Bladder cancer is a disease in which malignant cells arise in the bladder. Symptoms can include blood in the urine, pain during urination, increased frequency of passing urine, or feeling the need to urinate but with nothing coming out. The bulk of bladder cancers are histlogically classed as transitional cell carcinomas which arise in the uroepithelium (lining of the bladder). Other types include squamous cell carcinomas, and adenocarcinomas. Treatment will depend on how far the tumour has invaded the surrounding tissues, and if it has spread to other parts of the body. World-wide about 260,000 people are diagnosed with bladder cancer each year.
Cancer Research UK CancerHelp information is examined by both expert and lay reviewers. Content is reviewed every 12 to 18 months. Further info. Statistics for the UK, including incidence, mortality, survival, risk factors and stats related to treatment and symptom relief.
ABC A charity which works with healthcare professionals, patients, their carers and the general public, to help improve the care of people with bladder cancer through awareness raising, education and research projects
Mayo Clinic Dr. Jeff Karnes describes symptoms of bladder cancer, diagnosis, and treatment options. Dr. Karnes also discusses risk factors for bladder cancer.
Founded in September 2009, Bladder Cancer Canada is a patient advocacy organization dedicated to bladder cancer issues. Bladder Cancer Canada is a Canadian registered charitable non-profit corporation.
An association of individuals with bladder cancer, bladder polyps / papillomas and their relatives.
David I. Quinn, MD: Bladder Cancer 101
American Society of Clinical Oncology Dr. David Quinn, a bladder cancer expert, gives us an educational overview of bladder cancer. Risk factors, signs and symptoms and diagnosis. This 8 minute video interview was filmed at the American Society of Clinical Oncology Annual Meeting in Chicago 2012.
PubMed Central search for free-access publications about Bladder Cancer MeSH term: Urinary Bladder Neoplasms US National Library of Medicine PubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated.
Cancer Research UK CancerHelp information is examined by both expert and lay reviewers. Content is reviewed every 12 to 18 months. Further info. Statistics for the UK, including incidence, mortality, survival, risk factors and stats related to treatment and symptom relief.
This list of publications is regularly updated (Source: PubMed).
Li G, Liu Y, Yin H, et al. E-cadherin gene promoter hypermethylation may contribute to the risk of bladder cancer among Asian populations. Gene. 2014; 534(1):48-53 [PubMed] Related Publications
There are increasing scientific evidences suggesting that E-cadherin gene promoter hypermethylation may contribute to the development and progression of bladder cancer, but existing studies have yielded inconclusive results. This meta-analysis aims to assess the role of E-cadherin promoter hypermethylation in bladder carcinogenesis. We conducted an extensive literature search for relevant studies on PubMed, Embase, Web of Science, Cochrane Library, and CBM databases from their inception through May 1st, 2013. This meta-analysis was performed using the STATA 12.0 software. Crude risk ratio (RR) with 95% confidence interval (CI) was calculated. Ten clinical studies were included in this meta-analysis with a total of 620 bladder cancer samples,199 normal adjacent samples and 131 normal urothelium tissue. Our meta-analysis revealed that the methylation frequencies in bladder cancer tissues were obviously higher than those in normal control tissues (RR = 2.02, 95%CI: 1.00–4.12, P = 0.050). Subgroup analysis by ethnicity indicated that higher methylation frequencies were observed in bladder cancer tissues among Asian populations (RR = 2.35, 95%CI: 1.11–4.95, P = 0.025), but not among Caucasian populations (RR = 1.62, 95%CI: 0.48–5.53, P = 0.439). Univariate and multivariate meta-regression analyses showed that ethnicity may be the major source of heterogeneity (Pb0.05).No publication bias was detected in this meta-analysis (P=0.358). The present meta-analysis indicates that E-cadherin gene promoter hypermethylation may contribute to increased risk of bladder cancer among Asian populations.
