Advanced Bladder Carcinoma Research Articles

Early and Post-Treatment Imaging Findings in Perineural Spread: A Pathway to Diffuse Muscle Metastasis in Recurrent Bladder Carcinoma.

Perineural spread (PNS) from pelvic carcinoma has been regarded as a pathway to muscle and bone metastasis. However, few cases have been reported, especially in patients with bladder carcinoma. In the present report, we discuss a case of diffuse cancer involvement in the muscle 5 years after radical cystectomy for advanced bladder carcinoma. Careful observation of temporal changes on medical images confirmed PNS as the pathway to muscle metastasis (i.e., primary PNS). Our report presents early and post-treatment CT, MRI and FDG-PET/CT findings of PNS from the bladder carcinoma.

Programmed Cell Death Ligand 1 (PD-L1) Immunohistochemical Expression in Advanced Urothelial Bladder Carcinoma: An Updated Review with Clinical and Pathological Implications.

The management of advanced bladder carcinoma involves a multidisciplinary approach, but the prognosis remains poor for many patients. The immune system plays a crucial role in this disease, influencing both tumor development and response to treatment, and exploiting the immune system against the tumor can be a valuable strategy to destroy neoplastic cells. This is the biological principle underlying Bacillus Calmette-Guérin (BCG) use and, more recently, immune checkpoint inhibitors (ICIs), like PD-1 (programmed death-1)/PD-L1 (programmed death-ligand 1) inhibitors. In fact, one of the best studied immune checkpoints is represented by the PD-1/PD-L1 axis, which is a well-known immune escape system adopted by neoplastic bladder cells. PD-L1 expression has been associated with a higher pathologic stage and has shown prognostic value in bladder carcinoma. Interestingly, high-grade bladder cancers tend to express higher levels of PD-1 and PD-L1, suggesting a potential role of such an axis in mediating disease progression. Immunotherapy with PD-1 and PD-L1 inhibitors has therefore emerged as a valuable treatment option and has shown efficacy in advanced bladder cancer patients, with high PD-L1 expression levels associated with better treatment responses. Our review aims to provide a comprehensive overview of the role of PD-L1 in advanced bladder cancer, focusing on its implications for treatment decisions and the prediction of treatment response. Overall, our work aims to contribute to the understanding of PD-L1 as a predictive biomarker and highlight its role in shaping therapeutic approaches for advanced bladder cancer.

GCISAVE: A non-comparative randomized phase II study of combination of gemcitabine cisplatin (GCis) +/- avelumab (A) in 1st line treatment for locally advanced or metastatic urothelial bladder carcinoma (MUBC)—GETUG AFU V07.

GCISAVE: A non-comparative randomized phase II study of combination of gemcitabine cisplatin (GCis) +/- avelumab (A) in 1st line treatment for locally advanced or metastatic urothelial bladder carcinoma (MUBC)—GETUG AFU V07.

Malignancy-related Hypercalcemia Caused by Metameric Cutaneous Metastasis of Parathyroid Hormone-related Protein-producing Bladder Carcinoma with Squamous Cell Differentiation: An Autopsy Case of Cobb Syndrome.

A 74-year-old woman was admitted with hypercalcemia and prolonged disturbance of consciousness. The left buttock to the anterior aspect of the left thigh was swollen and erythematous, with a collection of 1.0-cm large, firm, elastic nodules distributed in a zosteriform pattern in the L1-L4 region. Based on autopsy findings, a very rare case of Cobb syndrome was diagnosed due to a spinal vascular malformation at the Th12-L4 level and L5 vertebral hemangioma. Cobb syndrome-associated cutaneous metastasis extending along the same metamere was complicated by immunohistochemically proven parathyroid hormone-related protein-producing advanced bladder carcinoma in this case.

