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.

The Role of Additional Epididymis Resection during Hydrocelectomy: Is It of Any Benefit in Comparison to Simple Hydrocelectomy?

INTRODUCTION: Open hydrocelectomy via scrotal incision is the standard approach for secondary hydroceles. Traditionally, the Swiss urologic community offer hydrocelectomy with additional resection of the epididymis in elderly men with completed family planning. It is believed that the additional resection of the epididymis reduces the postoperative recurrence rate of hydroceles. However, there is no evidence supporting this theory. Therefore, the aim of this study was to compare the recurrence and complication rates for patients with secondary hydroceles undergoing either pure hydrocelectomy (puH) or hydrocelectomy with additional resection of the epididymis (HRE). MATERIALS AND METHODS: We reviewed all male patients who underwent surgical therapy for secondary hydroceles between May 2003 and February 2019 at our institution. Patient's baseline and perioperative characteristics as well as postoperative characteristics including complications and recurrence rates were gathered and compared between different surgical techniques. RESULTS: A total of 234 patients were identified. puH was performed in 93 (40%) cases and HRE in 141 (60%) patients. Patients in the HRE group were older (median age: 62 vs. 38 years, p < 0.001), had a higher ASA-Score (p < 0.001), were more often on platelet aggregation inhibitors (19% vs. 7.5%, p = 0.01), and had a longer median operative time (75 vs. 64 min, p < 0.001). During a median follow-up of 46 months, a similar number of recurrent hydroceles were found for puH (7 [7.5%]) and HRE (6 [4.5%]) (p = 0.3). Complications were observed in 19 (20%) cases after puH compared to 25 (18%) cases after HRE (p = 0.6). Patients after puH experienced more often severe complications (Clavien-Dindo Grade 3b) compared to the HRE group (5 vs. 12%, p = 0.046). CONCLUSION: puH and HRE showed similar results in terms of overall low recurrence rates and also in terms of postoperative complications, even though patients who underwent puH experienced slightly higher severe complications. Both procedures are safe and effective, but it seems that HRE does not provide a relevant clinical benefit in comparison to puH for the management of men with secondary hydroceles.

Detection of recurrences using serum miR-371a-3p during active surveillance in men with stage I testicular germ cell tumours.

BACKGROUND: MiR-371a-3p predicts the presence of a macroscopic non-teratomatous germ cell tumour (GCT). We hypothesised that miR-371a-3p can also detect recurrence during active surveillance (AS) of stage I GCT. METHODS: We prospectively collected serum samples of 33 men. Relative expression of serum miR-371a-3p levels was determined at each follow-up visit using real-time quantitative reverse transcription-polymerase chain reaction. RESULTS: Recurrence was detected using standard follow-up investigations in 10/33 patients (30%) after a median of 7 months. Directly after orchiectomy, miR-371a-3p levels were not elevated in any of the 15 patients with available post-orchiectomy samples. However, all ten recurring patients exhibited increasing miR-371a-3p levels during follow-up, while miR-371a-3p levels remained non-elevated in all but one patient without recurrence. MiR-371a-3p detected recurrences at a median of 2 months (range 0-5) earlier than standard follow-up investigations. CONCLUSIONS: MiR-371a-3p levels immediately post orchiectomy are not predictive for recurrences and unfortunately cannot support decision-making for AS vs. adjuvant treatment. However, miR-371a-3p detects recurrences reliably and earlier than standard follow-up investigations. If this can be confirmed in larger cohorts, monitoring miR-371a-3p could replace surveillance imaging in seminomatous GCT and reduce the amount of imaging in non-seminomatous GCT. Earlier detection of disease recurrence may also reduce the overall treatment burden.

Prognostic Role of Preoperative Vascular Cell Adhesion Molecule-1 Plasma Levels in Urothelial Carcinoma of the Bladder Treated With Radical Cystectomy.

