Expanding inclusion criteria for active surveillance in intermediate-risk prostate cancer: a machine learning approach.

PURPOSE: To develop new selection criteria for active surveillance (AS) in intermediate-risk (IR) prostate cancer (PCa) patients. METHODS: Retrospective study including patients from 14 referral centers who underwent pre-biopsy mpMRI, image-guided biopsies and radical prostatectomy. The cohort included biopsy-naive IR PCa patients who met the following inclusion criteria: Gleason Grade Group (GGG) 1-2, PSA < 20 ng/mL, and cT1-cT2 tumors. We relied on a recursive machine learning partitioning algorithm developed to predict adverse pathological features (i.e., ≥ pT3a and/or pN + and/or GGG ≥ 3). RESULTS: A total of 594 patients with IR PCa were included, of whom 220 (37%) had adverse features. PI-RADS score (weight:0.726), PSA density (weight:0.158), and clinical T stage (weight:0.116) were selected as the most informative risk factors to classify patients according to their risk of adverse features, leading to the creation of five risk clusters. The adverse feature rates for cluster #1 (PI-RADS ≤ 3 and PSA density < 0.15), cluster #2 (PI-RADS 4 and PSA density < 0.15), cluster #3 (PI-RADS 1-4 and PSA density ≥ 0.15), cluster #4 (normal DRE and PI-RADS 5), and cluster #5 (abnormal DRE and PI-RADS 5) were 11.8, 27.9, 37.3, 42.7, and 65.1%, respectively. Compared with the current inclusion criteria, extending the AS criteria to clusters #1 + #2 or #1 + #2 + #3 would increase the number of eligible patients (+ 60 and + 253%, respectively) without increasing the risk of adverse pathological features. CONCLUSIONS: The newly developed model has the potential to expand the number of patients eligible for AS without compromising oncologic outcomes. Prospective validation is warranted.

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.

Grade group 1 prostate cancer on biopsy: are we still missing aggressive disease in the era of image-directed therapy?

PURPOSE: Recently, Eggener et al. reignited a debate consisting to redefine Gleason Grade Group (GGG) 1 prostate cancer (PCa) as a precancerous lesion to reduce overdiagnosis and overtreatment. However, historical cohorts showed that some GGG1-labeled disease at biopsy may be underestimated by the standard PCa diagnostic workup. The aim was to assess whether the risk of adverse features at radical prostatectomy (RP) in selected GGG1 patients still exists in the era of pre-biopsy mpMRI and image-guided biopsies. METHODS: We retrospectively reviewed our data from a European RP dataset to assess in contemporary patients with GGG1 at mpMRI-targeted biopsy the rate of adverse features at final pathology, defined as ≥ pT3a and/or pN+ and/or GGG ≥ 3. RESULTS: A total of 419 patients with cT1-T2 cN0 GGG1-PCa were included. At final pathology, 143 (34.1%) patients had adverse features. In multivariate analysis, only unfavorable intermediate-risk/high-risk disease (defined on PSA or stage) was predictive of adverse features (OR 2.45, 95% CI 1.11-5.39, p = 0.02). A significant difference was observed in the 3-year biochemical recurrence-free survival between patients with and without adverse features (93.4 vs 87.8%, p = 0.026). In sensitivity analysis restricted low- and favorable intermediate-risk PCa, 122/383 patients (31.8%) had adverse features and no preoperative factors were statistically associated with this risk. CONCLUSION: In this European study, we showed that there is still a risk of underestimating GGG1 disease at biopsy despite the routine use of image-guided biopsies. Future studies are warranted to improve the detection of aggressive disease in GGG1-labeled patients by incorporating the latest tools such as genomic testing or radiomics.

Association of Prostate Cancer with Nuts, Seeds, Alcohol and Processed Meats: A Worldwide Population-Based Study.

There are conflicting data with regards to the link between diet and the prostate cancer. The purpose of this study was to assess the association of dietary factors with incidence, prevalence and mortality rates of prostate cancer worldwide. We conducted an ecological study including 170 countries, whose data on incidence, prevalence and mortality rates of prostate cancer, dietary factors, and potentially confounding factors were available and collected in May 2020. Univariable and multivariable linear regression analyses were used. Consumption of nuts and seeds was inversely associated with incidence, prevalence and mortality rates of prostate cancer (ß -0.7, P < 0.001; ß -2.1, P < 0.001; ß -0.1, P = 0.02; respectively). Intake of alcohol was associated with increased incidence, prevalence and mortality rates of prostate cancer (ß 1.8, P < 0.001; ß 4.5, P < 0.001; ß 0.4, P < 0.001; respectively). Consumption of processed meats was also associated with increased incidence and prevalence rates of prostate cancer (ß 0.6, P = 0.003; ß 2.8, P = 0.001; respectively). These data suggest that consumption of nuts and seeds have a protective effect against prostate carcinogenesis, progression, and metastasis, while alcohol and processed meat increase these risks.

