Implications of the COVID19 pandemic on the need and timing of second transurethral bladder tumour resection in high-grade non-muscle invasive bladder cancer.

PURPOSE: Due to the COVID19 pandemic, the EAU has recommended to, if needed, postpone second transurethral resection of bladder tumour (TURBT) after BCG induction in selected patients. We aimed to evaluate the oncological outcomes of postponed TURBT and the potential to replace second TURBT by routine cystoscopy and cytology. METHODS: A single-center, retrospective analysis of patients with TaG3/high grade (HG) or T1HG urothelial bladder cancer was performed. All patients underwent a complete TURBT between 2000 and 2013 with presence of detrusor muscle, full BCG induction and routine cystoscopy and cytology, followed by a second TURBT. Results of the cystoscopy, cytology and pathology reports of the TURBT were analyzed by descriptive characteristics, sensitivity, specificity, negative and positive predictive values, as well as survival analyses. RESULTS: 112 patients were included. Residual tumour was present at second TURBT in 21.4%. Upstaging rate from pTaHG to pT1HG and pT1HG to pT2 was 0% and 2.7%, respectively. pT0 was confirmed in 79% of patients, but in 98% of patients with combined negative cytology and cystoscopy after BCG. With a median follow-up of 109 months, the 3-year OS was 85%, RFS 74% and PFS 89%. Sensitivity, specificity, negative predictive value and positive predictive value of cystoscopy and urinary cytology for the presence of residual tumour were 92%, 97%, 98% and 85%, respectively. CONCLUSION: This study underpins the recommendation of the EAU NMIBC guideline panel that, if needed and in selected patients, second TURBT may be postponed until after BCG induction treatment in pT1HG disease. Also, routine second TURBT can be omitted in pTaHG disease. Data on replacing second TURBT after BCG treatment by routine cystoscopy and cytology appear promising but require further confirmation in prospective studies.

What Is the Prognostic and Clinical Importance of Urothelial and Nonurothelial Histological Variants of Bladder Cancer in Predicting Oncological Outcomes in Patients with Muscle-invasive and Metastatic Bladder Cancer? A European Association of Urology Muscle Invasive and Metastatic Bladder Cancer Guidelines Panel Systematic Review.

CONTEXT: Variant histology of muscle-invasive (MIBC) and metastatic (mBC) bladder cancer may define the cancer treatment modality and oncological outcomes. OBJECTIVE: To determine the prognostic effect and impact of therapy of urothelial and nonurothelial histological variants on the oncological outcomes of MIBC and mBC. EVIDENCE ACQUISITION: Medline, Embase, Cochrane controlled trial databases, and ClinicalTrials.gov were systematically searched. Patients with histological variants of MIBC or/and mBC from prospective and retrospective comparative studies and single-arm case series published after the year of 2000 were included. Treatment outcomes (overall, recurrence-free, and disease-specific survival) were extracted and reported. Risk of bias (RoB) assessment was performed using Quality in Prognosis Studies tool. EVIDENCE SYNTHESIS: The search yielded 2450 unique articles, of which 41 articles involving a total of 27 672 patients with histological variants were included. Twenty-eight studies had a comparative study design. Two different study settings were seen: large database studies without centralised pathological review and small series with re-review by uropathologists. Although most of the histological variants show similar oncological outcomes after radical cystectomy (RC), signet ring cell, spindle cell, and neuroendocrine tumours showed inferior survival compared with pure urothelial bladder cancer (PUC). Owing to potential misleading interpretations and reporting as well as large heterogeneity between studies, a narrative synthesis approach instead of subgroup analyses was used. Most studies had a moderate RoB. CONCLUSIONS: The data about prognosis and treatment of the variant histology are still immature and assessed mostly in cystectomy patients. Based on this systematic review, all patients with MIBC should be treated with RC. Neoadjuvant chemotherapy may be beneficial for patients with micropapillary, plasmacytoid, sarcomatoid, and mixed variants, and especially for patients with neuroendocrine tumours. Metastatic bladder cancer should be treated as PUC. PATIENT SUMMARY: In this report, we looked at the prognosis and treatment of different bladder cancer histologies. We found that outcomes varied with divergent histologies and appropriate treatment should be based on the histological finding.

Benefits of Empiric Nutritional and Medical Therapy for Semen Parameters and Pregnancy and Live Birth Rates in Couples with Idiopathic Infertility: A Systematic Review and Meta-analysis.