HPV-positive clinically advanced squamous cell carcinoma of the urinary bladder (aBSCC): A comprehensive genomic profiling (CGP) study

BackgroundAdvanced bladder squamous cell carcinoma (aBSCC) is an uncommon form of urinary bladder malignancy when compared with the much higher urothelial carcinoma incidence. We studied the genomic alteration (GA) landscape in a series of aBSCC based on the association with human papilloma virus (HPV) to determine if differences in GA would be observed between the positive and negative groups. MethodsUsing a hybrid capture-based FDA-approved CGP assay, a series of 171 aBSCC were sequenced to evaluate all classes of GA. Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on up to 114 loci. Programmed cell death ligand -1 (PD-L1) expression was determined by IHC (Dako 22C3) with negative expression when PD-L1 was 0, lower expression of positivity set at 1 to 49%, and higher expression set at ≥50% expression. ResultsOverall, 11 (6.4%) of the aBSCC were found to harbor HPV sequences (10 HPV16 and 1 HPV 11). HPV+ status was identified slightly more often in women (NS) and in younger patients (P = 0.04); 2 female patients with aBSCC had a prior history of SCC including 1 anal SCC and 1 vaginal SCC. HPV+ aBSCC had fewer GA/tumor (P < 0.0001), more inactivating mutations in RB1 (P = 0.032), and fewer inactivating GA in CDKN2A (P < 0.0001), CDKN2B (P = 0.05), TERT promoter (P = 0.0004) and TP53 (P < 0.0001). GA in genes associated with urothelial carcinoma including FGFR2 and FGFR3 were similar in both HPV+ and HPV- aBSCC groups. MTAP loss (homozygous deletion) which has emerged as a biomarker for PRMT5 inhibitor-based clinical trials was not identified in any of the 11 HPV+ aBSCC cases, which was significantly lower than the 28% positive frequency of MTAP loss in the HPV- aBSCC group (P < 0.0001). MTOR and PIK3CA pathway GA were not significantly different in the 2 groups. Putative biomarkers associated with immunotherapy (IO) response, including MSI and TMB status, were also similar in the 2 groups. PD-L1 expression data was available for a subset of both HPV+ and HPV- cases and showed high frequencies of positive staining which was not different in the 2 groups. ConclusionsHPV+ aBSCC tends to occur more often in younger patients. As reported in other HPV-associated squamous cell carcinomas, HPV+ aBSCC demonstrates significantly reduced frequencies of inactivating mutations in cell cycle regulatory genes with similar GA in MTOR and PIK3CA pathways. The implication of HPV in the pathogenesis of bladder cancer remains unknown but warrants further exploration and clinical validation.

Fourier transform IR imaging of primary tumors predicts lymph node metastasis of bladder carcinoma

The process of metastasis is complex and often impossible to be recognized in conventional clinical diagnosis. Lymph node metastasis (LNM) of bladder carcinoma (BC) is often associated with muscle-invasive tumors. To prevent and recognize LNM, the standard treatment includes radical cystectomy with lymph node dissection and histological examination. Here, we propose infrared (IR) microscopy as a tool for the prediction of LNM. For this purpose, IR images of bladder biopsies from patients with diagnosed non-metastatic early (E BC) and advanced (A BC), as well as metastatic advanced (M BC) bladder cancer were first collected. Furthermore, this dataset was complemented with images of the secondary tumors from the lymph nodes (M LN) of the M BC patients. Unsupervised clustering was used to extract tissue structures from IR images to create a data set comprising 382 IR spectra of non-metastatic bladder tumors and 241 metastatic ones. Based on that, we next established discrimination models using PLS-DA with repeated random sampling double cross-validation, and permutation test to perform the classification. The accuracy of BC metastasis prediction from IR bladder biopsies was 83 % and 78 % for early and advanced BC, respectively, herein demonstrating a proof-of-concept IR detection of BC metastasis. The analysis of spectral profiles additionally showed molecular composition similarity between metastatic bladder and lymph node tumors. We also determined spectral biomarkers of LNM that are associated with sugar metabolism, remodeling of extracellular matrix, and morphological features of cancer cells. Our approach can improve clinical decision-making in urological oncology.