Does Overgrading on Targeted Biopsy of Magnetic Resonance Imaging-visible Lesions in Prostate Cancer Lead to Overtreatment?

BACKGROUND AND OBJECTIVE: Targeted biopsy of the index prostate cancer (PCa) lesion on multiparametric magnetic resonance imaging (MRI) is effective in reducing the risk of overdiagnosis of indolent PCa. However, it remains to be determined whether MRI-targeted biopsy can lead to a stage shift via overgrading of the index lesion by focusing only on the highest-grade component, and to a subsequent risk of overtreatment. Our aim was to assess whether overgrading on MRI-targeted biopsy may lead to overtreatment, using radical prostatectomy (RP) specimens as the reference standard. METHODS: Patients with clinically localized PCa who had positive MRI findings (Prostate Imaging-Reporting and Data System [PI-RADS] score ≥3) and Gleason grade group (GG) ≥2 disease detected on MRI-targeted biopsy were retrospectively identified from a prospectively maintained database that records all RP procedures from eight referral centers. Biopsy grade was defined as the highest grade detected. Downgrading was defined as lower GG for the RP specimen than for MRI-targeted biopsy. Overtreatment was defined as downgrading to RP GG 1 for cases with GG ≥2 on biopsy, or to RP low-burden GG 2 for cases with GG ≥3 on biopsy. KEY FINDINGS AND LIMITATIONS: We included 1020 consecutive biopsy-naïve patients with GG ≥2 PCa on MRI-targeted biopsy in the study. Pathological analysis of RP specimens showed downgrading in 178 patients (17%). The transperineal biopsy route was significantly associated with a lower risk of downgrading (odds ratio 0.364, 95% confidence interval 0.142-0.814; p = 0.022). Among 555 patients with GG 2 on targeted biopsy, only 18 (3.2%) were downgraded to GG 1 on RP. Among 465 patients with GG ≥3 on targeted biopsy, three (0.6%) were downgraded to GG 1 and seven were downgraded to low-burden GG 2 on RP. The overall risk of overtreatment due to targeted biopsy was 2.7% (28/1020). CONCLUSIONS AND CLINICAL IMPLICATIONS: Our multicenter study revealed no strong evidence that targeted biopsy results could lead to a high risk of overtreatment. PATIENT SUMMARY: In the diagnosis pathway for prostate cancer, results for targeted biopsies guided by magnetic resonance imaging (MRI) scans lead to a negligible proportion of overtreatment.

Lower Detrusor Apron-sparing Robot-assisted Radical Cystectomy and Intracorporeal Neobladder Reconstruction: Technique and Preliminary Outcomes.

BACKGROUND: Prior studies on robot-assisted laparoscopic prostatectomy (RALP) have shown that preservation of the anterior periprostatic structures is associated with good functional outcomes in terms of urinary continence and erectile function. With this in mind, we developed a technique for preservation of the lower part of the detrusor apron (LDA) and anterior periprostatic structures at the time of robot-assisted radical cystectomy (RARC) and intracorporeal neobladder (ICNB) reconstruction. OBJECTIVE: To describe our LDA-sparing RARC technique and to assess its safety and outcomes. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively evaluated 11 patients who underwent LDA-sparing RARC and ICNB reconstruction at our centre from January 2017 to May 2021. SURGICAL PROCEDURE: In brief, after developing the plane posterior to the bladder and prostate, the dissection proceeds laterally on both sides of the prostate in an effort to identify the prostatic pedicle. At this point, the bladder pedicles are sectioned in an antegrade fashion. Once the prostate is reached, the dissection is continued laterally by developing the plane that was previously identified. The neurovascular bundles and the lateral and anterior periprostatic structures are conserved in toto. Neobladder reconstruction is performed intracorporeally. OUTCOME MEASUREMENTS: Postoperative complications, urinary continence (UC), and erectile function (EF). RESULTS AND LIMITATIONS: The median console time was 290 min. The 30-d complication rate was 36%, with two Clavien-Dindo grade II and two grade III complications that were not attributable to the novel surgical technique. At 12 mo, all patients reported daytime UC or use of a safety pad; at night, seven patients were continent or used a safety pad. Regarding 12-mo EF, four patients were potent without a need for medications, while six were potent with the use of oral phosphodiesterase type 5 inhibitors and one with the use of intracavernosal injections. Limitations include the small number of cases. CONCLUSIONS: LDA-sparing RARC is an applicable and reproducible procedure. Our results suggest that this approach is associated with good functional outcomes in terms of UC and EF. PATIENT SUMMARY: We describe a novel approach for robot-assisted removal of the bladder that allows greater preservation of nerve bundles and other structures. Our study shows that the technique is safe and associated with good outcomes for urinary function and erectile function for patients eligible for this surgical procedure.