Han Y, Liu Y, Zhang H, et al. Hsa-miR-125b suppresses bladder cancer development by down-regulating oncogene SIRT7 and oncogenic long non-coding RNA MALAT1. FEBS Lett. 2013; 587(23):3875-82 [PubMed] Related Publications
MicroRNAs mainly inhibit coding genes and long non-coding RNA expression. Here, we report that hsa-miR-125b and oncogene SIRT7/oncogenic long non-coding RNA MALAT1 were inversely expressed in bladder cancer. Hsa-miR-125b mimic down-regulated, whereas hsa-miR-125b inhibitor up-regulated the expression of SIRT7 and MALAT1. Binding sites were confirmed between hsa-miR-125b and SIRT7/MALAT1. Up-regulation of hsa-miR-125b or down-regulation of SIRT7 inhibited proliferation, motility and increased apoptosis. The effects of up-regulation of hsa-miR-125b were similar to that of silencing MALAT1 in bladder cancer as we had previously described. These data suggest that hsa-miR-125b suppresses bladder cancer development via inhibiting SIRT7 and MALAT1.
Jensen BT, de Blok W, Kiesbye B, Kristensen SA Validation of the urostomy education scale: the European experience. Urol Nurs. 2013 Sep-Oct; 33(5):219-29 [PubMed] Related Publications
Bladder cancer is the fourth most common cancer among European males. Once diagnosed with muscle invasive bladder cancer, a radical cystectomy is the first line treatment, which results in a urostomy. The placement of a urostomy and the care required impacts the patient's life. Previous research validated the Urostomy Education Scale as the first standardized tool capable of documenting the patients' level of stoma self-care skills and useful to guide patient education interventions. A Danish-Dutch Fellowship was established to support and provide further evidence of applicability of the Urostomy Education Scale.
Lopez-Beltran A, Montironi R, Vidal A, et al. Urothelial dysplasia of the bladder: diagnostic features and clinical significance. Anal Quant Cytol Histol. 2013; 35(3):121-9 [PubMed] Related Publications
The 2004 World Health Organization classification system for urothelial neoplasia identifies urothelial dysplasia (low-grade intraurothelial neoplasia) as a premalignant lesion of the urothelium. Although diagnostic criteria of urothelial dysplasia have been improved in recent years, there is a frequent lack of interobserver reproducibility. Follow-up studies suggest that dysplasia is a marker for urothelial instability and disease progression in up to 19% of patients, thus supporting an active clinical follow-up in these patients. The main differential diagnosis of urothelial dysplasia includes flat urothelial lesions with atypia, mainly flat (simple) urothelial hyperplasia, reactive urothelial atypia, urothelial atypia of unknown significance, and urothelial carcinoma in situ (high-grade intraurothelial neoplasia). In most cases, morphologic features alone suffice for diagnosis. Some cases may require a panel of immunohistochemical antibodies consisting of cytokeratin 20, p53 and CD44 for diagnosis. We present pathologic features and clinical significance of urothelial dysplasia with emphasis on differential diagnosis from common flat urothelial lesions with atypia.
Patel P, Gotto G, Kavanagh A, et al. Urinary bladder melanosis associated with urothelial dysplasia and invasive urothelial carcinoma: a report of two cases. Anal Quant Cytol Histol. 2013; 35(5):294-300 [PubMed] Related Publications
BACKGROUND: Melanosis is defined as an abnormal or excessive deposition of melanin within cells and/or tissues. It typically presents as a cutaneous or buccal mucosal lesion, but rare cases of bladder melanosis have also been documented. Melanosis of the urinary bladder is typically considered a benign condition, but it has also been described in association with malignant melanoma and urothelial carcinoma. CASES: We report the cases of 2 patients who presented with melanosis of the urinary bladder. One patient presented with melanosis of the urinary bladder together with urothelial dysplasia. Melanosis was incidentally identified during a cystoscopy for ureteral stones. A second patient presented with hematuria and was found to have a muscle invasive urothelial carcinoma with focal small nested morphology together with melanosis. We also present a literature review of the bladder melanosis and an overview of other bladder melanocytic lesions, which include primary and metastatic melanoma and blue nevus. CONCLUSION: Initial evaluation for bladder melanosis should include cystoscopy and upper urinary tract imaging. Biopsy is essential to establish the diagnosis and rule out associated malignancy.