Immune checkpoint inhibitors therapy in advanced bladder carcinoma: A meta-analysis of phase III randomized controlled trials.

e16584 Background: Currently, platinum-based chemotherapy is the standard treatment for advanced bladder cancer. Immune checkpoint inhibitors (ICIs) have been evaluated in these patients with clinical trials. There is no meta-analysis available of phase III randomized controlled trials comparing immune checkpoint inhibitors therapy versus chemotherapy/placebo in these patients. In this article, we write about the meta-analysis of ICIs use in advanced bladder cancer. Methods: Systemic searches of PubMed, Embase, the Cochrane Library, Google scholar, and ClinicalTrials.gov were searched for relevant studies with prespecified terms. We included only phase III randomized controlled trials comparing immune checkpoint inhibitors therapy versus chemotherapy/placebo in patients with advanced bladder carcinoma. Outcomes studied were Overall survival (OS), Progression-free survival (PFS), Objective response rate (ORR), and Grade 3 or higher adverse events (AE). We used a random effects model via RevMan 5.4 software to perform the meta-analysis. Results: 8 phase III RCTs met the inclusion criteria with a total of 5041 patients (immune checkpoint inhibitors = 2481 patients, Chemotherapy/placebo = 2560 patients) and a median follow-up of 24 months. Compared to the chemotherapy/placebo group, immune checkpoint inhibitors showed higher OS [HR = 0.83 (0.73-0.93) P = 0.002]. No significant differences were observed in PFS [HR = 0.84(0.68-1.05) P = 0.13] and ORR [HR = 2.15(0.51-9.09) P = 0.30] between the two groups. Compared to the chemotherapy group, immune checkpoint inhibitors showed significantly fewer severe adverse events [HR = 0.21 (0.14-0.32) P &lt; 0.00001]. Conclusions: The use of immune checkpoint inhibitors in patients with advanced bladder carcinoma is associated with favorable overall survival and fewer severe adverse events. The two groups observed no significant differences between progression-free survival and objective response rates.

Comparison of the genomic profiles of primary and recurrent lesions in patients with advanced bladder carcinomas.

e16575 Background: Bladder carcinomas (BCs) is featured by high incidence of recurrence which remains to be a big clinical challenge. This study aimed to compare the genomic profiles of primary and recurrent BCs in advanced stage. Methods: Primary and recurrent tissues (and control blood) were collected and somatic variants including short variants, copy number variations, gene rearrangements and TMB (Tumor Mutation Burden) were analyzed following the CAP/CLIA-certificated workflows. Chi-Square Test/Fisher Test was applied to compare the difference between two variables. Results: To eliminate the impact of stage, only patients in advanced stages were included (stage III-IV) in this study. 53 patients were investigated, including 43 primary and 10 recurrent (evidence of tumor observed after radical treatment). It should be noted that matched primary and recurrent samples were not obtained from the same patient. Median age of the patients was 64 years old. The proportion of male patients was 86% (n = 37) in the primary cohort and 60% (n = 6) in the recurrent cohort. Among the primary cases, the most frequent alterations were detected in TP53 (58.1%), TERT (51.2%), KMT2D (27.9%), KDM6A (23.3%) and RB1 (23.3%). Among the recurrent cases, the most frequent alternations were showed in TERT (70%), KMT2D (50%), PIK3CA (50%), TP53 (50%) and KDM6A (40%). PIK3CA substitution and KRAS substitution showed significant difference when comparing between the two cohorts. PIK3CA substitution preferentially occurred in recurrent samples (50% recurrent vs 14% primary, p-value = 0.01), mostly occurred in E545K; while KRAS substitution showed 4.7% in primary and 30% in recurrent with p-value = 0.04, all presented as G12V. TMB showed no significant difference between the two cohorts (6.2 vs 6.3 muts/Mb, p-value = 0.72). Conclusions: By NGS, we observed that substitutions in PIK3CA and KRAS showed significant difference between primary and recurrent samples from advanced BCs patients. PIK3CA and KRAS mutations were reported to be associated with local recurrence in CRC, but no association was observed in early stage non-muscle-invasive BCs. Our findings may provide a different insight into the treatment selections for advanced BCs, although the sample size is small.

