Delaying BCG immunotherapy onset after transurethral resection of non-muscle-invasive bladder cancer is associated with adverse survival outcomes.

PURPOSE: This study was carried out to assess whether a prolonged time between primary transurethral resection of non-muscle-invasive bladder cancer (TURB) and implementation of bacillus Calmette-Guerin (BCG) immunotherapy (time to BCG; TTBCG) is associated with adverse oncological survival in patients with T1 high-grade (HG) non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: Data on 429 patients from 13 tertiary care centers with primary T1HG NMIBC treated with reTURB and maintenance BCG between 2001 and 2019 were retrospectively reviewed. Change-point regression was applied following Muggeo's approach. The population was divided into subgroups according to TTBCG, whereas the recurrence-free survival (RFS) and progression-free survival (PFS) were estimated with log-rank tests. Additionally, Cox regression analyses were performed. Due to differences in baseline patient characteristics, propensity-score-matched analysis (PSM) and inverse-probability weighting (IPW) were implemented. RESULTS: The median TTBCG was 95 days (interquartile range (IQR): 71-127). The change-point regression analysis revealed a gradually increasing risk of recurrence with growing TTBCG. The risk of tumor progression gradually increased until a TTBCG of approximately 18 weeks. When the study population was divided into two subgroups (time intervals: ≤ 101 and > 101 days), statistically significant differences were found for both RFS (p = 0.029) and PFS (p = 0.005). Furthermore, in patients with a viable tumor at reTURB, there were no differences in RFS and PFS. After both PSM and IPW, statistically significant differences were found for both RFS and PFS, with worse results for longer TTBCG. CONCLUSION: This study shows that delaying BCG immunotherapy after TURB of T1HG NMIBC is associated with an increased risk of tumor recurrence and progression.

Oncological outcomes of laparoscopic versus open nephroureterectomy for the treatment of upper tract urothelial carcinoma: an updated meta-analysis.

BACKGROUND: During the past two decades, laparoscopic radical nephroureterectomy (LRNU) has been proposed as an alternative technique to open radical nephroureterectomy (ORNU) and has become increasingly accepted for the treatment of patients with upper tract urothelial carcinoma (UTUC). Nevertheless, the oncologic efficacy of LRNU remains controversial, especially for the treatment of locally advanced (T3/T4 and/or N+) UTUC. In this meta-analysis, we aimed to cumulatively compare the oncological outcomes of LRNU versus ORNU. MATERIALS AND METHODS: The present meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A search was conducted of three electronic databases, namely, Medline, Embase, and Cochrane Library. Outcome measurements of cancer-specific survival (CSS), overall survival (OS), intravesical recurrence-free survival (IVRFS), and recurrence-free survival (RFS), including hazard ratios (HRs) and 95% confidence intervals (CIs), were extracted and pooled. RESULTS: Eighteen articles published from 2007 to 2020 were included in the final quantitative analysis. One study was a randomized controlled trial (RCT), and the remaining articles had a retrospective design. Among a total of 10,730 participants in the selected papers, 5959 (55.5%) and 4771 (44.5%) underwent ORNU and LRNU, respectively. The results of pooled analyses revealed no significant differences in CSS (HR 0.84, 95% CI 0.60-1.19, p = 0.33), OS (HR 0.84, 95% CI 0.62-1.13, p = 0.25), IVRFS (HR 1.08, 95% CI 0.85-1.39, p = 0.52), and RFS (HR 1.09, 95% CI 0.94-1.25, p = 0.26) between LRNU and ORNU groups. Furthermore, the results of subgroup analyses for pT3/T4 and pTany N+ populations did not confirm any statistically significant differences between LRNU and ORNU in terms of any survival parameter. CONCLUSIONS: Our present meta-analysis of current evidence suggests that LRNU and ORNU have comparable oncological outcomes in patients with UTUC, even in those with locally advanced disease. Further multicenter RCTs with large sample sizes and uniform data regarding specific surgical procedures, such as bladder cuff excision, are required to establish definitive conclusions.

Influence of Transurethral Resection of Bladder Cancer on Sexual Function, Anxiety, and Depression.

