Fascin-1 expression is associated with neuroendocrine prostate cancer and directly suppressed by androgen receptor.

BACKGROUND: Neuroendocrine prostate cancer (NEPC) is an aggressive form of prostate cancer, arising from resistance to androgen-deprivation therapies. However, the molecular mechanisms associated with NEPC development and invasiveness are still poorly understood. Here we investigated the expression and functional significance of Fascin-1 (FSCN1), a pro-metastasis actin-bundling protein associated with poor prognosis of several cancers, in neuroendocrine differentiation of prostate cancer. METHODS: Differential expression analyses using Genome Expression Omnibus (GEO) database, clinical samples and cell lines were performed. Androgen or antagonist's cellular treatments and knockdown experiments were used to detect changes in cell morphology, molecular markers, migration properties and in vivo tumour growth. Chromatin immunoprecipitation-sequencing (ChIP-Seq) data and ChIP assays were analysed to decipher androgen receptor (AR) binding. RESULTS: We demonstrated that FSCN1 is upregulated during neuroendocrine differentiation of prostate cancer in vitro, leading to phenotypic changes and NEPC marker expression. In human prostate cancer samples, FSCN1 expression is restricted to NEPC tumours. We showed that the androgen-activated AR downregulates FSCN1 expression and works as a transcriptional repressor to directly suppress FSCN1 expression. AR antagonists alleviate this repression. In addition, FSCN1 silencing further impairs in vivo tumour growth. CONCLUSION: Collectively, our findings identify FSCN1 as an AR-repressed gene. Particularly, it is involved in NEPC aggressiveness. Our results provide the rationale for the future clinical development of FSCN1 inhibitors in NEPC patients.

Unilateral Pelvic Lymph Node Dissection in Prostate Cancer Patients Diagnosed in the Era of Magnetic Resonance Imaging-targeted Biopsy: A Study That Challenges the Dogma.

PURPOSE: Bilateral extended pelvic lymph node dissection at the time of radical prostatectomy is the current standard of care if pelvic lymph node dissection is indicated; often, however, pelvic lymph node dissection is performed in pN0 disease. With the more accurate staging achieved with magnetic resonance imaging-targeted biopsies for prostate cancer diagnosis, the indication for bilateral extended pelvic lymph node dissection may be revised. We aimed to assess the feasibility of unilateral extended pelvic lymph node dissection in the era of modern prostate cancer imaging. MATERIALS AND METHODS: We analyzed a multi-institutional data set of men with cN0 disease diagnosed by magnetic resonance imaging-targeted biopsy who underwent prostatectomy and bilateral extended pelvic lymph node dissection. The outcome of the study was lymph node invasion contralateral to the prostatic lobe with worse disease features, ie, dominant lobe. Logistic regression to predict lymph node invasion contralateral to the dominant lobe was generated and internally validated. RESULTS: Overall, data from 2,253 patients were considered. Lymph node invasion was documented in 302 (13%) patients; 83 (4%) patients had lymph node invasion contralateral to the dominant prostatic lobe. A model including prostate-specific antigen, maximum diameter of the index lesion, seminal vesicle invasion on magnetic resonance imaging, International Society of Urological Pathology grade in the nondominant side, and percentage of positive cores in the nondominant side achieved an area under the curve of 84% after internal validation. With a cutoff of contralateral lymph node invasion of 1%, 602 (27%) contralateral pelvic lymph node dissections would be omitted with only 1 (1.2%) lymph node invasion missed. CONCLUSIONS: Pelvic lymph node dissection could be omitted contralateral to the prostate lobe with worse disease features in selected patients. We propose a model that can help avoid contralateral pelvic lymph node dissection in almost one-third of cases.

Focal therapy for primary tumor and metastases in de novo or recurrent oligometastatic prostate cancer: current standing and future perspectives.

