on demographics, prostate-specific antigen (PSA), microRNA (miRNA), and MRI for the detection of prostate cancer (PCa) and clinical significant (cs) PCa, and to assess if this system performs better compared to MRI alone., Methods: This retrospective, multicenter, observational study included 222 patients (mean age 66, range 46-75 years) who underwent prostate MRI, miRNA (let-7a-5p and miR-103a-3p) assessment, and biopsy. Monoparametric and multiparametric models including age, PSA, miRNA, and MRI outcome were trained on 65% of the data and then validated on the remaining 35% to predict both PCa (any Gleason grade [GG]) and csPCa (GG ≥ 2 vs GG = 1/negative). Accuracy, sensitivity, specificity, positive and negative predictive value (NPV), and area under the receiver operating characteristic curve were calculated., Results: MRI outcome was the best predictor in the monoparametric model for both detection of PCa, with sensitivity of 90% (95%CI 73-98%) and NPV of 93% (95%CI 82-98%), and for csPCa identification, with sensitivity of 91% (95%CI 72-99%) and NPV of 95% (95%CI 84-99%). Sensitivity and NPV of PSA + miRNA for the detection of csPCa were not statistically different from the other models including MRI alone., Conclusion: MRI stand-alone yielded the best prediction models for both PCa and csPCa detection in biopsy-naïve patients. The use of miRNAs let-7a-5p and miR-103a-3p did not improve classification performances compared to MRI stand-alone results., Clinical Relevance Statement: The use of miRNA (let-7a-5p and miR-103a-3p), PSA, and MRI in a clinical decision support system (CDSS) does not improve MRI stand-alone performance in the detection of PCa and csPCa., Key Points: • Clinical decision support systems including MRI improve the detection of both prostate cancer and clinically significant prostate cancer with respect to PSA test and/or microRNA. • The use of miRNAs let-7a-5p and miR-103a-3p did not significantly improve MRI stand-alone performance. • Results of this study were in line with previous works on MRI and microRNA., (© 2024. The Author(s).)

Introduction: We sought to investigate whether surgical delay may be associated with pathological upstaging in patients treated with robot assisted radical prostatectomy (RARP) for localized and locally advanced prostate cancer (PCa)., Materials and Methods: Consecutive firstly-diagnosed PCa patients starting from March 2020 have been enrolled. All the patients were categorized according to EAU risk categories for PCa risk. Uni- and multivariate analysis were fitted to explore clinical and surgical predictors of pathological upstaging to locally advanced disease (pT3/pT4 - pN1 disease)., Results: Overall 2017 patients entered the study. Median age at surgery was 68 (IQR 63-73) years. Overall low risk, intermediate risk, localized high risk and locally advanced disease were recorded in 368 (18.2 %), 1071 (53.1 %), 388 (19.2 %) and 190 (9.4 %), respectively. Median time from to diagnosis to treatment was 51 (IQR 29-70) days. Time to surgery was 56 (IQR 32-75), 52 (IQR 30-70), 45 (IQR 24-60) and 41 (IQR 22-57) days for localized low, intermediate and high risk and locally advanced disease, respectively. Considering 1827 patients with localized PCa, at multivariate analysis ISUP grade group ≥4 on prostate biopsy (HR: 1.30; 95 % CI 1.07-1.86; p = 0.02) and surgical delay only in localized high-risk disease (HR: 1.02; 95 % CI 1.01-1.54; p = 0.02) were confirmed as independent predictors of pathological upstaging to pT3-T4/pN1 disease at final histopathological examination., Conclusions: In localized high-risk disease surgical delay could be associated with a higher risk of adverse pathologic findings., (© 2024 Published by Elsevier Ltd.)

Purpose: We assessed the prognostic impact of the 2012 Briganti nomogram on prostate cancer (PCa) progression in intermediate-risk (IR) patients presenting with PSA <10ng/mL, ISUP grade group 3, and clinical stage up to cT2b treated with robot assisted radical prostatectomy eventually associated with extended pelvic lymph node dissection., Materials and Methods: From January 2013 to December 2021, data of surgically treated IR PCa patients were retrospectively evaluated. Only patients presenting with the above-mentioned features were considered. The 2012 Briganti nomogram was assessed either as a continuous and a categorical variable (up to the median, which was detected as 6%, vs. above the median). The association with PCa progression, defined as biochemical recurrence, and/or metastatic progression, was evaluated by Cox proportional hazard regression models., Results: Overall, 147 patients were included. Compared to subjects with a nomogram score up to 6%, those presenting with a score above 6% were more likely to be younger, had larger/palpable tumors, presented with higher PSA, underwent tumor upgrading, harbored non-organ confined disease, and had positive surgical margins at final pathology. PCa progression, which occurred in 32 (21.7%) cases, was independently predicted by the 2012 Briganti nomogram both considered as a continuous (Hazard Ratio [HR]:1.04, 95% Confidence Interval [CI]:1.01-1.08;p=0.021), and a categorical variable (HR:2.32; 95%CI:1.11-4.87;p=0.026), even after adjustment for tumor upgrading., Conclusions: In IR PCa patients with PSA <10ng/mL, ISUP grade group 3, and clinical stage up to cT2b, the 2012 Briganti nomogram independently predicts PCa progression. In this challenging subset of patients, this tool can identify prognostic subgroups, independently by upgrading issues., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Robotic surgery with Da Vinci has revolutionized the treatment of several diseases, including prostate cancer; nevertheless, costs remain the major drawback. Recently, new robotic platforms entered the market aiming to reduce costs and improve the access to robotic surgery. The aim of the study is to compare direct cost for initial hospital stay of radical prostatectomy performed with two different robotic systems, the Da Vinci and the new Hugo RAS system. This is a projection study that applies cost of robotic surgery, derived from a local tender, to the clinical course of robotic radical prostatectomy (RALP) performed with Da Vinci and Hugo RAS. The study was performed in a public referral center for robotic surgery equipped with both systems. The cost of robotic surgery from a local tender were considered and included rent, annual maintenance, and a per-procedure fee covering the setup of four robotic instruments. Those costs were applied to patients who underwent RALP with both systems since November 2022. The primary endpoint is to evaluate direct costs of initial hospital stay for Da Vinci and Hugo RAS, by considering equipment costs (as derived from the tender), and costs of theater and of hospitalization. The direct per-procedure cost is €2,246.31 for a Da Vinci procedure and €1995 for a Hugo RALP. In the local setting, Hugo RAS provides 11% of cost saving for RALP. By applying this per-procedure cost to our clinical data, the expenditure for the entire index hospitalization is € 6.7755,1 for Da Vinci and € 6.637,15 for Hugo RALP. The new Hugo RAS system is willing to reduce direct expenditures of robotic surgery for RALP; furthermore, it provides similar peri-operative outcomes compared to the Da Vinci. However, other drivers of costs should be taken into account, such as the duration of OR use-that is more than just console time and may depend on the facility's background and organization. Further variations in direct costs of robotic systems are related to caseload, local agreements and negotiations. Thus, cost comparison of new robotic platform still remains an ongoing issue., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: The aim is to evaluate factors impacting operating time (OT) during robot-assisted radical prostatectomy (RARP) with or without extended pelvic lymph node dissection (ePLND) for prostate cancer., Methods: Overall, 1289 patients underwent RARP from January 2013 to December 2021. ePLND was performed in 825 cases. Factors potentially associated with OT variations were assessed. Three low-volume (LVS) and two high-volume surgeons (HVS) performed the procedures. A linear regression model was computed to assess associations with OT variations., Results: When RARP was performed by HVS an OT decrease was observed independently by significant clinical (Body Mass Index [BMI]; prostate volume [PV]) and anatomical/perioperative features (prostate weight [PW]; intraoperative blood loss [BL]) both in clinical (change in OT: -42.979 minutes; 95% CI: -51.789; -34.169; P<0.0001) and anatomical/perioperative models (change in OT: -40.020 minutes; 95% CI: -48.494; -31.587; P<0.0001). A decreased OT was observed in clinical (change in OT: -27.656 minutes; 95% CI: -33.449; -21.864; P<0.0001) and anatomical/perioperative (change in OT: -24.935 minutes; 95% CI: -30.562; -19.308; P<0.0001) models also in case of RARP with ePLND performed by HVS, independently by BMI, PV, PSA as well as for PW, seminal vesicle invasion, positive surgical margins, and BL., Conclusions: In a tertiary academic referral center, OT decreased when RARP was performed by HVS, independently of adverse clinical and anatomical/perioperative factors. Available OT loads can be planned to optimize waiting lists, teaching tasks, operative costs, and surgeon's volume.

