Prediction models for postoperative renal function after living donor nephrectomy: a systematic review.

INTRODUCTION: Living-donor nephrectomy (LDN) is the most valuable source of organs for kidney transplantation worldwide. The current preoperative evaluation of a potential living donor candidate does not take into account formal estimation of postoperative renal function decline after surgery using validated prediction models. The aim of this study was to summarize the available models to predict the mid- to long-term renal function following LDN, aiming to support both clinicians and patients during the decision-making process. EVIDENCE ACQUISITION: A systematic review of the English-language literature was conducted following the principles highlighted by the European Association of Urology (EAU) guidelines and following the PRISMA 2020 recommendations. The protocol was registered in PROSPERO on December 10, 2022 (registration ID: CRD42022380198). In the qualitative analysis we selected the models including only preoperative variables. EVIDENCE SYNTHESIS: After screening and eligibility assessment, six models from six studies met the inclusion criteria. All of them relied on retrospective patient cohorts. According to PROBAST, all studies were evaluated as high risk of bias. The models included different combinations of variables (ranging between two to four), including donor-/kidney-related factors, and preoperative laboratory tests. Donor age was the variable more often included in the models (83%), followed by history of hypertension (17%), Body Mass Index (33%), renal volume adjusted by body weight (33%) and body surface area (33%). There was significant heterogeneity in the model building strategy, the main outcome measures and the model's performance metrics. Three models were externally validated. CONCLUSIONS: Few models using preoperative variables have been developed and externally validated to predict renal function after LDN. As such, the evidence is premature to recommend their use in routine clinical practice. Future research should be focused on the development and validation of user-friendly, robust prediction models, relying on granular large multicenter datasets, to support clinicians and patients during the decision-making process.

Transperineal laser ablation of the prostate as a treatment for benign prostatic hyperplasia and prostate cancer: The results of a Delphi consensus project.

Objective: To evaluate transperineal laser ablation (TPLA) with Echolaser® (Echolaser® TPLA, Elesta S.p.A., Calenzano, Italy) as a treatment for benign prostatic hyperplasia (BPH) and prostate cancer (PCa) using the Delphi consensus method. Methods: Italian and international experts on BPH and PCa participated in a collaborative consensus project. During two rounds, they expressed their opinions on Echolaser® TPLA for the treatment of BPH and PCa answering online questionnaires on indications, methodology, and potential complications of this technology. Level of agreement or disagreement to reach consensus was set at 75%. If the consensus was not achieved, questions were modified after each round. A final round was performed during an online meeting, in which results were discussed and finalized. Results: Thirty-two out of forty invited experts participated and consensus was reached on all topics. Agreement was achieved on recommending Echolaser® TPLA as a treatment of BPH in patients with ample range of prostate volume, from <40 mL (80%) to >80 mL (80%), comorbidities (100%), antiplatelet or anticoagulant treatment (96%), indwelling catheter (77%), and strong will of preserving ejaculatory function (100%). Majority of respondents agreed that Echolaser® TPLA is a potential option for the treatment of localized PCa (78%) and recommended it for low-risk PCa (90%). During the final round, experts concluded that it can be used for intermediate-risk PCa and it should be proposed as an effective alternative to radical prostatectomy for patients with strong will of avoiding urinary incontinence and sexual dysfunction. Almost all participants agreed that the transperineal approach of this organ-sparing technique is safer than transrectal and transurethral approaches typical of other techniques (97% of agreement among experts). Pre-procedural assessment, technical aspects, post-procedural catheterization, pharmacological therapy, and expected outcomes were discussed, leading to statements and recommendations. Conclusion: Echolaser® TPLA is a safe and effective procedure that treats BPH and localized PCa with satisfactory functional and sexual outcomes.

The ERUS course on robot-assisted kidney transplantation.

