Interest of the POSPOM score in estimating postoperative complication risk after radical cystectomy.

INTRODUCTION: Identifying patients at risk after cystectomy for cancer is essential. The POSPOM score is a non-specific urological surgery score for estimating postoperative hospital mortality. This study sought to validate the POSPOM score for predicting postoperative morbidity and mortality after cystectomy. METHODS: The study retrospectively included all patients undergoing cystectomy for muscle-invasive or locally advanced bladder cancer between 2010 and 2019 in one center. The primary objective was validation of the POSPOM score for calculating severe postoperative morbidity [Clavien-Dindo (CDC)≥3] and 90-day mortality after cystectomy. Secondary objectives were comparison to other predictive scores [Charlson (CCI), ASA]. RESULTS: At 90days, out of 167 patients, 26% (n=44) had a CDC≥3 complication and 8.4% (n=14) had died. POSPOM correlated with the risk of death at 90days (P<0.001) and postoperative transfusion (P<0.01). Patients with CDC≥3 complications had higher CCI and POSPOM (median 6.5 vs. 5, P<0.01 and 6.49% vs. 5.58%, P=0.029, respectively). Patients who died postoperatively had higher CCI and POSPOM (median 8 vs. 6, P<0.001 and 23.9% vs. 5.58%, P<0.001, respectively). The prognostic value of the POSPOM score for predicting mortality appears better [AUC=0.886 (0.798-0.973)] compared with CCI [AUC=0.812 (0.710-0.915)] and ASA [AUC=0.739 (0.630-0.849)], but not for predicting morbidity. CONCLUSION: This study confirms the robustness of the POSPOM score for estimating mortality and its limitations for predicting postoperative morbidity.

Performance of a Region of Interest-based Algorithm in Diagnosing International Society of Urological Pathology Grade Group ≥2 Prostate Cancer on the MRI-FIRST Database-CAD-FIRST Study.

BACKGROUND AND OBJECTIVE: Prostate multiparametric magnetic resonance imaging (MRI) shows high sensitivity for International Society of Urological Pathology grade group (GG) ≥2 cancers. Many artificial intelligence algorithms have shown promising results in diagnosing clinically significant prostate cancer on MRI. To assess a region-of-interest-based machine-learning algorithm aimed at characterising GG ≥2 prostate cancer on multiparametric MRI. METHODS: The lesions targeted at biopsy in the MRI-FIRST dataset were retrospectively delineated and assessed using a previously developed algorithm. The Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) score assigned prospectively before biopsy and the algorithm score calculated retrospectively in the regions of interest were compared for diagnosing GG ≥2 cancer, using the areas under the curve (AUCs), and sensitivities and specificities calculated with predefined thresholds (PIRADSv2 scores ≥3 and ≥4; algorithm scores yielding 90% sensitivity in the training database). Ten predefined biopsy strategies were assessed retrospectively. KEY FINDINGS AND LIMITATIONS: After excluding 19 patients, we analysed 232 patients imaged on 16 different scanners; 85 had GG ≥2 cancer at biopsy. At patient level, AUCs of the algorithm and PI-RADSv2 were 77% (95% confidence interval [CI]: 70-82) and 80% (CI: 74-85; p = 0.36), respectively. The algorithm's sensitivity and specificity were 86% (CI: 76-93) and 65% (CI: 54-73), respectively. PI-RADSv2 sensitivities and specificities were 95% (CI: 89-100) and 38% (CI: 26-47), and 89% (CI: 79-96) and 47% (CI: 35-57) for thresholds of ≥3 and ≥4, respectively. Using the PI-RADSv2 score to trigger a biopsy would have avoided 26-34% of biopsies while missing 5-11% of GG ≥2 cancers. Combining prostate-specific antigen density, the PI-RADSv2 and algorithm's scores would have avoided 44-47% of biopsies while missing 6-9% of GG ≥2 cancers. Limitations include the retrospective nature of the study and a lack of PI-RADS version 2.1 assessment. CONCLUSIONS AND CLINICAL IMPLICATIONS: The algorithm provided robust results in the multicentre multiscanner MRI-FIRST database and could help select patients for biopsy. PATIENT SUMMARY: An artificial intelligence-based algorithm aimed at diagnosing aggressive cancers on prostate magnetic resonance imaging showed results similar to expert human assessment in a prospectively acquired multicentre test database.

Transperineal Versus Transrectal Magnetic Resonance Imaging-targeted Biopsies for Prostate Cancer Diagnosis: Final Results of the Randomized PERFECT trial (CCAFU-PR1).