Introduction: The aim of this article was to offer a comprehensive non-systematic review of the literature about the use of Nuclear Medicine imaging exams for the evaluation of prostate cancer (PCa) in the recurrent setting, with a particular regard to positron emission tomography/computed tomography (PET/CT) imaging., Evidence Acquisition: A comprehensive nonsystematic literature review was performed in March 2024. Literature search was updated until March 2024. The most relevant studies have been summarized, giving priority to registered clinical trials and multicenter collaborations., Evidence Synthesis: Restaging BCR with advanced Nuclear Medicine Imaging, such as prostate-specific membrane antigen-PET/CT could lead to stage migration and pave the way for additional management strategies, such as stereotactic ablative radiotherapy in patients with low-burden or oligometastatic disease, potentially delaying the need of systemic therapies. While OS benefits of targeting PET/CT positive disease are still lacking, data on progression- and metastasis-free-survival are emerging. Improvements in quality-of-life assessments are already evident., Conclusions: PCa is one of the most common malignancy in men. In the last 10 years PCa imaging has become significantly more accurate and is now essential for the definition of the extent of the disease in different phases of its natural history. This opened the road to novel management strategies, especially in the recurrent setting, in which the oligometastatic state is now being explored in several trials regarding the prognostic significance of metastasis directed therapies aimed at personalizing the treatment for every single patient.

Background: Among prostate cancer (PCa) treatment options, mini-invasive surgical approaches have gained a wide diffusion in the last decades. The aim of this study was to present oncological, functional, and quality of life data after 10 years of follow-up of a prospective randomized controlled trial (RCT) (ISRCTN11552140) comparing robot-assisted radical prostatectomy (RARP) versus laparoscopic radical prostatectomy (LRP) for the treatment of PCa., Methods: Patients with localized PCa were randomized to undergo LRP or RARP between January 2010 and January 2011. Functional (continence and potency) and oncological (prostate-specific antigen, biochemical recurrence [BCR] and BCR-free survival [BCRFS]) variables were evaluated. BCRFS curves were estimated by the Kaplan-Meier method and compared using the log-rank test. Machine learning partial least square-discriminant analysis (PLS-DA) was used to identify the variables characterizing more the patients who underwent RARP or LRP., Results: Seventy-five of the originally enrolled 120 patients remained on follow-up for 10 years; 40 (53%) underwent RARP and 35 (47%) LRP. Continence and potency recovery rates did not show significant differences (p = 0.068 and p = 0.56, respectively), despite a Δ12% for continence and Δ8% for potency in favor of the robotic approach. However, the quality of continence (in terms of International Consultation on Incontinence Questionnaire-Short Form [ICIQ-SF] score) and erection (in terms of International Index of Erectile Function-5 [IIEF-5] score) was significantly better after 10 years in the robotic group (p = 0.02 and p < 0.001). PLS-DA revealed that LRP was characterized by the worst functional-related outcomes analyzing the entire follow-up period. Four (10%) and six (17%) patients experienced BCR in RARP and LRP groups, respectively (p = 0.36), with an overall 10-year BCR-free survival of 88% and 78% (p = 0.16)., Conclusions: Comparable continence and potency rates were observed between RARP and LRP after a 10-year follow-up. However, the RARP group exhibited superior totally dry rate and erection quality. No difference in terms of oncological outcomes was found., (© 2024 The Authors. The Prostate published by Wiley Periodicals LLC.)

Prostate cancer (PCa) remains a significant global health challenge, particularly in its advanced stages. Despite progress in early detection and treatment, PCa is the second most common cancer diagnosis among men. This review aims to provide an overview of current therapeutic approaches and innovations in PCa management, focusing on the latest advancements and ongoing challenges. We conducted a narrative review of clinical trials and research studies, focusing on PARP inhibitors (PARPis), phosphoinositide 3 kinase-protein kinase B inhibitors, immunotherapy, and radioligand therapies (RLTs). Data was sourced from major clinical trial databases and peer-reviewed journals. Androgen deprivation therapy and androgen-receptor pathway inhibitors remain foundational in managing castration-sensitive and early-stage castration-resistant PCa (CRPC). PARPi's, such as olaparib and rucaparib, have emerged as vital treatments for metastatic CRPC with homologous recombination repair gene mutations, highlighting the importance of personalized medicine. Immune checkpoint inhibitors (ICIs) have shown clinical benefit limited to specific subgroups of PCa, demonstrating significant improvement in efficacy in patients with microsatellite instability/mismatch repair or cyclin-dependent kinase 12 alteration, highlighting the importance of focusing ongoing research on identifying and characterizing these subgroups to maximize the clinical benefits of ICIs. RLTs have shown effectiveness in treating mCRPC. Different alpha emitters (like [ 225 Ac]PSMA) and beta emitters compounds (like [ 177 Lu]PSMA) impact treatment differently due to their energy transfer characteristics. Clinical trials like VISION and TheraP have demonstrated positive outcomes with RLT, particularly [ 177 Lu]PSMA-617, leading to FDA approval. Ongoing trials and future perspectives explore the potential of [ 225 Ac]PSMA, aiming to improve outcomes for patients with mCRPC. The landscape of PCa treatment is evolving, with significant advancements in both established and novel therapies. The combination of hormonal therapies, chemotherapy, PARPis, immunotherapy, and RLTs, guided by genetic and molecular insights, opens new possibilities for personalized treatment.