Olaya M, Vicioso L, Hierro I, et al. Granular cell tumor of the bladder: a case report. Anal Quant Cytol Histol. 2013; 35(5):289-93 [PubMed] Related Publications
BACKGROUND: Granular cell tumor is usually a benign tumor, generally believed to be of neural origin, most commonly affecting the tongue and skin. Although it can present in any part of the body, the bladder is a rare location, with only 16 cases found in the English-language literature. CASE: We report the case of a 54-year-old woman with hematuria who had a solid tumor in the posterior wall of the bladder. Histological study of the samples obtained by transurethral resection revealed a granular cell tumor, confirmed by immunohistochemical techniques. CONCLUSION: Granular cell tumors of the bladder are rare and generally benign but frequently present macroscopic features resembling those of urothelial carcinoma. The similarity can lead to an erroneous clinical diagnosis and unnecessary, aggressive treatment. A careful histopathological assessment is essential for an accurate diagnosis.
Pan JG, Luo RQ, Zhou X, et al. Potent antitumor activity of the combination of HSV-TK and endostatin by adeno-associated virus vector for bladder cancer in vivo. Clin Lab. 2013; 59(9-10):1147-58 [PubMed] Related Publications
BACKGROUND: Gene therapy may offer a new tool for the treatment of bladder cancer. Previously, we have shown a significant antitumor effect in bladder cancer xenografts in a nude mouse model using intratumoral herpes simplex virus thymidine (HSV-TK) and endostatin gene monotherapy. METHODS: Given the high vascularity of human bladder cancer and the ability of HSV-TK or endostatin monotherapy to eradicate the tumors, we decided to test a novel combination of cytotoxic and antiangiogenic gene therapy using intratumorally delivered HSV-TK and endostatin adeno-associated viruses (AAV). We constructed plasmid AAV-TK-IRES-Endostatin (pAAV-TIE) and packaged the AAV particles containing gene fragments of HSV-TK and endostatin. The combined anticancer effect of recombinant AAV-TIE (rAAV-TIE) was measured in vivo with rAAV-HSV-TK and rAAV-Endostatin as the control groups. RESULTS: The inverted terminal repeat sequence was amplified using only one primer and the fragment between two ITRs of pAAV-TIE measuring about 4 kb, which indicated a stable sequence of pAAV-TIE. Three clear bands representing the AAV capsid proteins VP1, VP2, and VP3 could be seen on both lanes against a very low background, which demonstrated that chloroform extraction could effectively extract contaminants from rAAV stock without significant loss of the rAAV. In vivo, our results showed that the tumors in mice injected with the rAAV-TIE not only took significantly longer to emerge but also that their growth, once established, was significant slower than that of tumors grown with single HSV-TK or endostatin treated animals. CONCLUSIONS: We concluded that the inhibition of angiogenesis using endostatin gene transfer, together with the cytotoxic HSV-TK gene therapy, resulted in a significant antitumor effect compared to the single gene based therapy in BTCC.
Pan JG, Luo RQ, Zhou X, et al. Suppression of bladder cancer growth by adeno-associated virus vector-mediated combination of HSV-TK and endostatin in vitro. Clin Lab. 2013; 59(9-10):1077-89 [PubMed] Related Publications
BACKGROUND: Gene therapy may offer a new tool for the treatment of bladder cancer. Previously, we have shown a significant antitumor effect in bladder cancer xenografts in a nude mouse model using intratumoral herpes simplex virus thymidine (HSV-TK) and endostatin gene monotherapy. OBJECTIVES: Given the high vascularity of human bladder cancer and the ability of HSV-TK or endostatin monotherapy to eradicate the tumors, we decided to test a novel combination of cytotoxic and antiangiogenic gene therapy using HSV-TK and endostatin adeno-associated viruses (AAV) in vitro. METHODS: We constructed the plasmid AAV-TK-IRES-Endostatin (pAAV-TIE) and packaged the AAV particles containing gene fragments of HSV-TK and endostatin. The combination anticancer effect of recombinant AAV-TIE (rAAV-TIE) was measured in vitro while rAAV-HSV-TK and rAAV-Endostatin were used as control groups. RESULTS: The inverted terminal repeat sequences were amplified using only one primer and the fragment between two ITRs of pAAV-TIE measuring about 4 kb, which indicated a stable sequence of pAAV-TIE. Three clear bands representing the AAV capsid proteins VP1, VP2, and VP3 could be seen on both lanes against a very low background, which demonstrated that chloroform extraction could effectively extract contaminants from rAAV stock without significant loss of the rAAV. In vitro, our results found that the transduction efficiency, measured from GFP-transduced tumors, was about 62%. The combination therapy led to an obvious apoptosis of bladder tumor cells compared with single HSV-TK or endostatin treatment. CONCLUSIONS: We concluded that the inhibition of angiogenesis using endostatin gene transfer, together with the cytotoxic HSV-TK gene therapy, resulted in a significant antitumor effect in vitro compared to the single gene based therapy in BTCC.