PURPOSE: Focal therapy (FT) is gaining increasing acceptance in the management of localized prostate cancer particularly due to its favorable safety. Preliminary evidence suggests advantageous utilization of local treatment in the field of oligometastatic prostate cancer (OMPC). Since data on the utilization of FT in OMPC are scarce, we sought to summarize available evidence. METHODS: For this narrative comprehensive review, we employed PubMed®, Web of Science™, Embase®, Scopus®, and clinicaltrial.gov databases and Google web search engine to seek peer-reviewed articles, published abstracts from international congresses, and ongoing trials in the English language using the terms "prostate cancer", "oligometastatic", "hormone-sensitive", "focal therapy", "focal treatment", "cryotherapy", "ablation", "cancer" as well as "metastasis-directed therapy. We focused on relevant publications on FT utilized in OMPC targeting the primary or metastatic sites as well as completed and ongoing clinical trials. RESULTS: Growing evidence points to distinct differences in the biologic behavior and molecular signaling processes of OMPC as compared to polymetastatic disease (PMPC). No established biomarkers are available to accurately identify OMPC yet, while several candidates are currently under investigation. The evolution of molecular imaging is set to aid in selecting patients benefitting most from local management. Differences between OMPC and PMPC should be considered when designing the optimal therapeutic strategy. While efficacy data for FT in comparison to standard care in OMPC are scarce, longer progression-free survival and time to castration resistance have been demonstrated for bone metastatic prostate cancer with the primary tumor treated by cryosurgery followed by androgen deprivation therapy (ADT) compared to ADT alone. CONCLUSION: Ongoing research efforts are eagerly awaited to better characterize OMPC and establish customized strategies for patients with this condition.

Late complications and 5 years outcomes of robotic partial nephrectomy in France: prospective assessment in the French Kidney Cancer Research Network (UroCCR 10).

PURPOSE: To describe the practice of robotic-assisted partial nephrectomy (RAPN) in France and prospectively assess the late complications and long-term outcomes. METHODS: Prospective, multicenter (n = 16), observational study including all patients diagnosed with a renal tumor who underwent RAPN. Preoperative, intraoperative, postoperative, and follow-up data were collected and stored in the French research network for kidney cancer database (UroCCR). Patients were included over a period of 12 months, then followed for 5 years. RESULTS: In total, 466 patients were included, representing 472 RAPN. The mean tumor size was 3.4 ± 1.7 cm, most of moderate complexity (median PADUA and RENAL scores of 8 [7-10] and 7 [5-9]). Indication for nephron-sparing surgery was relative in 7.1% of cases and imperative in 11.8%. Intraoperative complications occurred in 6.8% of patients and 4.2% of RAPN had to be converted to open surgery. Severe postoperative complications were experienced in 2.3% of patients and late complications in 48 patients (10.3%), mostly within the first 3 months and mainly comprising vascular, infectious, or parietal complications. At 5 years, 29 patients (6.2%) had chronic kidney disease upstaging, 21 (4.5%) were diagnosed with local recurrence, eight (1.7%) with contralateral recurrence, 25 (5.4%) with metastatic progression, and 10 (2.1%) died of the disease. CONCLUSION: Our results reflect the contemporary practice of French expert centers and is, to our knowledge, the first to provide prospective data on late complications associated with RAPN. We have shown that RAPN provides good functional and oncologic outcomes while limiting short- and long-term morbidity. TRIAL REGISTRATION: NCT03292549.

Nephrometry scores to predict oncological outcomes following partial nephrectomy (UroCCR Study 70).

PURPOSE: Partial nephrectomy (PN) for large or complex renal tumors can be difficult and associated with a higher risk of recurrence than radical nephrectomy. We aim to evaluate the clinical useful of nephrometry scores for predicting oncological outcomes in a large cohort of patients who underwent PN for renal cell carcinomas. METHODS: Our analysis included patients who underwent PN for renal cell carcinoma in 21 French academic centers (2010-2020). RENAL, PADUA, and SPARE scores were calculated based on preoperative imaging. Uni- and multivariate cox models were performed to identify predictors of recurrence-free survival and overall survival. The area under the curve (AUC) was used to identify models with the highest discrimination. Decision curve analyses (DCAs) determined the net benefit associated with their use. RESULTS: A total of 1927 patients were analyzed with a median follow-up of 32 months (14-45). RENAL score (p = 0.01), age (p = 0.002), histological type (p = 0.001), high nuclear grade (p = 0.001), necrotic component (p < 0.001), and positive margins (p = 0.005) were significantly related to recurrence in multivariate analyses. The discriminative performance of the 3 radiological scores was modest (65, 63, and 63%, respectively). All 3 scores showed good calibration, which, however, deteriorated with time. Decision curve analysis of the three models for the prediction of overall and recurrence-free survival was similar for all three scores and of limited clinical relevance. CONCLUSION: The association between nephrometry scores and oncological outcomes after NP is very weak. The use of these scores for predicting oncological outcomes in routine practice is therefore of limited clinical value.