Background: Urine is a promising biological fluid for prostate cancer (PCa) diagnostics due to its non-invasive collection and wide range of biomarkers. The aim of this study was to assess the role of urinary PSA (uPSA) and urinary Zinc (uZinc) as biomarkers for the diagnosis of PCa in combination with routine parameters of standard of care (SOC - blood PSA, abnormal DRE, age) and MRI in patients candidates for prostate biopsy., Methods: Urine samples after prostatic massages were collected from men with suspected PCa scheduled for prostate biopsy. Quantification of uPSA was performed by ECLIA platform and confirmed by ELISA assay, while uZinc measurement was evaluated by ICP-MS and confirmed by colorimetric in vitro assay. Six multivariate logistic regression analysis were performed to assess diagnostic performance of uPSA and uZinc (urine), SOC and MRI alone, and combination of MRI+SOC, MRI+urine and SOC+MRI+urine. The discriminative power of the logistic models was assessed by calculating the area under the receiver operating characteristic (ROC) curves (AUC)., Results: Two hundred thirty-eight patients were included in the analysis; 145 of them were diagnosed with PCa. Urine test showed a better discrimination of HS from CP, in respect of uPSA and uZinc alone, both for PCa of any grade and Gleason Score ≥7 (4+3) (AUC 0.804 and 0.823 respectively). ROC curve combining SOC+MRI+urine showed an AUC=0.882, that is statistically different from SOC or MRI alone, or MRI+SOC (P=0.0001, P=0.0001, and P=0.008 respectively). PCa risk algorithm designed considering SOC+MRI+urine results in potential reduction of 57% of unnecessary biopsies compared to the current standard parameters., Conclusions: The loss of uPSA and Zinc production and secretion during neoplastic transformation of the prostate could potentially represent a hallmark of PCa. Its combination with age, PSA and DRE, as well as with mpMRI could represent an interesting approach to improve the diagnostic accuracy of PCa.

Background: Urinary incontinence (UI) is a common complication after radical prostatectomy, significantly affecting patients' quality of life. This study aimed to correlate the length of preserved urethra in robotic radical prostatectomy (RALP) patients with short-term urinary continence rates within 90 days post-surgery., Methods: A prospective multicentric study enrolled 190 prostate adenocarcinoma patients undergoing RALP. Using preoperative magnetic resonance imaging (mpMRI), urethral length was measured from the external urethral sphincter to the bladder neck. After surgery, histological measurements of the removed urethra were compared to the preoperative mpMRI data. Patients were categorized into two groups at the three-month follow-up based on urinary continence assessed through Urodynamic Study (UDS): Group A (94 patients without UI) and Group B (96 patients with UI)., Results: Results revealed a significant difference in mean UI recovery time (Group A: 12.35 days, SD: 3.09 vs. Group B: 93.86 days, SD: 34.8, p < 0.0001). A ROC curve identified a 16.5% cut-off value (p < 0.000, sensitivity 87.5%, specificity 91.8%). Both groups showed a significant negative correlation between preserved urethral percentage and UI recovery time (Group A: r -0.655, p < 0.0001; Group B: r -0.340, p: 0.017). Group A had an average of 21.52% preserved urethra, while Group B had 13.86% (p < 0.0001). At one-year follow-up, 93.2% overall patients reported urinary continence without pads., Conclusions: This study emphasizes the positive correlation between preserved urethra percentage in RALP and early urinary continence recovery, highlighting its surgical significance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Introduction: The aim of this study is to assess the usefulness of the Prostate Health Index (PHI) as a triage tool for selecting patients at risk of prostate cancer (PCa) who should undergo multiparametric Magnetic Resonance Imaging (mpMRI)., Material and Methods: We enrolled 204 patients with suspected PCa. For each patient, a blood sample was collected before mpMRI to measure PHI. Findings on mpMRI were assessed according to the Prostate Imaging Reporting & Data System version 2.0 (PI-RADSv2) category scale., Results: According to PI-RADSv2, patients were classified into two groups: PI-RADS < 3 (48 %) and ≥ 3 (52 %). PHI showed the best performance for predicting PI-RADS ≥ 3 [AUC: 0,747 (0,679-0,815), 0,680(0,607-0,754), and 0,613 (0,535-0,690) for PHI, PSA ratio, and total PSA, respectively]. The best PHI cut-off was 30, with a sensitivity of 90%. At the univariate logistic regression, total PSA (p = 0.007), PSA ratio (p = 0.001), [-2]proPSA (p = 0.019) and PHI (p < 0.001) were associated with PI-RADS ≥ 3; however, at the multivariate analysis, only PHI (p < 0.001) was found to be an independent predictor of PI-RADS ≥ 3., Conclusion: PHI could represent a reliable noninvasive tool for selecting patients to undergo mpMRI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Purpose: Test whether a well-grounded KBP model trained on moderately hypo-fractionated prostate treatments can be used to satisfactorily drive the optimization of SBRT prostate treatments., Materials and Methods: A KBP model (SBRT-model) was developed, trained and validated using the first forty-seven clinically treated VMAT SBRT prostate plans (42.7 Gy/7fx or 36.25 Gy/5fx). The performance and robustness of this model were compared against a high-quality KBP-model (ST-model) that was already clinically adopted for hypo-fractionated (70 Gy/28fx and 60 Gy/20fx) prostate treatments. The two models were compared in terms of their predictions robustness, and the quality of their outcomes were evaluated against a set of reference clinical SBRT plans. Plan quality was assessed using DVH metrics, blinded clinical ranking, and a dedicated Plan Quality Metric algorithm., Results: The plan libraries of the two models were found to share a high degree of anatomical similarity. The overall quality (APQM%) of the plans obtained both with the ST- and SBRT-models was compatible with that of the original clinical plans, namely (93.7 ± 4.1)% and (91.6 ± 3.9)% vs (92.8.9 ± 3.6)%. Plans obtained with the ST-model showed significantly higher target coverage (PTV V95%): (97.9 ± 0.8)% vs (97.1 ± 0.9)% (p < 0.05). Conversely, plans optimized following the SBRT-model showed a small but not-clinically relevant increase in OAR sparing. ST-model generally provided more reliable predictions than SBRT-model. Two radiation oncologists judged as equivalent the plans based on the KBP prediction, which was also judged better that reference clinical plans., Conclusion: A KBP model trained on moderately fractionated prostate treatment plans provided optimal SBRT prostate plans, with similar or larger plan quality than an embryonic SBRT-model based on a limited number of cases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Prostate cancer, accounting for 375,304 deaths in 2020, is the second most prevalent cancer in men worldwide. While many treatments exist for prostate cancer, novel therapeutic agents with higher efficacy are needed to target aggressive and hormone-resistant forms of prostate cancer, while sparing healthy cells. Plant-derived chemotherapy drugs such as docetaxel and paclitaxel have been established to treat cancers including prostate cancer. Carnosic acid (CA), a phenolic diterpene found in the herb rosemary (Rosmarinus officinalis) has been shown to have anticancer properties but its effects in prostate cancer and its mechanisms of action have not been examined. CA dose-dependently inhibited PC-3 and LNCaP prostate cancer cell survival and proliferation (IC 50 : 64, 21 µM, respectively). Furthermore, CA decreased phosphorylation/activation of Akt, mTOR, and p70 S6K. A notable increase in phosphorylation/activation of AMP-activated kinase (AMPK), acetyl-CoA carboxylase (ACC) and its upstream regulator sestrin-2 was seen with CA treatment. Our data indicate that CA inhibits AKT-mTORC1-p70S6K and activates Sestrin-2-AMPK signaling leading to a decrease in survival and proliferation. The use of inhibitors and small RNA interference (siRNA) approaches should be employed, in future studies, to elucidate the mechanisms involved in carnosic acid's inhibitory effects of prostate cancer.