BACKGROUND: Recent guidelines favor transperineal (TP) prostate biopsies over the transrectal (TR) approach due to a reduced sepsis risk. Yet, evidence from controlled trial comparing both approaches within the MRI-targeted pathway for significant prostate cancer (PCa) detection is lacking. OBJECTIVE: To compare the significant PCa detection rate between magnetic resonance imaging (MRI)-targeted TR and TP approaches in biopsy-naïve patients. DESIGN, SETTING, AND PARTICIPANTS: In this noninferiority controlled trial, we randomized (ratio 1:1) 270 MRI-positive biopsy-naïve patients. INTERVENTION: MRI-targeted TP versus TR biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: The primary outcome was the detection rate of significant PCa (International Society of Urological Pathology [ISUP] ≥2) in MRI-targeted biopsies. Secondary outcomes were any-grade PCa detection, detection on concomitant systematic biopsy, complications, and functional outcomes. RESULTS AND LIMITATIONS: Targeted biopsies identified significant PCa in 47.2% of TP and 54.2% of TR participants (-7%, p = 0.6235). On a per-lesion analysis, posterior lesions yielded higher detection rates via TR (59.0% vs 44.3%, p = 0.0443), while anterior lesions were more frequently detected via TP (40.6% vs 26.5%, p = 0.2228). The overall (any grade) cancer detection rate in targeted biopsies was comparable between groups: 71.3% (TP) versus 64.1% (TR; p = 0.2209) with significantly more ISUP 1 cases detected in the TP arm. Adverse events of grade ≥2 were not different between TP (35.7%) and TR (40.5%, p = 0.4256). One TR patient (0.8%) experienced grade 3 sepsis. Quality of life, and urinary and sexual function, as well as pain scores, were comparable between groups. CONCLUSIONS: Despite a comparable overall detection rate for any-grade PCa, noninferiority of TP over TR for MRI-targeted biopsies for significant PCa detection was not demonstrated. However, MRI lesion location influenced biopsy route performance, suggesting that a pragmatic approach based on lesion location might enhance significant PCa assessment. PATIENT SUMMARY: This trial compared the efficacy and safety of two biopsy approaches for prostate cancer diagnosis. Both approaches seem complementary according to the lesion location.

Cohort profile: COBLAnCE: a French prospective cohort to study prognostic and predictive factors in bladder cancer and to generate real-world data on treatment patterns, resource use and quality of life.

PURPOSE: Bladder cancer is a complex disease with a wide range of outcomes. Clinicopathological factors only partially explain the variability between patients in prognosis and treatment response. There is a need for large cohorts collecting extensive data and biological samples to: (1) investigate gene-environment interactions, pathological/molecular classification and biomarker discovery; and (2) describe treatment patterns, outcomes, resource use and quality of life in a real-world setting. PARTICIPANTS: COBLAnCE (COhort to study BLAdder CancEr) is a French national prospective cohort of patients with bladder cancer recruited between 2012 and 2018 and followed for 6 years. Data on patient and tumour characteristics, treatments, outcomes and biological samples are collected at enrolment and during the follow-up. FINDINGS TO DATE: We describe the cohort at enrolment according to baseline surgery and tumour type. In total, 1800 patients were included: 1114 patients with non-muscle-invasive bladder cancer (NMIBC) and 76 patients with muscle-invasive bladder cancer (MIBC) had transurethral resection of a bladder tumour without cystectomy, and 610 patients with NMIBC or MIBC underwent cystectomy. Most patients had a solitary lesion (56.3%) without basement membrane invasion (71.7% of Ta and/or Tis). Half of the patients with cystectomy were stage ≤T2 and 60% had non-continent diversion. Surgery included local (n=298) or super-extended lymph node dissections (n=11) and prostate removal (n=492). Among women, 16.5% underwent cystectomy and 81.4% anterior pelvectomy. FUTURE PLANS: COBLAnCE will be used for long-term studies of bladder cancer with focus on clinicopathological factors and molecular markers. It will lead to a much-needed improvement in the understanding of the disease. The cohort provides valuable real-world data, enabling researchers to study various research questions, assess routine medical practices and guide medical decision-making.

A new scaffold-free tumoroid model provides a robust preclinical tool to investigate invasion and drug response in Renal Cell Carcinoma.

Clear cell Renal Cell Carcinoma (ccRCC) is one of the most prevalent kidney cancers, which is often asymptomatic and thus discovered at a metastatic state (mRCC). mRCC are highly heterogeneous tumors composed of subclonal populations that lead to poor treatment response rate. Several recent works explored the potential of ccRCC tumoroids culture derived from patients. However, these models were produced following a scaffold-based method using collagen I or Matrigel that exhibit lot variability and whose complexity could induce treatment response modifications and phenotypic alterations. Following the observation that ccRCC tumoroids can create their own niche by secreting extracellular matrix components, we developed the first scaffold-free tumoroid model of ccRCC tumors. Tumoroids from mice as well as from human tumors were generated with high success rate (≥90%) using a magnetic suspension method and standard culture media. Immunofluorescence analysis revealed their self-organization capacities to maintain multiple tumor-resident cell types, including endothelial progenitor cells. Transcriptomic analysis showed the reproducibility of the method highlighting that the majority of gene expression patterns was conserved in tumoroids compared to their matching tumor tissue. Moreover, this model enables to evaluate drug effects and invasiveness of renal cancer cells in a 3D context, providing a robust preclinical tool for drug screening and biomarker assessment in line with alternative ex vivo methods like tumor tissue slice culture or in vivo xenograft models.

