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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.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.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).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.

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.To assess the diagnostic accuracy of PSMA PET-targeted biopsy (PSMA-PET-TB) for csPCa detection.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.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.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.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.

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.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.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.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.

BACKGROUND Elevated preoperative plasma levels of the angiogenesis-related marker VEGF have been associated with worse oncological outcomes in various malignancies. OBJECTIVE To investigate the predictive/prognostic role of VEGF in patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC). DESIGN, SETTING, AND PARTICIPANTS VEGF plasma levels were measured preoperatively in 1036 patients with UCB who underwent RC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The correlation between plasma VEGF levels and pathological and survival outcomes was assessed using logistic regression and Cox regression analyses. Discrimination was assessed using the concordance index (C index). The clinical net benefit was evaluated using decision curve analysis (DCA). RESULTS AND LIMITATIONS Patients with higher pretreatment plasma VEGF levels had poorer recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) according to log-rank tests (all p 0.05). Preoperative plasma VEGF levels were independently associated with RFS, CSS, and OS in preoperative and postoperative multivariable models. However, in all cases the C index increased by

To test discontinuation rates during Active Surveillance (AS) in patients diagnosed with incidental prostate cancers (IPCa) vs. tumors diagnosed at prostate biopsies (BxPCa). Retrospective single center analysis of 961 vs. 121 BxPCa vs. IPCa patients (2008–2020). Kaplan–Meier plots and multivariable Cox regression models tested four different outcomes: (1) any-cause discontinuation; (2) discontinuation due to ISUP GG upgrading; (3) biopsy discontinuation due to ISUP GG upgrading or > 3 positive cores; (4) biopsy discontinuation or suspicious extraprostatic extension at surveillance mpMRI. Then, multivariable logistic regression models tested rates of clinically significant PCa (csPCa) (ISUP GG ≥ 3 or pT ≥ 3a or pN1) after radical prostatectomy (RP). Median time follow-up was 35 (19–64) months. IPCa patients were at lower risk of any-cause (3-year survival: 79.3 vs. 66%; HR: 0.5, p = 0.001) and biopsy/MRI AS discontinuation (3-year survival: 82.3 vs. 72.7%; HR: 0.5, p = 0.001), compared to BxPCa patients. Conversely, IPCa patients exhibited same rates of biopsy discontinuation and ISUP GG upgrading over time, relative to BxPCa. In multivariable logistic regression models, IPCa patients were associated with higher rates of csPCa at RP (OR: 1.4, p = 0.03), relative to their BxPCa counterparts. AS represents a safe management strategy for IPCa. Compared to BxPCa, IPCa patients are less prone to experience any-cause and biopsy/MRI AS discontinuation. However, the two mentioned groups present similar rates of biopsy discontinuation and ISUP GG upgrading over time. In consequence, tailored AS protocols with scheduled repeated surveillance biopsies should be offered to all newly diagnosed IPCa patients.

Purpose To examine the effect of lymph node dissection on the outcomes of patients who underwent salvage radical prostatectomy (SRP). Material and Methods We retrospectively reviewed data from radiation‐recurrent patients with prostate cancer (PCa) who underwent SRP from 2000–2016. None of the patients had clinical lymph node involvement before SRP. The effect of the number of removed lymph nodes (RLNs) and the number of positive lymph nodes (PLNs) on biochemical recurrence (BCR)‐free survival, metastases free survival, and overall survival (OS) was tested in multivariable Cox regression analyses. Results About 334 patients underwent SRP and pelvic lymph node dissection (PLND). Lymph node involvement was associated with increased risk of BCR (p