Human anterior gradient-2 (AGR2) has been implicated in carcinogenesis of various solid tumours, but the expression data in prostate cancer are contradictory regarding its prognostic value. The objective of this study is to evaluate the expression of AGR2 in a large prostate cancer cohort and to correlate it with clinicopathological data. AGR2 protein expression was analysed immunohistochemically in 1023 well-characterized prostate cancer samples with a validated antibody. AGR2 expression levels in carcinomas were compared with matched tissue samples of adjacent normal glands. AGR2 expression levels were dichotomized and tested for statistical significance. Increased AGR2 expression was found in 93.5% of prostate cancer cases. AGR2 levels were significantly higher in prostate cancer compared with normal prostate tissue. A gradual loss of AGR2 expression was associated with increasing tumour grade (ISUP), and AGR2 expression is inversely related to patient survival, however, multivariable significance is not achieved. AGR2 is clearly upregulated in the majority of prostate cancer cases, yet a true diagnostic value appears unlikely. In spite of the negative correlation of AGR2 expression with increasing tumour grade, no independent prognostic significance was found in this large-scale study., (© 2024 The Authors. APMIS published by John Wiley & Sons Ltd on behalf of Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

Background: Deep learning-based unsupervised image registration has recently been proposed, promising fast registration. However, it has yet to be adopted in the online adaptive magnetic resonance imaging-guided radiotherapy (MRgRT) workflow., Purpose: In this paper, we design an unsupervised, joint rigid, and deformable registration framework for contour propagation in MRgRT of prostate cancer., Methods: Three-dimensional pelvic T2-weighted MRIs of 143 prostate cancer patients undergoing radiotherapy were collected and divided into 110, 13, and 20 patients for training, validation, and testing. We designed a framework using convolutional neural networks (CNNs) for rigid and deformable registration. We selected the deformable registration network architecture among U-Net, MS-D Net, and LapIRN and optimized the training strategy (end-to-end vs. sequential). The framework was compared against an iterative baseline registration. We evaluated registration accuracy (the Dice and Hausdorff distance of the prostate and bladder contours), structural similarity index, and folding percentage to compare the methods. We also evaluated the framework's robustness to rigid and elastic deformations and bias field perturbations., Results: The end-to-end trained framework comprising LapIRN for the deformable component achieved the best median (interquartile range) prostate and bladder Dice of 0.89 (0.85-0.91) and 0.86 (0.80-0.91), respectively. This accuracy was comparable to the iterative baseline registration: prostate and bladder Dice of 0.91 (0.88-0.93) and 0.86 (0.80-0.92). The best models complete rigid and deformable registration in 0.002 (0.0005) and 0.74 (0.43) s (Nvidia Tesla V100-PCIe 32 GB GPU), respectively. We found that the models are robust to translations up to 52 mm, rotations up to 15 ∘ $^\circ$ , elastic deformations up to 40 mm, and bias fields., Conclusions: Our proposed unsupervised, deep learning-based registration framework can perform rigid and deformable registration in less than a second with contour propagation accuracy comparable with iterative registration., (© 2024 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Background: The antidiabetic drug metformin has known anticancer effects related to its antioxidant activity; however, its clinical benefit for prostate cancer (PCa) has thus far been inconclusive. Here, we investigate whether the efficacy of metformin in PCa is related to the expression status of NKX3.1, a prostate-specific homeobox gene that functions in mitochondria to protect the prostate from aberrant oxidative stress., Objective: To investigate the relationship of NKX3.1 expression and metformin efficacy in PCa., Design, Setting, and Participants: Functional studies were performed in vivo and in vitro in genetically engineered mouse models and human LNCaP cells, and organotypic cultures having normal or reduced/absent levels of NKX3.1. Correlative studies were performed using two independent retrospective tissue microarray cohorts of radical prostatectomies and a retrospective cohort of prostate biopsies from patients on active surveillance., Intervention: Metformin was administered before or after the induction of oxidative stress by treatment with paraquat., Outcome Measurements and Statistical Analysis: Functional endpoints included analyses of histopathology, tumorigenicity, and mitochondrial function. Correlative endpoints include Kaplan-Meier curves and Cox proportional hazard regression models., Results and Limitations: Metformin reversed the adverse consequences of NKX3.1 deficiency following oxidative stress in vivo and in vitro, as evident by reduced tumorigenicity and restored mitochondrial function. Patients with low NKX3.1 expression showed a significant clinical benefit from taking metformin., Conclusions: Metformin can overcome the adverse consequences of NKX3.1 loss for PCa progression by protecting against oxidative stress and promoting normal mitochondrial function. These functional activities and clinical correlates were observed only with low NKX3.1 expression. Thus, the clinical benefit of metformin in PCa may depend on the status of NKX3.1 expression., Patient Summary: Prostate cancer patients with low NKX3.1 are likely to benefit most from metformin treatment to delay disease progression in a precision interception paradigm., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