BACKGROUND: Angiogenesis-related marker vascular cell adhesion molecule-1 (VCAM-1) has been shown to be elevated in urothelial carcinoma of the bladder (UCB), but its predictive/prognostic role has not been determined. Thus, this study aimed to investigate the predictive/prognostic role of VCAM-1 for patients who have UCB treated with radical cystectomy (RC). METHODS: The study enrolled 1036 patients with clinically non-metastatic advanced UCB who underwent RC, and plasma VCAM-1 was evaluated preoperatively. The correlation of plasma VCAM-1 with pathologic and survival outcomes was assessed using binominal logistic regression and multivariable Cox regression analyses. Discrimination was assessed using the area under the curve and concordance indices. The clinical net benefit was evaluated using decision curve analysis (DCA). RESULTS: Preoperative VCAM-1 was significantly elevated in patients with adverse pathologic features. Higher VCAM-1 levels were independently associated with increased risk of lymph-node-metastasis (LNM), ≥pT3 disease, and non-organ-confined disease (NOCD (p < 0.001 for each). Preoperative plasma VCAM-1 was independently associated with recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) in pre- and postoperative multivariable models. Adding VCAM-1 to these predictive models improved their discriminatory ability to predict all outcomes by a significant margin. In the DCA, VCAM-1 addition to the reference models for prediction of LNM, NOCD, RFS, and CSS resulted in relevant improvement. CONCLUSIONS: Elevated plasma VCAM-1 was associated with biologically and clinically aggressive UCB disease features. After validation, preoperative VCAM-1 may serve as a biomarker to help identify patients likely to benefit from intensified/multimodal therapy. In addition, VCAM-1 improved the discriminatory power of predictive/prognostic models and can be used to refine personalized clinical decision-making.

A panel of systemic inflammatory response biomarkers for outcome prediction in patients treated with radical cystectomy for urothelial carcinoma.

OBJECTIVES: To determine the predictive and prognostic value of a panel of systemic inflammatory response (SIR) biomarkers relative to established clinicopathological variables in order to improve patient selection and facilitate more efficient delivery of peri-operative systemic therapy. MATERIALS AND METHODS: The preoperative serum levels of a panel of SIR biomarkers, including albumin-globulin ratio, neutrophil-lymphocyte ratio, De Ritis ratio, monocyte-lymphocyte ratio and modified Glasgow prognostic score were assessed in 4199 patients treated with radical cystectomy for clinically non-metastatic urothelial carcinoma of the bladder. Patients were randomly divided into a training and a testing cohort. A machine-learning-based variable selection approach (least absolute shrinkage and selection operator regression) was used for the fitting of several multivariable predictive and prognostic models. The outcomes of interest included prediction of upstaging to carcinoma invading bladder muscle (MIBC), lymph node involvement, pT3/4 disease, cancer-specific survival (CSS) and recurrence-free survival (RFS). The discriminatory ability of each model was either quantified by area under the receiver-operating curves or by the C-index. After validation and calibration of each model, a nomogram was created and decision-curve analysis was used to evaluate the clinical net benefit. RESULTS: For all outcome variables, at least one SIR biomarker was selected by the machine-learning process to be of high discriminative power during the fitting of the models. In the testing cohort, model performance evaluation for preoperative prediction of lymph node metastasis, ≥pT3 disease and upstaging to MIBC showed a 200-fold bootstrap-corrected area under the curve of 67.3%, 73% and 65.8%, respectively. For postoperative prognosis of CSS and RFS, a 200-fold bootstrap corrected C-index of 73.3% and 72.2%, respectively, was found. However, even the most predictive combinations of SIR biomarkers only marginally increased the discriminative ability of the respective model in comparison to established clinicopathological variables. CONCLUSION: While our machine-learning approach for fitting of the models with the highest discriminative ability incorporated several previously validated SIR biomarkers, these failed to improve the discriminative ability of the models to a clinically meaningful degree. While the prognostic and predictive value of such cheap and readily available biomarkers warrants further evaluation in the age of immunotherapy, additional novel biomarkers are still needed to improve risk stratification.