PURPOSE: Robot-assisted kidney transplantation (RAKT) is being increasingly performed at selected referral institutions worldwide. Yet, surgical training in RAKT is still unstructured and not grounded into formal credentialing courses including simulation, lab facilities, and modular training with animal models. As such, developing standardized, modular training programs is warranted to provide surgeons with the RAKT-specific skillset needed for a "safe" learning curve. METHODS: The 3-day course on RAKT developed at the EAU Skills Center in Orsi Academy was designed as a standardized, modular, step-by-step approach aiming to provide theoretical and practical skills. The course is held by expert proctors with extensive experience in RAKT. To maximize the course's usefulness, a solid knowledge of robotics and transplantation is desirable for participants. RESULTS: From January 2016 to July 2023, 87 surgeons from 23 countries (of which 36% from extra-European countries) participated in the RAKT course performed at the EAU Skills Center in Orsi Academy. Of these, 58/87 (67%) were urologists, while 27/87 (31%) were general surgeons and 2/87 (2%) were vascular surgeons. To date, 18 participants (20.6%) are actively involved in RAKT programs at institutions included in the European Association of Urology (EAU) Robotic Urology Section (ERUS)-RAKT network. CONCLUSION: Leveraging the potential of simulation, wet-lab training, live porcine models, and experienced proctors, the RAKT course performed at the EAU Skills Center in Orsi Academy represents the first structured teaching effort aiming to offer surgeons a full immersion in RAKT to train the core technical skills.

The prognostic role of histomorphological subtyping in nonmetastatic papillary renal cell carcinoma after curative surgery: is subtype really irrelevant? A propensity score matching analysis of a multi-institutional real life data.

BACKGROUND AND AIM: The role of histomorphological subtyping is an issue of debate in papillary renal cell carcinoma (papRCC). This multi-institutional study investigated the prognostic role of histomorphological subtyping in patients undergoing curative surgery for nonmetastatic papRCC. PATIENTS AND METHODS: A total of 1,086 patients undergoing curative surgery were included from a retrospectively collected multi-institutional nonmetastatic papRCC database. The patients were divided into 2 groups based on histomorphological subtyping (type 1, n = 669 and type 2, n = 417). Furthermore, a propensity score-matching (PSM) cohort in 1:1 ratio (n = 317 for each subtype) was created to reduce the effect of potential confounding variables. The primary outcome of the study, the predictive role of histomorphological subtyping on the prognosis (recurrence free survival [RFS], cancer specific survival [CSS] and overall survival [OS]) in nonmetastatic papRCC after curative surgery, was investigated in both overall and PSM cohorts. RESULTS: In overall cohort, type 2 group were older (66 vs. 63 years, P = 0.015) and more frequently underwent radical nephrectomy (37.4% vs. 25.6%, P < 0.001) and lymphadenectomy (22.3% vs. 15.1%, P = 0.003). Tumor size (4.5 vs. 3.8 cm, P < 0.001) was greater, and nuclear grade (P < 0.001), pT stage (P < 0.001), pN stage (P < 0.001), VENUSS score (P < 0.001) and VENUSS high risk (P < 0.001) were significantly higher in type 2 group. 5-year RFS (89.6% vs. 74.2%, P < 0.001), CSS (93.9% vs. 84.2%, P < 0.001) and OS (88.5% vs. 78.5%, P < 0.001) were significantly lower in type 2 group. On multivariable analyses, type 2 was a significant predictor for RFS (HR:1.86 [95%CI:1.33-2.61], P < 0.001) and CSS (HR:1.91 [95%CI:1.20-3.04], P = 0.006), but not for OS (HR:1.27 [95%CI:0.92-1.76], P = 0.150). In PSM cohort balanced with age, gender, symptoms at diagnosis, pT and pN stages, tumor grade, surgical margin status, sarcomatoid features, rhabdoid features, and presence of necrosis, type 2 increased recurrence risk (HR:1.75 [95%CI: 1.16-2.65]; P = 0.008), but not cancer specific mortality (HR: 1.57 [95%CI: 0.91-2.68]; P = 0.102) and overall mortality (HR: 1.01 [95%CI: 0.68-1.48]; P = 0.981) CONCLUSIONS: This multiinstitutional study suggested that type 2 was associated with adverse histopathologic outcomes, and predictor of RFS and CSS after surgical treatment of nonmetastatic papRCC, in overall cohort. In propensity score-matching cohort, type 2 remained the predictor of RFS. Eventhough 5th WHO classification for renal tumors eliminated histomorphological subtyping, these findings suggest that subtyping is relevant from the point of prognostic view.