Rosenkrantz AB, Haghighi M, Horn J, et al. Utility of quantitative MRI metrics for assessment of stage and grade of urothelial carcinoma of the bladder: preliminary results. AJR Am J Roentgenol. 2013; 201(6):1254-9 [PubMed] Related Publications
OBJECTIVE: The purpose of this study was to assess associations between quantitative MRI metrics and pathologic indicators of aggressiveness of urothelial carcinoma of the bladder. MATERIALS AND METHODS: In this retrospective biinstitutional study, 37 patients (28 men and nine women; mean age, 73 ± 12 years) who underwent pelvic MRI including diffusion-weighted imaging (b values 0, 400, and 800 s/mm(2)) and T2-weighted imaging before transurethral resection or cystectomy for urothelial carcinoma of the bladder were identified. Tumor diameter (measured on T2-weighted imaging), normalized T2 signal intensity (to muscle; hereafter labeled normalized T2) and apparent diffusion coefficient (ADC) were measured for all tumors. Mann-Whitney test and receiver operating characteristic analyses were used to identify associations between these metrics and histopathologic tumor stage and grade. RESULTS: Thirty-seven tumors were assessed (mean size, 35 ± 23 mm; range 8-88 mm). At histopathologic analysis, 16 of 37 (43%) tumors were stage T2 or greater and 21 of 37 (57%) were stage T1 or lower, whereas 34 of 37 (92%) were high grade and three of 37 (8%) were low grade. High-stage (≥ T2) tumors showed greater tumor diameter, lower normalized T2, and lower ADC (p = 0.005-0.032) than low-stage (≤ T1) tumors. Tumor diameter and ADC were significant independent predictors of stage (p ≤ 0.043), with their combination giving an area-under the-curve (AUC) of 0.804. High-grade tumors showed significantly lower ADC (p = 0.023) but no significant difference in tumor diameter or normalized T2 (p = 0.201-0.559). AUC for differentiating low- and high-grade tumors was higher for ADC (0.902) than for tumor diameter (0.603) or normalized T2 (0.725). CONCLUSION: A combination of size and quantitative MRI metrics can potentially be used as markers of stage and grade of bladder cancer.
Aron M, Luthringer DJ, McKenney JK, et al. Utility of a triple antibody cocktail intraurothelial neoplasm-3 (IUN-3-CK20/CD44s/p53) and α-methylacyl-CoA racemase (AMACR) in the distinction of urothelial carcinoma in situ (CIS) and reactive urothelial atypia. Am J Surg Pathol. 2013; 37(12):1815-23 [PubMed] Related Publications
Urothelial carcinoma in situ (CIS) is a prognostically and therapeutically significant lesion with considerable morphologic overlap with reactive conditions especially in the setting of prior therapy. Various markers including CK20, CD44s, and p53 have been used as an adjunct in making this distinction; however, the utility of these markers in the posttreatment scenario is not fully established. α-Methylacyl-CoA racemase (AMACR) is a tumor-associated marker that is expressed in a subset of high-grade urothelial carcinomas but has not been studied in CIS. This study was undertaken to evaluate the immunoreactivity of CK20, CD44s, and p53 as a triple antibody cocktail intraurothelial neoplasm-3 (IUN-3) in distinguishing CIS from its mimics and to compare its utility with AMACR in the diagnosis of CIS. A total of 135 specimens (7 benign ureters and 128 bladder biopsies-28 reactive, 33 posttherapy reactive, 43 CIS, 24 CIS posttherapy) were included in this study. Immunostaining for p53 (brown, nuclear), CD44s (brown, membranous), and CK20 (red, cytoplasmic and membranous) was performed as a cocktail, and the staining pattern was further classified as: malignant (full-thickness CK20 and/or full-thickness p53 with CD44s negativity), reactive/benign (CK20 limited to the umbrella cell layer, p53 negative, and CD44s positivity ranging from basal to full thickness), and indeterminate (CK20 and p53 positive but not full thickness and/or CD44s positive). AMACR staining was performed in 50 cases. Cytoplasmic staining for AMACR was graded as negative (absent to weak focal staining [<5% cells]) and positive (≥5%). The "IUN-3 malignant" pattern was observed in 84% of cases of CIS without a history of prior therapy and in 71% of the cases of CIS with a history of prior therapy. Cases with posttherapy reactive atypia showed an "IUN-3 reactive" pattern in 84% cases and "IUN-3 indeterminate" pattern in 16% of the cases; the IUN-3 malignant pattern was not identified in any of the cases. Benign and reactive urothelium (with and without a history of therapy) showed an IUN-3 reactive pattern and negative AMACR staining in all the cases (100%). AMACR positivity was observed in 78% of nontreated CIS cases and 50% of CIS posttherapy cases. In these cases, the IUN-3 cocktail showed an IUN-3 malignant pattern in 83% of untreated CIS cases and 88% of CIS posttherapy cases. AMACR positivity is a potentially useful marker of CIS. However, the IUN-3 malignant pattern is a more reliable indicator of CIS compared with AMACR, especially in the posttreatment setting. The simultaneous evaluation of all 3 markers (p53, CD44s, and CK20) in a single slide in the form of a cocktail is advantageous, especially in small biopsy specimens.