Selection and evaluation of preoperative systemic inflammatory response biomarkers model prior to cytoreductive nephrectomy using a machine-learning approach.

INTRODUCTION: This study aimed to determine the prognostic value of a panel of SIR-biomarkers, relative to standard clinicopathological variables, to improve mRCC patient selection for cytoreductive nephrectomy (CN). MATERIAL AND METHODS: A panel of preoperative SIR-biomarkers, including the albumin-globulin ratio (AGR), De Ritis ratio (DRR), and systemic immune-inflammation index (SII), was assessed in 613 patients treated with CN for mRCC. Patients were randomly divided into training and testing cohorts (65/35%). A machine learning-based variable selection approach (LASSO regression) was used for the fitting of the most informative, yet parsimonious multivariable models with respect to prognosis of cancer-specific survival (CSS). The discriminatory ability of the model was quantified using the C-index. After validation and calibration of the model, a nomogram was created, and decision curve analysis (DCA) was used to evaluate the clinical net benefit. RESULTS: SIR-biomarkers were selected by the machine-learning process to be of high discriminatory power during the fitting of the model. Low AGR remained significantly associated with CSS in both training (HR 1.40, 95% CI 1.07-1.82, p = 0.01) and testing (HR 1.78, 95% CI 1.26-2.51, p = 0.01) cohorts. High levels of SII (HR 1.51, 95% CI 1.10-2.08, p = 0.01) and DRR (HR 1.41, 95% CI 1.01-1.96, p = 0.04) were associated with CSS only in the testing cohort. The exclusion of the SIR-biomarkers for the prognosis of CSS did not result in a significant decrease in C-index (- 0.9%) for the training cohort, while the exclusion of SIR-biomarkers led to a reduction in C-index in the testing cohort (- 5.8%). However, SIR-biomarkers only marginally increased the discriminatory ability of the respective model in comparison to the standard model. CONCLUSION: Despite the high discriminatory ability during the fitting of the model with machine-learning approach, the panel of readily available blood-based SIR-biomarkers failed to add a clinical benefit beyond the standard model.

Pretreatment clinical and hematologic prognostic factors of metastatic urothelial carcinoma treated with pembrolizumab: a systematic review and meta-analysis.

Pembrolizumab is the standard for the first and second lines in treating metastatic urothelial carcinoma (UC). This systematic review and meta-analysis aimed to assess the value of pretreatment clinical characteristics and hematologic biomarkers for prognosticating response to pembrolizumab in patients with metastatic UC. PUBMED®, Web of Science™, and Scopus® databases were searched for articles published before May 2021 according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Studies were deemed eligible if they evaluated overall survival (OS) in patients with metastatic urothelial carcinoma treated with pembrolizumab and pretreatment clinical characteristics or laboratory examination. Overall, 13 studies comprising 1311 patients were eligible for the meta-analysis. Several pretreatment patients' demographics and hematologic biomarkers were significantly associated with worse OS as follows: Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≥ 2 (Pooled hazard ratio [HR]: 3.24, 95% confidence interval [CI] 2.57-4.09), presence of visceral metastasis (Pooled HR: 1.84, 95% CI 1.42-2.38), presence of liver metastasis (Pooled HR: 4.23, 95% CI 2.18-8.20), higher neutrophil-lymphocyte ratio (NLR) (Pooled HR: 1.29, 95% CI 1.07-1.55) and, higher c-reactive protein (CRP) (Pooled HR: 2.49, 95% CI 1.52-4.07). Metastatic UC patients with poor PS, liver metastasis, higher pretreatment NLR and/or CRP have a worse survival despite pembrolizumab treatment. These findings might help to guide the prognostic tools for clinical decision-making; however, they should be interpreted carefully, owing to limitations regarding the retrospective nature of primary data.