Proposal of a standardized training curriculum for open and robot-assisted kidney transplantation.

Standardized training programs for open (OKT) and robot-assisted kidney transplantation (RAKT) remain unmet clinical needs. To fill this gap, we designed a modified Delphi Consensus aiming to propose the first structured surgical curricula for both OKT and RAKT, involving a multispecialty international panel of experts. Two web-based surveys were built drafting two separate series of statements (for OKT and RAKT, respectively). The two surveys were delivered to a panel of 63 experts (for OKT) and 21 experts (for RAKT), selected considering their experience, academic profile and involvement in international associations. Consensus was defined as ≥75% agreement between the responders. Overall, 25/63 (40%) and 14/21 (67%) participated in the first round of the Delphi Consensus for the development of the structured curriculum for OKT and RAKT, respectively. During the second round, the experts reached consensus on all statements, as well as on the domains composing the structure of the training pathway: 1) eligibility criteria for trainees and host centres; 2) theoretical training; 3) simulation; 4) real case observation; and 5) modular training in the operating theatre. To the best of our knowledge, this is the first proposal of a dedicated curriculum for OKT and RAKT grounded on insights from international experts of different specialties. Our proposed curriculum provides the foundation to standardize the education and training in KT across Europe and beyond.

Impact of minimally invasive surgical procedures for Male Lower Urinary Tract Symptoms due to benign prostatic hyperplasia on ejaculatory function: a systematic review.

BACKGROUND: Surgical treatments for lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO) are affected by potentially bothersome side effects on sexual, and, above all, ejaculatory function. Several minimally invasive techniques have been proposed in the last years in order to overcome these consequences. Our aim is to summarize and evaluate the efficacy on LUTS relieve and the impact on sexual/ejaculatory function of Rezum, prostate artery embolization (PAE), implantation of a prostatic urethral lift (PUL) and the temporary implantable nitinol device (TIND). METHODS: A systematic review of the English-language literature was conducted using the MEDLINE, Embase, and Web of Science databases from January 2000 to October 2022, according to the PRISMA guidelines (PROSPERO ID: CRD42023466515). Randomized controlled trials (RCTs), prospective studies and non-comparative or comparative studies assessing the impact on functional and ejaculatory function after minimally invasive surgical therapies for Male LUTS were evaluated. Risk of bias assessment was performed according to the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool for comparative studies, and the revised Cochrane risk-of-bias tool for randomized trials (RoB 2) for RCTs. RESULTS: Overall, 47 studies were included (n = 4 for TIND; n = 9 for Rezum; n = 13 for PUL; n = 21 for PAE). Most studies relied on prospective patient cohorts and were rated as low risk of bias. Across studies assessing the efficacy of Rezum, a significant improvement in terms of IPSS (ranging from -47% to -56%) and Qmax (ranging from +39% to +87%) was reported. On the other hand, according to IIEF-5 score, Rezum had a minimal impact on sexual function (ranging from -1% to -3%). PUL showed a positive impact on IPSS (ranging from -35% to -58.2%) and Qmax (ranging from +49.9% to +114.7%) and sexual function. Finally, PAE showed encouraging functional results with IPSS score reducing from -12.8% to 63.3% and Qmax improving from +8% to 114.9% but the available evidence regarding the potential impact of PAE on sexual outcomes were limited. CONCLUSION: Rezum, PAE, PUL and TIND are safe and feasible techniques associated with a significant functional improvement. While available data suggest a minimal impact of Rezum and PUL on ejaculatory function, the evidence after PAE and TIND are still limited. Therefore, our review lays the foundation for further research aiming to identify the criteria to select best candidates for uMIST to tailor the management in light of specific patient- and disease- factors.

Hyperglycemia and microRNAs in prostate cancer.