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.

Minimally invasive nephron-sparing treatments for T1 renal cell cancer in patients over 75 years: a comparison of outcomes after robot-assisted partial nephrectomy and percutaneous ablation.

PURPOSE: To compare the oncological and perioperative outcomes of robot-assisted partial nephrectomy (RPN) and percutaneous thermal ablation (PTA) for treatment of T1 renal cell cancer (RCC) in patients older than 75 years. MATERIALS AND METHODS: Retrospective national multicenter study included all patients older than 75 years treated for a T1 RCC by RPN or PTA between January 2010 and January 2021. Patients' characteristics, tumor data, and perioperative and oncological outcomes were compared. RESULTS: A total of 205 patients for 209 procedures (143 RPN and 66 PTA) were included. In the PTA group, patients were older (80.4 ± 3.7 vs. 79 ± 3.7 years (p = 0.01)); frailer (ASA score (2.43 ± 0.6 vs. 2.17 ± 0.6 (p < 0.01)); and more frequently had a history of kidney surgery (16.7% [11/66] vs. 5.6% [8/143] (p = 0.01)) than in the RPN group. Tumors were larger in the RPN group (2.7 ± 0.7 vs. 3.2 ± 0.9 cm (p < 0.01)). Operation time, length of hospital stay, and increase of creatinine serum level were higher in RPN (respectively 92.1 ± 42.7 vs. 150.7 ± 61.3 min (p < 0.01); 1.7 ± 1.4 vs. 4.2 ± 3.4 days (p < 0.01); 1.9 ± 19.3% vs. 10.1 ± 23.7 (p = 0.03)). Disease-free survival and time to progression were similar (respectively, HR 2.2; 95% CI 0.88-5.5; p = 0.09; HR 2.1; 95% CI 0.86-5.2; p = 0.1). Overall survival was shorter for PTA that disappeared after Cox adjusting model (HR 3.3; 95% CI 0.87-12.72; p = 0.08). CONCLUSION: Similar oncological outcomes are observed after PTA and RPN for T1 RCC in elderly patients. CLINICAL RELEVANCE STATEMENT: Robot-assisted partial nephrectomy and percutaneous thermal ablation have similar oncological outcomes for T1a kidney cancer in patients over 75 years; however, operative time, decrease in renal function, and length of hospital stay were lower with ablation. KEY POINTS: • After adjusting model for age and ASA score, similar oncological outcomes are observed after percutaneous thermal ablation and robot-assisted partial nephrectomy for T1 renal cell cancer in elderly patients. • Operation time, length of hospital stay, and increase of creatinine serum level were higher in the robot-assisted partial nephrectomy group.

Who Is at Risk of Death after Renal Trauma? An Analysis of Thirty-Day Mortality after 1,799 Cases of Renal Trauma.

INTRODUCTION: The aim of the study was to report the 30-day mortality (30DM) after renal trauma and identify the risk factors associated with death. METHODS: The TRAUMAFUF project was a retrospective multi-institutional study including all patients with renal trauma admitted to 17 French hospitals between 2005 and 2015. The included population focused on patients of all age groups who underwent renal trauma during the study period. The primary outcome was death within 30 days following trauma. The multivariate logistic regression model with a stepwise backward elimination was used to identify predictive factors of 30DM. RESULTS: Data on 1,799 renal trauma were recorded over the 10-year period. There were 59 deaths within 30 days of renal trauma, conferring a 30DM rate of 3.27%. Renal trauma was directly involved in 5 deaths (8.5% of all deaths, 0.3% of all renal trauma). Multivariate stepwise logistic regression analysis revealed that age >40 years (odds ratio [OR] 2.18; 95% confidence interval [CI]: 1.20-3.99; p = 0.01), hemodynamic instability (OR 4.67; 95% CI: 2.49-9; p < 0.001), anemia (OR 3.89; 95% CI: 1.94-8.37; p < 0.001), bilateral renal trauma (OR 6.77; 95% CI: 2.83-15.61; p < 0.001), arterial contrast extravasation (OR 2.09; 95% CI: 1.09-3.96; p = 0.02), and concomitant visceral and bone injuries (OR 6.57; 95% CI: 2.41-23.14; p < 0.001) were independent predictors of 30DM. CONCLUSION: Our large multi-institutional study supports that the 30DM of 3.27% after renal trauma is due to the high degree of associated injuries and was rarely a consequence of renal trauma alone. Age >40 years, hemodynamic instability, anemia, bilateral renal trauma, arterial contrast extravasation, and concomitant visceral and bone lesions were predictors of death. These results can help clinicians to identify high-risk patients.