Introduction The novel optical techniques such as blue light cystoscopy (BLC) during transurethral resection of bladder tumor (TURBT) has been shown to improve the tumor detection rate and recurrence rate. Whether a single immediate intravesical chemotherapy (SIIC) still has an additive therapeutic effect in the setting of these novel optical techniques (e.g., photodynamic diagnosis (PDD) and narrow band imaging (NBI)) remains unclear. The main aim of this systematic review and network meta-analysis was to assess whether SIIC still adds value to bladder tumor management in combination with optical techniques- enhanced TURBT. Methods A systematic search was performed using PubMed and Web of Science databases in September 2020 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) extension statement for network meta-analysis. Studies that compared recurrence rates between intervention groups (TURBT by PDD ± SIIC, NBI ± SIIC, or WLC + SIIC) and control group (TURBT by WLC alone) were included. We used the Bayesian approach in the network meta-analysis. Results Twenty-two studies (n= 4,519) met our eligibility criteria. Out of six different interventions including three different optical techniques, compared to WLC alone, BLC plus SIIC (odds ratio (OR): 0.349, 95% credible interval (CrI):0.196-0.601) and BLC alone (OR: 0.668, 95% CrI:0.459-0.931) were associated with a significantly lower likelihood of 12-month recurrence rate. In the sensitivity analysis, out of eight different interventions compared to WLC alone, PDD by 5-aminolevulinic plus SIIC (OR: 0.327, 95% CrI:0.159-0.646) and by hexaminolevulinic acid plus SIIC (OR: 0.376, 95% CrI:0.172-0.783) were both associated with a significantly lower likelihood of 12-month recurrence rate. NBI with and without SIIC were not associated with a significantly lower likelihood of 12-month recurrence rate (OR: 0.385, 95% CrI:0.105-1.29 and OR: 0.653, 95% CrI:0.343-1.15). Conclusion BLC during TURBT with concomitant SIIC seems to yieled superior recurrence outcomes in patients with non-muscle invasive bladder cancer. The Use of PDD was able to reduce the 12-month recurrence rate; moreover, a concomitant SIIC increased this risk benefit by 32% additional reduction of odds ratio. Although using PDD could reduce the recurrence rate, SIIC remains necessary. Moreover, the ranking analysis showed that both PDD and NBI, plus SIIC were better than these techniques alone.

To identify risk factors for upper urinary tract recurrence (UUTR) in patients treated with radical cystectomy (RC) for urothelial bladder carcinoma (UBC). The PubMed, Web of Science, and Cochrane Library were searched on March 2022 to identify relevant studies according to the Preferred Reporting Items for Systematic Review (PRISMA) statement. We included studies that provided multivariate logistic regression analyses. The pooled UUTR rate was calculated using a fixed effect model. We identified 235 papers, of which seven and 6 articles, comprising a total of 8981 and 8404 UBC patients, were selected for qualitative and quantitative analyses, respectively. Overall, 418 (4.65%) patients were diagnosed with UUTR within a median time of 1.4 to 3.1 years after RC. Risk factors for UUTR were surgical margin (hazard ratio [HR] 3.41, 95% confidence interval [CI] 2.59-4.49, P.00001), preoperative hydronephrosis (HR: 1.74, 95% CI: 1.25-2.43, P = .001), ureteral margin (HR: 4.34, 95% CI: 2.75-6.85, P.00001), and pT stage (HR: 2.69, 95% CI: 1.37-5.27, P.004). Incorporation of established risk factors into a clinical prediction model might aid in the decision-making process regarding the intensity and type of surveillance protocols after RC as well as help determine the pretest probability of UUTR.

Objective: To evaluate the current literature on the accuracy of fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography (FDG PET-CT) for lymph node (LN) staging in urothelial carcinoma (UC), as robust evidence on the value of this technology in UC is still lacking. Methods: The Medical Literature Analysis and Retrieval System Online (MEDLINE)/PubMed, Cochrane Library, and Scopus databases were searched for eligible studies. We included all original studies evaluating FDG PET-CT in bladder or upper tract UC. The search results were restricted to the English language, and included prospective and retrospective studies without time restriction. We included only studies reporting the sensitivity and specificity of FDG PET-CT in detecting UC LN metastases. Results: We identified 23 articles meeting our inclusion criteria. In the preoperative setting, the sensitivity of FDG PET-CT for detecting LN metastases in patients with bladder cancer was widely variable ranging from 23% to 89%; the specificity ranged from 81% to 100%; and the overall accuracy ranged from 65% to 89%. During bladder cancer monitoring the sensitivity for detecting LN metastases ranged from 75% to 92% and the specificity ranged from 60% to 92%. The sensitivity for LN staging in upper tract UC ranged between 82% and 95%, with a specificity of 84–91%. Conclusion: Despite the inconsistencies in sensitivity between the reports, FDG PET-CT seems to have a high specificity for LN staging in patients with UC. Future prospective, well-designed studies are necessary to evaluate the role of FDG PET-CT in UC management. Abbreviations: FDG: fluoro-2-deoxy-D-glucose; LN: lymph node; PET: positron emission tomography; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-analyses; PSMA: prostate-specific membrane antigen; (N)(P)PV: (negative) (positive) predictive value; QUADAS-2: Quality Assessment of Diagnostic Accuracy Studies-2; SUVmax: maximum standard uptake value; (UT)UC: (upper urinary tract) urothelial carcinoma

