The Prognostic Value of Tumor Infiltrating Lymphocytes After Radical Cystectomy for Bladder Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: We aimed to assess the prognostic value of tumor infiltrating lymphocytes (TILs) in patients with bladder cancer (BC) after radical cystectomy (RC). MATERIALS AND METHODS: We searched Pubmed, Web of Science and Scopus in April 2022 to identify studies assessing the prognostic value of TILs, including a subset of lymphocytes (eg, CD3, CD8, FOXP3), after RC. The endpoints were overall survival and recurrent free survival. Subgroup analyses were performed based on the evaluation method for TILs (ie, CD3, CD8, FOXP3, HE staining). RESULTS: Overall, 9 studies comprising 1413 patients were included in this meta-analysis. The meta-analysis revealed that elevated expressions of TILs were significantly associated with favorable OS (pooled hazard ratio [HR]: 0.65, 95% confidence interval [CI]: 0.51-0.83) and RFS (pooled HR: 0.48, 95% CI: 0.35-0.64). In subgroup analyses, high CD8+ TILs were also associated with favorable OS (HR: 0.51, 95% CI: 0.33-0.80) and RFS (pooled HR: 0.53, 95% CI: 0.36-0.76). Among 3 studies comprising 146 patients, high intratumoral TILs were significantly associated with favorable OS (pooled HR: 0.34, 95% CI: 0.19-0.60). CONCLUSION: TILs are useful prognostic markers in patients treated with RC for BC. Although the prognostic value of TILs is varied, depending on the subset and infiltration site, CD8+ TILs and intratumoral TILs are associated with oncologic outcomes. Further studies are warranted to explicate the predictive value of TILs on the response to perioperative systemic therapy to help clinical decision-making in patients with BC.

Advancing Intraoperative Assessment of Urethral Stricture Anatomic Variation: A Prospective Proof-of-Concept Study.

INTRODUCTION: Urethral strictures, particularly those refractory to endoscopic interventions, are commonly treated through open urethroplasty. However, predicting recurrence in homogeneous patient populations remains challenging. METHODS: To address this, we developed an intraoperative urethral stricture assessment tool aiming to identify comprehensive risk predictors. The assessment includes detailed parameters on stricture location, length, urethral bed width, spongiosum thickness, obliteration grade, and spongiofibrosis extension. The tool was prospectively implemented in 106 men with anterior one-stage augmentation urethroplasty from April 2020 to October 2021. RESULTS: An intraoperative granular assessment of intricate stricture characteristics is feasible. Comparative analyses revealed significant differences between bulbar and penile strictures. Bulbar strictures exhibited wider urethral beds and thicker spongiosum compared to penile strictures (all p < 0.001). The assessment showed marked variations in the degree of obliteration and spongiofibrosis extension. CONCLUSION: Our tool aligns with efforts to standardize urethral surgery, providing insights into subtle disease intricacies and enabling comparisons between institutions. Notably, intraoperative assessment may surpass the limitations of preoperative imaging, emphasizing the necessity of intraoperative evaluation. While limitations include a single-institution study and limited sample size, future research aims to refine this tool and determine its impact on treatment strategies, potentially improving long-term outcomes for urethral strictures.

Comprehensive Evaluation of the Ability of Comorbidity and Health Status Indices to Improve the Prediction of Perioperative Morbidity and Long-Term Survival Outcomes After Radical Cystectomy.

BACKGROUND: In the era of standardized outcome reporting, it remains unclear if widely used comorbidity and health status indices can enhance predictive accuracy for morbidity and long-term survival outcomes after radical cystectomy (RC). PATIENTS AND METHODS: In this monocentric study, we included 468 patients undergoing open RC with pelvic lymph node dissection for bladder cancer between January 2009 and December 2017. Postoperative complications were meticulously assessed according to the EAU guideline criteria for standardized outcome reporting. Multivariable regression models were fitted to evaluate the ability of ASA physical status (ASA PS), Charlson comorbidity index (± age-adjustment) and the combination of both to improve prediction of (A) 30-day morbidity key estimates (major complications, readmission, and cumulative morbidity as measured by the Comprehensive Complication index [CCI]) and (B) secondary mortality endpoints (overall [OM], cancer-specific [CSM], and other-cause mortality [OCM]). RESULTS: Overall, 465 (99%) and 52 (11%) patients experienced 30-day complications and major complications (Clavien-Dindo grade ≥IIIb), respectively. Thirty-seven (7.9%) were readmitted within 30 days after discharge. Comorbidity and health status indices did not improve the predictive accuracy for 30-day major complications and 30-day readmission of a reference model but were associated with 30-day CCI (all P < .05). When ASA PS and age-adjusted Charlson index were combined, ASA PS was no longer associated with 30-day CCI (P = .1). At a median follow-up of 56 months (IQR 37-86), OM, CSM, and 90-day mortality were 37%, 24%, and 2.9%, respectively. Both Charlson and age-adjusted Charlson index accurately predicted OCM (all P < .001) and OM (all P ≤ .002) but not CSM (all P ≥ .4) and 90-day mortality (all P > .05). ASA PS was not associated with oncologic outcomes (all P ≥ .05). CONCLUSION: While comorbidity and health status indices have a role in predicting OCM and OM after RC, their importance in predicting postoperative morbidity is limited. Especially ASA PS performed poorly. This highlights the need for procedure-specific comorbidity assessment rather than generic indices.