The Detection of Prostate Cancer with Magnetic Resonance Imaging-Targeted Prostate Biopsies is Superior with the Transperineal vs the Transrectal Approach. A European Association of Urology-Young Academic Urologists Prostate Cancer Working Group Multi-Institutional Study.

PURPOSE: Our aim was to evaluate whether transperineal (TP) MRI-targeted prostate biopsy (TBx) may improve the detection of clinically significant prostate cancer (csPCa), defined as International Society of Urological Pathology ≥2, in comparison to transrectal (TR) TBx. MATERIALS AND METHODS: A multicenter retrospective cohort study comprising patients who underwent MRI-guided prostate biopsy was conducted. To address possible benefits of TP-TBx in the detection of prostate cancer (PCa) and csPCa, a cohort of patients undergoing TP-TBx were compared to patients undergoing TR-TBx. Multivariable logistic regression analyses were performed to assess predictors of PCa and csPCa detection. RESULTS: Overall, 1,936 and 3,305 patients who underwent TR-TBx vs TP-TBx at 10 referral centers were enrolled. The rate of PCa and csPCa diagnosed was higher for TP-TBx vs TR-TBx (64.0% vs 50%, p <0.01 and 49% vs 35%, p <0.01). At multivariable analysis adjusted for age, biopsy naïve/repeated biopsy, cT stage, Prostate Imaging-Reporting and Data System®, prostate volume, PSA, and number of biopsy cores targeted, TP-TBx was an independent predictor of PCa (odds ratio [OR] 1.37, 95% CI 1.08-1.72) and csPCa (1.19, 95% CI 1.12-1.50). When considering the approach according to the site of the index lesion, TP-TBx had a significantly higher likelihood than TR-TBx to detect csPCa in the apex (OR 4.81, 95% CI 1.03-6.27), transition/central zone (OR 2.67, 95% CI 1.42-5.00), and anterior zone (OR 5.62, 95% CI 1.74-8.13). CONCLUSIONS: The use of TP-TBx allows a better cancer grade definition and PCa risk assessment. This has important implication in the decision-making process and in patient counseling for further therapies.

Impact of Renal Cell Carcinoma Histological Variants on Recurrence After Partial Nephrectomy: A Multi-Institutional, Prospective Study (UROCCR Study 82).

BACKGROUND: The prognostic impact of renal cell carcinoma (RCC) morphotype remains unclear in patients who undergo partial nephrectomy (PN). Our objective was to determine the risk factors for recurrence after PN, including RCC morphotype. METHODS: Patients with RCC who had undergone PN were extracted from the prospective, national French database, UroCCR. Patients with genetic predisposition, bilateral or multiple tumours, and those who had undergone secondary totalization were excluded. Primary endpoint was 5-year, recurrence-free survival (RFS), and secondary endpoint was overall survival (OS). Risk factors for recurrence were assessed by multivariable Cox regression analysis. RESULTS: Overall, 2,767 patients were included (70% male; median age: 61 years [interquartile range (IQR) 51-69]). Most (71.5%) of the PN procedures were robot-assisted. Overall, 2,573 (93.0%) patients were recurrence free, and 74 died (2.7%). Five-year RFS was 84.9% (IQR 82.4-87.4). A significant difference in RFS was observed between RCC morphotypes (p < 0.001). Surgical margins (hazard ratio [HR] = 2.0 [95% confidence interval (CI): 1.3-3.2], p < 0.01), pT stage >1 (HR = 2.6 [95% CI: 1.8-3.7], p < 0.01]) and Fuhrmann grade >2 (HR = 1.9 [95% CI: 1.4-2.6], p < 0.001) were risk factors for recurrence, whereas chromophobe subtype was a protective factor (HR = 0.08 [95% CI: 0.01-0.6], p = 0.02). Five-year OS was 94.0% [92.4-95.7], and there were no significant differences between RCC subgroups (p = 0.06). The main study limitation was its design (multicentre national database), which may be responsible for declarative bias. CONCLUSIONS: Chromophobe morphotype was significantly associated with better RFS in RCC patients who underwent PN. Conversely, pT stage, Fuhrman group and positive surgical margins were risk factors for recurrence.