To evaluate the prognostic potential of the 2012 Briganti nomogram for pelvic lymph node invasion on disease progression after surgery in intermediate-risk (IR) prostate cancer (PCa) patients with favorable tumor grade (International Society of Urological Pathology grade group 1 or 2), eventually associated with adverse clinical features as PSA between 10 and 20 ng/mL and/or clinical stage T2b. All IR PCa patients treated with robot-assisted radical prostatectomy and eventually extended pelvic lymph node dissection at the Department of Urology of the Integrated University Hospital of Verona between 2013 and 2021, with the abovementioned features, and available follow-up were considered. The 2012 Briganti nomogram score was assessed both as a continuous and dichotomous variable, where a mean risk score of 4% was used a threshold. The independent predictor status of the nomogram score on disease progression defined as the occurrence of biochemical recurrence and/or metastatic progression was evaluated using the Cox regression analysis. Overall, 348 patients were enrolled in the study. Median (interquartile range) follow-up was 98 (83.5-112.4) months. At multivariable Cox regression analysis, PCa progression, which occurred in 65 (18.7%) cases, was independently predicted only by the 2012 Briganti nomogram score evaluated as a continuous variable, among all considered clinical features (HR 1.16; 95%CI 1.08-1.24; p < 0.001). In addition, patients presenting with a nomogram score ≥ 4% were more likely to experience disease progression even after adjustment for clinical (HR 2.22, 95%CI 1.02-4.79; p = 0.043) and pathological (HR 1.80; 95%CI 1.06-3.05; p = 0.031) factors. In the examined patient population, the 2012 Briganti nomogram predicted PCa progression after surgery. Accordingly, as the risk score increased, patients were more likely to progress, independently by the occurrence of adverse pathology in the surgical specimen. The 2012 Briganti nomogram score categorized according to the mean value allowed to identify prognostic subgroups., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: Robot-assisted radical prostatectomy (RARP) with extended lymphadenectomy (ePLND) is the gold standard for surgical treatment of prostate cancer (PCa). Recently, the en-bloc ePLND has been proposed but no studies reported on the standardization of the technique. The aim of the study is to describe different standardized en-bloc ePLND, the antegrade and the retrograde ePLND, and to compare their surgical and oncological outcomes., Materials & Methods: From January 2018 to September 2019, all patients subjected to RARP plus ePLND by one single surgeon were enrolled. ePLND was performed in a retrograde fashion by starting laterally to the medial umbilical ligament from the internal inguinal ring proceeding towards the ureter, or in an antegrade way by starting from the ureter at its crossing with the common iliac artery and proceeding towards the femoral canal. Patients' demographic data, clinical and surgical data were collected. Each en-bloc ePLND was categorized as "efficient" or "inefficient" by the operator, as surrogate of surgeon's satisfaction., Results: Antegrade and retrograde ePLND were performed in 41/105 (group A) and 64/105 (group R) patients, respectively. The two groups (A vs R) had similar median (IQR) number of lymph nodes retrieved [20 (16.25-31.5) vs 19 (15-26.25); p = 0.18], ePLND time [33.5 (29.5-38.5) min vs 33.5 (26.5-37.5) min; p = 0.4] and post-operative complications [8/41 (19.5%) vs 9/64 (14.1%); p = 0.61]. In group A, 3/41 (7.3%) clinically significant lymphoceles were reported, while 1/64 (1.6%) in group R (p = 0.3). 33/41 (80.5%) and 28/64 (44%) procedures were scored as efficient 59 in group A and R, respectively (p = 0.01). On multivariate regression, only BMI (B = 0.93; 95% CI 0.29-1.56; p = 0.005) was associated with a longer ePLND time., Conclusions: The study indicates that antegrade and retrograde en-bloc extended pelvic lymph node dissection (ePLND) have comparable surgical and oncologic outcomes, supporting the importance of standardizing the procedure rather than focusing on the direction. Although both techniques aligned with current evidence regarding lymph node invasion and complications, the antegrade approach was subjectively perceived as safer due to early isolation of critical anatomical landmarks. Encouragement for the use of en-bloc ePLND, regardless of direction, is emphasized to improve prostate cancer staging accuracy and procedural standardization., (© 2024. The Author(s).)

Context: Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein overexpressed in most prostate cancers and exploited as a target for PSMA-targeted therapies. Different approaches to target PSMA-expressing cancer cells have been developed, showing promising results in clinical trials., Objective: To discuss the regulation of PSMA expression and the main PSMA-targeted therapeutic concepts illustrating their clinical development and rationalizing combination approaches with examples., Evidence Acquisition: We performed a detailed literature search using PubMed and reviewed the American Society of Clinical Oncology and European Society of Medical Oncology annual meeting abstracts up to September 2023., Evidence Synthesis: We present an overarching description of the different strategies to target PSMA. The outcomes of PSMA-targeted therapies strongly rely on surface-bound PSMA expression. However, PSMA heterogeneity at different levels (interpatient and inter/intratumoral) limits the efficacy of PSMA-targeted therapies. We highlight the molecular mechanisms governing PSMA regulation, the understanding of which is crucial to designing therapeutic strategies aimed at upregulating PSMA expression. Thus far, homeobox B13 (HOXB13) and androgen receptor (AR) have emerged as critical transcription factors positively and negatively regulating PSMA expression, respectively. Furthermore, epigenetic regulation of PSMA has been also reported recently. In addition, many established therapeutic approaches harbor the potential to upregulate PSMA levels as well as potentiate DNA damage mediated by current radioligands., Conclusions: PSMA-targeted therapies are rapidly advancing, but their efficacy is strongly limited by the heterogeneous expression of the target. A thorough comprehension of how PSMA is regulated will help improve the outcomes through increasing PSMA expression and will provide the basis for synergistic combination therapies., Patient Summary: Prostate-specific membrane antigen (PSMA) is overexpressed in most prostate cancers. PSMA-targeted therapies have shown promising results, but the heterogeneous expression of PSMA limits their efficacy. We propose to better elucidate the regulation of PSMA expression to increase the levels of the target and improve the therapeutic outcomes., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