What do patients with Peyronie's disease expect from therapy? A prospective multi-center study.

BACKGROUND: Little is known about patients' pre-treatment expectations in Peyronie's disease (PD). OBJECTIVE: To evaluate in detail patients' expectations of conservative therapy and surgery. PATIENTS AND METHODS: This multi-center study prospectively enrolled 317 PD patients, who were scheduled to receive conservative therapy or surgery between 2019 and 2022 at the Department of Urology of the University Medical Center Hamburg-Eppendorf, and the Center of Reproductive Medicine and Andrology, University Medical Center Muenster, both Germany. The primary end-point was patients' pre-treatment expectations of conservative therapy and surgery, measured with the Stanford Expectations of Treatment Scale (SETS). Secondary end-points included patient-reported psychological and physical symptoms, penile pain, symptom bother and erectile function, measured with the Peyronie's disease questionnaire (PDQ) and International Index of Erectile Function Erectile Function Domain (IIEF-EF). RESULTS: In total, 239 (75%) and 78 (25%) patients were scheduled for the conservative therapy and surgery, respectively. Patients undergoing surgery had higher positive and negative mean SETS expectations scores (14 vs. 11, p < 0.001; 9.6 vs. 6.0, p < 0.001). In multivariable analysis, surgery was an independent predictor of positive and negative patients' pre-treatment expectations (all p ≤ 0.001). In thematic analysis, patients undergoing surgery emphasized distinct themes of pre-treatment expectations. Patients undergoing surgery had higher mean PDQ symptom bother as well as higher psychological and physical symptom scores (14 vs. 10, p < 0.001; 9.2 vs. 7.1, p = 0.001). There were significant positive correlations between SETS negative expectation score and PDQ symptom bother (|ρ| = 0.25; p < 0.001) as well as PDQ psychological and physical symptoms score, respectively (|ρ| = 0.21; p = 0.001). CONCLUSION: PD patients expect both more benefit and more harm from surgery. In addition, patients undergoing surgery have more psychological and physical symptoms and more symptom bother. To set realistic expectations, it is of pivotal importance to assess patients' expectations before starting treatment.

Mucomucosal anastomotic non-transecting augmentation (MANTA) urethroplasty: a ventral modification for obliterative strictures.

OBJECTIVES: To present a surgical modification for the repair of bulbar urethral strictures containing short, highly obliterative segments and report on long-term objective and patient-reported outcomes. PATIENTS AND METHODS: We considered patients undergoing bulbar buccal mucosal graft urethroplasty (BMGU) between July 2016 and December 2019. Eligibility criteria for mucomucosal anastomotic non-transecting augmentation (MANTA) urethroplasty were strictures of ≥2 cm with an obliterative segment of ≤1.5 cm. The stricture is approached ventrally to avoid extensive dissection and mobilisation. Dorsally, the scar is superficially excised and the spongiosum is left intact. Dorsal mucomucosal anastomosis is complemented by ventral onlay graft. Perioperative characteristics were prospectively collected including uroflowmetry data and validated patient-reported outcome measures on voiding, erectile, and continence function. We evaluated functional follow-up, incorporating patient-reported (lower urinary tract symptoms [LUTS] score) and functional success. Recurrence was defined as need of re-treatment. RESULTS: Of 641 men treated with anterior BMGU, 54 (8.4%) underwent MANTA urethroplasty. Overall, 26 (48%) and 45 (83%) had a history of dilatation and urethrotomy, respectively, and 14 (26%) were redo cases. Location was bulbar in 38 (70%) and penobulbar in 16 patients (30%), and the mean (SD) graft length was 4.5 (1.4) cm. At a median (interquartile range) follow-up of 41 (27-53) months, the functional success rate was 93%. Whereas the median LUTS score significantly improved from baseline to postoperatively (13 vs 3.5; P < 0.001), there was no change in erectile function (median International Index of Erectile Function - erectile function domain score 27 vs 24) or urinary continence (median International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form sum score 0 vs 0; all P ≥ 0.4). All patients were 'satisfied' (27%) or 'very satisfied' (73%) with the outcome of their operation. CONCLUSION: With excellent long-term objective and patient-reported outcomes, MANTA urethroplasty adds to the armamentarium for long bulbar strictures with a short obliterative segment.

Comparison between different neoadjuvant chemotherapy regimens and local therapy alone for bladder cancer: a systematic review and network meta-analysis of oncologic outcomes.

