Which Patients with Prostate Cancer and Lymph Node Uptake at Preoperative Prostate-specific Membrane Antigen Positron Emission Tomography/Computerized Tomography Scan Are at a Higher Risk of Prostate-specific Antigen Persistence After Radical Prostatectomy? Identifying Indicators of Systemic Disease by Integrating Clinical, Magnetic Resonance Imaging, and Functional Imaging Parameters.

BACKGROUND: The role of local therapies including radical prostatectomy (RP) in prostate cancer (PCa) patients with clinical lymphadenopathies on prostate-specific membrane antigen (PSMA) positron emission tomography/computerized tomography (PET/CT) has scarcely been explored. Limited data are available to identify men who would benefit from RP; on the contrary, those more likely to benefit already have systemic disease. OBJECTIVE: We aimed to assess the predictors of prostate-specific antigen (PSA) persistence in surgically managed PCa patients with lymphadenopathies on a PSMA PET/CT scan by integrating clinical, magnetic resonance imaging (MRI), and PSMA PET/CT parameters. DESIGN, SETTING, AND PARTICIPANTS: We identified 519 patients treated with RP and extended lymph node dissection, and who received preoperative PSMA PET between 2017 and 2022 in nine referral centers. Among them, we selected 88 patients with nodal uptake at preoperative PSMA PET (miTxN1M0). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcome was PSA persistence, defined as a PSA value of ≥0.1 ng/ml at the first measurement after surgery. Multivariable logistic regression models tested the predictors of PSA persistence. Covariates consisted of biopsy International Society of Urological Pathology (ISUP) grade group, clinical stage at MRI, and number of positive spots at a PET/CT scan. A regression tree analysis stratified patients into risk groups based on preoperative characteristics. RESULTS AND LIMITATIONS: Overall, lymph node invasion (LNI) was detected in 63 patients (72%) and 32 (36%) experienced PSA persistence after RP. At multivariable analyses, having more than two lymph nodal positive findings at PSMA PET, seminal vesicle invasion (SVI) at MRI, and ISUP grade group >3 at biopsy were independent predictors of PSA persistence (all p < 0.05). At the regression tree analysis, patients were stratified in four risk groups according to biopsy ISUP grade, number of positive findings at PET/CT, and clinical stage at MRI. The model depicted good discrimination at internal validation (area under the curve 78%). CONCLUSIONS: One out of three miN1M0 patients showed PSA persistence after surgery. Patients with ISUP grade 2-3, as well as patients with organ-confined disease at MRI and a single or two positive nodal findings at PET are those in whom RP may achieve the best oncological outcomes in the context of a multimodal approach. Conversely, patients with a high ISUP grade and extracapsular extension or SVI or more than two spots at PSMA PET should be considered as potentially affected by systemic disease upfront. PATIENT SUMMARY: Our novel and straightforward risk classification integrates currently available preoperative risk tools and should, therefore, assist physician in preoperative counseling of men candidates for radical treatment for prostate cancer with positive lymph node uptake at prostate-specific membrane antigen positron emission tomography.

Pharmacokinetic/Pharmacodynamic Target Attainment of Continuous Infusion Piperacillin-Tazobactam or Meropenem and Microbiological Outcome among Urologic Patients with Documented Gram-Negative Infections.