Purpose The De Ritis ratio (aspartate aminotransferase/alanine aminotransferase, DRR) has been linked to oncological outcomes in several cancers. We aimed to assess the association of DRR with recurrence-free survival (RFS) and progression-free survival (PFS) in patients with non-muscle-invasive bladder cancer (NMIBC). Methods We conducted a retrospective analysis of 1117 patients diagnosed with NMIBC originating from an established multicenter database. To define the optimal pretreatment DRR cut‐off value, we determined a value of 1.2 as having a maximum Youden index value. The overall population was therefore divided into two De Ritis ratio groups using this cut‐off (lower, Results Overall, 405 (36%) patients had a DRR ≥ 1.2. On univariable Cox regression analysis, DRR was significantly associated with RFS (HR: 1.23, 95% CI 1.02–1.47, p = 0.03), but not with PFS (HR: 0.96, 95% CI 0.65–1.44, p = 0.9). On multivariable Cox regression analysis, which adjusted for the effect of established clinicopathologic features, DRR ≥ 1.2 remained significantly associated with worse RFS (HR:1.21, 95% CI 1.00–1.46, p = 0.04). The addition of DRR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index = 0.683 vs. C-index = 0.681). On DCA the inclusion of DRR did not improve the net-benefit of the prognostic model. Conclusion Despite the statistically significant association of the DRR with RFS in patients with NMIBC, it does not seem to add any prognostic or clinical benefit beyond that of currently available clinical factors.

Objectives To evaluate recurrence and progression risk after simultaneous endoscopic surgery of bladder cancer and benign prostatic hyperplasia (BPH), as simultaneous surgery is not an unusual scenario and theoretically simultaneous transurethral resection of bladder tumour (TURBT) and transurethral resection of the prostate (TURP) can lead to an increased risk of recurrence in the bladder neck and prostatic urethra (BN/PU). Methods We conducted a systematic review and meta-analysis to assess the risk of recurrence (i.e. whole bladder and/or BN/PU) and tumour progression as outcomes after a simultaneous endoscopic surgery of bladder tumour and BPH, as compared to TURBT alone. We queried PubMed and Web of Science database on 1 January 2020. We used random- and/or fixed-effects meta-analytic models in the presence or absence of heterogeneity according to the I2 statistic, respectively. Results Nine retrospective and three clinical trial studies were selected after considering inclusion and exclusion criteria. We conducted the meta-analysis on retrospective and randomised controlled trials (RCTs) separately. Eight retrospective and three RCT studies were included to assess the BN/PU recurrence risk and the summarised risk ratio (RR) was 1.02 (95% confidence interval [CI] 0.74-1.41) and 0.93 (95% CI 0.47-1.84), respectively. Five retrospective and two RCT studies were included to assess the progression risk and the summarised RR was 0.91 (95% CI 0.56-1.48) and 1.16 (95% CI 0.30-4.51), respectively. Eight retrospective and three RCT studies were included to assess the whole bladder recurrence risk and the summarised RR was 0.87 (95% CI 0.78-0.97) and 0.89 (95% CI 0.65-1.21), respectively. Conclusion We did not observe any increased risk of total bladder recurrence, BN/PU recurrence, or progression after a simultaneous endoscopic surgery of bladder tumour and BPH, as compared to TURBT alone.