Gailey MP, Bellizzi AM Immunohistochemistry for the novel markers glypican 3, PAX8, and p40 (ΔNp63) in squamous cell and urothelial carcinoma. Am J Clin Pathol. 2013; 140(6):872-80 [PubMed] Related Publications
OBJECTIVES: To examine squamous cell carcinomas (SCCs) from diverse anatomic sites and invasive urothelial carcinomas (UCs) for expression of the oncofetal antigen glypican 3 (GPC3), the paired box transcription factor PAX8, and the ΔN isoform of p63 (p40). METHODS: Immunohistochemistry for GPC3, PAX8, and p40 was performed on whole sections of 107 SCCs from 11 anatomic sites and 49 UCs; evaluation included extent and intensity of staining. RESULTS: GPC3 was detected in 20% of SCCs and 12% of UCs and PAX8 in 3% of SCCs, limited to the uterine cervix, and 10% of UCs. p40 Was found in 99% of SCCs and 96% of UCs. CONCLUSIONS: GPC3 expression is frequent in SCC/UC, awareness of which should guard against an incorrect diagnosis of hepatocellular carcinoma, while PAX8, limited in distribution, may have some use in suggesting a cervical or urothelial tract origin in a metastatic squamotransitional carcinoma of unknown primary. There is no drop-off in sensitivity for the diagnoses of SCC or UC with ΔNp63-specific immunohistochemistry, and if this performance can be extended to other applications, p40 may supplant the dominant "pan-p63" antibody clone.
Meeks JJ, Herr HW Office-based management of nonmuscle invasive bladder cancer. Urol Clin North Am. 2013; 40(4):473-9 [PubMed] Related Publications
Bladder cancer is extremely common in the United States and extremely costly because of the high cost of surveillance. In some patients, office-based surveillance may be a safe, cost-reducing alternative. This article attempts to identify ideal candidates and highlights surveillance strategies that can be employed in an office-based setting.
Yang D, Liu C, Shi J, et al. Association of XRCC1 Arg399Gln polymorphism with bladder cancer susceptibility: a meta-analysis. Gene. 2014; 534(1):17-23 [PubMed] Related Publications
Genetic variations in DNA repair genes are thought to modify DNA repair capacity and may to be related to cancer susceptibility. However, epidemiological study results have been inconsistent. In this meta-analysis, we assessed 24 case-control studies of association between the X-ray repair cross complementing group 1 (XRCC1) Arg399Gln polymorphism and bladder cancer susceptibility in the general population and in Asian and non-Asian subgroups. A moderately significant association with bladder cancer risk was found for AG vs GG (OR=1.110, 95% CI=1.018-1.210). No significant associations with bladder cancer risk were found for AA vs GG (OR=0.942, 95% CI=0.823-1.077), the dominant model AA/AG vs GG (OR=1.075, 95% CI=0.990-1.167) and the recessive model AA vs AG/GG(OR=0.890, 95% CI=0.788-1.005). In subgroup analysis, a moderately significant association was also found for AG vs GG (OR=1.091, 95% CI=1.008-1.180) in non-Asian subgroup. The analysis suggests that the XRCC1 Arg399Gln polymorphism might be a moderate risk factor for bladder cancer, especially in non-Asian population.