In the last years, theranostics has expanded the therapeutic options available for prostate cancer patients. In this review, we explore this dynamic field and its potential to revolutionize precision medicine for prostate cancer. We delve into the foundational principles, clinical applications, and emerging opportunities, emphasizing the potential synergy between radioligand therapy and other systemic treatments. Additionally, we address the ongoing challenges, including optimizing patient selection, assessing treatment responses, and determining the role of theranostics within the broader landscape of prostate cancer treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Importance: The risks and benefits of thromboprophylaxis therapy after cancer surgery are debated. Studies that determine thrombosis risk after cancer surgery with high accuracy are needed., Objectives: To evaluate 1-year risk of venous thromboembolic events after major cancer surgery and how these events vary over time., Design, Setting, and Participants: This register-based retrospective observational matched cohort study included data on the full population of Sweden between 1998 and 2016. All patients who underwent major surgery for cancer of the bladder, breast, colon or rectum, gynecologic organs, kidney and upper urothelial tract, lung, prostate, or gastroesophageal tract were matched in a 1:10 ratio with cancer-free members of the general population on year of birth, sex, and county of residence. Data were analyzed from February 13 to December 5, 2023., Exposure: Major surgery for cancer., Main Outcomes and Measures: The main outcome was incidence of venous thromboembolic events within 1 year after the surgery. Crude absolute risks and risk differences of events within 1 year and adjusted time-dependent cause-specific hazard ratios (HRs) of postdischarge events were calculated., Results: A total of 432 218 patients with cancer (median age, 67 years [IQR, 58-75 years]; 68.7% women) and 4 009 343 cancer-free comparators (median age, 66 years [IQR, 57-74 years]; 69.3% women) were included in the study. The crude 1-year cumulative risk of pulmonary embolism was higher among the cancer surgery population for all cancers, with the following absolute risk differences: for bladder cancer, 2.69 percentage points (95% CI, 2.33-3.05 percentage points); for breast cancer, 0.59 percentage points (95% CI 0.55-0.63 percentage points); for colorectal cancer, 1.57 percentage points (95% CI, 1.50-1.65 percentage points); for gynecologic organ cancer, 1.32 percentage points (95% CI, 1.22-1.41 percentage points); for kidney and upper urinary tract cancer, 1.38 percentage points (95% CI, 1.21-1.55 percentage points); for lung cancer, 2.61 percentage points (95% CI, 2.34-2.89 percentage points); for gastroesophageal cancer, 2.13 percentage points (95% CI, 1.89-2.38 percentage points); and for prostate cancer, 0.57 percentage points (95% CI, 0.49-0.66 percentage points). The cause-specific HR of pulmonary embolism comparing patients who underwent cancer surgery with matched comparators peaked just after discharge and generally plateaued 60 to 90 days later. At 30 days after surgery, the HR was 10 to 30 times higher than in the comparison cohort for all cancers except breast cancer (colorectal cancer: HR, 9.18 [95% CI, 8.03-10.50]; lung cancer: HR, 25.66 [95% CI, 17.41-37.84]; breast cancer: HR, 5.18 [95% CI, 4.45-6.05]). The hazards subsided but never reached the level of the comparison cohort except for prostate cancer. Similar results were observed for deep vein thrombosis., Conclusions and Relevance: This cohort study found an increased rate of venous thromboembolism associated with cancer surgery. The risk persisted for about 2 to 4 months postoperatively but varied between cancer types. The increased rate is likely explained by the underlying cancer disease and adjuvant treatments. The results highlight the need for individualized venous thromboembolism risk evaluation and prophylaxis regimens for patients undergoing different surgery for different cancers.