PURPOSE: The present systematic review and network meta-analysis (NMA) compared the current different neoadjuvant chemotherapy (NAC) regimes for bladder cancer patients to rank them. METHODS: We used the Bayesian approach in NMA of six different therapy regimens cisplatin, cisplatin/doxorubicin, (gemcitabine/cisplatin) GC, cisplatin/methotrexate, methotrexate, cisplatin, and vinblastine (MCV) and (MVAC) compared to locoregional treatment. RESULTS: Fifteen studies comprised 4276 patients who met the eligibility criteria. Six different regimes were not significantly associated with a lower likelihood of overall mortality rate compared to local treatment alone. In progression-free survival (PFS) rates, cisplatin, GC, cisplatin/methotrexate, MCV and MVAC were not significantly associated with a higher likelihood of PFS rate compared to locoregional treatment alone. In local control outcome, MCV, MVAC, GC and cisplatin/methotrexate were not significantly associated with a higher likelihood of local control rate versus locoregional treatment alone. Nevertheless, based on the analyses of the treatment ranking according to SUCRA, it was highly likely that MVAC with high certainty of results appeared as the most effective approach in terms of mortality, PFS and local control rates. GC and cisplatin/doxorubicin with low certainty of results was found to be the best second options. CONCLUSION: No significant differences were observed in mortality, progression-free survival and local control rates before and after adjusting the type of definitive treatment in any of the six study arms. However, MVAC was found to be the most effective regimen with high certainty, while cisplatin alone and cisplatin/methotrexate should not be recommended as a neoadjuvant chemotherapy regime.

Diagnostic Accuracy of Clinical Lymph Node Staging for Upper Tract Urothelial Cancer Patients: A Multicenter, Retrospective, Observational Study.

PURPOSE: Treatment options for the management of upper tract urothelial cancer are based on accurate staging. However, the performance of conventional cross-sectional imaging for clinical lymph node staging (N-staging) remains poorly investigated. This study aims to evaluate the diagnostic accuracy of conventional cross-sectional imaging for upper tract urothelial cancer N-staging. MATERIALS AND METHODS: This study was a multicenter, retrospective, observational study. We included 865 nonmetastatic (M0) upper tract urothelial cancer patients treated with curative intended surgery and lymph node dissection who had been staged with conventional cross-sectional imaging before surgery. We compared clinical (c) and pathological (p) N-staging results to evaluate the concordance of node-positive (N+) and node-negative (N0) disease and calculate cN-staging's diagnostic accuracy. RESULTS: Conventional cross-sectional imaging categorized 750 patients cN0 and 115 cN+. Lymph node dissection categorized 641 patients pN0 and 224 pN+. The cN-stage was pathologically downstaged in 6.8% of patients, upstaged in 19%, and found concordant in 74%. The sensitivity and specificity of cN-staging were 25% (95% CI 20; 31) and 91% (95% CI 88; 93). Positive and negative likelihood ratios were 2.7 (95% CI 2.0; 3.8) and 0.83 (95% CI 0.76; 0.89). The area under the receiver operating characteristics curve (0.58, 95% CI 0.55; 0.61) revealed low diagnostic accuracy. CONCLUSIONS: Conventional cross-sectional imaging had low sensitivity in detecting upper tract urothelial cancer pN+ disease. However, cN+ increased the likelihood of pN+ by almost threefold. Thus, conventional cross-sectional imaging is a rule-in but not a rule-out test. Lymph node dissection should remain the standard during extirpative upper tract urothelial cancer surgery to obtain accurate N-staging. cN+ could be a strong argument for early systemic treatment.

Sequencing impact and prognostic factors in metastatic castration-resistant prostate cancer patients treated with cabazitaxel: A systematic review and meta-analysis.

BACKGROUND: Cabazitaxel is an effective treatment of post-docetaxel metastatic castration-resistant prostate cancer (mCRPC). We aimed to assess the sequencing impact and identify prognostic factors of oncologic outcomes in mCRPC patients treated with cabazitaxel. METHODS: PUBMED, Web of Science, and Scopus databases were searched for articles published before January 2022 according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Studies were deemed eligible if they investigated pretreatment clinical or hematological prognostic factors of overall survival (OS) in mCRPC patients with progression after docetaxel treated with available treatments including cabazitaxel. RESULTS: Overall, 22 studies were eligible for the meta-analysis. In mCRPC patients treated with docetaxel, subsequent treatment with cabazitaxel was associated with better OS compared to that without cabazitaxel (pooled hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.56-0.89). Among the patients treated with cabazitaxel, several pretreatment clinical features and hematologic biomarkers were associated with worse OS as follows: poor performance status (PS) (pooled HR: 1.92, 95% CI: 1.33-2.77), presence of visceral metastasis (pooled HR: 2.13, 95% CI: 1.62-2.81), symptomatic disease (pooled HR: 1.47, 95% CI: 1.25-1.73), high PSA (pooled HR: 1.76, 95% CI: 1.27-2.44), high alkaline phosphatase (ALP) (pooled HR: 1.45, 95% CI: 1.28-1.65), high lactate dehydrogenase (LDH) (pooled HR: 1.54, 95% CI: 1.00-2.38), high c-reactive protein (CRP) (pooled HR: 4.40, 95% CI: 1.52-12.72), low albumin (pooled HR:1.09, 95% CI: 1.05-1.12) and low hemoglobin (pooled HR:1.55, 95% CI: 1.20-1.99). CONCLUSIONS: Sequential therapy with cabazitaxel significantly improves OS in post-docetaxel mCRPC patients. In mCRPC patients treated with cabazitaxel, patients with poor PS, visceral metastasis, and symptomatic disease were associated with worse OS. Further, pretreatment high PSA, ALP, LDH or CRP as well as low hemoglobin or albumin, were blood-based prognostic factors for OS. These findings might help guide the clinical decision-making for the use of cabazitaxel and prognostication of its OS benefit.