Prognostic impact of insulin-like growth factor-I and its binding proteins, insulin-like growth factor-I binding protein-2 and -3, on adverse histopathological features and survival outcomes after radical cystectomy.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

The role of lymph node dissection in salvage radical prostatectomy for patients with radiation recurrent prostate cancer.

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 < .001), metastasis (p < .001), and overall mortality (p = .006). In a multivariable Cox regression analysis, an increased number of RLNs significantly lowered the risk of BCR (hazard ratio [HR] 0.96, p = .01). In patients with positive lymph nodes, a higher number of RLNs and a lower number of PLNs were associated with improved freedom from BCR (HR 0.89, p = .001 and HR 1.34, p = .008, respectively). At a median follow-up of 23.9 months (interquartile range, 4.7-37.7), neither the number of RLNs nor the number of PLNs were associated with OS (p = .69 and p = .34, respectively). CONCLUSION: Pathologic lymph node involvement increased the risk of BCR, metastasis and overall mortality in radiation-recurrent PCa patients undergoing SRP. The risk of BCR decreased steadily with a higher number of RLNs during SRP. Further research is needed to support this conclusion and develop a precise therapeutic adjuvant strategy based on the number of RLNs and PLNs.

Prognostic Impact of Preoperative Plasma Levels of Urokinase Plasminogen Activator Proteins on Disease Outcomes after Radical Cystectomy.

PURPOSE: We sought to validate the association of plasma levels of urokinase-type plasminogen activator (uPA), its soluble receptor (SuPAR) and its inhibitor (PAI-one) with oncologic outcomes in a large cohort of patients treated with radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). MATERIALS AND METHODS: We collected preoperative blood samples from 1,036 consecutive patients treated with RC for UCB. Plasma specimens were assessed for levels of uPA, SuPAR and PAI-one. Retrospective logistic and Cox regression analyses were performed to assess their correlation with clinical outcomes. The additional clinical net benefit provided by the biomarkers was evaluated using decision curve analysis. RESULTS: Preoperative plasma uPA, SuPAR and PAI-one levels were significantly elevated in patients harboring adverse pathological features. Higher levels of all biomarkers were independently associated with an increased risk of lymph node metastasis; uPA levels were also independently associated with ≥pT3 disease. Preoperative uPA and SuPAR were independently associated with recurrence-free and cancer-specific survival. The addition of these biomarkers to standard pre-treatment and post-treatment models improved the discriminatory power for prediction of lymph node metastasis, ≥pT3 disease, and recurrence-free and cancer-specific survival by a prognostically significant margin. CONCLUSIONS: We confirmed that elevated preoperative plasma levels of uPA, SuPAR and PAI-one are associated with features of aggressive disease and worse survival outcomes in patients treated with RC for UCB. These biomarkers hold potential in identifying patients who are likely to benefit from intensified/multimodal therapy. They also demonstrated the ability to improve the discriminatory power of predictive/prognostic models, thus refining personalized clinical decision-making.

Impact of enhanced optical techniques at time of transurethral resection of bladder tumour, with or without single immediate intravesical chemotherapy, on recurrence rate of non-muscle-invasive bladder cancer: a systematic review and network meta-analysis of randomized trials.

OBJECTIVE: To assess whether single immediate intravesical chemotherapy (SIIC) adds value to bladder tumour management in combination with novel optical techniques: enhanced transurethral resection of bladder tumour (TURBT). METHODS: A systematic search was performed using the 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-analyses. Studies that compared recurrence rates among intervention groups (TURBT with photodynamic diagnosis [PDD] ± SIIC, narrow-band imaging [NBI] ± SIIC, or white-light cystoscopy [WLC] + SIIC) and a control group (TURBT with WLC alone) were included. We used the Bayesian approach in the network meta-analysis. RESULTS: Twenty-two studies (n = 4519) met our eligibility criteria. Out of six different interventions including three different optical techniques, compared to WLC alone, blue-light cystoscopy (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 acid 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 was 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: Blue-light cystoscopy during TURBT with concomitant SIIC seems to yield 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, concomitant SIIC increased this risk benefit by a 32% additional reduction in odds ratio. Although using PDD could reduce the recurrence rate, SIIC remains necessary. Moreover, ranking analysis showed that both PDD and NBI, plus SIIC, were better than these techniques alone.