CONTEXT: Empiric use of medical and nutritional supplements to improve semen parameters and pregnancy rates in couples with idiopathic infertility has reached global proportions, although the evidence base for their use in this setting is controversial. OBJECTIVE: We systematically reviewed evidence comparing the benefits of nutritional and medical therapy on pregnancy rates and semen parameters in men with idiopathic infertility. EVIDENCE ACQUISITION: A literature search was performed using MEDLINE, Embase, LILACS, and the Cochrane Library (searched from January 1, 1990 to September 19, 2017). using the methods detailed in the Cochrane Handbook. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the certainty of evidence. EVIDENCE SYNTHESIS: The literature search identified 5663 citations, and after screening of abstracts and full texts, 61 studies (59 randomised controlled trials and two nonrandomised comparative studies) were included. Pooled results demonstrated that pentoxyfylline, coenzyme Q10, L-carnitine, follicle-stimulating hormone, tamoxifen, and kallikrein all resulted in improvements in semen parameters. Individual studies identified several other medical and nutritional therapies that improved semen parameters, but data were limited to individual studies with inherent methodological flaws. There were limited data available on live birth and pregnancy rates for all interventions. The GRADE certainty of evidence for all outcomes was very low mainly owing to methodological flaws and inconsistencies in study design. Some outcomes were also downgraded owing to imprecision of results. CONCLUSIONS: There is some evidence that empiric medical and nutritional supplements may improve semen parameters. There is very limited evidence that empiric therapy leads to better live birth rates, spontaneous pregnancy, or pregnancy following assisted-reproductive techniques. However, the findings should be interpreted with caution as there were some methodological flaws, as a number of studies were judged to be either at high or unclear risk of bias for many domains. PATIENT SUMMARY: This review identified several medical and nutritional treatments, such as pentoxyfylline, coenzyme Q10, L-carnitine, follicle-stimulating hormone, tamoxifen, and kallikrein, that appear to improve semen parameters. However, there are limited data suggesting improvements in pregnancy and live birth rates. The lack of evidence can be attributed to methodological flaws in studies and the low number of pregnancies reported.

Effectiveness and Harms of Using Kidneys with Small Renal Tumors from Deceased or Living Donors as a Source of Renal Transplantation: A Systematic Review.

CONTEXT: Kidney transplantation is the best treatment for patients with end-stage renal disease. Incidence of small renal masses (SRMs), which most frequently are renal cell carcinomas (RCCs), is highest in patients aged >60 yr. The increasing age of donors can lead to the diagnosis of a higher number of SRMs when assessing the patient for transplantation, and so can theoretically decrease the number of kidneys suitable for transplantation. Aiming to increase the pool of kidneys suitable for transplantation, a number of studies have reported their experience using kidneys with SRMs for transplantation. OBJECTIVE: To systematically review all available evidence on the effectiveness and harm of using kidneys with SRMs as a source of transplantation. EVIDENCE ACQUISITION: A computerized bibliographic search of the Medline, Embase, and Cochrane databases was performed for all studies reporting outcomes of adult renal transplantation using kidneys with SRMs. EVIDENCE SYNTHESIS: Nineteen studies enrolling 109 patients were included and synthesized narratively. The mean recipient age was 44.2 yr, and kidneys used were retrieved from living donors in 86% (94/109) of cases. Tumor excision was performed ex vivo in all cases except for two. The vast majority of excised tumors were RCCs (88/109 patients), and clear-cell subtype was most common. The mean tumor size was 2cm (range 0.5-6.0cm) and tumor grade was G1-G2 in 93% (75/81) of patients. With a mean follow-up of 39.9 mo, overall survival rates at 1, 3, and 5 yr were 97.7%, 95.4%, and 92%, respectively, and the mean graft survival rates 99.2%, 95%, and 95.6%, respectively. Only one local relapse occurred 9 yr after transplantation, which was managed conservatively. Functional outcomes, although infrequently reported, appear to be similar to those of conventional transplants, with 1.6% of these patients needing reoperation. CONCLUSIONS: The current literature, although with low-level evidence, suggests that kidneys with excised SRMs are an acceptable source of transplantation without compromising oncological outcomes and with similar functional outcomes to other donor kidneys. PATIENT SUMMARY: Renal transplantation using a kidney with a small renal mass does not appear to increase the risk of cancer recurrence and can be a good option for selected patients after appropriate counseling and allocation.

Updated 2016 EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer.