Intra-operative fluorescence-based detection of positive surgical margins during radical prostatectomy: Lessons learned from a pilot ex vivo translational study.

OBJECTIVES: Nerve-sparing techniques during radical prostatectomy have been associated with an increased risk of positive surgical margins. The intra-operative detection of residual prostatic tissue could help mitigate this risk. The objectives of the present study were to assess the feasibility of using an anti-prostate-specific membrane antigen (anti-PSMA) antibody conjugated with a fluorophore to characterize fresh prostate tissue as prostatic or non-prostatic for intra-operative surgical margin detection. METHODS: Fresh prostatic tissue samples were collected from transurethral resections of the prostate (TURP) or prostate biopsies, and either immunolabelled with anti-PSMA antibody conjugated with Alexa Fluor 488 or used as controls. A dedicated, laparoscopy-compliant fluorescence device was developed for real-time fluorescence detection. Confocal microscopy was used as the gold standard for comparison. Spectral unmixing was used to distinguish specific, Alexa Fluor 488 fluorescence from nonspecific autofluorescence. RESULTS: The average peak wavelength of the immuno-labeled TURP samples (n = 4) was 541.7 ± 0.9 nm and of the control samples (n = 4) was 540.8 ± 2.2 nm. Spectral unmixing revealed that these similar measures were explained by significant autofluorescence, linked to electrocautery. Three biopsy samples were then obtained from seven patients and also displayed significant nonspecific fluorescence, raising questions regarding the reproducibility of the fixation of the anti-PSMA antibodies on the samples. Comparing the fluorescence results with final pathology proved challenging due to the small sample size and tissue alterations. CONCLUSIONS: This study showed similar fluorescence of immuno-labeled prostate tissue samples and controls, failing to demonstrate the feasibility of intra-operative margin detection using PSMA immuno-labeling, due to marked tissue autofluorescence. We successfully developed a fluorescence device that could be used intraoperatively in a laparoscopic setting. Use of the infrared range as well as newly available antibodies could prove interesting options for future research.

Accuracy of elastic fusion biopsy: Comparing prostate cancer detection between targeted and systematic biopsy.

INTRODUCTION: When performing targeted biopsy (TBx), the need to add systematic biopsies (SBx) is often debated. Aim of the study is to evaluate the added value of SBx in addition to TBx in terms of prostate cancer (PCa) detection rates (CDR), and to test the concordance between multiparametric magnetic resonance imaging (mpMRI) findings and fusion biopsy results in terms of cancer location. METHODS: We performed a retrospective, multicentric study that gathered data on 1992 consecutive patients who underwent elastic fusion biopsy between 2011 and 2020. A standardized approach was used, with TBx (2-4 cores per target) followed by SBx (12-14 cores). We assessed CDR of TBx, of SBx, and TBx+SBx for all cancers and clinically significant PCa (csPCa), defined as ISUP score ≥2. CDR was evaluated according to radiological and clinical parameters, with a particular focus on PI-RADS 3 lesions. In a subgroup of 1254 patients we tested the discordance between mpMRI findings and fusion biopsy results in terms of cancer location. Uni- and multivariable logistic regression analyses were performed to identify predictors of CDR. RESULTS: CDR of TBx+SBx was 63.0% for all cancers and 38.8% of csPCa. Per-patient analysis showed that SBx in addition to TBx improved CDR by 4.5% for all cancers and 3.4% for csPCa. Patients with lesions scored as PI-RADS 3, 4, and 5 were diagnosed with PCa in 27.9%, 72.8%, and 92.3%, and csPCa in 10.7%, 43.6%, and 69.3%, respectively. When positive, PI-RADS 3 lesions were ISUP grade 1 in 61.1% of cases. Per-lesion analysis showed that discordance between mpMRI and biopsy was found in 56.6% of cases, with 710 patients having positive SBx outside mpMRI targets, of which 414 (58.0%) were clinically significant. PSA density ≥0.15 was a strong predictor of CDR. CONCLUSIONS: The addition of systematic mapping to TBx contributes to a minority of per-patient diagnoses but detects a high number of PCa foci outside mpMRI targets, increasing biopsy accuracy for the assessment of cancer burden within the prostate. High PSA-density significantly increases the risk of PCa, both in the whole cohort and in PI-RADS 3 cases.

Robot-Assisted Laparoscopic Calyceo-Pyelostomy for Vascular Compression of the Upper Calyx (Fraley Syndrome).