Iatrogenic ureteric injury during abdominal or pelvic surgery: a meta-analysis.

OBJECTIVE: To assess the incidence of ureteric injuries, clinical value of prophylactic ureteric stenting and impact of intra- or postoperative detection of ureteric injuries in patients treated with gynaecological or colorectal surgery. METHODS: Multiple databases were searched for articles published before September 2021 according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. Studies were deemed eligible if they evaluated the differences in the rate of ureteric injuries between laparoscopic and open surgery, prophylactic ureteric stenting or not, and those of final treatment success between intra- and postoperative detection in patients who underwent gynaecological or colorectal surgery. RESULTS: Overall, 46 studies were eligible for this meta-analysis. Compared to open surgery, laparoscopic hysterectomy was associated with a higher incidence of ureteric injuries (pooled odds ratio [OR] 2.12, 95% confidence interval [CI] 1.71-2.62), but there was no statistically significant difference in colectomy (pooled OR 0.89, 95% CI 0.77-1.03). Prophylactic ureteric stenting was associated with a lower incidence of ureteric injuries during gynaecological surgery (pooled OR 0.61, 95% CI 0.39-0.96). The number needed to perform ureteric stenting to prevent one ureteric injury was 224 in gynaecological surgery. On the other hand, prophylactic ureteric stenting did not reduce the risk of ureteric injuries during colorectal surgery. Intraoperative detection of a ureteric injury was associated with a lower rate of complication management failure compared to postoperative detection (pooled OR 0.22, 95% CI 0.12-0.41). CONCLUSIONS: Laparoscopic hysterectomy seems to be associated with a higher rate of ureteric injuries compared to an open approach. Prophylactic ureteric stenting seems to reduce this risk during gynaecological surgery. Intraoperative detection of a ureteric injury during abdominal/pelvic surgery improves outcomes, suggesting the need for awareness and proactive problem identification. Further well-designed studies assessing the candidates who are more likely to benefit from prophylactic ureteric stenting including cost analysis are needed.

Oncological validation and discriminative ability of pentafecta criteria after open radical cystectomy.

OBJECTIVES: To validate the pentafecta criteria (PC) proposed by the PROMETRICS group for outcome reporting after radical cystectomy in an open radical cystectomy (ORC) cohort with long-term follow-up and to assess the discriminative ability of PC attainment for oncological endpoints. PATIENTS AND METHODS: Between January 2009 and December 2017, 420 patients underwent ORC with pelvic lymph node dissection and urinary diversion for non-metastatic bladder cancer. The PC were defined as reported by the PROMETRICS group. The primary endpoint was PC attainment, and oncological outcomes comprised further endpoints. We used uni- and multivariable logistic regression analysis to assess predictors of PC attainment. The discriminative ability of PC for overall mortality (OM), cancer-specific mortality (CSM) and other-cause mortality (OCM) was compared using Kaplan-Meier curves and cumulative incidence functions. After stratification by the number of PC attained, the association between PC attainment and the survival endpoints was tested on multivariable Cox regression and competing-risks models. RESULTS: A total of 108 patients (26%) fulfilled all PC, while 195 (46%), 77 (18%), 35 (8.3%) and five (1.2%) attained 4/5, 3/5, 2/5 and ≤1/5 PC, respectively. Increasing age-adjusted Charlson comorbidity index (odds ratio [OR] 0.80, P = 0.015) and incontinent diversion (OR 0.38, P = 0.005) were independent predictors of PC non-attainment. The median follow-up was 73 months. PC attainment (≥4/5 vs 3/5 vs ≤2/5 PC attained) was used to stratify patients into groups at significantly different risk of death (P < 0.001). A decreasing number of PC attained (<4/5) was associated with unfavourable survival estimates for both OM and CSM (all P ≤ 0.005) but not for OCM (all P ≥ 0.2). CONCLUSIONS: The PC proposed by the PROMETRICS group represent accurate quality indicators for oncological outcome reporting after ORC for non-metastatic bladder cancer and have a distinct discriminative ability to predict long-term OM and CSM.