The BETTY Score to Predict Perioperative Outcomes in Surgical Patients.

The aim of this study is to evaluate a new user-friendly scoring system, namely the BETTY score, that aims to predict 30-day patient outcomes after surgery. In this first description, we rely on a population of prostate cancer patients undergoing robot-assisted radical prostatectomy. The BETTY score includes the patient's American Society of Anesthesiologists score, the body mass index, and intraoperative data, including operative time, estimated blood loss, any major intraoperative complications, hemodynamic, and/or respiratory instability. There is an inverse relationship between the score and severity. Three clusters assessing the risk of postoperative events were defined: low, intermediate, and high risk of postoperative events. A total of 297 patients was included. The median length of hospital stay was 1 day (IQR1-2). Unplanned visits, readmissions, any complications, and serious complications occurred in 17.2%, 11.8%, 28.3%, and 5% of cases, respectively. We found a statistically significant correlation between the BETTY score and all endpoints analyzed (all p ≤ 0.01). A total of 275, 20, and 2 patients were classified as low-, intermediate-, and high-risk according to the BETTY scoring system, respectively. Compared with low-risk patients, patients at intermediate-risk were associated with worse outcomes for all endpoints analyzed (all p ≤ 0.04). Future studies, in various surgical subspecialties, are ongoing to confirm the usefulness of this easy-to-use score in routine.

MRI lesion size is more important than the number of positive biopsy cores in predicting adverse features and recurrence after radical prostatectomy: implications for active surveillance criteria in intermediate-risk patients.

INTRODUCTION: To determine associations between prostate cancer (PCa) tumor burden measured on biopsy or multiparametric magnetic resonance imaging (mpMRI) and outcomes in intermediate-risk (IR) International Society of Urological Pathology (ISUP) grade 2 men managed with primary radical prostatectomy (RP). METHODS: This retrospective, multicenter study was conducted in eight referral centers. The cohort included IR PCa patients who had ISUP 2 at biopsy. We defined biopsy tumor burden as low/high based on the absence/presence of more than 25% positive cores. Tumor burden on imaging was defined as low/high based on maximum lesion diameter, <15 mm and ≥15 mm at mpMRI, respectively. The histological endpoint of the study was adverse features at RP, defined as ≥pT3a stage and/or lymph node invasion and/or ISUP ≥3 at final pathology. The clinical endpoint was biochemical recurrence (BCR) after RP. RESULTS: A total of 698 IR patients was included, of whom 335 (48%) had adverse features. In multivariate logistic regression analysis, there was no statistical association between tumor burden at biopsy and adverse features (p = 0.7). Tumor size ≥15 mm at mpMRI was significantly associated with adverse pathology (OR 1.65, 95%CI 1.14-2.39; p = 0.01). No significant association was observed between tumor burden at biopsy and BCR (p = 0.4). Tumor size ≥15 mm at mpMRI was significantly associated with BCR (HR 1.96, 95% CI 1.01-3.80; p = 0.04). CONCLUSIONS: Our data support extending the inclusion criteria to ISUP 2 men with >25% positive cores, provided they have a low tumor size at mpMRI (<15 mm). Prospective studies should be performed to validate these findings.

Magnetic Resonance Imaging-based T-staging to Predict Biochemical Recurrence after Radical Prostatectomy: A Step Towards the iTNM Classification.