BACKGROUND: Hyperglycemia can promote the development of prostate cancer (PCa). Differential expression levels of miRNAs between PCa patients and controls were also reported. Therefore, we examined the relationship between hyperglycemia and miRNA levels in PCa. METHODS: Relative expression of urinary miR-574-3p, miR-375, miR-205-5p, miR-200b-3p, miR-187-3p, miR-182-5p, and miR-100-5p were investigated in 105 PCa patients and 138 noncancer controls by Real-Time quantitative PCR. Fasting plasma glucose measurements were retrieved from clinical records. The differential miRNA expressions among groups were compared using non-parametric tests. Correlations with glucose and prostate-specific antigen (PSA) were tested using Pearson correlation coefficient. RESULTS: When we analyzed miRNA expression according to glycemic state, significant down-regulations were found for miR-200b-3p, miR-187-3p, miR-182-5p, and miR-100-5p in noncancer controls with high glucose. The lowest down-regulations were observed for miR-187-3p, miR-182-5p, and miR-100-5p. Subsequently, when hyperglycemia was considered in PCa, significant dysregulations of selected miRNAs were found in hyperglycemic PCa patients than in controls with high glucose. In particular, miR-375 and miR-182-5p showed a 3-FC in hyperglycemic PCa patients than controls who left hyperglycemia untreated. Conversely, only a down-regulation of miR-574-3p was observed in PCa patients regardless of glycemic status and only modest down-regulation of miR-574-3p, miR-200b-3p, miR-187-3p and miR-182-5p were found in normoglycemic PCa patients. Next, significant correlations between miRNAs and glucose (miR-200b-3p, miR-100-5p) and PSA (miR-205-5p and miR-187-3p) were detected in controls. Similarly, miR-205-5p and miR-187-3p were correlated with glucose in PCa patients, while miR-574-3p and miR-375 showed inverse relationships. CONCLUSIONS: miRNA dysregulations can occur in hyperglycemic PCa patients as compared to noncancer controls who left hyperglycemia untreated. Hyperglycemia can consistently promote the expression of miR-375 and miR-182-5p. Uncontrolled hyperglycemic state could contribute to the creation of a suitable microenvironment for later PCa development by promoting gene expression.

The Oncological and Functional Prognostic Value of Unconventional Histology of Prostate Cancer in Localized Disease Treated with Robotic Radical Prostatectomy: An International Multicenter 5-Year Cohort Study.

BACKGROUND AND OBJECTIVE: The impact of prostate cancer of unconventional histology (UH) on oncological and functional outcomes after robot-assisted radical prostatectomy (RARP) and adjuvant radiotherapy (aRT) receipt is unclear. We compared the impact of cribriform pattern (CP), ductal adenocarcinoma (DAC), and intraductal carcinoma (IDC) in comparison to pure adenocarcinoma (AC) on short- to mid-term oncological and functional results and receipt of aRT after RARP. METHODS: We retrospectively collected data for a large international cohort of men with localized prostate cancer treated with RARP between 2016 and 2020. The primary outcomes were biochemical recurrence (BCR)-free survival, erectile and continence function. aRT receipt was a secondary outcome. Kaplan-Meier survival and Cox regression analyses were performed. KEY FINDINGS AND LIMITATIONS: A total of 3935 patients were included. At median follow-up of 2.8 yr, the rates for BCR incidence (AC 10.7% vs IDC 17%; p < 0.001) and aRT receipt (AC 4.5% vs DAC 6.3% [p = 0.003] vs IDC 11.2% [p < 0.001]) were higher with UH. The 5-yr BCR-free survival rate was significantly poorer for UH groups, with hazard ratios of 1.67 (95% confidence interval [CI] 1.16-2.40; p = 0.005) for DAC, 5.22 (95% CI 3.41-8.01; p < 0.001) for IDC, and 3.45 (95% CI 2.29-5.20; p < 0.001) for CP in comparison to AC. Logistic regression analysis revealed that the presence of UH doubled the risk of new-onset erectile dysfunction at 1 yr, in comparison to AC (grade group 1-3), with hazard ratios of 2.13 (p < 0.001) for DAC, 2.14 (p < 0.001) for IDC, and 2.01 (p = 0.011) for CP. Moreover, CP, but not IDC or DAC, was associated with a significantly higher risk of incontinence (odds ratio 1.97; p < 0.001). The study is limited by the lack of central histopathological review and relatively short follow-up. CONCLUSIONS AND CLINICAL IMPLICATIONS: In a large cohort, UH presence was associated with worse short- to mid-term oncological outcomes after RARP. IDC independently predicted a higher rate of aRT receipt. At 1-yr follow-up after RP, patients with UH had three times higher risk of erectile dysfunction post RARP; CP was associated with a twofold higher incontinence rate. PATIENT SUMMARY: Among patients with prostate cancer who undergo robot-assisted surgery to remove the prostate, those with less common types of prostate cancer have worse results for cancer control, erection, and urinary continence and a higher probability of receiving additional radiotherapy after surgery.