(1) Objectives: To describe the relationship between pharmacokinetic/pharmacodynamic (PK/PD) target attainment of continuous infusion (CI) piperacillin-tazobactam or meropenem monotherapy and microbiological outcome in a case series of urological patients with documented Gram-negative infections. (2) Methods: Patients admitted to the urology ward who were treated with CI piperacillin-tazobactam or meropenem monotherapy for documented Gram-negative infections and underwent real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program from June 2021 to May 2023 were retrospectively retrieved. Average steady-state (Css) piperacillin-tazobactam and meropenem concentrations were determined, and the free fractions (fCss) were calculated. Optimal PK/PD target attainments were defined as an fCss/MIC ratio >4 for CI meropenem and an fCss/MIC ratio of piperacillin >4 coupled with an fCss/CT ratio for tazobactam >1 for piperacillin-tazobactam (joint PK/PD target). The relationship between beta-lactam PK/PD targets and microbiological outcome was explored. (3) Results: Sixteen urologic patients with documented Gram-negative infections (62.5% complicated urinary tract infections (cUTI)) had 30 TDM-guided ECPAs. At first TDM assessment, beta-lactam dosing adjustments were recommended in 11 out of 16 cases (68.75%, of which 62.5% decreases and 6.25% increases). Overall, beta-lactam dosing adjustments were recommended in 14 out of 30 ECPAs (46.6%). Beta-lactam PK/PD target attainments were optimal in 100.0% of cases. Microbiological failure occurred in two patients, both developing beta-lactam resistance. (4) Conclusion: A TDM-guided ECPA program may allow for optimizing beta-lactam treatment in urologic patients with documented Gram-negative infections, ensuring microbiological eradication in most cases.

An Apparent Diffusion Coefficient-Based Machine Learning Model Can Improve Prostate Cancer Detection in the Grey Area of the Prostate Imaging Reporting and Data System Category 3: A Single-Centre Experience.

The Prostate Imaging and Reporting Data System (PI-RADS) has a key role in the management of prostate cancer (PCa). However, the clinical interpretation of PI-RADS 3 score lesions may be challenging and misleading, thus postponing PCa diagnosis to biopsy outcome. Multiparametric magnetic resonance imaging (mpMRI) radiomic analysis may represent a stand-alone noninvasive tool for PCa diagnosis. Hence, this study aims at developing a mpMRI-based radiomic PCa diagnostic model in a cohort of PI-RADS 3 lesions. We enrolled 133 patients with 155 PI-RADS 3 lesions, 84 of which had PCa confirmation by fusion biopsy. Local radiomic features were generated from apparent diffusion coefficient maps, and the four most informative were selected using LASSO, the Wilcoxon rank-sum test (p < 0.001), and support vector machines (SVMs). The selected features where augmented and used to train an SVM classifier, externally validated on a holdout subset. Linear and second-order polynomial kernels were exploited, and their predictive performance compared through receiver operating characteristics (ROC)-related metrics. On the test set, the highest performance, equally for both kernels, was specificity = 76%, sensitivity = 78%, positive predictive value = 80%, and negative predictive value = 74%. Our findings substantially improve radiologist interpretation of PI-RADS 3 lesions and let us advance towards an image-driven PCa diagnosis.

Radical cystectomy in bladder cancer patients previously treated for prostate cancer: Insights from a large European multicentric series.

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.

Multiparametric magnetic resonance imaging for the differential diagnosis between granulomatous prostatitis and prostate cancer: a literature review to an intriguing diagnostic challenge.

Multiparametric magnetic resonance imaging (mpMRI) is currently the most effective diagnostic tool for detecting prostate cancer (PCa) and evaluating adenocarcinoma-mimicking lesions of the prostate gland, among which granulomatous prostatitis (GP) represents the most interesting diagnostic challenge. GP consists of a heterogeneous group of chronic inflammatory lesions that can be differentiated into four types: idiopathic, infective, iatrogenic, and associated with systemic granulomatous disease. The incidence of GP is growing due to the increase in endourological surgical interventions and the adoption of intravesical instillation of Bacillus Calmette-Guerin in patients with non-muscle invasive bladder cancer; therefore, the difficulty lies in identifying specific features of GP on mpMRI to avoid the use of transrectal prostate biopsy as much as possible.

Identification of the Optimal Candidates for Nodal Staging with Extended Pelvic Lymph Node Dissection Among Prostate Cancer Patients Who Underwent Preoperative Prostate-specific Membrane Antigen Positron Emission Tomography. External Validation of the Memorial Sloan Kettering Cancer Center and Briganti Nomograms and Development of a Novel Tool.