Liew MS, Azad A, Tafreshi A, et al. USANZ: Time-trends in use and impact on outcomes of perioperative chemotherapy in patients treated with radical cystectomy for urothelial bladder cancer. BJU Int. 2013; 112 Suppl 2:74-82 [PubMed] Related Publications
OBJECTIVE: To review time-trends in the use of perioperative chemotherapy and its impact on oncological outcomes in patients with bladder urothelial cancer (UC) at a single tertiary institution. PATIENTS AND METHODS: Using electronic and paper medical records, 89 patients were identified who underwent radical cystectomy with or without perioperative chemotherapy between 2004 and 2011 at Austin Health in Melbourne, Australia. Patient demographics, clinico-pathological characteristics and details of recurrence and death were assessed by retrospective chart review. Survival analysis was carried out using the Kaplan Meier method, with the impact of predictors assessed using Cox proportional hazard models. RESULTS: The median (range) age of this cohort was 65 (37-84) years, and 66 (74%) patients were male. Pathologic features included 68 (76%) pure UC, 21 (24%) mixed UC and 84 (94%) high grade tumours. On clinical staging, 63 (71%) patients had muscle-invasive bladder cancer (cT-stage ≥ T2), of whom 11 (17%) received neoadjuvant chemotherapy, with an increasing trend in use over time. Following radical cystectomy, pT-stage ≥ T3 and/or node positive were identified in 35 (39%) patients, of whom 16 (46%) received adjuvant chemotherapy. In addition, five patients with stage pT2 received adjuvant chemotherapy. Of the total cohort of patients, 31 (35%) suffered recurrences, and 33 died, 27 from urothelial carcinoma. On multivariate analysis, after adjusting for age, pT-stage and pN-stage, perioperative chemotherapy was associated with a significantly lower risk of recurrence [relative risk (RR) 0.41, p < 0.05], but not death from cancer or all causes. CONCLUSIONS: Perioperative chemotherapy, and in particular neoadjuvant chemotherapy, remains relatively under-utilised at our institution despite recent increases. The significant reduction in the risk of recurrence following treatment with perioperative chemotherapy with radical cystectomy highlights the importance of multi-modality treatment in bladder UC. Identifying barriers to more widespread implementation of perioperative chemotherapy is critical for enhancing outcomes in patients with bladder UC.
WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD? Urologists are often confronted with cystoscopic appearances that at times are abnormal but non-specific, may mimic urothelial carcinoma or in some instances are quite bizarre given the clinical scenarios in which they occur (e.g. changes associated with a catheter will be more obvious than a de-novo presentation of cystitis cystica). Metaplasias of the bladder urothelium make up the majority of such cases. Furthermore, when confronted with a pathological diagnosis of a metaplasia within the bladder- what are the implications for the patient and how should they be followed-up? This review provides a concise summary of the pathological features of the various metaplasias that occur in the bladder and briefly describes their current treatment and requirement for follow-up. Metaplasia of the bladder urothelium occurs commonly in response to local injury. Usually the changes are reversible, but some conditions may be premalignant. This review describes the different metaplastic entities and their clinical significance. Most importantly, keratinising squamous metaplasia is a precursor to the development of bladder cancer, and requires treatment and long term follow up. The role of intestinal metaplasia in the development of cancer is uncertain, and these patients require follow-up until further evidence is obtained on the outcome of this entity.
Eissa S, Badr S, Barakat M, et al. The diagnostic efficacy of urinary survivin and hyaluronidase mRNA as urine markers in patients with bladder cancer. Clin Lab. 2013; 59(7-8):893-900 [PubMed] Related Publications
BACKGROUND: A new, sensitive, noninvasive method for the detection of urothelial carcinomas of the bladder would open new possibilities in both the diagnosis and follow up of patients. METHODS: Voided urine specimens were collected from patients with histologically confirmed bladder urothelial carcinoma (Group 1: n = 60), urological patients without urothelial carcinoma (Group 2: n = 20), and healthy volunteers (Group 3: n = 20). All underwent serological assessment of schistosomiasis antibody, quantitative measurement of survivin by ELISA in urine supernatant, urine cytology, and detection of hyaluronidase (HYAL-1) by RT-PCR in urothelial cells of voided urine samples. RESULTS: Urinary survivin mean rank was higher in malignant and benign groups than in the healthy group (p < 0.001). Urinary survivin best-cutoff was determined using receiver operating characteristic curve to discriminate between malignant and nonmalignant groups (2537.25 pg/mg protein) at 78.33% sensitivity and 82.5% specificity. HAase mRNA showed superior sensitivity (86.67%) over cytology (38.33%) and urinary survivin (78.33%) with specificity of 97.5%, 100%, and 82.5%, respectively. The sensitivity of urine cytology was increased on combination with either survivin (83.33%) or HAase (90%). Also, the combination of both markers increased overall sensitivity (95%). CONCLUSIONS: Survivin can be reliably and quantitatively measured in urine of bladder cancer patients, improving the sensitivity and specificity of urine cytology for the diagnosis of bladder cancer. Combined use of cytology with survivin and HAase was the best recommended combination for bladder cancer detection.