BACKGROUND: Local staging of prostate cancer (PCa) still relies on digital rectal examination (DRE), which therefore remains the standard for risk stratification in guideline recommendations, clinical trials, and patient counseling. This issue is increasingly controversial as multiparametric magnetic resonance imaging (mpMRI) has become the most influential diagnostic tool for local staging of PCa over the past two decades. OBJECTIVE: To compare various models of T category based on DRE or mpMRI to predict early biochemical recurrence (BCR) after radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS: A retrospective multicenter cohort study was conducted between 2014 and 2021. A total of 1436 patients were recruited across eight referral centers in France, Italy, Switzerland, and Belgium. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: BCR was defined as two prostate-specific antigen values of ≥0.2 ng/ml during follow-up. Harrell's concordance index (C index) was used to compare the discrimination of four models of T staging based on DRE (model 1: cT1 vs cT2 vs cT3) or mpMRI (model 2: organ-confined disease vs extracapsular extension [iECE] vs seminal vesicle invasion [iSVI]; model 3: Prostate Imaging-Reporting and Data System [PI-RADS] ≤3 vs PI-RADS 4 vs PI-RADS 5; and model 4: iT2a [PI-RADS ≤3] vs iT2b [PI-RADS 4] vs iT2c [PI-RADS 5 excluding ECE or SVI] vs iT3a [ECE] vs iT3b [SVI]) to predict BCR. RESULTS AND LIMITATIONS: Overall, 74 (5%), 845 (59%), 482 (34%), and 35 (2%) patients had low-, intermediate-, high-, and very high-risk PCa, respectively, according to the Mazzone risk classification. After median follow-up of 16 mo, 113 patients experienced BCR. Although the new five-group mpMRI-based T classification system (model 4) had the highest prognostic discrimination (C index 0.694) for predicting early BCR on multivariable analysis, there was overlap between the 95% confidence intervals of the models. On sensitivity analysis, the new mpMRI-based T staging still had a higher C index than DRE for predicting BCR when excluding cN1 patients and comparing it with a five-group DRE-based T classification (cT1c vs cT2a vs cT2b vs cT2c vs cT3), but the overlap between the 95% confidence intervals of the models remained. The main limitation is the short follow-up. CONCLUSIONS: We described an alternative mpMRI-based T staging for prediction of early BCR after RP for PCa. Our results need to be validated externally before they can be applied in clinical practice. PATIENT SUMMARY: At present, digital rectal examination of the prostate is used to stage prostate cancer. We developed an alternative model for staging that uses information from magnetic resonance imaging (MRI) scans to predict cancer outcomes for men undergoing surgical removal of the prostate.

Robot-assisted Radical Cystectomy with Orthotopic Neobladder Reconstruction: Techniques and Functional Outcomes in Males.

BACKGROUND: Little is known regarding functional outcomes after robot-assisted radical cystectomy (RARC) and intracorporeal neobladder (ICNB) reconstruction. OBJECTIVE: To report on urinary continence (UC) and erectile function (EF) at 12 mo after RARC and ICNB reconstruction and investigate predictors of these outcomes. DESIGN, SETTING, AND PARTICIPANTS: We used data from a multi-institutional database of patients who underwent RARC and ICNB reconstruction for bladder cancer. SURGICAL PROCEDURE: The cystoprostatectomy sensu stricto followed the conventional steps. ICNB reconstruction was performed at the physician's discretion according to the Studer/Wiklund, S pouch, Gaston, vescica ileale Padovana, or Hautmann technique. The techniques are detailed in the video accompanying the article. MEASUREMENTS: The outcomes measured were UC and EF at 12 mo. RESULTS AND LIMITATIONS: A total of 732 male patients were identified with a median age at diagnosis of 64 yr (interquartile range 58-70). The ICNB reconstruction technique was Studer/Wiklund in 74%, S pouch in 1.5%, Gaston in 19%, vescica ileale Padovana in 1.5%, and Hautmann in 4% of cases. The 12-mo UC rate was 86% for daytime and 66% for nighttime continence, including patients who reported the use of a safety pad (20% and 32%, respectively). The 12-mo EF rate was 55%, including men who reported potency with the aid of phosphodiesterase type 5 inhibitors (24%). After adjusting for potential confounders, neobladder type was not associated with UC. Unilateral nerve-sparing (odds ratio [OR] 3.85, 95% confidence interval [CI] 1.88-7.85; p < 0.001) and bilateral nerve-sparing (OR 6.25, 95% CI 3.55-11.0; p < 0.001), were positively associated with EF, whereas age (OR 0.93, 95% CI 0.91-0.95; p < 0.001) and an American Society of Anesthesiologists score of 3 (OR 0.46, 95% CI 0.25-0.89; p < 0.02) were inversely associated with EF. CONCLUSIONS: RARC and ICNB reconstruction are generally associated with good functional outcomes in terms of UC. EF is highly affected by the degree of nerve preservation, age, and comorbidities. PATIENT SUMMARY: We investigated functional outcomes after robot-assisted removal of the bladder in terms of urinary continence and erectile function. We found that, in general, patients have relatively good functional outcomes at 12 months after surgery.