BACKGROUND: Although the therapeutic role of extended pelvic lymph node dissection (ePLND) in patients with prostate cancer (PCa) is still under debate, this procedure is recommended for staging purposes in selected cases. Nomograms for predicting lymph node invasion (LNI) do not account for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging, which is characterized by a high negative predictive value for nodal metastases. OBJECTIVE: To externally validate models predicting LNI in patients with miN0M0 PCa at PSMA PET and to develop a novel tool in this setting. DESIGN, SETTING, AND PARTICIPANTS: Overall, 458 patients with miN0M0 disease undergoing radical prostatectomy (RP) and ePLND at 12 centers between 2017 and 2022 were identified. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Available tools were externally validated using calibration plots, the area under the receiver operating characteristic curve (AUC), and decision curve analyses to assess calibration, discrimination, and the net benefit. A novel coefficient-based model was developed, internally validated, and compared with available tools. RESULTS AND LIMITATIONS: Overall, 53 patients (12%) had LNI. The AUC was 69% for the Briganti 2012, 64% for the Briganti 2017, 73% for the Briganti 2019, and 66% for the Memorial Sloan Kettering Cancer Center nomogram. Multiparametric magnetic resonance imaging stage, biopsy grade group 5, the diameter of the index lesion, and the percentage of positive cores at systematic biopsy were independent predictors of LNI (all p ≤ 0.04). Internal cross-validation confirmed a coefficient-based model with AUC of 78%, better calibration, and a higher net benefit in comparison to the other nomograms assessed. Use of a 5% cutoff would have spared 47% ePLND procedures (vs 13% for the Briganti 2019 nomogram) at the cost of missing only 2.1% LNI cases . The lack of central review of imaging and pathology represents the main limitation. CONCLUSIONS: Tools for predicting LNI are associated with suboptimal performance for men with miN0M0 PCa. We propose a novel model for predicting LNI that outperforms available tools in this population. PATIENT SUMMARY: Tools currently used to predict lymph node invasion (LNI) in prostate cancer are not optimal for men with negative node findings on PET (positron emission tomography) scans, leading to a high number of unnecessary extended pelvic lymph node dissection (ePLND) procedures. A novel tool should be used in clinical practice to identify candidates for ePLND to reduce the risk of unnecessary procedures without missing LNI cases.

PSMA-PET Guided Treatment in Prostate Cancer Patients with Oligorecurrent Progression after Previous Salvage Treatment.

BACKGROUND: Prostate Specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) is used to select recurrent prostate cancer (PCa) patients for metastases-directed therapy (MDT). We aimed to evaluate the oncologic outcomes of second-line PSMA-guided MDT in oligo-recurrent PCa patients. METHODS: we performed a retrospective analysis of 113 recurrent PCa after previous radical prostatectomy and salvage therapies with oligorecurrent disease at PSMA-PET (≤3 lesions in N1/M1a-b) in three high-volume European centres. Patients underwent second-line salvage treatments: MDT targeted to PSMA (including surgery and/or radiotherapy), and the conventional approach (observation or Androgen Deprivation Therapy [ADT]). Patients were stratified according to treatments (MDT vs. conventional approach). Patients who underwent MDT were stratified according to stage in PSMA-PET (N1 vs. M1a-b). The primary outcome of the study was Progression-free survival (PFS). Secondary outcomes were Metastases-free survival (MFS) and Castration Resistant PCa free survival (CRPC-FS). Kaplan-Meier analyses assessed PFS, MFS and CRPC-FS. Multivariable Cox regression models identified predictors of progression and metastatic disease. RESULTS: Overall, 91 (80%) and 22 (20%) patients were treated with MDT and the conventional approach, respectively. The median follow-up after PSMA-PET was 31 months. Patients who underwent MDT had a similar PFS compared to the conventional approach (p = 0.3). Individuals referred to MDT had significantly higher MFS and CRPC-FS compared to those who were treated with the conventional approach (73.5% and 94.7% vs. 30.5% and 79.5%; all p ≤ 0.001). In patients undergoing MDT, no significant differences were found for PFS and MFS according to N1 vs. M1a-b disease, while CRPC-FS estimates were significantly higher in patients with N1 vs. M1a-b (100% vs. 86.1%; p = 0.02). At multivariable analyses, age (HR = 0.96) and ADT during second line salvage treatment (HR = 0.5) were independent predictors of PFS; MDT (HR 0.27) was the only independent predictor of MFS (all p ≤ 0.04) Conclusion: Patients who underwent second-line PSMA-guided MDT experienced higher MFS and CRPC-FS compared to men who received conventional management.