Tumor-associated macrophages (TAMs) as Biomarker for urinary bladder tumor

Tumor associated macrophage (TAMs) are alternatively activated macrophages that enhance tumor progression by prompting tumor cell invasion ,migration and angiogenesis .The study aimed to detect of the distribution TAM bladder tumor tissues , and to clarify the relationship between the TAMs and clinicopathological grade of bladder cancer. Immunohisochemistry was used to detect CD68 as general marker for TAMs macrophage in tissue . Fifty patients with urinary bladder carcinoma and twenty benign bladder biopsies from patients with urinary bladder diseases (UBD) were included in this study . Our data showed a high positive immunohistochemical CD68 expression of UBC tumor tissues than in UBD tumor tissues (84% versus 45% ; p≤ 0.01) , also a significant difference was observed in grades among patients with UBC in CD68+ expression, high grade tumor cases showed positive immunohistochemical CD68 expression in 27(96.4%), while only 15 cases (68.2%) of low grade tumor showed positive CD68 expression . The results showed that the infiltration of CD68-positive may contribute to poor prognosis in advanced urinary bladder carcinoma

Atezolizumab for the treatment of advanced recurrent basal cell carcinoma and urothelial carcinoma of bladder: a case report

BackgroundThe use of checkpoint inhibitors has become increasingly important in the treatment of different cancers, including advanced muscle-invasive urothelial cancer and even in basal cell carcinoma. We present the case of a patient with advanced basal cell carcinoma and metastatic muscle-invasive urothelial cancer, who was treated with the programmed death-ligand 1 inhibitor, atezolizumab for both cancers.Case presentationA 72-year-old Caucasian female patient, with a history of smoking without any comorbidities developed periocular basal cell carcinoma, which was surgically removed but relapsed 4 years later. Surgical excision was carried out twice, but with positive margins, therefore definitive radiotherapy was given. Subsequently, the patient developed non-muscle-invasive papillary urothelial carcinoma, which was removed by transurethral resection. Follow-up was irregular owing to the patient’s inadequate compliance, and within 2 years, the patient’s cancer relapsed and histology confirmed muscle-invasive urothelial carcinoma. Definitive radiochemotherapy was not accepted by the patient. Meanwhile, the patient’s basal cell carcinoma had also progressed, despite receiving vismodegib therapy. Therefore, the patient was administered epirubicin-cisplatin. Having reached the maximum cumulative dose of epirubicin, treatment with this chemotherapeutic agent could not be continued. The patient developed bladder cancer metastasis in her left suprainguinal lymph nodes. Owing to the presence of both types of tumors, programmed death-ligand 1 inhibitor atezolizumab treatment was chosen. In just over 1 year, the patient received 17 cycles of atezolizumab altogether, which was tolerated well without any adverse or side effects. Follow-up imaging scans indicated complete remission of the metastatic bladder cancer and stable disease of the basal cell carcinoma. The patient subsequently passed away in hospital due to a complication of COVID-19 infection.ConclusionsOur patient attained stable disease in advanced basal cell carcinoma and complete remission in metastatic muscle-invasive urothelial cancer after receiving programmed death-ligand 1 inhibitor, atezolizumab, therapy. To our knowledge, this is the first paper to report the use of programmed death-ligand 1 inhibitor, atezolizumab, as treatment for advanced basal cell carcinoma. This case may also be of interest for clinicians when treating patients with two synchronous cancers.

18P Trastuzumab in HER2-amplified or overexpressed gallbladder cancer: Experience from an Indian cancer center

The prognosis of advanced gall bladder carcinoma (GBC) remains poor despite the addition of newer targeted therapies. HER2 is a potential therapeutic target expressed in up to 20% GBC. We present an analysis of advanced or metastatic HER2-amplified or overexpressed GBC treated with trastuzumab and chemotherapy from an Indian cancer center.