Positive family history as a predictor for disease outcomes after radical prostatectomy for nonmetastatic prostate cancer.

Background: While family history (FHx) of prostate cancer (PCa) increases the risk of PCa, comparably less is known regarding the impact of FHx on pathologic and oncologic outcomes after radical prostatectomy (RP). Methods: We retrospectively reviewed our multicenter database comprising 6,041 nonmetastatic PCa patients treated with RP. Patients with a FHx of PCa in one or more first-degree relatives were considered as FHx positive. We examined the association of FHx with pathologic outcomes and biochemical recurrence (BCR) using logistic and Cox regression models, respectively. Results: In total, 1,677 (28%) patients reported a FHx of PCa. Compared to patients without FHx, those with, were younger at RP (median age of 59 vs. 62 years, p < 0.01), and had significantlymore favorable biopsy and RP histopathologic findings. On multivariable logistic regression analysis, positive FHx was associated with extracapsular extension (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.66-0.90, p < 0.01; model AUC 0.73) and upgrading (OR 0.70, 95% CI 0.62-0.80, p < 0.01; model AUC 0.68). Incorporating FHx significantly improved the AUC of the base model for upgrading (p < 0.01). Positive FHx was not associated with BCR in pre- and postoperative multivariable models (p = 0.1 and p = 0.7); c-indexes of Cox multivariable models were: 0.73 and 0.82, respectively. Conclusions: We found that patients with clinically nonmetastatic PCa who have positive FHx of PCa undergo RP at a younger age and have more favorable pathologic outcomes. Nevertheless, FHx of PCa did not confer better BCR rates, suggesting that FHx leads to potentially early detection and treatment without impact on BCR.

A Systematic Review and Meta-Analysis of Prognostic Nomograms After UTUC Surgery.

Background: Current guidelines recommend assessing the prognosis in high-risk upper tract urothelial carcinoma patients (UTUC) after surgery. However, no specific method is endorsed. Among the various prognostic models, nomograms represent an easy and accurate tool to predict the individual probability for a specific event. Therefore, identifying the best-suited nomogram for each setting seems of great interest to the patient and provider. Objectives: To identify, summarize and compare postoperative UTUC nomograms predicting oncologic outcomes. To estimate the overall performance of the nomograms and identify the most reliable predictors. To create a reference tool for postoperative UTUC nomograms, physicians can use in clinical practice. Design: A systematic review was conducted following the recommendations of Cochrane's Prognosis Methods Group. Medline and EMBASE databases were searched for studies published before December 2021. Nomograms were grouped according to outcome measurements, the purpose of use, and inclusion and exclusion criteria. Random-effects meta-analyses were performed to estimate nomogram group performance and predictor reliability. Reference tables summarizing the nomograms' important characteristics were created. Results: The systematic review identified 26 nomograms. Only four were externally validated. Study heterogeneity was significant, and the overall Risk of Bias (RoB) was high. Nomogram groups predicting overall survival (OS), recurrence-free survival (RFS), and intravesical recurrence (IVR) had moderate discrimination accuracy (c-Index summary estimate with 95% confidence interval [95% CI] and prediction interval [PI] > 0.6). Nomogram groups predicting cancer-specific survival (CSS) had good discrimination accuracy (c-Index summary estimate with 95% CI and PI > 0.7). Advanced pathological tumor stage (≥ pT3) was the most reliable predictor of OS. Pathological tumor stage (≥ pT2), age, and lymphovascular invasion (LVI) were the most reliable predictors of CSS. LVI was the most reliable predictor of RFS. Conclusions: Despite a moderate to good discrimination accuracy, severe heterogeneity discourages the uninformed use of postoperative prognostic UTUC nomograms. For nomograms to become of value in a generalizable population, future research must invest in external validation and assessment of clinical utility. Meanwhile, this systematic review serves as a reference tool for physicians choosing nomograms based on individual needs. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=282596, identifier PROSPERO [CRD42021282596].

Diagnostic Performance of Prostate-specific Membrane Antigen Positron Emission Tomography-targeted biopsy for Detection of Clinically Significant Prostate Cancer: A Systematic Review and Meta-analysis.