Role of systemic immune-inflammation index in patients treated with salvage radical prostatectomy.

PURPOSE: To examine the predictive and prognostic value of preoperative Systemic Immune-inflammation Index (SII) in patients with radio-recurrent prostate cancer (PCa) treated with salvage radical prostatectomy (SRP). MATERIALS AND METHODS: This multicenter retrospective study included 214 patients with radio-recurrent PCa, treated with SRP between 2007 and 2015. SII was measured preoperatively (neutrophils × platelets/lymphocytes) and the cohort was stratified using optimal cut-off. Uni- and multivariable logistic and Cox regression analyses were performed to evaluate the predictive and prognostic value of SII as a preoperative biomarker. RESULTS: A total of 81 patients had high preoperative SII (≥ 730). On multivariable logistic regression modeling, high SII was predictive for lymph node metastases (OR 3.32, 95% CI 1.45-7.90, p = 0.005), and non-organ confined disease (OR 2.55, 95% CI 1.33-4.97, p = 0.005). In preoperative regression analysis, high preoperative SII was an independent prognostic factor for cancer-specific survival (CSS; HR 10.7, 95% CI 1.12-103, p = 0.039) and overall survival (OS; HR 8.57, 95% CI 2.70-27.2, p < 0.001). Similarly, in postoperative multivariable models, SII was associated with worse CSS (HR 22.11, 95% CI 1.23-398.12, p = 0.036) and OS (HR 5.98, 95% CI 1.67-21.44, p = 0.006). Notably, the addition of SII to preoperative reference models improved the C-index for the prognosis of CSS (89.5 vs. 80.5) and OS (85.1 vs 77.1). CONCLUSIONS: In radio-recurrent PCa patients, high SII was associated with adverse pathological features at SRP and survival after SRP. Preoperative SII could help identify patients who might benefit from novel imaging modalities, multimodal therapy or a closer posttreatment surveillance.

Prognostic value of the systemic immune-inflammation index in non-muscle invasive bladder cancer.

PURPOSE: We assessed the prognostic value of systemic immune-inflammation index (SII) to refine risk stratification of the heterogeneous spectrum of patients with non-muscle-invasive bladder cancer (NMIBC) METHODS: In this multi-institutional cohort, preoperative blood-based SII was retrospectively assessed in 1117 patients with NMIBC who underwent transurethral resection of bladder (TURB) between 1996 and 2007. The optimal cut-off value of SII was determined as 580 using the best Youden index. Cox regression analyses were performed. The concordance index (C-index) and decision curve analysis (DCA) were used to assess the discrimination of the predictive models. RESULTS: Overall, 309 (28%) patients had high SII. On multivariable analyses, high SII was significantly associated with worse PFS (hazard ratio [HR] 1.84; 95% confidence interval [CI] 1.23-2.77; P = 0.003) and CSS (HR 2.53; 95% CI 1.42-4.48; P = 0.001). Subgroup analyses, according to the European Association of Urology guidelines, demonstrated the main prognostic impact of high SII, with regards to PFS (HR 3.39; 95%CI 1.57-7.31; P = 0.002) and CSS (HR 4.93; 95% CI 1.70-14.3; P = 0.005), in patients with intermediate-risk group; addition of SII to the standard predictive model improved its discrimination ability both on C-index (6% and 12%, respectively) and DCA. In exploratory intergroup analyses of patients with intermediate-risk, the improved discrimination ability was retained the prediction of PFS and CSS. CONCLUSION: Preoperative SII seems to identify NMIBC patients who have a worse disease and prognosis. Such easily available and cheap standard biomarkers may help refine the decision-making process regarding adjuvant treatment in patients with intermediate-risk NMIBC.