The SelectMDx test is a promising biomarker that is developed based on detecting urinary messenger RNA in combination with clinical prostate cancer (PCa) risk factors. We aimed to compare SelectMDx and mpMRI as a diagnostic test in detecting PCa and high grade(HG)-PCa in men suspected to have PCa.According to PRISMA, a systematic search was performed using major web databases for studies published before September 30, 2021. Studies that compared sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of SelectMDx and/or mpMRI were included. The bivariate random model that plotted sensitivity, specificity, PPV, NPV, and likelihood ratio (LR) for PCa and HG-PCa detection was applied to compare SelectMDx, mpMRI, and combination strategies (both positive and one or both positive).Seven studies comprising 1328 patients who had undergone SelectMDx and mpMRI to detect PCa were included. Regarding PCa detection, SelectMDx had a pooled sensitivity of 81%, specificity of 69.8%, PPV of 64.7%, NPV of 85%, and LRs of +2.68 to -0.27, while mpMRI had a pooled sensitivity of 80.8%, specificity of 73.4%, PPV of 72.4%, NPV of 83.5%, and LRs of +3.03 to -0.26. The one or both positive strategy had the highest sensitivity (96.3%), NPV (95.7%), and the lowest -LR (0.06). While the both positive strategy had the highest specificity (80.9%), the PPV (76.5%) and +LR (3.68). In the scenario of PI-RADS 3 lesions not being biopsied in case of a negative SelectMDx (n = 44), unnecessary biopsies would be reduced by 42% (44/105) while the risk of missing HG-PCa would be 9% (4/44).The performance of SelectMDx is comparable to that of mpMRI with regards to PCa and HG-PCa detection. In addition, this biomarker could help refine the clinical decision-making regarding the necessity of a biopsy in patients suspected to has been PCa.

Insulin-like growth factor-I and its binding proteins are involved in cancer development, progression, and metastasis. In urothelial carcinoma, the impact of this pathway is still poorly investigated. The present large cohort study aimed to evaluate the association of preoperative circulating levels of insulin-like growth factor-I, insulin-like growth factor-I binding protein-2 and -3 on outcomes after radical cystectomy.A retrospective cohort study of the plasma specimens from 1036 consecutive urothelial carcinoma patients who were treated with radical cystectomy. The primary and secondary outcomes were adverse histopathological features and survival outcomes. Binominal logistic regression and multivariable Cox regression analyses were performed to assess the association of plasma levels of insulin-like growth factor-I, insulin-like growth factor-I binding protein-2 and -3 with outcomes.On multivariable analysis adjusting for the effects of preoperative variables, lower insulin-like growth factor-I binding protein-2 levels were associated with an increased risk of lymph node metastasis and (any non-organ confined disease) any non-organ confined disease. Insulin-like growth factor-I binding protein-3 levels were also inversely independently associated with lymph node metastasis. Receiver operating characteristic curve analysis showed that the addition of insulin-like growth factor-I binding proteins biomarkers to a reference model significantly improved the discriminating ability for the prediction of lymph node metastasis (+10.0%, P 0.001). On multivariable Cox regression models, lower levels of both insulin-like growth factor-I binding protein-2 and -3 plasma levels were associated with recurrence-free survival, cancer-specific survival, and overall survival. insulin-like growth factor-I binding protein-2 and -3 levels and improved the discrimination of a standard reference model for the prediction of recurrence-free survival, cancer-specific survival, and overall survival (+4.9%, 4.9%, 2.3%, respectively).Preoperative insulin-like growth factor-I binding protein-2 and -3 are significantly associated with features of biologically and clinically aggressive urothelial carcinoma. These biomarkers improved prognostic urothelial carcinoma models.

To present an update of the available literature on external beam radiation therapy (EBRT) with or without brachytherapy (BT) compared to radical prostatectomy (RP) for patients with high-risk localised prostate cancer (PCa). We conducted a systematic review and meta-analysis of the literature assessing the survival outcomes in patients with high-risk PCa who received EBRT with or without BT compared to RP as the first-line therapy with curative intent. We queried PubMed and Web of Science database in January 2021. Moreover, we used random or fixed-effects meta-analytical models in the presence or absence of heterogeneity per the I2 statistic, respectively. We performed six meta-analyses for overall survival (OS) and cancer-specific survival (CSS). A total of 27 studies were selected with 23 studies being eligible for both OS and CSS. EBRT alone had a significantly worse OS and CSS compared to RP (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.16–1.65; and HR 1.55, 95% CI 1.25–1.93). However, there was no difference in OS (HR 1.1, 95% CI 0.76–1.34) and CSS (HR 0.69, 95% CI 0.45–1.06) between EBRT plus BT compared to RP. While cancer control affected by EBRT alone seems inferior to RP in patients with high-risk PCa, BT additive to EBRT was not different from RP. These data support the need for BT in addition to EBRT as part of multimodal RT for high-risk PCa. Abbreviations: ADT: androgen-deprivation therapy; BT: brachytherapy; CSS: cancer-specific survival; HR: hazard ratio; MFS, metastatic-free survival; MOOSE: Meta-analyses of Observational Studies in Epidemiology; OR: odds ratio; OS: overall survival; PCa: prostate cancer; RR: relative risk; RP: radical prostatectomy; RCT: randomised controlled trials; (EB)RT: (external beam) radiation therapy