Impact of positive vascular margins status after surgical resection of non-metastatic renal cell carcinoma with caval tumour thrombus: a propensity score multicentre study.

BACKGROUND: Data evaluating the impact of positive vascular margins (PVMs) following surgical resection of non-metastatic renal cell carcinoma (RCC) with inferior vena cava (IVC) tumor thrombus are lacking. OBJECTIVE: To analyze the oncological impact of positive vascular margins following surgical resection of RCC with IVC tumor thrombus. METHODS: Patients who underwent radical nephrectomy with the removal of IVC tumour thrombus for RCC between 2000 and 2019 were included. PVMs were identified from pathology reports defined as microscopically identified tumour present in the IVC wall at the site of resection or in case of thrombus was not completely removed. To achieve balance in baseline characteristics between patients with PVMs versus negative vascular margins, we used inverse probability of treatment weighting (IPTW) based on the propensity score. Local recurrence, distant metastasis and overall mortality were evaluated between groups using Cox proportional hazards regression models. RESULTS: 209 patients were analyzed. Among them, 49 (23%) patients with PVMs were identified. Median follow-up was 55 months. After adjustment, excellent balance was achieved for most propensity score variables. In IPTW analysis, PVMs was associated with a higher risk of local recurrence (HR = 3.66; p < 0.001) without any impact on systemic recurrence (HR = 1.15; p = 0.47) or overall mortality (HR = 1.23; p = 0.48). Limitations include the sample size and unmeasured confounding. CONCLUSION: Our results suggest that a PVMs in patients with RCC after nephrectomy with thrombectomy is associated with a higher risk of local recurrence, however, it did not appear to influence the risk of distant metastasis or death.

Heterogeneity of contemporary grade group 4 prostate cancer in radical prostatectomy specimens.

PURPOSE: The aim was to evaluate the prognostic role of sub-categories of ISUP 4 prostate cancer (PCa) on final pathology, and assess the tumor architecture prognostic role for predicting biochemical recurrence (BCR) after radical prostatectomy. METHODS: From a prospectively-maintained database, we included 370 individuals with ISUP 4 on final pathology. The main outcomes were to evaluate the relationship between different ISUP patterns within the group 4 with pathological and oncological outcomes. Binary logistic regression and Kaplan-Meier estimator were used to evaluate the role of the different categories (3 + 5, 4 + 4, 5 + 3) and tumor architecture (intraductal and/or cribriform) on pathological and oncological outcomes. RESULTS: Among the 370 individuals with ISUP considered for the study, 9, 85 and 6% had grade 3 + 5, 4 + 4 and 5 + 3 PCa, respectively. Overall, 74% had extracapsular extension, while lymph node invasion (LNI) was documented in 9%. A total of 144 patients experienced BCR during follow-up. After adjusting for PSA, pT, grade group, LNI and positive surgical margins (PSM), grade 3 + 5 was a protective factor (HR: 0.30, 95% CI: 0.13,0.68, p = 0.004) in predicting BCR relative to grade 4 + 4. Intraductal or cribriform architecture was correlated with BCR (HR: 5.99, 95% CI: 2.68, 13.4, p < 0.001) after adjusting for PSA, pT, grade group, LNI and PSM. CONCLUSIONS: Patients with tumor grade 3 + 5 had better pathological and prognostic outcomes compared to 4 + 4 or 5 + 3. When accounting for tumor architecture, the sub-stratification into subgroups lost its prognostic role and tumor architecture was the sole predictor of poorer prognosis in terms of biochemical recurrence.

Features and management of men with pN1 cM0 prostate cancer after radical prostatectomy and lymphadenectomy: a systematic review of population-based evidence.

PURPOSE OF REVIEW: To investigate the features and optimal management of pN+ cM0 prostate cancer (PCa) according to registry-based studies. RECENT FINDINGS: Up to 15% of PCa patients harbor lymph node invasion (pN+) at radical prostatectomy plus lymph node dissection. Nonetheless, the optimal management strategy in this setting is not well characterized. SUMMARY: We performed a systematic review including n = 13 studies. Management strategies comprised 13 536 men undergoing observation, 11 149 adjuvant androgen deprivation therapy (aADT), 7,075 adjuvant radiotherapy (aRT) +aADT and 705 aRT. Baseline features showed aggressive PCa in the majority of men. At a median follow-up ranging 48-134months, Cancer-related death was 5% and overall-mortality 16.6%. aADT and aRT alone had no cancer-specific survival or overall survival advantages over observation only and over not performing aRT, respectively. aADT plus aRT yielded a survival benefit compared to observation and aADT, which in one study, were limited to certain intermediate-risk categories. Age, Gleason, Charlson score, positive surgical margins, pathological stage, and positive nodes number, but not prostate specific antigen, were most relevant prognostic factors. Our work further confirmed pN+ PCa is a multifaceted disease and will help future research in defining its optimal management based on different risk categories to maximize survival and patient's quality of life.