Oncologic impact of delaying radical prostatectomy in men with intermediate- and high-risk prostate cancer: a systematic review.

PURPOSE: To summarize the available evidence on the survival and pathologic outcomes after deferred radical prostatectomy (RP) in men with intermediate- and high-risk prostate cancer (PCa). METHODS: The PubMed database and Web of Science were searched in November 2020 according to the PRISMA statement. Studies were deemed eligible if they reported the survival and pathologic outcomes of patients treated with deferred RP for intermediate- and high-risk PCa compared to the control group including those patients treated with RP without delay. RESULTS: Overall, nineteen studies met our eligibility criteria. We found a significant heterogeneity across the studies in terms of definitions for delay and outcomes, as well as in patients' baseline clinicopathologic features. According to the currently available literature, deferred RP does not seem to affect oncological survival outcomes, such as prostate cancer-specific mortality and metastasis-free survival, in patients with intermediate- or high-risk PCa. However, the impact of deferred RP on biochemical recurrence rates remains controversial. There is no clear association of deferring RP with any of the features of aggressive disease such as pathologic upgrading, upstaging, positive surgical margins, extracapsular extension, seminal vesicle invasion, and lymph node invasion. Deferred RP was not associated with the need for secondary treatments. CONCLUSIONS: Owing to the different definitions of a delayed RP, it is hard to make a consensus regarding the safe delay time. However, the current data suggest that deferring RP in patients with intermediate- and high-risk PCa for at least around 3 months is generally safe, as it does not lead to adverse pathologic outcomes, biochemical recurrence, the need for secondary therapy, or worse oncological survival outcomes.

Intracorporeal versus extracorporeal urinary diversion in robot-assisted radical cystectomy: a systematic review and meta-analysis.

This systematic review and meta-analysis aimed to assess and compare the perioperative and oncological outcomes of intracorporeal (ICUD) and extracorporeal (ECUD) urinary diversion following robot-assisted radical cystectomy (RARC). A systematic literature search of articles was performed in PubMed®, Web of Science®, and Scopus® databases according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. We included studies that compared patients who underwent RARC with ICUD to those with ECUD. Twelve studies including 3067 patients met the eligibility criteria. There were no significant differences between ICUD and ECUD in overall and major complications, regardless of the period (short-term [≤ 30 days] or mid-term [> 30 days]). Subgroup analyses demonstrated that ICUD performed by high-volume centers exhibited a significantly reduced risk of major complications (short-term: OR 0.57, 95% CI 0.37-0.86, p = 0.008, mid-term: OR 0.66, 95% CI 0.46-0.94, p = 0.02). Patients who underwent ICUD had lower estimated blood loss (MD -102.3 ml, 95% CI - 132.8 to - 71.8, p < 0.00001), less likely to receive blood transfusion rates (OR 0.36, 95% CI 0.20-0.62, p = 0.00003); and these findings were consistent in subgroup analyses by low-volume centers (MD-121.6 ml, 95% CI - 160.9 to - 82.3, p < 0.00001 and OR 0.36, 95% CI 0.20-0.62, p = 0.00003, respectively). ICUD had a higher lymph node yield (MD 3.68, 95% CI 0.80-6.56, p = 0.01). Patients receiving ICUD provided comparable complications, superior perioperative outcomes, and similar oncological outcomes compared with ECUD. Centralization of patients may contribute to a reduction of postoperative complications, while maintaining the advantages.

Is loss of power output due to laser fiber degradation still an issue during prostate vaporization using the 180 W GreenLight XPS laser?