Badr S, Salem A, Yuosif AH, et al. Hypoxia inducible factor-1alpha and microvessel density as angiogenic factors in bilharzial and non-bilharzial bladder cancer. Clin Lab. 2013; 59(7-8):805-12 [PubMed] Related Publications
BACKGROUND: Hypoxia inducible factor (HIF)-1alpha is a critical regulatory protein of cellular response to hypoxia and is closely related to angiogenic processes. Microvessel density (MVD), a measure of tumor angiogenesis has been shown to be predictive of progression and poor prognosis in bladder urothelial carcinoma. Most research has relied on measuring HIF-1alpha by immunohistochemistry on tissue sections and studying its prognostic value. However, no study has investigated HIF-1alpha expression by ELISA technique in association with angiogenesis in bilharzial and nonbilharzial bladder carcinoma. The primary objective of this pilot case control study was to measure HIF-1alpha level by ELISA technique in voided urine samples in a trial to find a diagnostic applicability in patients with bilharzial and nonbilharzial bladder carcinoma. Secondary objectives were assessment of MVD in relation to HIF-1alpha positivity as well as correlating them with clinicopathological variables to get insight in their potential prognostic and predictive value in bladder cancer. METHODS: Voided urine specimens were collected from patients with histologically confirmed bladder urothelial carcinoma (Group 1: n = 39), urological patients without urothelial carcinoma (Group 2: n = 15), and healthy volunteers (Group 3: n = 15). All underwent serological assessment of bilharzial antibody, quantitative measurement of HIF-1alpha by ELISA in urothelial cells of voided urine samples and urine cytology. MVD was calculated by immunohistochemical staining of endothelial cells with CD34 on tumor tissue paraffin sections. RESULTS: There was a statistically significant difference between benign and malignant groups regarding HIF-1alpha positivity rate (p < 0.001). Urinary HIF-1alpha best cut-off was determined using receiver operating characteristic curves to discriminate between malignant and nonmalignant groups (21.7 ng/mg protein) at 82.1% sensitivity and 63.3% specificity. The sensitivity of urine cytology was increased on combination with HIF-1alpha from 53.8% to 92.8%. In the malignant group, MVD revealed a high score in 70% and a low score in 30% of cases compared to 0% and 100%, respectively, in the benign group. The difference was highly significant (p < 0.001). There was no significant relationship between HIF-1alpha positivity rate or MVD and stage, as well as histologic grade of the tumor (p > 0.05) denoting no prognostic significance. CONCLUSIONS: HIF-1alpha can be reliably and quantitatively measured in urine of bladder cancer patients, improving the sensitivity and specificity of urine cytology for the diagnosis of bladder cancer. Independent studies, however, will be required on larger cohorts to validate these findings.