A placebo is an inert substance normally used in clinical trials for comparison with an active substance. However, a placebo has been shown to have an effect on its own; commonly known as the placebo effect. A placebo is an essential component in the design of conclusive clinical trials but has itself become the focus of intense research. The placebo effect is partly the result of positive expectations of the recipient on the state of health. Conversely, a nocebo effect is when negative expectations from a substance lead to poor treatment outcomes and/or adverse events. Randomized controlled trials in functional urology have demonstrated the importance of the placebo and nocebo effects across different diseases such as overactive bladder, urinary incontinence, lower urinary tract symptoms and interstitial cystitis/painful bladder syndrome, as well as male and female sexual dysfunction. Understanding the true nature of the placebo-nocebo complex and the scope of its effect in functional urology could help urologists to maximize the positive effects of this phenomenon while minimizing its potentially negative effects.

Introduction: It has been hypothesized that transurethral en bloc (TUEB) of bladder tumor offers benefits over conventional transurethral resection of bladder tumor (cTURBT). This study aimed to co...

We determined the oncologic outcomes and safety profiles of adjuvant immune checkpoint inhibitors (ICIs) compared to adjuvant tyrosine kinase inhibitors (TKIs) in patients at high risk after nephrectomy for clinically nonmetastatic renal cell carcinoma (RCC). Network meta-analyses were conducted for disease-free survival (DFS), overall survival (OS), and adverse events (AEs) with placebo as the common comparator arm. Six trials (KEYNOTE-564, S-TRAC, ASSURE, PROTECT, ATLAS, and SORCE) were included in our analysis. Compared to placebo, both pembrolizumab (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.51-0.92) and pazopanib 800 mg (HR 0.69, 95% CI 0.49-0.97) were significantly associated with better DFS. Adjuvant pembrolizumab (HR 0.54, 95% CI 0.30-0.97) was significantly associated with better OS compared to TKIs (HR 0.93, 95% CI 0.83-1.04). Analysis of treatment ranking revealed that pembrolizumab was the best treatment with regard to both DFS and OS and had the lowest likelihood of any-grade and high-grade AEs in comparison to TKIs. The superior oncologic benefit of pembrolizumab and its better toxicity profile support it as the new standard of care in the adjuvant setting for nephrectomy patients at high risk of RCC relapse. PATIENT SUMMARY: For patients with kidney cancer at high risk of relapse after surgical removal of their kidney, postoperative therapy with the immune checkpoint inhibitor pembrolizumab offers the best risk/benefit ratio.

Serum albumin-to-globulin ratio (AGR) has been shown to be associated with poor prognosis in different malignancies. In this study we aimed to evaluate the predictive value of preoperative AGR for oncological outcomes in patients with radiation recurrent prostate cancer (PCa) treated with salvage radical prostatectomy (SRP).A retrospective review of 214 consecutive patients with radiation recurrent PCa who underwent SRP at five referral centers. Levels of albumin and globulin were obtained before SRP and used to calculate the preoperative AGR level. The optimal cut off value of preoperative AGR was 1.4. Univariable and multivariable Cox regression analyses were performed.Overall 89 (41.6%) patients had a low preoperative AGR. Low serum AGR was associated with biochemical recurrence (BCR) in univariable Cox regression analysis (HR 1.60, 95%CI 1.06-2.43, P=0.026). When adjusted for the effects of established preoperative and postoperative clinicopathologic confounders in different multivariable Cox regression models, this association did not retain its statistical significance. Moreover, preoperative AGR was not associated with metastasis free survival (P=0.21), overall survival (P=0.91) or cancer specific survival (P=0.61).In patients with radiation recurrent PCa undergoing SRP, low preoperative AGR was associated with the risk of BCR only in univariable analysis. There was no association with metastasis or survival outcomes. Further studies are needed to evaluate this biomarker in the setting of primary PCa and to identify the patients most likely to benefit from a local therapy.