Fraley's Syndrome is a rare anatomic vascular malformation described in 1966 where an aberrant crossing vessel compresses the upper infundibulum and leads to upper calyx massive dilation. It is mostly asymptomatic and the diagnosis often missed; however, surgery is usually required for symptomatic cases. Open surgery is still frequently used while minimally invasive management is anecdotal in the literature. We report the first robot-assisted calyceo-pyelostomy. An 18-year-old female patient presented with intermittent, recurring, severe left flank pain leading to insomnia, evolving in the last 3 months. A 3-phases computerized tomography scan (CT-scan) showed a rotated left kidney, with upper calyx massive dilation and thinning of the upper renal parenchyma without any evident obstacle. Cystocopy and retrograde pyelography were performed. It confirmed a single ureteral meatus, a single ureter, and a narrowed upper calyx with upper calyx dilation. An ureteral catheter (JJ stent) was inserted in the upper calyx and the patient was planned for surgical exploration. During robotic surgery, an abnormal crossing vessel was identified and the diagnosis of Fraley's syndrome was made intraoperatively. According to previous literature, a calyceo-pyelostomy with uncrossing of the upper major calyx and resection of the narrowed upper infundibulum was performed. Total operative time was 114 min, pneumoperitoneum time was 96 min, blood loss less than 10 ml, and patient was released on post-operative day 2. The ureteral stent was removed 4 weeks after the intervention. At 12 postoperative weeks, the patient had complete regression of pain and the 12 postoperative week CT-scan showed a reduction of the dilation and a patent anastomosis. Fraley's syndrome is a rare entity. In our case, the diagnosis of Fraley syndrome was made intraoperatively after an extensive previous workup, underlining the difficulty to make this diagnosis. We report and provide a video of the first robot-assisted procedure for Fraley's syndrome in a nephron-sparing technique. Patient was pain-free at the 3-month.

Pathological features of Prostate Imaging Reporting and Data System (PI-RADS) 3 MRI lesions in biopsy and radical prostatectomy specimens.

OBJECTIVE: To assess the whole pathology spectrum of Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, identified on magnetic resonance imaging, using systematic (SB), targeted biopsy (TB) and radical prostatectomy (RP) specimen analysis. METHODS: From a prospective database of patients undergoing RP after a combination of SB (median 12 cores) and fusion TB (median 3 cores), we included 150 PI-RADS 3 cases. Clinically significant prostate cancer (csPCa) was defined by a Grade Group 2 or more. The primary endpoints were unfavourable features in RP specimens. RESULTS: Targeted biopsy was negative in 20.7% of patients. Final Grade Group 3 or more and a pT3 stage was reported in 36.7% and 38.7% of RP specimens. The upgrading rate was 38.2% between biopsy and RP specimens. The concordance rate between Grade Group on TB and RP was only 38.0%. The two independent predictive factors for unfavourable disease (pT3-4 and/or final Grade Group 3-5) were prostate-specific antigen density (PSAD; P = 0.001) and presence of csPCa on TB (odds ratio 3.7; P = 0.001). The risk of unfavourable disease was increased 2.3-fold and 5.8-fold, respectively, for patients with a PSAD between 0.15 and 0.20, and a PSAD >0.20 ng/mL/g. The 5-year biochemical recurrence-free survival rate was 93.2%. CONCLUSIONS: PI-RADS 3 lesions exhibited aggressive features in almost 40% of cases. PSAD and presence of csPCa on TB are independent predictive factors for high-grade and/or extraprostatic disease. A combination of SB and TB improve grade prediction compared to use of TB alone.

Superselective Ischemia in Robotic Partial Nephrectomy Does Not Provide Better Long-term Renal Function than Renal Artery Clamping in a Randomized Controlled Trial (EMERALD): Should We Take the Risk?

BACKGROUND: Superselective clamping of tumor-targeted arteries aims to eliminate ischemia of the remnant kidney while keeping tumor bed bloodless during excision. OBJECTIVE: To evaluate the impact of superselective clamping on long-term renal function, compared with renal artery early unclamping. DESIGN, SETTING, AND PARTICIPANTS: A randomized monocentric single-blind trial (1:1) was conducted from February 2018 to August 2019. Patients with a single renal tumor were candidates for a robot-assisted partial nephrectomy (RAPN) in a referral center. EMERALD (NCT03679572) was powered to include 50 patients with an interim analysis after 30 cases. INTERVENTION: Superselective RAPN (SS-RAPN) with near-infrared fluorescence (NIRF) or conventional RAPN with renal artery early unclamping. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the percent change of estimated glomerular filtration rate (eGFR) in the operated kidney after 6 mo (combination of eGFR and relative function on 99mTc-DMSA scintigraphy). Secondary endpoints assessed feasibility and safety of the technique. RESULTS AND LIMITATIONS: Relative eGFR reduction in the operated kidney at 6 mo did not differ significantly (-21.4% vs -23.4%, p=0.66). This absence of difference remained after adjusting on percentage of kidney volume preserved, which was an independent predictor of functional preservation. There were no significant differences in terms of blood loss, change in hemoglobin, postoperative complications, transfusion, and conversion to radical nephrectomy (two vs zero) or to open surgery (one vs zero). Despite a good accrual, the steering committee interrupted the trial after the interim analysis for futility given the absence of trend in favor of SS-RAPN. CONCLUSIONS: SS-RAPN using NIRF does not provide better renal function preservation than renal artery clamping, questioning the interest of this technique at a higher risk of bleeding. PATIENT SUMMARY: In this randomized controlled trial, superselective clamping of tumor feeding arteries did not show any advantage in terms of long-term renal function compared with conventional artery clamping.