Effectiveness of Radiomic ZOT Features in the Automated Discrimination of Oncocytoma from Clear Cell Renal Cancer.

BACKGROUND: Benign renal tumors, such as renal oncocytoma (RO), can be erroneously diagnosed as malignant renal cell carcinomas (RCC), because of their similar imaging features. Computer-aided systems leveraging radiomic features can be used to better discriminate benign renal tumors from the malignant ones. The purpose of this work was to build a machine learning model to distinguish RO from clear cell RCC (ccRCC). METHOD: We collected CT images of 77 patients, with 30 cases of RO (39%) and 47 cases of ccRCC (61%). Radiomic features were extracted both from the tumor volumes identified by the clinicians and from the tumor's zone of transition (ZOT). We used a genetic algorithm to perform feature selection, identifying the most descriptive set of features for the tumor classification. We built a decision tree classifier to distinguish between ROs and ccRCCs. We proposed two versions of the pipeline: in the first one, the feature selection was performed before the splitting of the data, while in the second one, the feature selection was performed after, i.e., on the training data only. We evaluated the efficiency of the two pipelines in cancer classification. RESULTS: The ZOT features were found to be the most predictive by the genetic algorithm. The pipeline with the feature selection performed on the whole dataset obtained an average ROC AUC score of 0.87 ± 0.09. The second pipeline, in which the feature selection was performed on the training data only, obtained an average ROC AUC score of 0.62 ± 0.17. CONCLUSIONS: The obtained results confirm the efficiency of ZOT radiomic features in capturing the renal tumor characteristics. We showed that there is a significant difference in the performances of the two proposed pipelines, highlighting how some already published radiomic analyses could be too optimistic about the real generalization capabilities of the models.

Histology and PSMA Expression on Immunohistochemistry in High-Risk Prostate Cancer Patients: Comparison with 68Ga-PSMA PET/CT Features in Primary Staging.

PSMA-PET/CT is a suitable replacement for conventional imaging in the primary staging of PCa. The aim of this retrospective study was to assess the correlation between parameters discovered by PSMA PET/CT in primary staging and either prostate histopathology (pT) findings or PSMA-IHC expression in a cohort of biopsy-proven high-risk PCa candidates for surgery. Clinical information (age, iPSA-value, and grading group) and PSMA-PET/CT parameters (SUVmax, PSMA tumor volume [PSMA-TV], and total lesion [PSMA-TL]) were compared with pT (including histologic pattern, Gleason grade, and lymphovascular invasion [LVI]) and PSMA-IHC features, including visual quantification (VS) with a four-tiered score (0 = negative, 1+ = weak, 2+ = moderate, 3+ = strong), growth pattern (infiltrative vs expansive), and visual pattern (cytoplasmic vs membranous). In total, 44 patients were enrolled, with a median age of 67 (IQR 57-77); the median iPSA was 9.4 ng/dL (IQR 12.5-6.0). One patient (3%) was grading group (GG) 3, 27/44 (61%) were GG4, and 16/44 (36%) were GG5. PSMA-PET/CT detection rate for the presence of primary prostate cancer was 100%. Fused/poorly formed Gleason grade 4 features were predominant (22/44-50%); a cribriform pattern was present in 18/44 (41%) and acinar in 4/44 (9%). We found that lower PSMA-TVs were mostly related to acinar, while higher PSMA-TVs correlated with a higher probability to have a cribriform pattern (p-value 0.04). LVI was present in 21/44(48%) patients. We found that higher PSMA-TV and PSMA-TL are predictive of LVI p-value 0.002 and p-value 0.01, respectively. There was no correlation between PET-parameters and perineural invasion (PNI), probably because this was present in almost all the patients. Moreover, patients with high PSMA-TL values displayed the highest PSMA-IHC expression (VS3+) with a membranous pattern. In conclusion, PSMA-TV and PSMA-TL are predictors of a cribriform pattern and LVI. These conditions are mostly related to higher aggressiveness and worse outcomes.