PURPOSE: To investigate whether heat-induced fiber degradation and loss of power output, which occurred during GreenLight laser vaporization (LV) of the prostate using the first- and second-generation 80 and 120 W laser, are still an issue during LV using the upgraded third generation 180 W GreenLight XPS™ laser. METHODS: Laser beam power output of 53 laser fibers was measured at baseline and after every 25 kJ of delivered energy during routine 180 W GreenLight XPS™ LV in 47 patients with prostatic bladder outflow obstruction. After the procedures, the fiber tips were microscopically examined. RESULTS: The median applied energy per patient was 178 kJ [interquartile range (IQR): 106-247]. Loss of power output during the procedure was detectable in all fibers. After the application of 25, 150, and 250 kJ, the median power output decreased to 77% (IQR 59-87), 57% (IQR 32-71), and 51% (IQR 37-64) of the baseline value. Nine fibers (17%) remained on a relatively high power output level (> 80% of the initial output), while 13 fibers (25%) showed an end-of-procedure power output of less than 20%. Microscopy of the fiber tip revealed mild-to-moderate overall degradation and increasing degradation with higher energy delivered. CONCLUSION: Despite changes in fiber design, heat-induced fiber damage and loss of power output remain an issue during 180 W GreenLight XPS™ LV. Whether modifications of the surgical technique can prevent impairment of fiber performance needs to be further evaluated.

Prostate volume reduction following pure transurethral bipolar plasma vaporization and conventional transurethral resection of the prostate: a prospective investigation using transrectal 3D ultrasound volumetry.

PURPOSE: To evaluate and compare postoperative changes in prostate volume and clinical outcome after bipolar plasma vaporization (BPV) and conventional transurethral resection of the prostate (TURP). PATIENTS AND METHODS: Consecutive series of patients undergoing BPV or TURP were included in this prospective, nonrandomized study. Planimetric volumetry after transrectal three-dimensional ultrasound of the prostate was performed preoperatively and postoperatively after 6 weeks, 6 months and 12 months. Additionally, changes in clinical outcome parameters were assessed and compared between the groups. The reduction ratio and analysis of covariance were used to compare volume changes between BPV and TURP. Multiple regression analysis was performed to assess a possible interaction between preoperative prostate volume and effect of therapy. RESULTS: A total of 157 patients were included (BPV: n = 68, TURP: n = 89). Median preoperative prostate volume was 43.1 ml in the BPV group and 45.9 ml in the TURP group (p = 0.43). Postoperatively, the prostate volumes decreased significantly in both groups. After catheter removal, the relative residual prostate volume was significantly higher in the BPV group (66.6 vs. 60.8 %; p = 0.02). Thereafter, significant differences were not detectable anymore (12 months: 46.6 vs. 47.1 %; p = 0.82). Regression analysis revealed that tissue ablation after BPV was superior to TURP in prostates <45 ml but inferior in prostates >45 ml. All clinical outcome parameters improved significantly and were not significantly different between the groups. CONCLUSIONS: Volume reduction and short-term clinical outcome following pure BPV was excellent and comparable to conventional TURP. However, volume reduction seems to be limited in patients with larger prostates.

Absorption of irrigation fluid during XPS™ GreenLight laser vaporization of the prostate: results from a prospective breath ethanol monitoring study.

PURPOSE: To assess whether and to what extent irrigation fluid absorption occurs during laser vaporization (LV) of the prostate using the 180 W XPS™ GreenLight laser. METHODS: This prospective investigation was performed in a tertiary care center with a consecutive series of patients undergoing 180 W LV of the prostate. Intraoperative irrigation was performed with isotonic saline containing 1 % ethanol. The volume of irrigation fluid absorption was calculated from periodically performed breath ethanol measurements during LV. Additionally, intraoperative changes in biochemical and hematological blood parameters were assessed. RESULTS: Positive breath ethanol tests were detectable in 22 of 54 patients. The median absorption volume in these patients was 950 ml (range 208-4579 ml). Ten patients absorbed more than 2000 ml. Absorbers had smaller prostates, more capsular perforations and injuries to venous sinuses, and more total energy was applied with higher output power. Five patients had transient symptoms potentially related to fluid absorption. A significant drop in hemoglobin, hematocrit, venous pH and bicarbonate and an increase in chloride were detectable in the absorber group. These changes were significantly different in the non-absorber group. CONCLUSIONS: Absorption of irrigation fluid did occur in a relevant proportion of patients undergoing XPS™ GreenLight LV. High-volume absorption (≥2000 ml), which might be clinically relevant, was detectable in almost 20 % of all procedures. Absorption of saline irrigation fluid does not result in a classical TUR syndrome, but fluid and chloride overload can lead to serious complications, particularly in cardiovascular high-risk patients. Thus, patients with symptoms potentially related to fluid absorption should be monitored carefully.