INTRODUCTION AND OBJECTIVE:Prostate cancer (PCa) recurrence after primary radiotherapy is increasingly encountered. Radical prostatectomy is a salvage local treatment with potentially durable disea...

To determine the oncologic and toxicity outcomes of adjuvant immunotherapy with immune checkpoint inhibitors (ICIs) compared to adjuvant chemotherapy in patients treated with radical surgery for urothelial carcinoma (UC).We used the Bayesian approach in the network meta-analysis of different therapy regimens compared to observation or placebo.Nine studies comprised of 2,444 patients met the eligibility criteria. In bladder UC, chemotherapy, atezolizumab, and nivolumab did not improve disease progression compared to observation/placebo. In upper tract UC (UTUC), chemotherapy was significantly associated with a lower likelihood of disease progression compared to observation/placebo, while atezolizumab and nivolumab were not. Based on the analysis of the treatment ranking, adjuvant chemotherapy appeared as the best treatment approach in both bladder UC and UTUC. The risk of adverse events with ICIs was comparable to that of observation/placebo.Our analysis suggests a superior oncologic benefit to adjuvant chemotherapy over ICIs in patients treated with radical surgery for both bladder UC and UTUC.

Context Degarelix is associated with high rates of injection site reaction. The US Food and Drug Administration approved relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, for the treatment of advanced prostate cancer patients. Objective This systematic review and network meta-analysis aimed to compare the efficacy and safety of relugolix versus degarelix. Evidence acquisition A systematic search was performed using major web databases for studies published before January 30, 2021, according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) extension statement for a network meta-analysis. Studies that compared the efficacy (12-mo castration rate with testosterone ≤50 ng/dl) and safety (adverse events [AEs]) of relugolix or degarelix and of the control group (GnRH agonists) were included. We used the Bayesian approach in the network meta-analysis. Evidence synthesis Four studies (n = 2059) met our eligibility criteria. The main efficacy analysis was conducted for two different treatments (relugolix and all doses of degarelix vs GnRH agonists); relugolix (risk ratio [RR] 1.09, 95% credible interval [CrI]: 0.95–1.23) and degarelix (RR 0.98, 95% CrI: 0.91–1.06) were not associated with different 12-mo castration rates. In the subgroup analysis, degarelix 480 mg was significantly associated with a lower castration rate (RR 0.46, 95% CrI: 0.07–0.92). In all efficacy ranking analyses, relugolix achieved the best rank. The safety analyses showed that relugolix (RR 0.99, 95% CrI: 0.6–1.6 and RR 0.72, 95% CrI: 0.4–1.3, respectively) and degarelix (RR 1.1, 95% CrI: 0.75–1.35 and RR 1.05, 95% CrI: 0.42–2.6, respectively) were not associated with either all AE or serious AE rates. In the ranking analyses, degarelix achieved the worst rank of all AEs and the best rank of serious AEs. Relugolix (RR 0.44, 95% CrI: 0.16–1.2) and degarelix (RR 0.74, 95% CrI: 0.37–1.52) were not associated with different cardiovascular event (CVE) rates; both were associated with lower CVE rates than GnRH agonists in the ranking analyses. Conclusions We found that the efficacy and safety of relugolix are comparable with those of degarelix, albeit with no injection site reaction. Such data should be interpreted with caution until large-scale direct comparison studies with a longer follow-up are available. Patient summary We found that relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, has comparable efficacy and safety with degarelix, a parenteral GnRH antagonist, for the treatment of advanced prostate cancer patients.