External validation of a prostate biopsy simulator.

INTRODUCTION: Simulation-based training has proven to be a promising option allowing for initial and continuous training while limiting the impact of the learning curve on the patient. The Biopsym simulator was developed as a complete teaching environment for the prostate biopsy procedure. This paper presents the results of an external validation of this simulator, involving urology residents recruited during a regional teaching seminar. METHODS: Residents from 4 academic urology departments of the French Auvergne Rhône-Alpes region, who did not take part in the previous simulator validation studies, were enrolled. After a short presentation and standardized initiation session, residents carried out a simulated systematic 12-core biopsy procedure and were asked to fill in a questionnaire collecting their expectations and evaluation of the Biopsym simulator. The number of biopsies reaching each targeted sector, the total score provided by the simulator and the duration of the procedure were recorded. RESULTS: Twenty-three residents were recruited. The overall added value (/100) for learning was rated at a median of 100 (interquartile range 83-100), overall realism of the biopsy procedure at 80 (65-89). The median percentage of biopsies reaching the targeted sector was 66.7% (62-75). The median score provided by the simulator was 50% (37-60). For both, the difference between residents with or without prior biopsy experience was not statistically significant. The median duration of the simulated biopsy procedure was 4:58 (minutes: seconds) (3:49-6:00). Resident with prior experience required less time to complete the biopsy procedure 3:53 (3:39-4:56) vs. 5:10 (4:59-7:10), P=0.01. CONCLUSION: This external validation study confirms a high acceptance of the simulator by the target audience. To our knowledge, the Biopsym simulator is the only prostate biopsy simulator that demonstrated such validity as evaluated by clinicians, outside the center involved in its early development. LEVEL OF EVIDENCE: 3.

Cooperative Blockade of CK2 and ATM Kinases Drives Apoptosis in VHL-Deficient Renal Carcinoma Cells through ROS Overproduction.

Kinase-targeted agents demonstrate antitumor activity in advanced metastatic clear cell renal cell carcinoma (ccRCC), which remains largely incurable. Integration of genomic approaches through small-molecules and genetically based high-throughput screening holds the promise of improved discovery of candidate targets for cancer therapy. The 786-O cell line represents a model for most ccRCC that have a loss of functional pVHL (von Hippel-Lindau). A multiplexed assay was used to study the cellular fitness of a panel of engineered ccRCC isogenic 786-O VHL- cell lines in response to a collection of targeted cancer therapeutics including kinase inhibitors, allowing the interrogation of over 2880 drug-gene pairs. Among diverse patterns of drug sensitivities, investigation of the mechanistic effect of one selected drug combination on tumor spheroids and ex vivo renal tumor slice cultures showed that VHL-defective ccRCC cells were more vulnerable to the combined inhibition of the CK2 and ATM kinases than wild-type VHL cells. Importantly, we found that HIF-2α acts as a key mediator that potentiates the response to combined CK2/ATM inhibition by triggering ROS-dependent apoptosis. Importantly, our findings reveal a selective killing of VHL-deficient renal carcinoma cells and provide a rationale for a mechanism-based use of combined CK2/ATM inhibitors for improved patient care in metastatic VHL-ccRCC.

Prognostic Impact of pT3 Subclassification in a Multicentre Cohort of Patients with Urothelial Carcinoma of the Renal Pelvicalyceal System Undergoing Radical Nephroureterectomy: A Propensity Score-weighted Analysis After Central Pathology Review.