Transverse prostate maximum sectional area can predict clinically significant prostate cancer in PI-RADS 3 lesions at multiparametric magnetic resonance imaging.

Background: To evaluate multiparametric magnetic resonance imaging (mpMRI) parameters, such as TransPA (transverse prostate maximum sectional area), TransCGA (transverse central gland sectional area), TransPZA (transverse peripheral zone sectional area), and TransPAI (TransPZA/TransCGA ratio) in predicting prostate cancer (PCa) in prostate imaging reporting and data system (PI-RADS) 3 lesions. Methods: Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), the area under the receiver operating characteristic curve (AUC), and the best cut-off, were calculated. Univariate and multivariate analyses were carried out to evaluate the capability to predict PCa. Results: Out of 120 PI-RADS 3 lesions, 54 (45.0%) were PCa with 34 (28.3%) csPCas. Median TransPA, TransCGA, TransPZA and TransPAI were 15.4cm2, 9.1cm2, 5.5cm2 and 0.57, respectively. At multivariate analysis, location in the transition zone (OR=7.92, 95% CI: 2.70-23.29, P<0.001) and TransPA (OR=0.83, 95% CI: 0.76-0.92, P<0.001) were independent predictors of PCa. The TransPA (OR=0.90, 95% CI: 0.082-0.99, P=0.022) was an independent predictor of csPCa. The best cut-off of TransPA for csPCa was 18 (Sensitivity 88.2%, Specificity 37.2%, PPV 35.7%, NPV 88.9%). The discrimination (AUC) of the multivariate model was 0.627 (95% CI: 0.519-0.734, P<0.031). Conclusions: In PI-RADS 3 lesions, the TransPA could be useful in selecting patients requiring biopsy.

A Planned Multidisciplinary Surgical Approach to Treat Primary Pelvic Malignancies.

The pelvic anatomy poses great challenges to orthopedic surgeons. Sarcomas are often large in size and typically enclosed in the narrow confines of the pelvis with the close proximity of vital structures. The aim of this study is to report a systematic planned multidisciplinary surgical approach to treat pelvic sarcomas. Seventeen patients affected by bone and soft tissue sarcomas of the pelvis, treated using a planned multidisciplinary surgical approach, combining the expertise of orthopedic oncology and other surgeons (colleagues from urology, vascular surgery, abdominal surgery, gynecology and plastic surgery), were included. Seven patients were treated with hindquarter amputation; 10 patients underwent excision of the tumor. Reconstruction of bone defects was conducted in six patients with a custom-made 3D-printed pelvic prosthesis. Thirteen patients experienced at least one complication. Well-organized multidisciplinary collaborations between each subspecialty are the cornerstone for the management of patients affected by pelvic sarcomas, which should be conducted in specialized centers. A multidisciplinary surgical approach is of paramount importance in order to obtain the best successful surgical results and adequate margins for achieving acceptable outcomes.

Twenty Years' Experience in Retroperitoneal Lymph Node Dissection for Testicular Cancer in a Tertiary Referral Center.

Background and Objectives: The aim of this article is to present a single-surgeon, open retroperitoneal lymph node dissection (RPLND) series for testicular cancer in a high-volume center. Materials and Methods: We reviewed data from patients who underwent RPLND performed by an experienced surgeon at our institution between 2000 and 2019. We evaluated surgical and perioperative outcomes, complications, Recurrence-Free Survival (RFS), Overall Survival (OS), and Cancer-Specific Survival (CSS). Results: RPLND was performed in primary and secondary settings in 21 (32%) and 44 (68%) patients, respectively. Median operative time was 180 min. Median hospital stay was 6 days. Complications occurred in 23 (35%) patients, with 9 (14%) events reported as Clavien grade ≥ 3. Patients in the primary RPLND group were significantly younger, more likely to have NSGCT, had higher clinical N0 and M0, and had higher nerve-sparing RPLND (all p ≤ 0.04) compared to those in the secondary RPLND group. In the median follow-up of 120 (56-180) months, 10 (15%) patients experienced recurrence. Finally, 20-year OS, CSS, and RFS were 89%, 92%, and 85%, respectively, with no significant difference in survival rates between primary vs. secondary RPLND subgroups (p = 0.64, p = 0.7, and p = 0.31, respectively). Conclusions: Open RPLND performed by an experienced high-volume surgeon achieves excellent oncological and functional outcomes supporting the centralization of these complex procedures.