1745P Phase II study of neoadjuvant chemotherapy with 4 cycles of dose dense MVAC followed by radical surgery in Korean patients with MIBC and locally advanced urothelial carcinoma of bladder (NCT04047693)

Neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is standard for patients with muscle-invasive bladder cancer (MIBC). When previous western studies using retrospective or phase II studies showed that dd-MVAC (dose dense methotrexate, vinblastine, doxorubicin and cisplatin) for NAC was beneficial, while none was reported in Asian population. Also, there has been no study related with dd-MVAC in locally advanced urothelial carcinoma (UC). This prospective phase II study aimed to evaluate efficacy and safety of dd-MVAC in Korean MIBC or locally advanced UC patients.

The effect of postoperative pathological findings related to the eligibility of adjuvant immunotherapy on oncologic outcomes in patients with locally advanced urothelial cancer.

254 Background: The CheckMate 274 trial demonstrated a benefit in disease-free survival (DFS) with adjuvant nivolumab therapy in patients at high risk of muscle-invasive UC and may become a standard of care in the future. In that study, postoperative pT3-4/ypT2-4 or pN+ was used as an inclusion criterion for the high-risk group, but the validity of this criterion in clinical practice remains unclear. Also, there is an urgent need for the proportion of patients who are eligible for adjuvant immunotherapy in clinical practice. We aimed to evaluate the effect of postoperative pathological findings related to the eligibility of adjuvant immunotherapy on oncologic outcomes in patients with localized and locally advanced muscle-invasive bladder carcinoma (MIBC) and upper tract urothelial carcinoma (UTUC). Methods: We retrospectively evaluated 1082 patients treated with radical cystectomy (n = 597) and nephroureterectomy (n = 485) between January 2000 and April 2021. Patients were divided into two groups: pT3-4 or pN+ without neoadjuvant chemotherapy and ypT2-4 or pN+ treated with neoadjuvant chemotherapy (trial-eligible group) or others (trial-ineligible group). The primary outcome was the effect of trial eligibility for adjuvant immunotherapy on disease-free survival (DFS) and overall survival (OS). Secondary outcomes included the additional effect of lymphovascular invasion (LVI) status to the clinical trial criteria on prognosis and a risk model development. Results: The median age of the patients was 69 and 72 years in the MIBC and UTUC groups, respectively. Fifty-two percent of patients met the trial inclusion criteria. Trial eligibility was significantly associated with poor DFS and OS among patients with MIBC and UTUC. LVI-positive status was significantly associated with poor prognosis among patients in the trial-eligible group. A very high risk (LVI+ or pN+ among the pT3-4 or ypT2-4) was significantly associated with poor prognosis. Conclusions: A total of 52% of patients were eligible for adjuvant immunotherapy. Trial eligibility was significantly associated with a poor prognosis. LVI+ and pN+ may play a key role in candidate selection for adjuvant immunotherapy.

Concomitant endoscopic biliary, duodenal and colonic stent placement for advanced carcinoma of gall bladder

Concomitant endoscopic biliary, duodenal and colonic stent placement for advanced carcinoma of gall bladder

Prognostic impact of eligibility for adjuvant immunotherapy in locally advanced urothelial cancer.

ObjectiveTo evaluate the effect of postoperative pathological findings related to the eligibility of adjuvant immunotherapy on oncologic outcomes in patients with localized and locally advanced muscle‐invasive bladder carcinoma (MIBC) and upper tract urothelial carcinoma (UTUC).Patients and methodsWe retrospectively evaluated 1082 patients treated with radical cystectomy (n = 597) and nephroureterectomy (n = 485) between January 2000 and April 2021. Patients were divided into two groups: pT3‐4 or pN+ without neoadjuvant chemotherapy and ypT2‐4 or pN+ treated with neoadjuvant chemotherapy (trial‐eligible group) or others (trial‐ineligible group). The primary outcome was the effect of trial eligibility for adjuvant immunotherapy on disease‐free survival (DFS) and overall survival (OS). Secondary outcomes included the additional effect of lymphovascular invasion (LVI) status to the clinical trial criteria on prognosis and a risk model development.ResultsThe median ages of the patients were 69 and 72 years in the MIBC and UTUC groups, respectively. Fifty‐two percent of patients met the trial inclusion criteria. Trial eligibility was significantly associated with poor DFS and OS among patients with MIBC and UTUC. LVI‐positive status was significantly associated with poor prognosis among patients in the trial‐eligible group. A very high risk (LVI+ or pN+ among the pT3‐4 or ypT2‐4) was significantly associated with poor prognosis.ConclusionA total of 52% of patients were eligible for adjuvant immunotherapy. Trial eligibility was significantly associated with a poor prognosis. LVI+ and pN+ may play a key role in candidate selection for adjuvant immunotherapy.