Context The choice of the most efficacious drug for patients with idiopathic overactive bladder (IOAB) remains challenging. Objective The aim of this network meta-analysis was to determine the most efficacious oral antimuscarinic or β-adrenoceptor agonist accounting for adverse events for the management of IOAB. Evidence acquisition A comprehensive electronic search was done in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Ovid for studies in any language in February 2021 considering the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. We included all randomized controlled trials assessing oral antimuscarinics or β-adrenoceptor agonists for the treatment of IOAB. We determined the effect of specific bothersome symptoms separately. Evidence synthesis Fifty-four articles were included in our analysis. The most efficacious agents considering the evaluated outcomes were oxybutynin 15 mg/d in reducing incontinence episodes, imidafenacin 0.5 mg/d together with solifenacin 10 and 5 mg/d in reducing micturition episodes, fesoterodine 4 and 8 mg/d as well as solifenacin 10 mg/d in reducing urgency episodes, imidafenacin 0.5 mg/d and solifenacin 10 mg/d in reducing urgency urinary incontinence episodes, and solifenacin 10 mg/d, vibegron 50 mg/d, and fesoterodine 8 mg/d in improving the voided volume. Gastrointestinal problems, especially due to antimuscarinic agents, were the most prevalent adverse events. Conclusions Taken together, there is only minimal difference between the efficacy of oral antimuscarinics and that of β-adrenoceptor agonists. Although finding the best medication for all is impossible, finding the best treatment for every individual patient can be done by considering the efficacy of a medicine for the most bothersome symptom(s) in balance with drug-specific adverse events. Patient summary This study aimed to find the most efficient oral medication to treat overactive bladder, taking into consideration the adverse events. Based on our study, there is a minimal difference in the efficacy between the two major drug classes used to treat overactive bladder. Gastrointestinal problems were the most common adverse events in medical treatment of overactive bladder. Selection of the best treatment is possible through shared decision-making between the doctor and the patient based on the patient’s most bothersome symptom. We provide a framework for physicians to facilitate shared decision-making with each individual patient.

Purpose The present systematic review aimed to identify prognostic values of blood-based biomarkers in patients treated with neoadjuvant chemotherapy (NAC) for urothelial carcinoma of the bladder (UCB). Material and Methods The PubMed, Web of Science, and Scopus databases were searched in August 2020 according to the PRISMA statement. Studies were deemed eligible if they compared oncological outcomes in patients treated with NAC for UCB with and without pretreatment laboratory abnormalities. Results Overall, ten studies, including 966 patients who underwent NAC, met our eligibility criteria. Six studies provided data on pretreatment neutrophil to lymphocyte ratio (NLR) with contradicting results on its association with pathologic response (PR) and complete pathologic response (pCR); some studies reported a strong association between a high level of pretreatment NLR and worse survival outcomes. Two studies reported that higher pretreatment platelet-lymphocyte ratio (PLR) is associated with a lower likelihood of achieving PR and/or pCR, while lymphocyte count alone had the opposite association. One study reported a negative association between pretreatment blood-based myeloid-derived suppressors cells and pCR. Patients who experienced a remission have been reported to have higher level of lymphocyte subsets (CD3+, CD4+, CD57+ cells, the ratio of CD4+/CD8+) compared to those who had progression. One study found that low pretreatment blood-based human chorionic gonadotrophin b subunit (hCGβ) was associated with improved overall survival (OS). High levels of epithelial tumor markers (CA-125, CA 19-9) were also associated with worse OS and recurrence-free survival in the NAC setting. Conclusion Current evidence suggests that several readily available, easy measurable blood-based biomarkers hold promise to improve our selection of UCB patients who are likely benefit from NAC. However, their role as an adjunct to established histopathologic characteristics for clinical decision-making requires further validation along the biomarker phased approach.

Androgen deprivation therapy is a standard therapy for some patients with localized and almost all patients with metastatic prostate cancer. Although several clinical cohort studies have identified an impact of androgen deprivation therapy on cognitive function, the previous reviews were not able to perform a well designed quantitative synthesis to summarize the risk of dementia and/or Alzheimer disease. Consequently there is still a lack of systematic review and meta-analysis regarding the impact of this risk including more recent studies.We conducted a systematic review and meta-analysis of the literature assessing the differential incidence of dementia and/or Alzheimer disease as outcomes in patients with prostate cancer who did vs did not receive androgen deprivation therapy. We queried PubMed® and Web of Science™ databases from January 1 to 3, 2020. We used random or fixed effects meta-analytic models in the presence or absence of heterogeneity per the IA total of 14 studies were selected after considering inclusion and exclusion criteria. Nine of them reported all cause dementia (ie all types of dementia including Alzheimer disease), with 8 reporting Alzheimer disease. Five studies assessed these outcomes according to the duration of androgen deprivation therapy. The risk of new onset dementia (all cause) and Alzheimer disease was higher in patients with prostate cancer who received androgen deprivation therapy compared to those who did not (HR 1.21, 95% CI 1.11-1.33 and HR 1.16, 95% CI 1.09-1.24). The risk of dementia (all cause) was higher in patients with prostate cancer who received androgen deprivation therapy for more than 12 months (HR 1.36, 95% CI 1.07-1.72); however, for those who had less than 12 months of androgen deprivation therapy exposure the difference was not statistically significant 1.06 (95% CI 0.77-1.28). There was no association between the androgen deprivation therapy duration and the risk of Alzheimer disease (HR 1.21, 95% CI 0.97-1.51 for exposure up to 12 months and HR 1.39, 95% CI 0.69-2.79 for exposure greater than 12 months).Men who receive androgen deprivation therapy for prostate cancer have an increased risk of dementia and/or Alzheimer disease compared to men who do not receive androgen deprivation therapy; this was more pronounced when androgen deprivation therapy was given longer than 12 months.