CONTEXT: Prostate-specific membrane antigen positron emission tomography (PSMA-PET) has gained acceptance as a staging tool for prostate cancer (PCa). Recent reports suggest an association between PSMA PET and detection of clinically significant PCa (csPCa) on prostate biopsy. OBJECTIVE: To assess the diagnostic accuracy of PSMA PET-targeted biopsy (PSMA-PET-TB) for csPCa detection. EVIDENCE ACQUISITION: We searched PubMed, Web of Science, and Scopus in December 2021 to identify studies assessing the accuracy of PSMA-PET-TB for csPCa detection. A diagnostic meta-analysis was performed to calculate pooled sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of PSMA-PET-TB alone and in combination with magnetic resonance imaging (MRI)-TB for detecting csPCa. EVIDENCE SYNTHESIS: Overall, five prospective studies involving 497 patients were eligible for this meta-analysis. For csPCa detection, PSMA-PET-TB had pooled sensitivity, specificity, PPV, and NPV of 0.89 (95% confidence interval [CI] 0.85-0.93), 0.56 (95% CI 0.29-0.80), 0.69 (95% CI 0.58-0.79), and 0.78 (95% CI 0.50-0.93), respectively. Among the three studies assessing the PSMA-PET + MRI-TB strategy, the pooled sensitivity, specificity, PPV, and NPV for csPCa detection were 0.91 (95% CI 0.77-0.97), 0.64 (95% CI 0.40-0.82), 0.75 (95% CI 0.56-0.87), and 0.85 (95% CI 0.62-0.95), respectively. For lesions with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 3, the sensitivity, specificity, PPV, and NPV were 0.69, 0.73, 0.48, and 0.86, respectively. CONCLUSIONS: PSMA-PET-TB appears to have favorable diagnostic accuracy for csPCa detection and combination with MRI seems to improve this. According to our meta-analysis, PSMA-PET has promising clinical application for detection of csPCa, namely in the case of PI-RADS 3 lesions. Further prospective studies are needed to explore the true clinical utility of a PSMA-PET-based diagnostic pathway. PATIENT SUMMARY: Prostate-specific membrane antigen positron emission tomography (PSMA-PET) is a promising imaging method for detecting clinically significant prostate cancer and seems to have additional value to magnetic resonance imaging (MRI) for detection.

Comparative Outcomes of Primary Versus Recurrent High-risk Non-muscle-invasive and Primary Versus Secondary Muscle-invasive Bladder Cancer After Radical Cystectomy: Results from a Retrospective Multicenter Study.

Background: Radical cystectomy (RC) is indicated in primary or secondary muscle-invasive bladder cancer (primMIBC, secMIBC) and in primary or recurrent high- or very high-risk non-muscle-invasive bladder cancer (primHR-NMIBC, recHR-NMIBC). The optimal timing for RC along the disease spectrum of nonmetastatic urothelial carcinoma remains unclear. Objective: To compare outcomes after RC between patients with primHR-NMIBC, recHR-NMIBC, primMIBC, and secMIBC. Design setting and participants: This retrospective, multicenter study included patients with clinically nonmetastatic bladder cancer (BC) treated with RC. Outcome measurements and statistical analysis: We assessed oncological outcomes for patients who underwent RC according to the natural history of their BC. primHR-NMIBC and primMIBC were defined as no prior history of BC, and recHR-NMIBC and secMIBC as previously treated NMIBC that recurred or progressed to MIBC, respectively. Log-rank analysis was used to compare survival outcomes, and univariable and multivariable Cox and logistic regression analyses were used to identify predictors for survival. Results and limitations: Among the 908 patients included, 211 (23%) had primHR-NMIBC, 125 (14%) had recHR-NMIBC, 404 (44%) had primMIBC, and 168 (19%) had secMIBC. Lymph node involvement and pathological upstaging were more frequent in the secMIBC group than in the other groups (p < 0.001). The median follow-up was 37 mo. The 5-year recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were 77.9%, 83.2%, and 72.7% in primHR-NMIBC, 60.0%, 59%, and 48.9% in recHR-NMIBC, 60.9%, 64.5%, and 54.8% in primMIBC, and 41.3%, 46.5%, and 39% in secMIBC, respectively, with statistically significant differences across all survival outcomes except between recHR-NMIBC and primMIBC. On multivariable Cox regression, recHR-NMIBC was independently associated with shorter RFS (hazard ratio [HR] 1.64; p = 0.03), CSS (HR 1.79; p = 0.01), and OS (HR 1.45; p = 0.03), and secMIBC was associated with shorter CSS (HR 1.77; p = 0.01) and OS (HR 1.57; p = 0.006). Limitations include the biases inherent to the retrospective study design. Conclusions: Patients with recHR-NMIBC and primHR-MIBC had similar survival outcomes, while those with sec-MIBC had the worst outcomes. Therefore, early radical intervention may be indicated in selected patients, and potentially neoadjuvant systemic therapies in some patients with recHR-NMIBC. Patient summary: We compared cancer outcomes in different bladder cancer scenarios in a large, multinational series of patients who underwent removal of the bladder with curative intent. We found that patients who experienced recurrence of non-muscle-invasive bladder cancer (NMIBC) had similar survival outcomes to those with initial muscle-invasive bladder cancer (MIBC), while patients who experienced progression of NMIBC to MIBC had the worst outcomes. Selected patients with non-muscle-invasive disease may benefit from early radical surgery or from perioperative chemotherapy or immunotherapy.

Circulating Tumour DNA Is a Strong Predictor of Outcomes in Patients Treated with Systemic Therapy for Urothelial Carcinoma.