CONTEXT: Invasive bladder cancer is a frequently occurring disease with a high mortality rate despite optimal treatment. The European Association of Urology (EAU) Muscle-invasive and Metastatic Bladder Cancer (MIBC) Guidelines are updated yearly and provides information to optimise diagnosis, treatment, and follow-up of this patient population. OBJECTIVE: To provide a summary of the EAU guidelines for physicians and patients confronted with muscle-invasive and metastatic bladder cancer. EVIDENCE ACQUISITION: An international multidisciplinary panel of bladder cancer experts reviewed and discussed the results of a comprehensive literature search of several databases covering all sections of the guidelines. The panel defined levels of evidence and grades of recommendation according to an established classification system. EVIDENCE SYNTHESIS: Epidemiology and aetiology of bladder cancer are discussed. The proper diagnostic pathway, including demands for pathology and imaging, is outlined. Several treatment options, including bladder-sparing treatments and combinations of treatment modalities (different forms of surgery, radiation therapy, and chemotherapy) are described. Sequencing of these modalities is discussed. Potential indications and contraindications, such as comorbidity, are related to treatment choice. There is a new paragraph on organ-sparing approaches, both in men and in women, and on minimal invasive surgery. Recommendations for chemotherapy in fit and unfit patients are provided including second-line options. Finally, a follow-up schedule is provided. CONCLUSIONS: The current summary of the EAU Muscle-invasive and Metastatic Bladder Cancer Guidelines provides an up-to-date overview of the available literature and evidence dealing with diagnosis, treatment, and follow-up of patients with metastatic and muscle-invasive bladder cancer. PATIENT SUMMARY: Bladder cancer is an important disease with a high mortality rate. These updated guidelines help clinicians refine the diagnosis and select the appropriate therapy and follow-up for patients with metastatic and muscle-invasive bladder cancer.

The effect of the time interval between diagnosis of muscle-invasive bladder cancer and radical cystectomy on staging and survival: A Netherlands Cancer Registry analysis.

INTRODUCTION: Data from single-center series suggest that a delay in time to radical cystectomy (RC) more than 3 months after diagnosis of muscle-invasive bladder cancer (MIBC) is associated with pathological upstaging and decreased survival. However, limited data is available from population-based studies. In this study, the effect of delayed RC was assessed in a nationwide cohort. MATERIALS AND METHODS: Patients who underwent RC between 2006 and 2010 with primary clinical T2-T4N0M0 urothelial bladder cancer were selected using the Netherlands Cancer Registry database. Data from the Netherlands Cancer Registry was supplemented with data from the Nationwide Network and Registry of Histo- and Cytopathology database in case of incomplete information. The cohort was divided in patients who underwent RC ≤3 months (group I) vs. patients who underwent RC >3 months (group II). Median time from MIBC diagnosis to RC, variables associated with delayed RC >3 and the effect of delayed RC on staging and overall survival (OS) were evaluated in patients who underwent neoadjuvant therapy and patients who did not. RESULTS: A total of 1,782 patients were included. Median follow-up time was 5.1 years for living patients and 1.3 years for deceased patients. Median time from MIBC diagnosis to RC was 50 days (interquartile range: 27 days) and 93% of patients underwent RC≤3 months. Patients older than 75 years (odds ratio [OR] = 0.50; 95% CI: 0.32-0.77), referred for RC (OR = 0.41; 95% CI: 0.26-0.69), and treated in a university hospital (OR = 0.34; 95% CI: 0.21-0.56) were less likely to undergo RC≤3 months. Pathologic upstaging rate (43.9% vs. 42.1%) and node-positive disease rate (20.2% vs. 21.7%) did not differ for group I and II. Delayed RC>3 months was not associated with decreased OS adjusting for confounding variables (hazard ratio = 1.16; 95% CI: 0.91-1.48; P = 0.25). Median time from MIBC diagnosis to RC in patients that received neoadjuvant therapy (n = 105) was 133 days (interquartile range: 62 days). Adjusting for confounding variables, delayed RC>3 months was not associated with OS (hazard ratio = 0.90; 95% CI: 0.45-1.82). CONCLUSIONS: The vast majority of patient underwent RC within 3 months after diagnosis of MIBC, as recommended in the European Association of Urology MIBC guideline. Delayed RC for more than 3 months had no adverse effect on staging and survival.

The association of preoperative serum albumin level and American Society of Anesthesiologists (ASA) score on early complications and survival of patients undergoing radical cystectomy for urothelial bladder cancer.