PD-1/PD-L1 Immune Checkpoint Inhibitors after Platinum-based Chemotherapy in Metastatic or Locally Advanced Urothelial Bladder Carcinoma: A Systematic Review and Meta-analysis

Objective: This study aimed to assess the effect of anti-programmed cell death-1/programmed cell death-ligand-1 (PD-1/PD-L1) agents compared with second-line therapy in patients with metastatic or locally advanced urothelial bladder carcinoma following previous platinum-containing chemotherapy.Material and Methods: We systematically searched three electronic databases. The protocol of the study was registered in Prospero (CRD42019142494). Using the Grading of Recommendations Assessment, Development, and Evaluation approach, the certainty of evidence (CoE) was estimated.Results: The search results initially found 8168 publications. For qualitative synthesis, two publications were included. Pooled results indicated that patients treated with anti-PD-1/PD-L1 agents had significantly prolonged overall survival (hazard ratio (HR) 0.80; 95% confidence interval (CI) 0.7-0.9; I2 21.0%; moderate CoE). According to positive PD-L1 expression, PD-1/PD-L1 inhibitors had significantly more survival than chemotherapy (HR 0.75; 95% CI 0.5-0.9, I2 57.0%, low CoE). Furthermore, there was no significant difference in adverse events (AE) between the anti-PD-1/PDL1 agents and second-line chemotherapy (risk ratio 0.68; 95% CI 0.3-1.4; I2 97.0%, low CoE).Conclusion: The present meta-analysis and systematic review provide strong evidence that anti-PD-1/PD-L1 agents could improve overall survival and have similar results in AEs compared with second-line chemotherapy. Further studies will confirm the power of immunotherapy for the treatment of metastatic or locally advanced urothelial bladder carcinoma.

Signet-Ring Cell Carcinoma of the Urinary Bladder: A Review and Update

Signet-Ring Cell Carcinoma of the Urinary Bladder: A Review and Update

HPV-16 positive clinically advanced squamous cell carcinoma of the urinary bladder (mBSCC): A comprehensive genomic profiling (CGP) study.

481 Background: mBSCC is an uncommon form of urinary bladder malignancy when compared with the much higher urothelial carcinoma incidence. We studied the genomic alteration (GA) landscape in a series of mBSCC based on the association with HPV-16 to determine if differences would be observed between the positive and negative groups. Methods: Using a hybrid capture-based FDA-approved CGP assay, a series of 171 mBSCC were sequenced to evaluate all classes of GA. Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. PD-L1 expression was determined by IHC (Dako 22C3) with low tumor cell positive staining set at 1-49% and high staining at ≥50% expression. Results: Overall, 11 (6.4%) of the mBSCC were found to harbor HPV-16 sequences (Table). HPV-16+ status was identified slightly more often in women (NS) and in younger patients (P = .04); 2 female patients with mBSCC had prior history of SCC including 1 anal SCC and 1 vaginal SCC. HPV-16+ mBSCC had fewer GA/tumor (P &lt; .0001), and fewer inactivating GA in CDKN2A (P &lt; .0001), CDKN2B (P = .05), TERT promoter (P = .0004) and TP53 (P &lt; .0001). GA in genes associated with urothelial carcinoma including FGFR2 and FGFR3 were similar in both HPV-16+ and HPV-16- mBSCC groups. MTOR and PIK3CA pathway GA were not significantly different in the 2 groups. MSI and TMB were also similar in the 2 groups. The 3 HPV-16+ mBSCC cases showed high positive PD-L1 IHC staining. Conclusions: HPV-16+ mBSCC tends to occur more often in women and younger patients. As reported in other HPV-associated squamous cell carcinomas, HPV-16+ mBSCC demonstrates significantly reduced frequencies of inactivating mutations in cell cycle regulatory genes with similar GA in MTOR and PIK3CA pathways. The implication of HPV in the pathogenesis of bladder cancer remains unknown but warrants further exploration and clinical validation. [Table: see text]