Background: The European Association of Urology (EAU) has proposed a risk stratification for patients harboring biochemical recurrence (BCR) after radical prostatectomy (RP)., Objective: To assess whether this risk stratification helps in choosing patients for salvage radiotherapy (SRT)., Design, Setting, and Participants: Analyses of 2379 patients who developed BCR after RP (1989-2020), within ten European high-volume centers, were conducted. Early and late SRT were defined as SRT delivered at prostate-specific antigen values <0.5 and ≥0.5 ng/ml, respectively., Outcome Measurements and Statistical Analysis: Multivariable Cox models tested the effect of SRT versus no SRT on death and cancer-specific death. The Simon-Makuch method tested for survival differences within each risk group., Results and Limitations: Overall, 805 and 1574 patients were classified as having EAU low- and high-risk BCR. The median follow-up was 54 mo after BCR for survivors. For low-risk BCR, 12-yr overall survival was 87% versus 78% (p = 0.2) and cancer-specific survival was 100% versus 96% (p = 0.2) for early versus no SRT. For high-risk BCR, 12-yr overall survival was 81% versus 66% (p < 0.001) and cancer-specific survival was 98% versus 82% (p < 0.001) for early versus no SRT. In multivariable analyses, early SRT decreased the risk for death (hazard ratio [HR]: 0.55, p < 0.01) and cancer-specific death (HR: 0.08, p < 0.001). Late SRT was a predictor of cancer-specific death (HR: 0.17, p < 0.01) but not death (p = 0.1)., Conclusions: Improved survival was recorded within the high-risk BCR group for patients treated with early SRT compared with those under observation. Our results suggest recommending early SRT for high-risk BCR men. Conversely, surveillance might be suitable for low-risk BCR, since only nine patients with low-risk BCR died from prostate cancer during follow-up., Patient Summary: The impact of salvage radiotherapy (SRT) on cancer-specific outcomes stratified according to the European Association of Urology biochemical recurrence (BCR) risk classification was assessed. While men with high-risk BCR should be offered SRT, surveillance might be a suitable option for those with low-risk BCR., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the influence of endogenous testosterone density (ETD) and tumor load density (TLD) in the surgical specimen of prostate cancer (PCa) patients., Methods: ETD was assessed as the ratio of endogenous testosterone (ET) to prostate volume (PV). TLD was calculated as the ratio of tumor load (TL) to prostate weight. Preoperative prostate-specific antigen relative densities (PSAD) and percentage of biopsy-positive cores (BPCD) were also assessed. The association of high TLD (above the first quartile) with clinical and pathological factors was assessed by the logistic regression model (univariate and multivariate analysis)., Results: Between November 2014 and December 2019, ET was measured in 805 cases treated with radical prostatectomy (RP). Median (IQR) of ET and ETD was 412 (321.4-519 ng/dL) and 9.8 (6.8-14.4 ng/(dLxmL)) as well as for TL and TLD was 20 (10-30%) and 0.33 (0.17-0.58%/gr), respectively. As a result, high TLD was detected in 75% of cases. A positive independent association was found between high TLD and ETD. Accordingly, as ETD levels increased, the risk of detecting high TLD in the surgical specimen increased, regardless of PSAD and BPCD., Conclusions: At diagnosis of PCa, a positive independent association was found between ETD and risk of high TLD. Subjects with increasing ETD levels were more likely to have high TLD, associated with unfavorable pathology features. The positive association between ETD and TLD in the prostate microenvironment might adversely influence PCa's natural history., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Phase III evidence showed that next-generation imaging (NGI), such as prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT), provides higher diagnostic accuracy than bone scan and contrast-enhanced computed tomography (conventional imaging, CI) in the primary staging of intermediate-to-high-risk prostate cancer (PCa) patients. However, due to the lack of outcome data, the introduction of NGI in routine clinical practice is still debated. Analysing the oncological outcome of patients upstaged by NGI (though managed according to CI) might shed light on this issue, supporting the design of randomised trials comparing the effects of treatments delivered based on NGI vs. CI., Methods: We prospectively enrolled a cohort of 100 biopsy-proven intermediate-to-high-risk PCa patients staged with CI and PSMA PET/CT (though managed according to the CI stage), to assess the frequency of the stage migration phenomenon. Stage migration was then assessed as biochemical recurrence-free survival (bRFS) predictor., Results: Three patients were lost at follow-up after imaging. PSMA PET/CT upstaged 26.8% of patients compared to CI, while it downstaged 6.1% of patients. Notably, 50% of patients excluded from surgery due to the presence of bone metastases at CI would have been treated with radical-intent approaches if PSMA PET/CT had guided the treatment choice. After a median follow-up of 6 months of surgically treated patients, 22/83 (26.5%) had biochemical recurrence (BCR). PSMA PET/CT-driven upstaging determined a significant risk increase for BCR (HR:3.41, 95%CI:1.21-9.56, p = 0.019). Including stage migration in a univariable and multivariable model identified PSMA PET/CT-upstaging as an independent predictor of bRFS., Conclusions: In conclusion, implementing NGI for staging purposes improves the prediction of bRFS. Although phase III evidence is still needed, this advancement suggests that NGI may better identify patients who would benefit from local treatments than those who may achieve better oncological outcomes through systemic treatment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To identify the predictive factors of prostate cancer extracapsular extension (ECE) in an institutional cohort of patients who underwent multiparametric MRI of the prostate prior to radical prostatectomy (RP)., Patients and Methods: Overall, 126 patients met the selection criteria, and their medical records were retrospectively collected and analysed; 2 experienced radiologists reviewed the imaging studies. Logistic regression analysis was conducted to identify the variables associated to ECE at whole-mount histology of RP specimens; according to the statistically significant variables associated, a predictive model was developed and calibrated with the Hosmer-Lomeshow test., Results: The predictive ability to detect ECE with the generated model was 81.4% by including the length of capsular involvement (LCI) and intraprostatic perineural invasion (IPNI). The predictive accuracy of the model at the ROC curve analysis showed an area under the curve (AUC) of 0.83 [95% CI (0.76-0.90)], p < 0.001. Concordance between radiologists was substantial in all parameters examined (p < 0.001). Limitations include the retrospective design, limited number of cases, and MRI images reassessment according to PI-RADS v2.0., Conclusion: The LCI is the most robust MRI factor associated to ECE; in our series, we found a strong predictive accuracy when combined in a model with the IPNI presence. This outcome may prompt a change in the definition of PI-RADS score 5., (© 2024. The Author(s).)

While RECIST 1.1 is well established in radiological response assessment, it is of limited use in prostate cancer (PCa) considering that the disease is often seen only as sclerotic bone changes on conventional imaging. Therefore, a molecular imaging-based response assessment including bone scans has been proposed and used in clinical trials, however, due to the flare phenomenon on bone scans this assessment leads to substantial delays in the detection of progression. Indeed, a robust and reliable imaging tool to assess response to chemotherapy in PCa is still warranted. Whether Positron Emission Tomography (PET) targeting the Prostate-Specific Membrane Antigen (PSMA) could achieve this, is still controversial. In this review, we summarized the available data on cytotoxic agents and their impact on PSMA expression, as well as the available data on PSMA PET imaging for response assessment., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Irene A. Burger has an Advisory role (compensated, institutional) for: GE-Healthcare, AAA (Novartis), Merck; Research support (institutional): GE-Healthcare, Bayer; Travel support: GE-Healthcare, Bayer; Speakers Bureau (compensated, institutional): GE-Healthcare, AAA (Novartis) Bayer, Astellas, Janssen. The authors declare that they have no further conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