Negative Prebiopsy Magnetic Resonance Imaging and Risk of Significant Prostate Cancer: Baseline and Long-Term Followup Results.

PURPOSE: Prostate biopsy should be discussed with the patient in cases of negative magnetic resonance imaging and low clinical suspicion of prostate cancer.Our primary objective was to describe the risk of clinically significant prostate cancer in a negative magnetic resonance imaging biopsy naïve population at baseline and during long-term followup. The secondary objective was to evaluate clinical factors and prostate specific antigen as predictors of clinically significant prostate cancer at baseline. MATERIALS AND METHODS: All 503 consecutive patients who were biopsy naïve referred from 2007 to 2017 for biopsy with negative magnetic resonance imaging (PI-RADS™ 1-2) who had systematic 12-core biopsies at baseline were included. Clinical factors were digital rectal examination, prostate cancer family history and prostate specific antigen. In case of suspicious digital rectal examination or prostate specific antigen kinetics during followup, magnetic resonance imaging and biopsy were performed. Clinically significant prostate cancer was defined as either Gleason Grade 1 with cancer core length greater than 5 mm or 3 or more positive systematic 12-core biopsies in addition to Gleason Grade 2 or greater (clinically significant prostate cancer-1) or any Gleason Grade 2 or greater (clinically significant prostate cancer-2). Nonclinically significant prostate cancer was defined as either Gleason Grade 1 with cancer core length 5 mm or less and fewer than 3 positive systematic 12-core biopsies (nonclinically significant prostate cancer-1) or any Gleason Grade 1 (nonclinically significant prostate cancer-2). Definition of high risk clinically significant prostate cancer was Gleason Grade 3 or greater. Univariate and multivariate models were fitted to identify predictors of clinically significant prostate cancer risk. RESULTS: At baseline, biopsy showed clinically significant prostate cancer-1 in 9% (45), clinically significant prostate cancer-2 in 6% (29) and nonclinically significant prostate cancer in 22% (111). At median followup of 4 years (IQR 1.6-7.1), 31% (95% CI 27-36) of 415 untreated patients had a second magnetic resonance imaging and 24% (95% CI 20-28) a second biopsy that showed clinically significant prostate cancer-1 in 5% (21/415, 95% CI 3-7), clinically significant prostate cancer-2 in 2% (7/415, 95% CI 1-3) and nonclinically significant prostate cancer in 8%. Overall incidence was 13% (66/503, 95% CI 7-21) for clinically significant prostate cancer-1, 7% (36/503, 95% CI 5-9%) for clinically significant prostate cancer-2 and 2% (12/503, 95% CI 1.1-3.7) for high risk prostate cancer. Predictors of clinically significant prostate cancer risk were prostate specific antigen density 0.15 ng/ml/ml or greater (OR 2.43, 1.19-4.21), clinical stage T2a or greater (OR 3.32, 1.69-6.53) and prostate cancer family history (OR 2.38, 1.10-6.16). Performing biopsy in patients with negative magnetic resonance imaging and prostate specific antigen density 0.15 ng/ml/ml or greater or abnormal digital rectal examination or prostate cancer family history would have decreased from 9% to 2.4% the risk of missing clinically significant prostate cancer-1 at baseline while avoiding biopsy in 56% of cases. CONCLUSIONS: The risk of clinically significant prostate cancer in a negative magnetic resonance imaging biopsy naïve population was 6% to 9% at baseline and 7% to 13% at long-term followup depending on clinically significant prostate cancer definitions.

The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study.

OBJECTIVE: To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. PATIENTS AND METHODS: This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. RESULTS: Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3-34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1-30.2), UTUC (n = 128) 1.14% (95% CI 0.77-1.52), renal cancer (n = 107) 1.05% (95% CI 0.80-1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32-2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03-1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90-4.15; P < 0.001), male sex 1.30 (95% CI 1.14-1.50; P < 0.001), and smoking 2.70 (95% CI 2.30-3.18; P < 0.001). CONCLUSIONS: A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer.