We summarise the available data for and assess the prognostic value of circulating tumour DNA (ctDNA) in patients treated with systemic therapy for urothelial carcinoma (UC). Studies were deemed eligible if they reported on oncologic outcomes for patients with UC treated with systemic therapy according to the baseline ctDNA profile (before starting systemic therapy) and/or changes over the course of therapy. Five studies met the eligibility criteria. We found a strong association between high baseline ctDNA levels and worse disease-free survival (DFS; hazard ratio [HR] 3.53, 95% confidence interval [CI] 2.58-4.84) and overall survival (OS; HR 2.99, 95% CI 2.17-4.13). Patients with a decline in ctDNA level after immunotherapy had better DFS (HR 0.25, 95% CI 0.13-0.49) and OS (HR 0.10, 95% CI 0.03-0.42) in comparison to patients without a ctDNA decline. Conversely, an increase in ctDNA levels after immunotherapy was associated with worse survival outcomes. Patients with UC who exhibited a decrease in ctDNA levels during systemic therapy had better survival outcomes compared to those with stable or increasing ctDNA levels. PATIENT SUMMARY: Measurement of tumour DNA in blood may help in identifying patients with cancer of the urinary tract who are unlikely to respond to chemotherapy or immunotherapy. This could serve as a biomarker for monitoring cancer treatment.

Differential efficacy of ablation therapy versus partial nephrectomy between clinical T1a and T1b renal tumors: A systematic review and meta-analysis.

PURPOSE: To assess the differential clinical outcomes of patients treated with partial nephrectomy (PN) vs. those treated with ablation therapy (AT) such as radiofrequency ablation, cryoablation and microwave ablation for cT1b compared to cT1a renal tumors. MATERIALS AND METHODS: Multiple databases were searched for articles published before August 2021. Studies were deemed eligible if they compared clinical outcomes in patients who underwent PN with those who underwent AT for cT1a and/or cT1b renal tumors. RESULTS: Overall, 27 studies comprising 13,996 patients were eligible for this meta-analysis. In both cT1a and cT1b renal tumors, there was no significant difference in the percent decline of estimated glomerular filtration rates or in the overall/severe complication rates between PN and AT. Compared to AT, PN was associated with a lower risk of local recurrence in both patients with cT1a and cT1b tumors (cT1a: pooled risk ratio [RR]; 0.43, 95% confidence intervals [CI]; 0.28-0.66, cT1b: pooled RR; 0.41, 95%CI; 0.23-0.75). Subgroup analyses regarding the technical approach revealed no statistical difference in local recurrence rates between percutaneous AT and PN in patients with cT1a tumors (pooled RR; 0.61, 95%CI; 0.32-1.15). In cT1b, however, PN was associated with a lower risk of local recurrence (pooled RR; 0.45, 95%CI; 0.23-0.88). There was no difference in distant metastasis or cancer mortality rates between PN and AT in patients with cT1a, or cT1b tumors. CONCLUSIONS: AT has a substantially relevant disadvantage with regards to local recurrence compared to PN, particularly in cT1b renal tumors. Despite the limitations inherent to the nature of retrospective and unmatched primary cohorts, percutaneous AT could be used as a reasonable alternative treatment for well-selected patients with cT1a renal tumors.

Quality indicators for the management of muscle-invasive bladder cancer in the perioperative setting of radical cystectomy: a narrative review.

Background and Objective: Identifying evidence-based and measurable quality-of-care indicators is crucial for optimal management of patients requiring radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). RC with urinary diversion and lymphadenectomy is the standard treatment for patients with MIBC. Preoperatively, neoadjuvant chemotherapy (NAC) with cisplatin-based combinations improves survival outcomes and is the recommended standard of care for eligible patients. Intraoperatively, lymph node dissection (LND) by, at least, following a standard pelvic lymph node template improves overall- and recurrence-free survival and allows for accurate tumour staging. Avoiding positive soft tissue surgical margins (STSM) should be a main target intraoperatively since they are almost universally associated with mortality. Implementing enhanced recovery after surgery (ERAS) programs can reduce lengths of hospital stay (LOS) and postoperative complication rates without increasing readmission rates after RC. Moreover, several studies have shown that smoking negatively affects local and systemic treatment outcomes in bladder cancer (BC) patients. Therefore, smoking cessation counselling for smokers should be an essential part of bladder cancer management regardless of the disease state. Methods: We performed a comprehensive, non-systematic review of the latest literature to define indicators representing the best evidence available for optimal care of MIBC patients treated with RC. Key Content and Findings: In this review, we propose five major quality indicators that are easily implementable for optimized management of MIBC patients treated with RC, including: usage of cisplatin-based NAC in eligible patients, ensurance of negative STSM, performance of (at least) a standard pelvic template LND, implementation of ERAS strategies, and professional smoking cessation counselling. Conclusions: Optimal management of MIBC needs to be framed by evidence-based, reproducible, and measurable quality indicators that will allow for guidance and comparative effectiveness assessment of clinical practices; adherence to them is likely to improve patients' prognoses by a tensible margin. For the treatment of MIBC patients with RC, we identified five essential quality indicators. Keywords: Assessment; bladder cancer (BC); muscle-invasive bladder cancer (MIBC); cystectomy; radical cystectomy (RC); quality.