In the last years, PSMA-PET imaging and multiparametric MRI (mpMRI) have improved the clinical management of prostate cancer (PCa) patients. Currently, mpMRI is recommended by the EAU (European Association of Urology) guidelines for the primary diagnosis of PCa, whereas PSMA-PET is reserved for disease staging, particularly in high risk localized or locally advanced disease, as well as for biochemical recurrence after surgery. Nevertheless, several studies have explored the added value of PSMA-PET in other clinical scenarios, including primary diagnosis and especially for the detection of clinically significant PCa (csPCa). In the present contribution, we will provide an overview and an update on the current literature on imaging detection of csPCa, with a particular focus on mpMRI, PSMA-PET and their comparison., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to reveal the association between the other-cause mortality (OCM) and post-radical prostatectomy (RP) salvage radiotherapy (sRT) in men with prostate cancer (PCa)., Methods: A retrospective study was carried out with patients who had PCa and underwent RP ± sRT in a high-volume cancer center between 2005 and February 2019. Data from 1955 patients were subjected to a 1:1 matching for age, initial PSA, pathological (p)T/N stages, and ISUP score, which yielding 439 RP + RT (group 1) vs 439 RP-only cases (group 2), without any residual difference. Primary and secondary endpoints of the study were OCM and cancer-specific mortality (CSM). Kaplan-Meier, log-rank, and cox regression tests were used for purpose of the study., Results: The median follow-up time after RP was 5.3 years (interquartile range: 4.0-7.3). After matching, of all deaths that occurred during the study period, 16 in group 1 and 35 in group 2 were attributed to other causes (p = 0.006). 5-year OCM rate of patients who received sRT (1.2%) was significantly lower compared to patients that underwent RP-only (4.4%, p < 0.001). 19 versus 16 patients died of PCa, respectively (p = 0.61). There was no CSM risk difference between groups (p = 0.29). Older patients had an increased risk of OCM (hazard ratio [HR]:1.10 [95%CI 1.05-1.17], p < 0.001) and post-RP RT was associated with lower OCM (HR: 0.28 [95%CI 0.15-0.51], p < 0.001) in multivariable model. pT/N stages and ISUP score were strongly associated with CSM, but not with OCM., Conclusion: OCM was not higher in patients who had sRT with or without ADT. Excess OCM in favor of RP-only patients may be cautiously explained with higher-performance status/life expectancy of patients who selected for RT after RP in our cohort., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: The primary aim of this study was to evaluate if exposure to 5-alpha-reductase inhibitors (5-ARIs) modifies the effect of MRI for the diagnosis of clinically significant Prostate Cancer (csPCa) (ISUP Gleason grade ≥ 2)., Methods: This study is a multicenter cohort study including patients undergoing prostate biopsy and MRI at 24 institutions between 2013 and 2022. Multivariable analysis predicting csPCa with an interaction term between 5-ARIs and PIRADS score was performed. Sensitivity, specificity, and negative (NPV) and positive (PPV) predictive values of MRI were compared in treated and untreated patients., Results: 705 patients (9%) were treated with 5-ARIs [median age 69 years, Interquartile range (IQR): 65, 73; median PSA 6.3 ng/ml, IQR 4.0, 9.0; median prostate volume 53 ml, IQR 40, 72] and 6913 were 5-ARIs naïve (age 66 years, IQR 60, 71; PSA 6.5 ng/ml, IQR 4.8, 9.0; prostate volume 50 ml, IQR 37, 65). MRI showed PIRADS 1-2, 3, 4, and 5 lesions in 141 (20%), 158 (22%), 258 (37%), and 148 (21%) patients treated with 5-ARIs, and 878 (13%), 1764 (25%), 2948 (43%), and 1323 (19%) of untreated patients (p < 0.0001). No difference was found in csPCa detection rates, but diagnosis of high-grade PCa (ISUP GG ≥ 3) was higher in treated patients (23% vs 19%, p = 0.013). We did not find any evidence of interaction between PIRADS score and 5-ARIs exposure in predicting csPCa. Sensitivity, specificity, PPV, and NPV of PIRADS ≥ 3 were 94%, 29%, 46%, and 88% in treated patients and 96%, 18%, 43%, and 88% in untreated patients, respectively., Conclusions: Exposure to 5-ARIs does not affect the association of PIRADS score with csPCa. Higher rates of high-grade PCa were detected in treated patients, but most were clearly visible on MRI as PIRADS 4 and 5 lesions., Trial Registration: The present study was registered at ClinicalTrials.gov number: NCT05078359., (© 2023. The Author(s).)

Background Current predictive tools to estimate the risk of biochemical recurrence (BCR) after treatment of prostate cancer do not consider multiparametric MRI (mpMRI) information. Purpose To develop a risk prediction tool that considers mpMRI findings to assess the risk of 5-year BCR after radical prostatectomy. Materials and Methods In this retrospective single-center analysis in 1459 patients with prostate cancer who underwent mpMRI before radical prostatectomy (in 2012-2015), the outcome of interest was 5-year BCR (two consecutive prostate-specific antigen [PSA] levels > 0.2 ng/mL [0.2 µg/L]). Patients were randomly divided into training (70%) and test (30%) sets. Kaplan-Meier plots were applied to the training set to estimate survival probabilities. Multivariable Cox regression models were used to test the relationship between BCR and different sets of exploratory variables. The C-index of the final model was calculated for the training and test sets and was compared with European Association of Urology, University of California San Francisco Cancer of the Prostate Risk Assessment, Memorial Sloan-Kettering Cancer Center, and Partin risk tools using the partial likelihood ratio test. Five risk categories were created. Results The median duration of follow-up in the whole cohort was 59 months (IQR, 32-81 months); 376 of 1459 (25.8%) patients had BCR. A multivariable Cox regression model (referred to as PIPEN, and composed of PSA density, International Society of Urological Pathology grade group, Prostate Imaging Reporting and Data System category, European Society of Urogenital Radiology extraprostatic extension score, nodes) fitted to the training data yielded a C-index of 0.74, superior to that of other predictive tools (C-index 0.70 for all models; P ≤ .01) and a median higher C-index on 500 test set replications (C-index, 0.73). Five PIPEN risk categories were identified with 5-year BCR-free survival rates of 92%, 84%, 71%, 56%, and 26% in very low-, low-, intermediate-, high-, and very high-risk patients, respectively (all P < .001). Conclusion A five-item model for predicting the risk of 5-year BCR after radical prostatectomy for prostate cancer was developed and internally verified, and five risk categories were identified. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Aguirre and Ortegón in this issue.

Introduction: Previous radical prostatectomy (RP) for prostate cancer (PCa) might impair feasibility of radical cystectomy (RC) for bladder cancer (BCa). The current study addressed morbidity, operative time (OT), and length of stay (LOS) of RC, within the largest available series of patients with history of previous RP., Materials and Methods: All patients previously submitted to RP for PCa and subsequently submitted to RC for BCa, at six high-volume European institutions between 2010 and 2019, were identified. Presence of either PCa or BCa metastases, RT as primary treatment for PCa, and palliative RC represented exclusion criteria. The quality criteria for accurate and comprehensive reporting of intra- and post-operative surgical outcomes, recommended by the European Association of Urology guidelines, were fulfilled. Multivariable logistic and Poisson regression analyses were performed., Results: Overall, 140 RC patients with history of RP were identified. After RP, 69 (49%) patients received radiotherapy (RT) for PCa, either in adjuvant (n = 50, 36%) or salvage setting (n = 19, 13%). Median age-adjusted Charlson comorbidity index was 6 (IQR 5, 7). Median OT, estimated blood loss and LOS were, respectively, 300 min, 500 ml, and 16 days. Intra-operative transfusions rate was 47% (n = 65). One intra-operative complication occurred (EAUiaiC grade 2, perforation of the rectum managed with immediate repair). Eighty-two (59%) patients experienced a total of 107 post-operative complications during the hospital stay, and seven (5%) patients required hospital readmission. In multivariable regression analyses, RT for PCa was associated with higher risk of post-operative complications (odds ratio 1.82, p = 0.039), longer OT (incidence rate ratio 1.09, p < 0.001), and longer LOS (incidence rate ratio 1.24, p < 0.001)., Conclusions: RC in patients with history of RP is feasible, albeit burdened by remarkable morbidity, even in centers of excellence. RT after RP for PCa portends worse surgical outcomes., (Copyright © 2023 Elsevier Ltd. All rights reserved.)