En-bloc resection of non-muscle invasive bladder cancer: does it really make a difference?

PURPOSE OF REVIEW: Transurethral resection of bladder tumour (TURBT) followed by pathology investigation of the obtained specimens is the initial step in the management of urinary bladder cancer (UBC). By following the basic principles of oncological surgery, en-bloc resection of bladder tumour (ERBT) aims to overcome the limitations associated with conventional transurethral resection, and to improve the quality of pathological specimens for a better decision making. The current bulk of evidence provides controversial results regarding the superiority of one technique over the other. The aim of this article is to summarize the recent data and provide evidence on this unanswered question. RECENT FINDINGS: Despite heterogeneous and controversial data, ERBT seems to have a better safety profile and deliver higher quality pathologic specimens. However, the recent evidence failed to support the hypothesized oncological potential benefits of ERBT in the initial surgical treatment of patients with UBC. SUMMARY: ERBT has gained increasing interest globally in the past decade. It continues to represent a promising strategy with a variety of features intended to solve the inherent limitations of TURBT. However, the current quality of evidence does not allow solid conclusions to be drawn about its presumed superiority compared with the conventional technique.

Comparison of prostate cancer detection rate at targeted biopsy of hub and spoke centers mpMRI: experience matters.

BACKGROUND: Latest changes in European guidelines on prostate cancer determined a widespread of multiparametric magnetic resonance imaging (mpMRI) even in less experienced centers due to an increased demand. This could decrease diagnostic accuracy of targeted biopsy (TB) since image interpretation can be challenging and requires adequate and supervised training. Therefore we aimed to evaluate the prostate cancer (PCa) detection rate on TB according to mpMRI center's volume and experience. METHODS: We retrospectively analyzed data of 737 patients who underwent mpMRI-TB at our institution. Patients were stratified according to mpMRI center: Hub (high volume >100 exams/year with dedicated radiologists and supervised training) and Spoke center (low volume <100 exams/year without dedicated radiologists and/or supervised training). Detection rate of PCa at TB and possible predictors of clinically significant PCa (csPCa) at TB. Differences in detection rate were explored using Chi-square test. Predictors of csPCa were evaluated through uni and multivariable logistic regression. The adjustment for casemix included: age, PSA, mpMRI center, lesion's location, PSA density, PI-RADS score and index lesion's size. RESULTS: Four hundred forty-nine (60.9%) and 288 (39.1%) patients underwent mpMRI at a Hub or Spoke center, respectively. Hub group had higher detection rate for both any (60.3% vs. 48.1%) and csPCa (46.9% vs 38.7%; all P≤0.001). After stratifying for PI-RADS score, Hub group had higher detection rate for PI-RADS score 3 (csPCA 25.2% vs. 15.7%; p 0.04) and 4 (csPCa 65.7% vs. 45.7%; P=0.001). At multivariable analyses, receiving an mpMRI scan at a Spoke center was an independent predictor for csPCa on TB (OR 0.65; P=0.04). CONCLUSIONS: mpMRI performed in Hub centers provided a significantly higher PCa yield on TB. A dedicated team of experienced radiologist, a supervised training for mpMRI and a central revision of mpMRI performed in non-experienced centres are essential to avoid unnecessary and potentially harmful procedures.

Site-specific concordance of targeted and systematic biopsy cores at the index lesion on multiparametric magnetic resonance: can we spare the double-tap?