The standard of care in non-muscle invasive bladder cancer consists of transurethral tumor resection. The aim of this study was to evaluate the influence of transurethral resection of bladder tumor (TURB) on the patients' self-reported depression, anxiety, sexual satisfaction, and erectile dysfunction. Psychological condition of 252 male patients who underwent TURB was prospectively evaluated. The Hospital Anxiety and Depression Scale (HADS), simplified International Index of Erectile Function (IIEF-5), and Sexual Satisfaction Questionnaires (SSQ) were administered to patients before and 10 days after tumor resection. We found that primary anxiety, depression, and erectile dysfunction were all worse in cancer patients than those in the general population, and all further worsened after tumor resection. The post-resection worsening was influenced by the operation and catheterization time, complications, and the tumor characteristics. Taxonomical analysis shows that the greatest risk of depression aggravation concerned patients who were younger, had a higher body mass index, and a medium-sized tumor. We conclude that transurethral resection of non-muscle invasive bladder cancer may adversely affect sexual function, anxiety, and depression. Patients should be informed about potential complications to prevent the abandonment of a follow-up. The findings of this study stress the role of personalized medicine pursued by a multidisciplinary medical team.

[Lymphocele--urological complication after renal transplantation]. / Limfocele--powiklanie urologiczne po przeszczepie nerki.

Renal transplantation is the best renal replacement treatment. It provides longer survival and a better quality of life. The outcome of renal transplantation is influenced by the occurrence of various complications, including urological. One of the most frequently occurring complications is lymphocele. Most cases of lymphocele develop during a period of several weeks after the procedure of transplantation. However, there are some literature reports concerning lymphocele diagnosis in the later period, even after several years. Most cases of lymphocele are asymptomatic and are diagnosed accidentally. Nevertheless, a large lymphocele may press the kidney, ureter, urinary bladder or neighbouring blood vessels, causing deterioration of renal function, leg oedema and thrombosis of iliac vessels. Among other complications there are infections. The cause of lymphocele is collection of the lymph drained from damaged lymph vessels surrounding iliac blood vessels and/or lymph vessels of the graft. Important factors predisposing to lymphocele are immunosuppressive treatment, including mTOR inhibitors, mycophenolic acid derivatives and high doses of glucosteroids. Factors favouring occurrence of lymphocele comprise obesity, diabetes, elderly age of recipient, long time of warm ischaemia, acute rejection episodes and delayed graft function. The authors describe presently available treatment methods including aspiration and percutaneous drainage, with or without sclerotisation, drainage using the Tenckhoff catheter and laparoscopic or open fenestration. At present, laparoscopic fenestration is considered to be the most efficient and the safest method. However, there are clinical cases where open surgical treatment is necessary.

Prognosis of patients with T1 low-grade urothelial bladder cancer treated with bacillus Calmette-Guérin immunotherapy.

BACKGROUND: The existence and prognosis of T1LG (T1 low-grade) bladder cancer is controversial. Also, because of data paucity, it remains unclear what is the clinical history of bacillus Calmette-Guérin (BCG) treated T1LG tumors and if it differs from other NMIBC (non-muscle-invasive bladder cancer) representatives. The aim of this study was to analyse recurrence-free survival (RFS) and progression-free survival (PFS) in patients with T1LG bladder cancers treated with BCG immunotherapy. METHODS: A multi-institutional and retrospective study of 2510 patients with Ta/T1 NMIBC with or without carcinoma in situ (CIS) treated with BCG (205 T1LG patients) was performed. Kaplan-Meier estimates and log-rank test for RFS and PFS to compare the survival between TaLG, TaHG, T1LG, and T1HG NMIBC were used. Also, T1LG tumors were categorized into EAU2021 risk groups and PFS analysis was performed, and Cox multivariate model for both RFS and PFS were constructed. RESULTS: The median follow-up was 52 months. For the T1LG cohort, the estimated RFS and PFS rates at 5-year were 59.3% and 89.2%, respectively. While there were no differences in RFS between NMIBC subpopulations, a slightly better PFS was found in T1LG NMIBC compared to T1HG (5-year PFS; T1LG vs. T1HG: 82% vs. 89%; P<0.001). A heterogeneous classification of patients with T1LG NMIBC was observed when EAU 2021 prognostic model was applied, finding a statistically significant worse PFS in patients classified as high-risk T1LG (5-year PFS; 81.8%) compared to those in intermediate (5-year PFS; 93,4%), and low-risk T1LG tumors (5-year PFS; 98,1%). CONCLUSIONS: The RFS of T1LG was comparable to other NMIBC subpopulations. The PFS of T1LG tumors was significantly better than of T1HG NMIBC. The EAU2021 scoring model heterogeneously categorized the risk of progression in T1LG tumors and the high-risk T1LG had the worst PFS.