Prevalence of lower urinary tract symptoms in taxi drivers: a cross-sectional web-based survey.

PURPOSE: Aim of the study was to evaluate the prevalence of LUTS in taxi drivers. METHODS: Between February 24th 2021 and March 26th 2021 a web based survey was administered to Taxi drivers in the city of Florence. Taxi drivers were evaluated with baseline characteristics such as: age, BMI, smoking, career length, comorbidities, and treatment. LUTS were evaluated using the international prostate symptom score (IPSS) and the overactive bladder (OAB) score. As well sexual function was evaluated using the international index erectile function (IIEF) and female sexual function index (FSFI) questionnaires. Risk factors for LUTS were evaluated using regression analysis. RESULTS: The overall response rate was 64.6% (537/830 taxi drivers filled the questionnaires). Among them, 449 (83.6%) were men and 88 (16.4%) females. Overall, median IPSS was 5 (2/9) and median OAB score was 10 (7/14). On multivariate binary regression analysis age > 50 (OR:1.60; p < 0,05), Smoking (OR:1.57; p < 0,05), chronic treatment (OR:1.57; p < 0,05), recurrent cystitis (OR: 2.66; p < 0,05) and chronic pelvic pain (OR:4.94; p < 0,05) were independent risk factors for moderate/severe LUTS. On multivariate binary logistic regression analysis, risk factors for erectile dysfunction were age older than 50 years (OR = 3.64; p < 0.05) and urinary incontinence (OR = 5.53; p = 0.005). CONCLUSIONS: According to our web-based survey, Taxi drivers in the metropolitan city of Florence had non-negligible symptomatic LUTS and even sexual dysfunction. Our data suggest as LUTS are particular influenced by several life-style and behavioural factors as type and duration of work.

Could transperineal interstitial laser ablation of the prostate be the right option for highly-comorbid patients with lower urinary tract symptoms due to benign prostatic obstruction? A preliminary single-center experience focusing on functional and safety outcomes.

In this paper, we aimed to highlight functional and safety outcomes of highly-comorbid patients undergoing transperineal laser ablation (TPLA) of prostate at a referral academic center. Patients undergoing TPLA from April 2021 and February 2023 with moderate to severe lower urinary tract symptoms (LUTS), prostate volume ranging from 30 to 100 mL, and an American Society of Anesthesiologists (ASA) Score ≥3 were included. All patients were evaluated as unfit for standard surgery. Procedures were performed in an outpatient setting using local anesthesia. Failure after the procedure was defined as the shift to other ultra-minimally invasive surgical treatment or the need for long-term indwelling catheter replacement. Overall, 23 patients were enrolled with a median age of 76 years. Median ASA Score and Charlson Comorbidity Index were 3 and 5, respectively. Of these, 11 (48%) were under antiplatelets, 4 (17%) under new oral anticoagulants (NOACs) and 3 (13%) under warfarin. Six (26%) patients had an indwelling catheter preoperatively. Median prostate volume was 42 mL. Median follow-up was 12 months. No Clavien-Dindo Grade ≥2 complications were recorded. Four/six (66%) patients with an indwelling catheter before TPLA achieved spontaneous micturition. Treatment failure occurred in 2 (8.5%) patients. Of the remaining 21 patients, 12/21 (57%) patients reported an improvement in International Prostate Symptoms Score (IPSS) symptoms class (i.e., severe to moderate, moderate to mild, etc.); all patients whose IPSS symptoms class remained stable (N.=8 [38%]) had a significant improvement of the IPSS score as compared to the preoperative period, while 1 (4.5%) patient reported worsening of LUTS. In conclusion, TPLA appears to be a safe and feasible ultra-minimally-invasive option for LUTS due to benign prostatic obstruction (BPO) in patients with significant comorbidities at high-risk for standard surgical options.