PURPOSE: To define the impact of systematic biopsy (SB) cores directed in the same area of index lesion in patients undergoing targeted biopsy (TB) and SB for prostate cancer (PCa) suspicion. METHODS: We retrospectively analyzed data of biopsy-naïve patients with one single suspicious lesion at mpMRI who underwent TB plus SB at our institution between January 2015 and September 2021. A convenient sample of 336 patients was available for our analyses. The primary outcome was to evaluate the impact of overlapping SB cores directed to the index lesion at mpMRI. The secondary outcome was to evaluate the SB cores concordance in terms of highest Gleason Score Detection with TB cores. RESULTS: 56% of patients were found to have site-specific concordance. SB cores determined disease upgrade in 22.1% patients. Thirty-one (16.4%) site-concordant patients experienced upgrade through overlapping SB cores, while 149 (79.3%) had no benefit by SB cores, and 8 (4.3%) patients had the worst ISUP at TB cores. 50% of the patients with negative-TB were upgraded to insignificant PCa, and 17.5% was upgraded from negative to unfavorable-intermediate- or high-risk PCa. Overall, 14 (19.4%) patients were also upgraded from ISUP 1 on TB to csPCa, with 28.5% of these harboring high-risk PCa. In csPCas at TB, 9 (12.5%) patients were upgraded from intermediate- to high-risk disease by SB. CONCLUSIONS: TB alone consents to identify worst ISUP PCa in vast majority of patients scheduled for biopsy. A non-negligible number of patients are upgraded via-SB cores, including also index lesion overlapping cores. Omitting these cores might lead to a suboptimal patient management.

Unraveling the safety of adjuvant radiotherapy in prostate cancer: impact of older age and hypofractionated regimens on acute and late toxicity - a multicenter comprehensive analysis.

Background: The objective of this study was to assess the impact of age and other patient and treatment characteristics on toxicity in prostate cancer patients receiving adjuvant radiotherapy (RT). Materials and methods: This observational study (ICAROS-1) evaluated both acute (RTOG) and late (RTOG/EORTC) toxicity. Patient- (age; Charlson's comorbidity index) and treatment-related characteristics (nodal irradiation; previous TURP; use, type, and duration of ADT, RT fractionation and technique, image-guidance systems, EQD2 delivered to the prostate bed and pelvic nodes) were recorded and analyzed. Results: A total of 381 patients were enrolled. The median EQD2 to the prostate bed (α/ß=1.5) was 71.4 Gy. The majority of patients (75.4%) were treated with intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). Acute G3 gastrointestinal (GI) and genitourinary (GU) toxicity rates were 0.5% and 1.3%, respectively. No patients experienced >G3 acute toxicity. The multivariable analysis of acute toxicity (binomial logistic regression) showed a statistically significant association between older age (> 65) and decreased odds of G≥2 GI acute toxicity (OR: 0.569; 95%CI: 0.329-0.973; p: 0.040) and decreased odds of G≥2 GU acute toxicity (OR: 0.956; 95%CI: 0.918-0.996; p: 0.031). The 5-year late toxicity-free survival rates for G≥3 GI and GU toxicity were 98.1% and 94.5%, respectively. The only significant correlation found (Cox's regression model) was a reduced risk of late GI toxicity in patients undergoing hypofractionation (HR: 0.38; 95% CI: 0.18-0.78; p: 0.008). Conclusions: The unexpected results of this analysis could be explained by a "response shift bias" concerning the protective effect of older age and by treatment in later periods (using IMRT/VMAT) concerning the favorable effect of hypofractionation. However, overall, the study suggests that age should not be a reason to avoid adjuvant RT and that the latter is well-tolerated even with moderately hypofractionated regimens.

Beyond Multiparametric MRI and towards Radiomics to Detect Prostate Cancer: A Machine Learning Model to Predict Clinically Significant Lesions.