Assessment of the oncological outcomes of three different bacillus Calmette-Guérin strains in patients with high-grade T1 non-muscle-invasive bladder cancer.

OBJECTIVE: : To determine whether there are significant differences in oncological outcomes between three different bacillus Calmette-Guérin (BCG) strains used for adjuvant intravesical immunotherapy in patients with high-grade T1 (T1HG) non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: : Data of 590 patients with a diagnosis of primary T1HG NMIBC were retrospectively reviewed. The study included 138 (23.4%) patients who were treated with the Moreau, 272 (46.1%) with the TICE, and 180 (30.5%) with the RIVM strains. All patients included in the analysis received at least five instillations of an induction course and at least two installations of a maintenance course. Due to existing differences in baseline patient characteristics, the association between oncological outcomes and strain groups was investigated by complementary analysis with the implementation of inverse probability weighting (IPW). RESULTS: : The 5-year recurrence-free survival (RFS) rate was 70.5%, 66.7% and 55.2% for the Moreau, TICE and RIVM groups, respectively (P = 0.016). The 5-year progression-free survival (PFS) rates were 84.4%, 85% and 77.8% in the Moreau, TICE and RIVM groups, respectively (P = 0.215). The IPW-adjusted Cox proportional hazard regression analysis did not show any differences in RFS between the Moreau and TICE groups (P = 0.69), whereas the RIVM strain was significantly associated with worse RFS compared to the Moreau (hazard ratio [HR] 1.69 for RIVM; P = 0.034) and TICE (HR 1.87 for RIVM; P = 0.002) strains. The IPW-adjusted analysis did not show any significant differences between study groups in terms of PFS. CONCLUSIONS: : The results of the present study suggest that the Moreau and TICE strains might be superior to the RIVM strain in terms of RFS in patients with T1HG NMIBC.Abbreviations: CIS: carcinoma in situ; IPW: inverse probability weighting; IQR: interquartile range; HR: hazard ratio; HG: high grade; LVI: lymphovascular invasion; MP: muscularis priopria; NMIBC: non-muscle-invasive bladder cancer; PFS: progression-free survival; RCT: randomised controlled trial; RFS: recurrence-free survival; T1HG, high-grade T1; (re-)TURB: (re-staging) transurethral resection of bladder; VH: variant histology.

Combination of histological and molecular data for improving outcome prediction in non-muscle invasive bladder cancer-narrative review.

The majority of patients with bladder cancer are diagnosed in non-muscle invasive stage. Most of them will experience recurrence or progression to more aggressive disease during follow-up. That raises the need for improvements with regard to risk assessment. Current risk stratification, based only on clinicopathologic features, does not fully reflect biological heterogeneity of the cancer and its role in prognosis. Many studies addressed the topic of variant histology and its influence on treatment and outcomes. It has been shown that accurate identification of variant histology implicates patient prognosis and inform right treatment decisions. Most studies on histological variants of bladder cancer suggest a more aggressive clinical course, with higher risk of recurrence and progression than in conventional urothelial cancer, even when diagnosed in non-muscle invasive stage. That prompts early aggressive treatment approach whenever variant histology is detected. Emerging genomic information are expected to complement clinical and pathological data and change the paradigms in the management of bladder cancer. Several reports highlighted the clinical significance of molecular stratification of bladder cancer, but the available evidence is based on retrospective data. Molecular subtyping gives promise not only for improving risk assessment, but also in predicting response to Bacillus Calmette-Guerin (BCG) or chemotherapy. Finally, molecular alterations might become targets for novel drugs to improve the overall response of these patients. However, its implementation into clinical practice requires further validation in prospective trials, especially in the context of non-muscle invasive bladder cancer.

Clinical outcomes and survival differences between primary, secondary and concomitants carcinoma in situ of urinary bladder treated with BCG immunotherapy.