Artificial urinary sphincter implantation in non-neurogenic men: a place for out-patient surgery.

OBJECTIVE: To assess feasibility, safety and risk factors for failure associated with out-patient surgery for artificial urinary sphincter (AUS) implantation/revision in non-neurogenic men. MATERIALS: In the present retrospective monocentric study conducted between May 2016 and March 2020, 81 patients undergoing AUS implantation or revision during an out-patient surgery were included. The primary outcome was the success rate of out-patient surgery. Success was assessed using two distinct definitions, a narrow definition, where success was defined as a one-day hospitalization and the absence of any unscheduled consultation or re-hospitalization within the 3 days following surgery, a broad definition, where success was defined as a one-day hospitalization and the absence of any unscheduled re-hospitalization within the 3 days following surgery. In parallel, risk factors for failure of out-patient surgery, as well as efficacy and safety were assessed. RESULTS: Eighty-one patients were enrolled, with a mean age of 71.2 years ± 5.9. Out-patient surgery was successfully completed in 58 men (71.6% [95% CI 60.5-81.1]) and in 76 men (93.8% [95% CI 86.2-97.9]) according to the narrow and the broad definition, respectively. After multivariate analysis, anticoagulant therapy (OR 25.97 [95% CI 4.44-152.04]) and low socio-professional status (OR 22.1 [95% CI 3.701-131.95]) were statistically associated with failure of out-patient surgery. The continence rate after a 90-day follow-up was 79%. CONCLUSION: AUS implantation/revision in non-neurogenic men could be safely proposed in out-patient surgery. Special attention may however be paid to patients undergoing anticoagulant therapy or belonging to a low socio-professional category. TRIAL REGISTRATION NUMBER: DEC20-173 (French National Commission for Data Protection and Liberties).

Predictive factors of urinary incontinence after holmium laser enucleation of the prostate: a multicentric evaluation.

OBJECTIVE: To evaluate predictive factors of urinary incontinence (UI) after holmium laser enucleation of the prostate (HoLEP). METHODS: Patients (n = 2346) were included in a retrospective multicentric study from April 2012 to November 2017. Patients' characteristics (age, BMI, percentage with diabetes), preoperative data (IPSS score, whole gland volume, urinary drainage), operative data (enucleation time, enucleation efficiency, tissue enucleated weight, total delivered energy) and postoperative data were recorded. Absence of UI was defined as no pads at 3 and 6 months. Surgeon experience was stratified in three categories: beginners (< 21 cases), intermediate (21-40 cases) and experienced (> 40 cases). Multivariate logistic regression analysis was performed. RESULTS: UI was observed in 14.5% of patients (340/2346) at 3 months (95%CI 13-16%) and in 4.2% (98/2346) at 6 months (95%CI 3-5%). On multivariate analysis at 3 months, increasing age (OR per SD = 1.3 [1.14-1.48]), elevated BMI (OR per SD = 1.23 [1.09-1.38]), preoperative urinary drainage (OR = 0.62 [0.45-0.85]), increasing enucleated tissue weight (OR per SD = 1.29 [1.16-1.45]) and experienced surgeon with at least 40 cases (OR = 0.56 [0.42-0.75]) were significantly associated with UI. At 6 months, increasing age (OR per SD = 1.25 [1.01-1.53]), elevated BMI (OR per SD = 1.25 [1.03-1.5]), increasing whole gland volume (OR per one SD log = 1.24 [1.01-1.53]) and diabetes disorder (OR = 1.7 [1.03-2.78]) were significantly associated with UI. CONCLUSION: UI after HoLEP was observed in 14.5% of patients at 3 months and 4.2% at 6 months, with stress UI in half of the cases. Surgeon experience with at least 40 cases was the main predictive factor of 3 months UI after HoLEP and diabetes disorder of persistent UI at 6 months.

Observation vs. early drainage for grade IV blunt renal trauma: a multicenter study.