The risk of misclassifying clinically significant prostate cancer (csPCa) by multiparametric magnetic resonance imaging is consistent, also using the updated PIRADS score and although different definitions of csPCa, patients with Gleason Grade group (GG) ≥ 3 have a significantly worse prognosis. This study aims to develop a machine learning model predicting csPCa (i.e., any GG ≥ 3 lesion at target biopsy) by mpMRI radiomic features and analyzing similarities between GG groups. One hundred and two patients with 117 PIRADS ≥ 3 lesions at mpMRI underwent target+systematic biopsy, providing histologic diagnosis of PCa, 61 GG < 3 and 56 GG ≥ 3. Features were generated locally from an apparent diffusion coefficient and selected, using the LASSO method and Wilcoxon rank-sum test (p < 0.001), to achieve only four features. After data augmentation, the features were exploited to train a support vector machine classifier, subsequently validated on a test set. To assess the results, Kruskal−Wallis and Wilcoxon rank-sum tests (p < 0.001) and receiver operating characteristic (ROC)-related metrics were used. GG1 and GG2 were equivalent (p = 0.26), whilst clear separations between either GG[1,2] and GG ≥ 3 exist (p < 10−6). On the test set, the area under the curve = 0.88 (95% CI, 0.68−0.94), with positive and negative predictive values being 84%. The features retain a histological interpretation. Our model hints at GG2 being much more similar to GG1 than GG ≥ 3.

3D renal model for surgical planning of partial nephrectomy: A way to improve surgical outcomes.

Objective: to evaluate the impact of 3D model for a comprehensive assessment of surgical planning and quality of partial nephrectomy (PN). Materials and methods: 195 patients with cT1-T2 renal mass scheduled for PN were enrolled in two groups: Study Group (n= 100), including patients referred to PN with revision of both 2D computed tomography (CT) imaging and 3D model; Control group (n= 95), including patients referred to PN with revision of 2D CT imaging. Overall, 20 individuals were switched to radical nephrectomy (RN). The primary outcome was the impact of 3D models-based surgical planning on Trifecta achievement (defined as the contemporary absence of positive surgical margin, major complications and ≤30% postoperative eGFR reduction). The secondary outcome was the impact of 3D models on surgical planning of PN. Multivariate logistic regressions were used to identify predictors of selective clamping and Trifecta's achievement in patients treated with PN (n=175). Results: Overall, 73 (80.2%) patients in Study group and 53 (63.1%) patients in Control group achieved the Trifecta (p=0.01). The preoperative plan of arterial clamping was recorded as clampless, main artery and selective in 22 (24.2%), 22 (24.2%) and 47 (51.6%) cases in Study group vs. 31 (36.9%), 46 (54.8%) and 7 (8.3%) cases in Control group, respectively (p<0.001). At multivariate logistic regressions, the use of 3D model was found to be independent predictor of both selective or super-selective clamping and Trifecta's achievement. Conclusion: 3D-guided approach to PN increase the adoption of selective clamping and better predict the achievement of Trifecta.

A case report of myoid gonadal stromal tumor treated with testis sparing surgery.

Background: Myoid gonadal stromal tumors (MGST) of the testis represent a very rare finding. They are an emerging clinicopathological entity with specific features and identity. Nowadays, pathological recognition and diagnosis of MGSTs still represents a difficult challenge in most cases and there are no data of specific radiological features of these tumors expect for what seen by ultrasound; besides a conservative surgical approach was never performed to treat these lesions. Case Description: We present the case of a 20-year-old young man patient with symptoms suspicious for left varicocele, who was incidentally diagnosed with right testicular nodule via scrotal doppler ultrasound powered with contrast enhancement infusion and subsequent multiparametric magnetic resonance imaging. Then, lesion was treated through a testis sparing surgical approach. Histopathology, which included an external revision by an experienced Center, revealed a MGST with benign features, so that no further treatment was considered. 3 and 12 months after surgery a contrast enhancement ultrasound was performed with no evidence of recurrence. Conclusions: Previous reported cases of MGST were all difficult to characterize as a specific pathological entity; treatment usually applied was radical orchiectomy and a subsequent total Body CT was performed for staging purpose. No metastatic spreading nor recurrence were ever reported. Considering the favorable behavior of this pathologic entity, testis-sparing surgery with no radiation exposure during follow-up is a safe and effective strategy.