Morbidity of Transrectal MRI-Fusion Targeted Prostate Biopsy at a Tertiary Referral Academic Centre: An Audit to Guide the Transition to the Transperineal Approach.

Despite transrectal prostate biopsy (TRPB) being still widespread globally, the EAU Guidelines strongly recommend the transperineal approach, due to the reported lower infectious risk. Our study aims to evaluate the impact of a standardized clinical pathway for TRPB on post-operative complications. We prospectively collected data from all patients undergoing mpMRI-targeted TRPB at our Academic Centre from January 2020 to December 2022. All patients followed a standardized, structured multistep pathway. Post-procedural complications were collected and classified according to the Clavien-Dindo (CD) Classification. Among 458 patients, post-procedural adverse events were reported by 203 (44.3%), of which 161 (35.2%) experienced CD grade 1 complications (hematuria [124, 27.1%], hematochezia [22, 4.8%], hematospermia [14, 3.1%], or a combination [20, 4.4%]), and 45 (9.0%) reported CD grade 2 complications (acute urinary retention or hematuria needing catheterization, as well as urinary tract infections, of which 2 cases required hospitalization). No major complications, including sepsis, were observed. At uni- and multivariable analysis, age > 70 years and BMI > 25 kg/ m2 for patients were identified as predictors of post-operative complications. The results of our study confirm that TRPB is a safe and cost-effective procedure with a low risk of severe adverse events in experienced hands and following a standardized pathway.

PERSIAN trial (NCT05717660): an ongoing randomized trial testing androgen deprivation therapy, apalutamide and stereotactic body radiotherapy. An alternative "triplet" for oligometastatic hormone sensitive prostate cancer patients.

Earlier treatment intensification with systemic potent androgen receptor inhibition has been shown to improve clinical outcomes in metastatic hormone sensitive prostate cancer. Nonetheless, oligometastatic patients may benefit from local treatment approaches such as stereotactic body radiotherapy (SBRT). Aiming to explore the benefit of SBRT in this scenario, we designed this trial to specifically test the hypothesis that SBRT will improve clinical outcomes in select population affected by metachronous oligometastatic HSPC treated with androgen deprivation therapy + apalutamide. Enrolled patients will be randomized to receive the standard systemic treatment alone or in combination with SBRT on all metastatic sites of disease. Here we report the protocol design and an overview of the ongoing trials testing different integration strategies between RT and systemic therapies.

Could a Risk-adapted Approach Support Shared Decision-making Regarding Eligibility for Adjuvant Pembrolizumab for Patients with Clear Cell Renal Cell Carcinoma at High Risk of Recurrence? A Multicentre Cohort Study.