INTRODUCTION: The aim of this study was to compare observation and early drainage by ureteral stenting in patients with blunt renal trauma and urinary extravasation. MATERIALS AND METHODS: A retrospective national multicenter study was performed including all patients admitted for renal trauma at 17 hospitals between 2005 and 2015. Patients presenting with a urinary extravasation on initial imaging were considered for inclusion. Patients were divided in two groups according to the initial approach: observation vs. early drainage by ureteral stent (within 48 h after admission). The primary endpoint was the persistence of urinary extravasation on follow-up imaging. RESULTS: Out of 1799 patients with renal trauma, 238 were included in the analysis (57 in the early drainage and 181 in the observation group). In the early drainage group, 29 patients had persistent urinary extravasation vs. 77 in the observation group (50.9% vs. 42.5%; p value = 0.27). The rates of secondary upper urinary tract drainage did not differ significantly between the early drainage group (26.4%) and the observation group (16%) (p = 0.14). There were no statistically significant differences between the two groups in terms of secondary nephrectomy (0% vs. 2.8%; p = 0.34), and death from trauma (0% vs. 1.8%; p = 0.99). In multivariate analysis, early drainage remained not statistically associated with persistence of urinary extravasation on follow-up imaging (OR = 1.35; p = 0.36) CONCLUSION: In this multicenter cohort, observation was not different from early drainage in terms of persistent urinary extravasation after grade IV blunt renal trauma. Further randomized controlled prospective trials are needed to confirm these findings.

Early discharge in selected patients with low-grade renal trauma.

INTRODUCTION: The aim of this study was to assess whether early discharge could be non-inferior to inpatient management in selected patients with low-grade renal trauma (AAST grades 1-3). MATERIALS AND METHODS: A retrospective national multicenter study was conducted including all patients who presented with renal trauma at 17 hospitals between 2005 and 2015. Exclusion criteria were iatrogenic and AAST grades 4 and 5 trauma, non-conservative initial management, Hb < 10 g/dl or transfusion within the first 24 h, and patients with concomitant injuries. Patients were divided into two groups according to the length of hospital stay: ≤ 48 h (early discharge), and > 48 h (inpatient). The primary outcome was "Intervention" defined as any interventional procedure needed within the first 30 days. A Stabilized Inverse Probability of Treatment Weighting (SIPTW) propensity score based binary response model was used to estimate risk difference. RESULTS: Out of 1764 patients with renal trauma, 311 were included in the analysis (44 in the early discharge and 267 in the inpatient group). In the early discharge group, only one patient required an intervention within the first 30 days vs. 10 in the inpatient group (3.7% vs. 5.2%; p = 0.99). Adjusted analysis using SIPTW propensity score showed a risk difference of - 2.8% [- 9.3% to + 3.7%] of "interventions" between the two groups meeting the non-inferiority criteria. CONCLUSION: In a highly selected cohort, early discharge management of low-grade renal trauma was not associated with an increased risk of early "intervention" compared to inpatient management. Further prospective randomized controlled trials are needed to confirm these findings.

Low-risk prostate cancer selected for active surveillance with negative MRI at entry: can repeat biopsies at 1 year be avoided? A pilot study.

PURPOSE: In patients considered for active surveillance (AS), the use of MRI and targeted biopsies (TB) at entry challenges the approach of routine "per protocol" repeat systematic biopsies (SB) at 1 year. This pilot study aimed to assess whether an approach of performing repeat biopsies only if PSA kinetics are abnormal would be safe and sufficient to detect progression. METHODS: Prospective single-centre study of 149 patients on AS with low-risk PCa, a negative MRI at entry, followed for a minimum of 12 months between 01/2007 and 12/2015. Group 1 (n = 78) patients had per-protocol 12-month repeat SB; group 2 (n = 71) patients did not. Surveillance tests for tumour progression were for both groups: for cause SB and MRI-TB biopsies if PSA velocity (PSA-V) > 0.75 ng/ml/year, or PSA doubling time (PSADT) < 3 years. The main objectives are to compare the 2-year rates of tumour progression and AS discontinuation between groups. The secondary objectives are to estimate the diagnostic power of PSA-V and PSA-DT, to predict the risk of tumour progression. RESULTS: Overall, 21 out of 149 patients (14.1%) showed tumour progression, 17.1% for group 1 and 12.3% for group 2, and 31 (21.2%) discontinued AS at 2 years. There was no difference between the 2 groups (p = 0.56). The area under the PSA-V and PSADT curves to predict tumour progression was 0.92 and 0.83, respectively. CONCLUSIONS: We did not find any significant difference for progression and AS discontinuation rate between the 2 groups. The PSA kinetic seems accurate as a marker of tumour progression. These results support the conduct of a multi-centre prospective trial to confirm these findings.