BACKGROUND: The current pathological tumour-node-metastasis (pTNM) classification for upper tract urothelial carcinoma (UTUC) does not include any risk stratification of pT3 renal pelvicalyceal tumours. OBJECTIVE: To assess the prognostic impact of pT3 subclassification in a multicentre cohort of patients with UTUC of the renal pelvicalyceal system undergoing radical nephroureterectomy (RNU). DESIGN, SETTING, AND PARTICIPANTS: Data from all consecutive patients treated with RNU for pT3 renal pelvicalyceal UTUC at 14 French centres from 1995 to 2013 were reviewed retrospectively. INTERVENTION: A central pathology review (CPR) was used to stratify pT3 patients into those with infiltration of the renal parenchyma on a microscopic level (pT3a) versus those with infiltration of the renal parenchyma visible on gross inspection of the resection specimen and/or invasion of peripelvic fat (pT3b). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Inverse probability weighting (IPW)-adjusted Cox regression analyses were used to compare recurrence-free survival (RFS) and cancer-specific survival (CSS) between pT3a and pT3b patients. RESULTS AND LIMITATIONS: Overall, 202 patients were included and further stratified into pT3a (n = 98; 48.5%) and pT3b (n = 104; 51.5%) subgroups. Median time to follow-up in the weighted population was 68 (interquartile range, 50-95) mo. In IPW-adjusted Cox regression analyses, pT3b versus pT3a substage was associated with a significant adverse effect on RFS (hazard ratio [HR] = 2.02; 95% confidence interval [CI] = [1.36-3.01]; p < 0.001) and CSS (HR = 1.84; 95% CI = [1.20-2.82]; p = 0.005). The study is limited by its retrospective design. CONCLUSIONS: Using IPW-adjusted analyses after the CPR, we observed that RNU patients with pT3b renal pelvicalyceal UTUC had adverse prognosis as compared with those with pT3a disease. As such, this subclassification could help refine the current pTNM system for UTUC. PATIENT SUMMARY: In this report, we looked at the prognostic interest of stratifying patients with pT3 renal pelvicalyceal upper tract urothelial carcinoma based on the extent of local invasion. We found that those with extensive infiltration (pT3b) had adverse prognosis as compared with those with limited infiltration (pT3a). This information could be provided on pathology reports to further guide clinical decision making.

Timing and delay of radical prostatectomy do not lead to adverse oncologic outcomes: results from a large European cohort at the times of COVID-19 pandemic.

PURPOSE: The current COVID-19 pandemic is transforming our urologic practice and most urologic societies recommend to defer any surgical treatment for prostate cancer (PCa) patients. It is unclear whether a delay between diagnosis and surgical management (i.e., surgical delay) may have a detrimental effect on oncologic outcomes of PCa patients. The aim of the study was to assess the impact of surgical delay on oncologic outcomes. METHODS: Data of 926 men undergoing radical prostatectomy across Europe for intermediate and high-risk PCa according to EAU classification were identified. Multivariable analysis using binary logistic regression and Cox proportional hazard model tested association between surgical delay and upgrading on final pathology, lymph-node invasion (LNI), pathological locally advanced disease (pT3-4 and/or pN1), need for adjuvant therapy, and biochemical recurrence. Kaplan-Meier analysis was used to estimate BCR-free survival after surgery as a function of surgical delay using a 3 month cut-off. RESULTS: Median follow-up and surgical delay were 26 months (IQR 10-40) and 3 months (IQR 2-5), respectively. We did not find any significant association between surgical delay and oncologic outcomes when adjusted to pre- and post-operative variables. The lack of such association was observed across EAU risk categories. CONCLUSION: Delay of several months did not appear to adversely impact oncologic results for intermediate and high-risk PCa, and support an attitude of deferring surgery in line with the current recommendation of urologic societies.

Stratifying patients with intermediate-risk prostate cancer: Validation of a new model based on MRI parameters and targeted biopsy and comparison with NCCN and AUA subclassifications.

OBJECTIVE: Intermediate-risk prostate cancer regroups heterogeneous patients with different oncologic outcomes. Aim of the study is to validate a novel intermediate-risk subclassification ("magnetic resonance imaging [MRI] subclassification") that defines favorable and unfavorable diseases based on multiparametric MRI parameters and compare it to NCCN and AUA intermediate-risk subclassifications. METHODS: A total of 429 patients treated with radical prostatectomy for NCCN intermediate-risk prostate cancer were identified. Using MRI subclassification, a favorable disease was defined as an organ-confined disease on MRI and international society of urological pathology Grade Group 1 to 2 on targeted biopsy. Remaining was classified as unfavorable. Univariable and multivariable analysis tested MRI subclassification in predicting overall unfavorable disease (OUD: pT3-4 and/or pN1 and/or International Society of Urological Pathology Grade Group ≥ 3), the need for adjuvant therapy and early biochemical recurrence (eBCR). Performance of NCCN, AUA, and MRI models was compared in term of OUD proportion and eBCR prediction using Harrell's c-index, calibrations plots, and decision curve analysis. RESULTS: Median (interquartile range) follow-up was 12 months (4-28). In multivariable analysis, MRI subclassification was an independent factor for OUD (odds ratio [OR]: 4.54 [2.85-7.22], P < 0.001), the need for adjuvant therapy (OR: 3.42 [1.36-8.57], P = 0.009), and eBCR (HR: 2.62 [1.18-5.83], P = 0.018). Using this model, the proportion of unfavorable disease decreased from 73.7% and 63.9% to 35.9% (P < 0.001) associated to an increasing proportion of OUD when compared to NCCN and AUA models (63.9% and 67.1%-77.9% respectively, P < 0.001). Performance of the 3 models for eBCR prediction tended to be similar with a poor accuracy ranged from 58.7% to 66.7% (P > 0.05), permanent miscalibration and a net benefit at decision curve analysis. CONCLUSIONS: We validated an intermediate-risk subclassification based on MRI and targeted biopsy that potentially improves patient selection by reducing the number of patients considered at unfavorable risk while increasing proportion of patients harboring poor oncologic outcomes. Its performance for eBCR detection was comparable to NCCN and AUA models.