Primeiro consenso brasileiro sobre o manejo do câncer de bexiga urotelial localizado e localmente avançado: uma revisão do painel SBU-SBOC-SBRT-LACOG-GU

INTRODUCTION: Urothelial carcinoma, especially localized bladder cancer, has a substantial prevalence in Brazil with 9,480 new cases each year and 3,903 deaths, therefore progress is required in its management in order to decrease its recurrence and progression, and improve survival. MATERIAL AND METHODS: Medical oncologists, radiation oncologists, and urologists from Brazil conducted a meeting to vote the best approaches available in this country in the diagnosis, staging, and treatment of localized and locally advanced urothelial bladder carcinoma. The panel drew up 73 questions and answers were chosen considering the feasibility according to the access to drugs and the procedures used in this country. Each answer reaching 75% of voters was considered a consensus. The results of this consensus were compared with evidence published in the medical literature and rated with a level of evidence and grade of recommendation using the Oxford classification. RESULTS: Transurethral resection of bladder tumors confirms the diagnosis of and provides initial treatment for non-muscle-invasive bladder cancers. Repeated resection is necessary in selected cases and should not delay further treatment. The use of intravesical Bacillus Calmette-Guérin is performed according to risk stratification, showing a significant reduction in tumor recurrence and progression, and improved disease-specific survival in intermediate- and high-risk patients. Radical cystectomy should be considered for high-progression risk cases after Bacillus Calmette-Guérin treatment failure and for localized muscle-invasive bladder cancer. CONCLUSION: Management of urothelial carcinoma often requires a multidisciplinary team with surgical and clinical approaches, based on the expertise of professionals and evidence from the literature.

Radical cystectomy for locally advanced urothelial carcinoma of the urinary bladder: Health-related quality of life, oncological outcomes and predictors for survival

PurposeWhile survival outcomes of locally advanced bladder cancer patients undergoing radical cystectomy are known to be poor, less is known regarding patient-reported outcomes and predictive features for survival in this patient subgroup. MethodsOne hundred and eighteen consecutive patients with pT4a cM0 urothelial carcinoma of the bladder were included. Based on pathological review, patients were stratified into 3 subgroups based on existence of additional lesions and invasion depth of the respective lesions. Cancer-specific survival and overall survival (OS) was determined using Kaplan-Meier-analyses and multivariate Cox regression models (P <0.05). Health-related quality of life was assessed using the validated EORTC-QLQ-C30 questionnaire pre- and postoperatively. ResultsSeventy-two (61.0%) patients were ineligible for neoadjuvant chemotherapy. Median follow-up based on censored patients was 12 months. Twelve month OS rate was 56.1%, 24 months OS rate was 21.1%. A total of 44.4% of the patients stated good general health-related quality of life. In multivariate analysis, we found significantly adverse OS outcomes for female patients (hazard ratio 2.35, 95% confidence interval 1.09–5.08, P = 0.030). Patients with at least 1 additional locally advanced tumor had significantly worse OS outcomes compared to patients who had no additional lesions in multivariate Cox regression analysis (hazard Ratio 3.37, 95% confidence interval 1.29–8.78, P = 0.013). ConclusionExistence of multiple locally advanced lesions and female gender is an independent predictor of worse survival outcomes in patients with pT4a urothelial carcinoma undergoing radical cystectomy.