The KEYNOTE-564 randomised controlled trial showed a disease-free survival benefit of adjuvant pembrolizumab (aPZB) in comparison to placebo for patients with clear cell renal cell carcinoma (ccRCC) at high risk of recurrence. Despite its recommendation by the European Association of Urology guidelines, the ultimate value of aPZB has recently been questioned. Arguably, patients who might benefit the most from aPZB are those whose probability of RCC recurrence outweighs their probability of dying from other causes over a reasonable timeframe after surgery. To assess the potential impact of this hypothesis on "eligibility" for aPZB, we queried our prospectively collected multi-institutional database for consecutive patients undergoing surgery for nonmetastatic renal masses (cT1-4 N0-1 M0) between 2015 and 2021 to identify ccRCC cases meeting the KEYNOTE-564 criteria. We stratified the patients using the risk-adapted model proposed by Stewart-Merrill et al (whereby stopping follow-up is warranted when the estimated risk of other-cause mortality [OCM] outweighs the estimated risk of RCC recurrence). Then we explored the proportion of patients whose follow-up could theoretically be stopped at 2, 5, 10, or 20 yr, for whom "eligibility" for aPZB might be more controversial. Overall, 1745 patients with ccRCC were included, of whom 419 (24%) met the KEYNOTE-564 criteria. The proportion of patients "not eligible" for aPZB because of higher probability of OCM than of RCC recurrence would have been 81%, 66%, 43%, and 29% at "recommended" follow-up of ≤2.0, ≤5, ≤10, and ≤20 yr, respectively. To the best of our knowledge, this is the first study providing insights to support shared decision-making regarding eligibility for aPZB for patients with nonmetastatic ccRCC with a focus on patient-related factors beyond tumour-driven prognostic scores. PATIENT SUMMARY: An immunotherapy drug call pembrolizumab given after surgery for nonmetastatic kidney cancer may benefit some patients who have a high risk of disease recurrence, but it can have immune-related side effects. We found that comparing the risk of death from other causes and the risk of cancer recurrence could help in reducing overtreatment of patients who might not benefit from this drug.

The impact of a second MRI and re-biopsy in patients with initial negative mpMRI-targeted and systematic biopsy for PIRADS ≥ 3 lesions.

OBJECTIVE: To evaluate the proportions of detected prostate cancer (PCa) and clinically significant PCa (csPCa), as well as identify clinical predictors of PCa, in patients with PI-RADS > = 3 lesion at mpMRI and initial negative targeted and systematic biopsy (initial biopsy) who underwent a second MRI and a re-biopsy. METHODS: A total of 290 patients from 10 tertiary referral centers were included. The primary outcome measures were the presence of PCa and csPCa at re-biopsy. Logistic regression analyses were performed to evaluate predictors of PCa and csPCa, adjusting for relevant covariates. RESULTS: Forty-two percentage of patients exhibited the presence of a new lesion. Furthermore, at the second MRI, patients showed stable, upgrading, and downgrading PI-RADS lesions in 42%, 39%, and 19%, respectively. The interval from the initial to repeated mpMRI and from the initial to repeated biopsy was 16 mo (IQR 12-20) and 18 mo (IQR 12-21), respectively. One hundred and eight patients (37.2%) were diagnosed with PCa and 74 (25.5%) with csPCa at re-biopsy. The presence of ASAP on the initial biopsy strongly predicted the presence of PCa and csPCa at re-biopsy. Furthermore, PI-RADS scores at the first and second MRI and a higher number of systematic biopsy cores at first and second biopsy were independent predictors of the presence of PCa and csPCa. Selection bias cannot be ruled out. CONCLUSIONS: Persistent PI-RADS ≥ 3 at the second MRI is suggestive of the presence of a not negligible proportion of csPca. These findings contribute to the refinement of risk stratification for men with initial negative MRI-TBx.

Stereotactic reirradiation with CyberknifeR for locally recurrent prostate cancer, long-term toxicity and clinical outcomes from a monocentric cohort.