Absorption of irrigation fluid occurs frequently during high power 532 nm laser vaporization of the prostate.

PURPOSE: Absorption of irrigation fluid was not detected during GreenLight™ laser vaporization of the prostate using the first generation 80 W laser. However, data are lacking on intraoperative irrigation fluid absorption using the second generation 120 W high power laser. We assessed whether fluid absorption occurs during high power laser vaporization of the prostate. MATERIALS AND METHODS: We performed this prospective investigation at a tertiary referral center in patients undergoing 120 W laser vaporization for prostatic bladder outlet obstruction. Normal saline containing 1% ethanol was used for intraoperative irrigation. The expired breath ethanol concentration was measured periodically during the operation using an alcometer. The volume of saline absorption was calculated from these concentrations. Intraoperative changes in hematological and biochemical blood parameters were also recorded. RESULTS: Of 50 investigated patients 22 (44%) had a positive breath ethanol test. Median absorption volume in the absorber group was 725 ml (range 138 to 3,452). Ten patients absorbed more than 1,000 ml. Absorbers had a smaller prostate, more capsular perforation, higher bleeding intensity and more laser energy applied during the operation. Three patients (13%) had symptoms potentially related to fluid absorption. Hemoglobin, hematocrit and serum chloride were the only blood parameters that changed significantly in the absorber group. The changes were significantly different than those in nonabsorbers. CONCLUSIONS: Fluid absorption occurs frequently during high power laser vaporization of the prostate. This should be considered in patients who present with cardiopulmonary or neurological symptoms during or after the procedure.

Is conservative management safe in patients with acute ureterolithiasis and perirenal stranding?

In patients presenting with ureterolithiasis, perirenal stranding is frequently observed in non-contrast computed tomography. Because perirenal stranding may be caused by tears in the collecting system, previous studies have described an increased risk of infectious complications and suggested broad empiric antibiotic therapy and immediate decompressing of the upper urinary tract. We hypothesized that these patients can also be managed conservatively. Therefore, we retrospectively identified patients with ureterolithiasis and perirenal stranding and compared diagnostic and treatment characteristics as well as treatment outcomes between patients undergoing conservative versus interventional management by ureteral stenting, percutaneous drainage or primary ureteroscopic stone removal. We classified perirenal stranding as mild, moderate or severe based on its radiological extent. Of 211 patients, 98 were managed conservatively. Patients in the interventional group had larger ureteral stones, more proximal ureteral stone location, more severe perirenal stranding, higher systemic and urinary infectious parameters, higher creatinine levels, and received more frequent antibiotic therapy. The conservatively managed group experienced a spontaneous stone passage rate of 77%, while 23% required delayed intervention. In the interventional and conservative groups, 4% and 2% of patients, respectively, developed sepsis. None of the patients in either group developed a perirenal abscess. Comparison of perirenal stranding grade between mild, moderate and severe in the conservatively treated group showed no difference in the spontaneous stone passage and infectious complications. In conclusion, conservative management without prophylactic antibiotics for ureterolithiasis and perirenal stranding is a valid treatment option as long as no clinical or laboratory signs of renal failure or infections are observed.