Purpose of review There is heightened awareness and trends towards centralizing high-risk, complex surgeries such as radical cystectomy to minimize complications and improve survival. However, after nearly a decade of mandated and/or passive centralization of care, debate regarding its benefits and harms continues. Recent findings During the past decade, mandated and passive centralization has led to an increase in radical cystectomies performed in high-volume hospitals (HVHs) and, perhaps by high-volume surgeons (HVS), in addition to efforts to increase the uptake of multidisciplinary strategies in the management of radical cystectomy patients. Consequently, 30 and 90-day mortality rates and overall survival have improved, and major complications and transfusion rates have decreased. Factors impacting surgical quality, such as negative surgical margin(s), pelvic lymphadenectomy and/or lymph node yield rates have increased. However, current studies have not demonstrated a coadditive impact of centralization on oncological outcomes (i.e. cancer-specific and recurrence-free survival). The benefits of centralization on oncologic survival of radical cystectomy remain unclear given the varied definitions of HVHs and HVSs across studies. In fact, centralization of radical cystectomy could lead to an increase in patient load in HVHs and for HVSs, thereby leading to longer surgery waiting times, a factor that is important in the management of muscle-invasive bladder cancer. Summary The benefits of centralization of radical cystectomy with multidisciplinary management are shown increasingly and convincingly. More studies are necessary to prospectively test the benefits, risks and harms of centralization.

Purpose of review The aim of this article is to review incidence, risk factors, and optimal management of de-novo urothelial carcinoma in transplant recipients. Recent findings There is a two to three-fold increased risk for de-novo malignant tumors after solid-organ transplantation, but there is currently no consensus regarding optimal management of de-novo urothelial carcinoma in transplanted patients. Known risk factors include polyomavirus BK, aristolochic acid, and smoking. Data suggest a higher rate of high-grade tumors, as well as predominantly higher stage at primary diagnosis, for both NMIBC and muscle-invasive bladder cancer (MIBC). Treatment for NMIBC includes TURB, mitomycin, and Bacille de Calmette-Guerin instillation with special concern to the immunosuppressive regime. Treatment of MIBC or advanced urothelial carcinoma includes radical cystectomy with chemotherapy if the patient is eligible. A screening should be performed in all transplant recipients, to allow early diagnosis. Summary De-novo urothelial carcinoma in transplant recipients is more frequent than in the general population and these tumors were more likely to be high-grade tumors and diagnosed at an advanced stage. There is very little information available on the optimal treatment for these patients. However, aggressive treatment and a strict management according the given recommendations are of the utmost importance.

PURPOSE To investigate the predictive and prognostic value of the preoperative systemic immune-inflammation index (SII) in patients undergoing radical cystectomy (RC) for clinically non-metastatic urothelial cancer of the bladder (UCB). METHODS Overall, 4,335 patients were included, and the cohort was stratified in two groups according to SII using an optimal cut-off determined by the Youden index. Uni- and multivariable logistic and Cox regression analyses were performed, and the discriminatory ability by adding SII to a reference model based on available clinicopathologic variables was assessed by area under receiver operating characteristics curves (AUC) and concordance-indices. The additional clinical net-benefit was assessed using decision curve analysis (DCA). RESULTS High SII was observed in 1879 (43%) patients. On multivariable preoperative logistic regression, high SII was associated with lymph node involvement (LNI; P = 0.004), pT3/4 disease (P