External evaluation of the Briganti nomogram to predict lymph node metastases in intermediate-risk prostate cancer patients.

PURPOSE: The Briganti nomogram can be used with a threshold of 5% to decide when to offer lymph node dissection during radical prostatectomy. The objective of the study was to assess the accuracy of the Briganti nomogram on intermediate-risk prostate cancer patients managed in a single academic department. METHODS: We retrospectively reviewed the files of all patients managed by radical prostatectomy (RP) and bilateral pelvic lymph node dissection (BPLND) in our center between 2005 and 2017. The overall accuracy of the model in predicting metastatic lymph node disease was quantified by the construction of a receiver-operator characteristic (ROC) curve. A calibration plot was drawn to represent the relationship between the predicted and observed frequencies. RESULTS: We included 285 patients, among whom 175 (61.4%) were classified as intermediate risk as defined by D'Amico. The median follow-up was 60 (34-93) months. Twenty-seven patients (9.5%) were diagnosed with lymph node metastases. The median number of lymph nodes removed was 10 (7-14). The mean Briganti score was 19.3% in patients with lymph node involvement (LNI) and 6.3% in patients without LNI. Focusing on intermediate-risk patients, 91(52%) and 84 (48%) had a Briganti score < 5% and ≥ 5%, respectively, among whom 6 (6.6%) and 7(8.3%) had lymph node metastases. The accuracy of the score was low for intermediate risk patients with an area under the curve (AUC) of 53.1% (95% CI 0.45-0.61). CONCLUSION: The Briganti nomogram in our retrospective cohort showed low accuracy for the prediction of lymph node involvement in an intermediate-risk prostate cancer population.

The Mayo Adhesive Probability score can help predict intra- and postoperative complications in patients undergoing laparoscopic donor nephrectomy.

PURPOSE: Living donor nephrectomy is a high-stake procedure involving healthy individuals, therefore every effort should be made to define each patient's individualized risk and improve potential donors' information. The aim of this study was to evaluate the interest of the Mayo adhesive probability (MAP) score, an imaging-based score initially designed to estimate the risk of adherent perinephric fat in partial nephrectomy, to predict intra- and postoperative complications of living donor nephrectomy. MATERIALS AND METHODS: We retrospectively reviewed the imaging, clinical, and follow-up data of 452 kidney donors who underwent laparoscopic donor nephrectomy in two academic centers. RESULTS: Imaging and follow-up data were available for 307 kidney donors, among which 44 (14%) had a high MAP score (≥ 3). Intraoperative difficulties were encountered in 50 patients (16%), including difficult dissection (n = 35) and bleeding (n = 17). Conversion to open surgery was required for 13 patients (4.2%). On multivariate analysis, a MAP score ≥ 3 was significantly associated with the risk of intraoperative difficulty [OR 14.12 (5.58-35.7), p < 0.001] or conversion to open surgery [OR 18.96 (3.42-105.14), p = 0.0042]. Postoperative complications were noted in 99 patients (32%), including 12 patients (3.9%) with Clavien-Dindo grade III-IV complications. On multivariate analysis, a high MAP score was also associated with the risk of postoperative complications [OR 2.55 (1.20-5.40), p = 0.01]. CONCLUSIONS: In this retrospective bicentric study, a high MAP score was associated with the risk of intra- and postoperative complications of laparoscopic donor nephrectomy. The MAP score appears of interest in the living donor evaluation process to help improve donors' information and outcomes.

External Validation of a Multiparametric Magnetic Resonance Imaging-based Nomogram for the Prediction of Extracapsular Extension and Seminal Vesicle Invasion in Prostate Cancer Patients Undergoing Radical Prostatectomy.