Clinical Trial Protocol for PERFECT: A Randomised Controlled Trial Comparing the Efficiency and Tolerance of Transperineal Fusion Versus Transrectal Imaging-targeted Prostate Biopsies (CCAFU-PR1 Study).

PERFECT is a multicentre randomised controlled clinical trial that evaluates the efficiency of fusion magnetic resonance imaging-targeted biopsies in the transperineal (TP) versus transrectal (TR) approach in terms of the detection of significant cancers. Our study builds on the hypothesis that the TP approach for prostate biopsies has at least the same diagnostic accuracy as the TR approach, with lower morbidity. Here, we describe the clinical protocol, study population, and primary and secondary outcomes.

Overdiagnosis and stage migration of ISUP 2 disease due to mpMRI-targeted biopsy: facts or fictions.

Recently, the use of targeted biopsy has been subject to critics, as it has been speculated that targeted biopsy might lead to overdiagnosis of clinically significant prostate cancer (PCa). In this study, we tried to evaluate whether targeted sampling in patients with organ-confined disease and ISUP 2 disease was associated with downgrading of the prostatectomy specimen, hence, leading to an unnecessary treatment, in terms of radical surgery. We relied on a prospectively-maintained multi-institutional database and identified 1293 patients with ISUP 2 disease on targeted biopsy only. Median (IQR) patients' age at diagnosis was 65 (60, 70) years. Median PSA was 6.8 (5.0, 9.6) ng/ml. Overall, only 33 (2.6%) patients presented downgrading on their RP specimens. Patients who experienced downgrading were biopsied more frequently trans-rectally, had a lower total tumor length in mm and lower percentage of maximum core involvement and lower rates of cancer on systematic biopsy (all p ≤ 0.03). The strongest factors associated with reduced risk of downgrading were total tumor length, in mm, (OR: 0.71, 95% CI: 0.62,0.82, p < 0.001) and transperineal biopsy route (OR: 0.38, 95% CI: 0.14,1.00, p = 0.05).

[Isolated male epispadias]. / Epispadias masculin isolé.

Epispadias is a rare urogenital malformation characterized by more or less complete aplasia of the upper part of the urethra. It is commonly associated with bladder exstrophy. Isolated epispadias occurs in 10% of cases. Continent and incontinent epispadias may be distinguished. We report the case of a 29-year old patient presenting with dysuria associated with the impossibility of having sexual intercourses. Physical examination of the external genitalia showed slit-like abnormal urethral opening on the distal half of the dorsal side of the penis. Patient's penis didn't have dorsal curvature (chordee), the corpus cavernosum was palpated and slightly lateralized. The abdominal wall was without abnormalities. The remainder of the clinical examination was normal. Given this anomaly, the diagnosis of balano-pubic continent epispadias was retained. Ultrasound of the urinary tract was normal and pelvis X-ray without preparation showed interpubic diastasis. The patient underwent single-stage surgery using Cantwell-Young technique. Immediate postoperative outcome was without abnormalities; the urethral probe was removed 21 days later, after wound healing. Functional and aesthetics outcome evaluated at three and six months was satisfactory without penis shortness.

Bilateral kidney matrix stones: a rare case.

Kedney matrix stones are a rare form of calculi. Flank pain and urinary tract infections (UTI) are the most common presentations of matrix calculi. The diagnosis is usually made at surgery, but some preoperative radiographic findings might be suggestive. Open surgery was the method of choice for treatment. However, combination of ureterorenoscopy and percutaneous nephrolithotomy (PCNL) was found to be safe and effective. We report a rare case of renal and ureteral matrix stones that were diagnosed and treated by open surgery. We also describe its clinical, radiological and therapeutic features through a review of the literature.