Urethrectomy at the time of radical cystectomy for non-metastatic urothelial carcinoma of the bladder: a collaborative multicenter study.

INTRODUCTION: The optimal management of the urethra in patients planned for radical cystectomy (RC) remains unclear. We sought to evaluate the impact of urethrectomy on perioperative and oncological outcomes in patients treated with RC for non-metastatic urothelial carcinoma of the bladder (UCB). MATERIALS AND METHODS: We assessed the retrospective data from patients treated with RC for UCB of five European University Hospitals. Associations of urethrectomy with progression-free (PFS), cancer-free (CSS), and overall (OS) survivals were assessed in univariable and multivariable Cox regression models. We performed a subgroup analysis in patients at high risk for urethral recurrence (UR) (urethral invasion and/or bladder neck invasion and/or multifocality and/or prostatic urethra involvement). RESULTS: A total of 887 non-metastatic UCB patients were included. Among them, 146 patients underwent urethrectomy at the time of RC. Urethrectomy was performed more often in patients with urethral invasion, T3/4 tumor stage, CIS, positive frozen section analysis of the urethra, and those who received neoadjuvant chemotherapy, underwent robotic RC, and/or received an ileal conduit urinary diversion (all p < 0.001). Estimated blood loss and the postoperative complication rate were comparable between patients who received an urethrectomy and those who did not. Urethrectomy during RC was not associated with PFS (HR 0.83, p = 0.17), CSS (HR 0.93, p = 0.67), or OS (HR 1.08, p = 0.58). In the subgroup of 276 patients at high risk for UR, urethrectomy at the time of RC decreased the risk of progression (HR 0.58, p = 0.04). CONCLUSION: In our study, urethrectomy at the time of RC seems to benefit only patients at high risk for UR. Adequate risk assessment of UCB patients' history may allow for better clinical decision-making and patient counseling.

Hematological prognosticators in metastatic renal cell cancer treated with immune checkpoint inhibitors: a meta-analysis.

Aim: We aimed to assess the prognostic value of pretreatment hematological biomarkers in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICIs). Methods: PubMed, Web of Science and Scopus databases were searched for articles according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Results: Fifteen studies comprising 1530 patients were eligible for meta-analysis. High levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein and lactate dehydrogenase were significantly associated with worse progression-free survival. High NLR and PLR were significantly associated with worse overall survival. Conclusion: High pretreatment NLR and PLR appear to be hematological prognostic factors of progression and overall mortality in mRCC patients treated with ICIs. These findings might help in the design of correlative biomarker studies to guide the clinical decision-making in the immune checkpoint inhibitor era.

Identifying the predictive/prognostic factors that can be applied to daily clinical practice is mandatory to facilitate the use of immune checkpoint inhibitors. Some pretreatment hematological markers used in daily clinical practice appear to be prognostic factors in metastatic renal cell carcinoma patients treated with immune checkpoint inhibitors. We believe that the findings of the present meta-analysis might help researchers to design prospective correlative biomarker studies to guide clinical decision-making in the immunotherapy era.

Pentafecta for Radical Nephroureterectomy in Patients with High-Risk Upper Tract Urothelial Carcinoma: A Proposal for Standardization of Quality Care Metrics.

Background: Measuring quality of care indicators is important for clinicians and decision making in health care to improve patient outcomes. Objective: The primary objective was to identify quality of care indicators for patients with upper tract urothelial carcinoma (UTUC) and to validate these in an international cohort treated with radical nephroureterectomy (RNU). The secondary objective was to assess the factors associated with failure to validate the pentafecta. Design: We performed a retrospective multicenter study of patients treated with RNU for EAU high-risk (HR) UTUC. Outcome measurements and statistical analysis: Five quality indicators were consensually approved, including a negative surgical margin, a complete bladder-cuff resection, the absence of hematological complications, the absence of major complications, and the absence of a 12-month postoperative recurrence. After multiple imputations and propensity-score matching, log-rank tests and a Cox regression were used to assess the survival outcomes. Logistic regression analyses assessed predictors for pentafecta failure. Results: Among the 1718 included patients, 844 (49%) achieved the pentafecta. The median follow-up was 31 months. Patients who achieved the pentafecta had superior 5-year overall- (OS) and cancer-specific survival (CSS) compared to those who did not (68.7 vs. 50.1% and 79.8 vs. 62.7%, respectively, all p < 0.001). On multivariable analyses, achieving the pentafecta was associated with improved recurrence-free survival (RFS), CSS, and OS. No preoperative clinical factors predicted a failure to validate the pentafecta. Conclusions: Establishing quality indicators for UTUC may help define prognosis and improve patient care. We propose a pentafecta quality criteria in RNU patients. Approximately half of the patients evaluated herein reached this endpoint, which in turn was independently associated with survival outcomes. Extended validation is needed.