PURPOSE: Up to 47% of patients with localized prostate cancer (PCa) treated with radiotherapy (EBRT) eventually develop local recurrence. To date, no clear consensus exists on optimal management. A growing body of interest supports the use of stereotaxic re-irradiation (rSBRT), with promising oncological outcomes and low toxicity profile. We collected a single-center case series of locally recurrent PCa who underwent re-irradiation after a previous course of postoperative or definitive radiotherapy. METHODS AND MATERIALS: Data from 101 patients treated at our institution for locally recurrent PCa from June 2012 to June 2021 were retrospectively collected. Patients underwent rSBRT with CyberKnife system (Accuray Inc., Sunnyvale, CA, USA), delivered to intraprostatic or macroscopic recurrences within the prostate bed, for a total dose of 30 Gy in 5 fractions. RESULTS: All patients received prior EBRT. The median EQD2 total dose was 75.0 Gy (range, 60-80 Gy). Thirty-two (32%) patients were receiving androgen deprivation therapy (ADT) after prior biochemical recurrence. After a median follow-up of 57.8 months, BR occurred in 55 patients (54.5%), with a median BR-free survival (BRFS) of 40.4 months (95% C.I. 34.3-58.3). Thirty-two patients (31.7%) developed metastatic disease, with a median metastasis-free survival (MFS) not reached. PSA ≥ 2.5 ng/ml and ADT were associated with worst BRFS (26.06 vs. 39.3 months, p = 0.03 and 22.7 vs. 27 months, p = 0.01, respectively). Castration-resistant status and ADT were found to be predictive of worst MFS (34.1 vs. 50.5 months, p = 0.02 and 33.5 vs. 53.1 months, p = 0.002, respectively). Concomitant ADT was confirmed as an independent factor for MFS (HR 4.8, 95% CI 1.5-10.6, p = 0.007). No grade > /2 adverse were recorded. CONCLUSIONS: After almost 5 years of follow-up, with a median BRFS of 40.4 months and no grade ≥ 2 AEs, CyberknifeR rSBRT proved effective and safe in a cohort of 101 patients affected by locally recurrent PCa.

Morbidity of elective surgery for localized renal masses among elderly patients: A contemporary multicenter study.

BACKGROUND: The aging population and the incidence of renal cell carcinoma (RCC) are increasing worldwide. Over 25% of newly diagnosed LRM (localized renal masses) occur in patients over the eighth decade of life. The decision-making and treatment approach to LRM in this population represents a clinical dilemma due to inherited decreased functional reserve and competing mortality risks. Current literature reports conflicting evidence regarding age as a risk factor for worst surgical outcomes. As such, we aimed to evaluate the contemporary morbidity of elective surgery for LRM among elderly patients, focusing on intraoperative and postoperative complications. METHODS: After Ethical Committee approval, we queried our prospectively maintained databases to identify patients with preoperative eGFR ≥60 ml/min/1.73 m [(David and Bloom, 2022) 22 and a normal contralateral kidney who underwent partial or radical nephrectomy (PN or RN) for a single cT1-T2N0M0 LRM between 1/2015-12/2021 at four high-volume European Academic Institutions. Patients were categorized by age groups: <50 yrs (young) vs. 50-75 (middle-aged) yrs vs.> 75 yrs (elderly). Postoperative complications were recorded according to Clavien-Dindo (CD) classification. The primary objectives were the proportion of patients experiencing intraoperative (IOC), any grade (AGC), and high-grade postoperative complications (HGC), defined as CD grade 3-5. RESULTS: Overall, 2469/3076 (80.2%) patients met the inclusion criteria. Of these, 363 (14.7%) were young, 1682 (68.1%) were middle-aged, and 424 (17.2%) were elderly. Compared to middle-aged and young patients, elderly patients had a higher median Charlson Comorbidity Index (6 vs. 4 vs. 0, p < 0.01) and a higher proportion of cT1 renal mass (87.6% vs. 93.0% vs. 93.6%, p < 0.01). No differences among the study groups were found regarding surgical approach (open vs. minimally-invasive) and type of surgery (PN vs. RN). We found that older patients experienced similar IOC (4.5% vs. 4.2% vs. 3.3%, p = 0.7) and AGC (23.1% vs. 20.0% vs. 21.5%, p = 0.4) compared to middle-aged and young patients, respectively. Similarly, there were no significant differences in HGC between the study cohorts (0.7% vs. 1.4% vs. 1.7%, p = 0.8). At multivariable analysis, open approach and PN significantly predicted the occurrence of AGCs, while only the open surgical approach was associated with the occurrence of HGCs. CONCLUSION: In kidney cancer tertiary referral centers, the risk of IOC and postoperative HGC after PN or RN for localized renal masses (LRM) is low, despite a non-negligible risk of AGC, especially in elderly patients. Further efforts should focus on identifying multidisciplinary strategies to select patients most likely to benefit from surgery among elderly candidates with LRMs and decrease the morbidity of surgery in this specific setting.