OBJECTIVE: To evaluate the impact of the preoperative American Society of Anesthesiologists (ASA) score and serum albumin level on complications, recurrences and survival rates of patients who underwent radical cystectomy (RC) for urothelial bladder cancer (UBC). PATIENTS AND METHODS: In all, 1964 patients underwent RC for UBC at our institution between 1971 and 2008. Preoperative serum albumin and ASA score were available in 1471 and 1140 patients, respectively. A complication was defined as any surgery related/unrelated event leading to lengthening hospital stay or re-admission. Endpoints were 90-day complication (90dC) rate, recurrence-free survival (RFS) and overall survival (OS). RESULTS: The median (range) follow-up was 12.4 (0.2-27.3) years. In all, 197 patients (13.4%) had a low albumin level (<3.5 g/dL) and 740 (64.8%) had a high ASA score (3 or 4). Low serum albumin and a high ASA score were associated with higher 90dC rate (42% vs 34%, P = 0.03 and 40% vs 28%, P < 0.001, respectively). On multiple logistic regression analysis, a high ASA score remained independently associated with increased 90dC rate (hazard ratio [HR] 1.52, P = 0.005) and decreased OS (HR 1.45, 95% confidence interval [CI] 1.13-1.86). A low serum albumin level was also independently associated with RFS (HR 1.68, 95% CI 1.16-2.43) and OS (HR 1.93, 95% CI 1.43-2.63). CONCLUSION: A low serum albumin level was independently associated with cancer recurrence and decreased OS after RC. A high ASA score was also independently associated with decreased OS. These parameters potentially could be used as prognosticators after RC.

Incidental prostate cancer in patients with bladder urothelial carcinoma: comprehensive analysis of 1,476 radical cystoprostatectomy specimens.

PURPOSE: We identified risk factors and determined the incidence and prognosis of incidental, clinically significant prostatic adenocarcinoma, prostatic urothelial carcinoma and HGPIN in patients treated with radical cystoprostatectomy for urothelial carcinoma of the bladder. MATERIALS AND METHODS: We analyzed the records of 1,476 patients without a history of prostatic adenocarcinoma. We determined the incidence of clinically significant prostatic adenocarcinoma, prostatic urothelial carcinoma and HGPIN in the total cohort and in select patient subgroups. Prostatic urothelial carcinoma was stratified as prostatic stromal and prostatic urethral/duct involvement. Univariate and multivariate analyses were performed with multiple variables. Recurrence-free and overall survival rates were calculated. Median followup was 13.2 years. RESULTS: Of the 1,476 patients 753 (51.0%) had cancer involving the prostate. Prostatic adenocarcinoma, clinically significant prostatic adenocarcinoma, prostatic urothelial carcinoma and HGPIN were present in 37.9%, 8.3%, 21.1% and 51.2% of patients, respectively. Of the 312 patients (21.1%) with prostatic urothelial carcinoma 163 (11.0%) had prostatic urethral/duct involvement only and 149 (10.1%) had prostatic stromal involvement. We identified risk factors for clinically significant prostatic adenocarcinoma, prostatic urothelial carcinoma and HGPIN but the absence of these risk factors did not rule out their presence. Ten-year overall survival in patients with no prostatic urothelial carcinoma, and prostatic urethral/duct and prostatic stromal involvement was 47.1%, 43.3% and 21.7%, respectively (p<0.001). No patient with clinically significant prostatic adenocarcinoma died of prostatic cancer. CONCLUSIONS: More than half of the patients undergoing radical cystoprostatectomy had cancer involving the prostate. Prostatic urothelial carcinoma, particularly with prostatic stromal involvement, was associated with a worse prognosis, while clinically significant prostatic adenocarcinoma did not alter survival. Preoperative clinical and histopathological risk factors are not reliable enough to accurately predict clinically significant prostatic adenocarcinoma and/or prostatic urothelial carcinoma.

Risk factors and clinical outcomes of patients with node-positive muscle-invasive bladder cancer.

Radical cystectomy and lymphadenectomy is a standard treatment for patients with high-grade, invasive bladder cancer. Although the absolute limits of lymphadectomy at the time of surgery have not been precisely defined, there is a growing body of evidence to suggest that an extended lymph node dissection may be beneficial for staging and survival in both node-negative and -positive bladder cancer patients. For lymph node-positive patients, several prognostic factors have been identified to provide risk stratification and direct the need for adjuvant treatment. These include: the pathological stage of the bladder tumor, extent of the lymphadenectomy and nodal tumor burden. The concept of lymph node density has also been identified as a prognostic factor. The literature and data on the extent of lymphadenectomy will be reviewed as well as the current prognostic variables and the benefits of adjuvant chemotherapy.