The nomogram reported by Gandaglia et al (The key combined value of multiparametric magnetic resonance imaging, and magnetic resonance imaging-targeted and concomitant systematic biopsies for the prediction of adverse pathological features in prostate cancer patients undergoing radical prostatectomy. Eur Urol 2020;77:733-41) predicting extracapsular extension (ECE) or seminal vesicle invasion (SVI) has been developed using multiparametric magnetic resonance imaging (MRI) parameters and MRI-targeted biopsy. We aimed to validate this nomogram externally by analyzing 566 patients harboring prostate cancer diagnosed on MRI-targeted biopsy followed by radical prostatectomy. At final pathology, 37% and 12% patients had ECE and SVI, respectively. Performance of the nomogram, in comparison with the Memorial Sloan Kettering Cancer Center (MSKCC) model and Partin tables, was evaluated using discrimination, calibration, and decision curve analysis. Regarding ECE prediction, the nomogram showed higher discrimination (71.8% vs 69.8%, p = 0.3 and 71.8% vs 61.3%, p < 0.001), and similar miscalibration and net benefit for probability threshold above 30% when compared with MSKCC model and Partin tables, respectively. Performance of the nomogram with regard to SVI was comparable in terms of discrimination (68.5% vs 70.4% vs 67.8%, p ≥ 0.6), presenting a slight overestimation on calibration plots and a net benefit for probability threshold above 7.5%. This is the first multicentric study that externally validates a nomogram predicting ECE and SVI in patients diagnosed with MRI-targeted biopsy. Its performance was less optimistic than expected, and implementation of MRI in this setting was not associated with a clear improvement in patient selection and clinical usefulness when compared with available models. We proposed an updated version of the nomogram predicting ECE using the recalibration method, which leads to an improvement in its performance and needs to be validated in another external set. PATIENT SUMMARY: We validate a prediction tool based on multiparametric magnetic resonance imaging (MRI) parameters and MRI-targeted biopsy predicting extracapsular extension and seminal vesicle invasion at radical prostatectomy. An improvement of patient selection was not clearly demonstrated when compared with available models based on clinical parameters, and implementation of MRI in this setting still needs to be clarified.

Does whole-body bone SPECT/CT provide additional diagnostic information over [18F]-FCH PET/CT for the detection of bone metastases in the setting of prostate cancer biochemical recurrence?

BACKGROUND: To assess whether whole-body (WB) bone SPECT/CT provides additional diagnostic information over [18F]-FCH PET/CT for the detection of bone metastases in the setting of prostate cancer biochemical recurrence (PC-BR). METHODS: Patients referred for a PC-BR and whom benefited from a WB bone SPECT/CT and FCH PET/CT were retrospectively included. Tests were classified as positive, equivocal, or negative for bone metastases. A best valuable comparator (BVC) strategy including imaging and follow-up data was used to determine the metastatic status in the absence of systematic histological evaluation. RESULTS: Between January 2011 and November 2017, 115 consecutive patients with a PC-BR were evaluated. According to the BVC, 30 patients had bone metastases and 85 patients did not present with bone lesions. The sensitivity, specificity, positive and negative predictive values were respectively 86.7% [69.3-96.2], 98.8% [93.6-100.0], 96.3% [78.7-99.5], and 95.5% [89.4-98.1] for WB bone SPECT/CT and 93.3% [77.9-99.2], 100.0% [95.8-100.0], 100.0 and 97.7% [91.8-99.4] for FCH PET/CT. There was no significant difference in diagnostic accuracy of bone metastases between WB Bone SPECT/CT (AUC 0.824 [0.74-0.90]) and FCH PET/CT (AUC 0.829 [0.75-0.90], p = 0.41). CONCLUSION: Despite good performances for the diagnosis of bone metastases in PC-BR, WB bone SPECT/CT does not provide additive diagnostic information over concomitant FCH PET/CT.

External validation of the Briganti nomogram predicting lymph node invasion in patients with intermediate and high-risk prostate cancer diagnosed with magnetic resonance imaging-targeted and systematic biopsies: A European multicenter study.

OBJECTIVE: To validate a nomogram predicting lymph node invasion (LNI) in prostate cancer patients undergoing radical prostatectomy taking into consideration multiparametric-magnetic resonance imaging (mp-MRI) parameters and targeted biopsies in a western European cohort. PATIENTS AND METHODS: A total of 473 men diagnosed by targeted biopsies, using software-based MRI-ultrasound image fusion system, and operated by radical prostatectomy with extended pelvic lymph node dissection across 11 Europeans centers between 2012 and 2019 were identified. Area under the curve of the receiver operator characteristic curve, calibration plot and decision curve analysis were used to evaluated the performance of the model. RESULTS: Overall, 56 (11.8%) patients had LNI on final pathologic examination with a median (IQR) of 13 (9-18) resected nodes. Significant differences (all P < 0.05) were found between patients with and without LNI in terms of preoperative PSA, clinical stage at DRE and mp-MRI, maximum diameter of the index lesion, PI-RADS score, Grade Group on systematic and targeted biopsies, total number of dissected lymph nodes, final pathologic staging and Grade Group. External validation of the prediction model showed a good accuracy with an area under the curve calculated as 0.8 (CI 95% 0.75-0.86). Graphic analysis of calibration plot and decision curve analysis showed a slight underestimation for predictive probability for LNI between 3% and 22% and a high net benefit. A cut-off at 7% was associated with a risk of missing LNI in 2.6%, avoiding unnecessary surgeries in 55.9%. CONCLUSIONS: We report an external validation of the nomogram predicting LNI in patients treated with extended pelvic lymph node dissection in a western European cohort and a cut-off at 7% seems appropriate.