BACKGROUND: The carcinoma in situ (CIS) of urinary bladder is a flat, high-grade and aggressive manifestation of urothelial cancer which carries a great risk for progression to muscle invasive disease and metastatic spread. The aim of the study was to analyse the clinical history and survival differences between primary, secondary and concomitants CIS of the bladder. METHODS: We analysed a database of 301 patients who were treated between 1998 and 2017 in university BCG outpatient department. Primary, secondary and concomitants CIS cases were included in the study with minimum follow-up of 12 months. Recurrence-free survival (RSF), progression-free survival (PFS) and cancer specific survival (CSS) were analysed by Kaplan-Meier curves and log-rank test. Additionally, Cox regression models were performed. RESULTS: Seventy-two patients with primary, 58 with secondary and 171 with CIS concomitants were analysed. The patients were followed from mean 61,9 months. RFS rates at 5-years follow-up were 54.9%, 55.3% and 60.4% for primary, concomitants and secondary CIS (P>0.05). PFS rates at 5-years follow-up were 65.8%, 72.1% and 77% for primary, concomitants and secondary CIS (P>0.05). CSS rates at 5-years follow-up were 83.1%, 81.9% and 90.1% for primary, concomitants and secondary CIS (P>0.05). There were no statistically significant differences between any CIS subtype in any of analysed endpoints in multivariate analysis. Female gender was associated with worse RFS and the instillation number was positively associated with all analysed survival rates. On contrary, age was not statistically related to RFS, PFS nor CSS. CONCLUSIONS: In this study it was shown that when compared with secondary and concomitants CIS, primary CIS presented the worst RFS and PFS, however, the differences between subgroups were not statistically significant.

Restaging Transurethral Resection of Bladder Tumours after BCG Immunotherapy Induction in Patients with T1 Non-Muscle-Invasive Bladder Cancer Might not Be Associated with Oncologic Benefit.

BACKGROUND AND PURPOSE: The European Association of Urology guidelines recommend restaging transurethral resection of bladder tumours (reTURB) 2-6 weeks after primary TURB. However, in clinical practice some patients undergo a second TURB procedure after Bacillus Calmette-Guérin immunotherapy (BCG)induction. To date, there are no studies comparing post-BCG reTURB with the classic pre-BCG approach. The aim of this study was to assess whether the performance of reTURB after BCG induction in T1HG bladder cancer is related to potential oncological benefits. MATERIALS AND METHODS: Data from 645 patients with primary T1HG bladder cancer treated between 2001 and 2019 in 12 tertiary care centres were retrospectively reviewed. The study included patients who underwent reTURB before BCG induction (Pre-BCG group: 397 patients; 61.6%) and those who had reTURB performed after BCG induction (Post-BCG group: 248 patients, 38.4%). The decision to perform reTURB before or after BCG induction was according to the surgeon's discretion, as well as a consideration of local proceedings and protocols. Due to variation in patients' characteristics, both propensity-score-matched analysis (PSM) and inverse-probability weighting (IPW) were implemented. RESULTS: The five-year recurrence-free survival (RFS) was 64.7% and 69.1% for the Pre- and Post-BCG groups, respectively, and progression-free survival (PFS) was 82.7% and 83.3% for the Pre- and Post-BCG groups, respectively (both: p > 0.05). Similarly, neither RFS nor PFS differed significantly for a five-year period or in the whole time of observation after the PSM and IPW matching methods were used. CONCLUSIONS: Our results suggest that there might be no difference in recurrence-free survival and progression-free survival rates, regardless of whether patients have reTURB performed before or after BCG induction.

Urinary diversion metabolic complications - underestimated problem.

Bladder cancer is one of the most frequent human cancers. In 2011 more than six thousand people in Poland developed BC and more than three thousand died because of it. Treatment of bladder cancer depends on its stage. In less advanced tumours (Ta, Tcis, T1) transurethral resection of bladder tumor with adjuvant immunotherapy is often therapeutic. In more advanced cases (≥ T2) radical cystectomy is needed. There are several surgical types of post-cystectomy urinary diversion divided into two fundamental types - enabling and not enabling urine continence. The most common procedures include ureterocutaneostomy, ileal or colon conduit, orthopic ileal bladder, heterotopic continent bladder replacement (pouch) and urinary diversion via the rectum. Depending on type of cystectomy, various metabolic complications occur, because the absorptive-secretory function of used bowel segment is intact. Complications include bowel dysfunction, malabsorption of various vitamins, acid-base imbalance, electrolyte imbalance, abnormalities in bone metabolism, formation of renal calculi, secondary malignancies and disturbances in function of kidneys or liver. Early diagnosed complications can be treated easier, recognised in advanced stages are often irreversible. In our paper we present review of different approaches to bladder cancer treatment and metabolic complications occurring after these procedures.