Harshman LC, Fougeray R, Choueiri TK, et al. The impact of prior platinum therapy on survival in patients with metastatic urothelial cancer receiving vinflunine. Br J Cancer. 2013; 109(10):2548-53 [PubMed] Article available free on PMC after 12/11/2014 Related Publications
BACKGROUND: A phase III trial demonstrated an overall survival advantage with the addition of vinflunine to best supportive care (BSC) in platinum-refractory advanced urothelial cancer. We subsequently examined the impact of an additional 2 years of survival follow-up and evaluated the influence of first-line platinum therapy on survival. METHODS: The 357 eligible patients from the phase III study were categorised into two cohorts depending on prior cisplatin treatment: cisplatin or non-cisplatin. Survival was calculated using the Kaplan-Meier method. RESULTS: The majority had received prior cisplatin (70.3%). Survival was higher in the cisplatin group (HR: 0.76; CI 95% 0.58-0.99; P=0.04) irrespective of treatment arm. Multivariate analysis including known prognostic factors (liver involvement, haemoglobin, performance status) and prior platinum administration did not show an independent effect of cisplatin. Vinflunine reduced the risk of death by 24% in the cisplatin-group (HR: 0.76; CI 95% 0.58-0.99; P=0.04) and by 35% in non-cisplatin patients (HR: 0.65; CI 95% 0.41-1.04; P=0.07). INTERPRETATION: Differences in prognostic factors between patients who can receive prior cisplatin and those who cannot may explain the survival differences in patients who undergo second line therapy. Prior cisplatin administration did not diminish the subsequent benefit of vinflunine over BSC.
Kitagawa Y, Izumi K, Miwa S, et al. Retrospective analysis of the efficacy of two cycles of M-VAC neoadjuvant chemotherapy followed by radical cystectomy for muscle-invasive bladder cancer. Anticancer Res. 2013; 33(10):4497-503 [PubMed] Related Publications
BACKGROUND: Neoadjuvant chemotherapy before radical cystectomy for muscle-invasive bladder cancer is a commonly used treatment modality. However, in terms of chemotherapeutic regimens and the number of cycles of neoadjuvant chemotherapy, there is yet no international consensus, as various studies indicate the efficacy of several platinum-based combination chemotherapeutic regimens. We determined the efficacy of two cycles of neoadjuvant chemotherapy with methotrexate, vinblastine, adriamycin, and cisplatin followed by radical cystectomy. PATIENTS AND METHODS: The study population included patients with clinical stage T2 - T4a, N0, M0 bladder cancer who underwent radical cystectomy. Clinical courses were compared between 27 patients treated with two cycles of M-VAC neoadjuvant chemotherapy and 25 treated with cystectomy alone. RESULTS: The incidence of pT0 was 25.9% in the group treated with neoadjuvant chemotherapy. The probabilities of disease-free and cause-specific survival were significantly higher in patients treated with, than without neoadjuvant chemotherapy. On univariate Cox proportional hazards regression analysis for the patients treated with neoadjuvant chemotherapy, pathological stage and the pathological findings of venous involvement were significant prognostic factors. CONCLUSION: The results of this retrospective study demonstrated the clinical effectiveness of two cycles of neoadjuvant M-VAC chemotherapy for muscle-invasive bladder cancer.
Zhao L, Antic T, Witten D, et al. Is GATA3 expression maintained in regional metastases?: a study of paired primary and metastatic urothelial carcinomas. Am J Surg Pathol. 2013; 37(12):1876-81 [PubMed] Related Publications
GATA3 has been recognized as a promising marker for primary urothelial carcinoma (UC), consistently showing higher expression levels than urothelial markers thrombomodulin and uroplakin III. However, expression of GATA3 in comparison with UC-associated markers CK7 and p63 has not been systematically studied. Moreover, no studies have been conducted to establish GATA3 sensitivity in regional metastases. In this study, high-density tissue microarrays were constructed from 69 matched paired primary and metastatic bladder tumors including pure urothelial UCs with papillary (n=48) or flat phenotype (n=9), mixed tumors with micropapillary, glandular, small cell, squamous, giant cell, and plasmacytoid features (n=9), and 3 adenocarcinomas. GATA3 was expressed in 62/69 (90%) primary UC and 64/69 (93%) metastases, with significantly higher staining intensity in nodal metastases (P=0.03). In primary tumors, GATA3 was positive in 44/48 (92%) papillary UCs, 9/9 (100%) flat UCs, 8/9 (89%) mixed UCs, and 1/3 (33%) adenocarcinomas, whereas in metastases these numbers were 45/48 (94%), 9/9 (100%), 8/9 (89%), and 2/3 (67%), respectively. The majority of positive cases showed strong diffuse nuclear reactivity: 75% of primary UCs and 79% of metastases. GATA3 sensitivity in primary and metastatic UCs was comparable to that of CK7 and superior to that of p63 (P<0.05). GATA3 specificity was computed in comparison with its morphologic mimics expressing CK7 and p63, including 208 primary and 24 metastatic tumors from the lung, cervix, and head and neck regions. Strong GATA3 expression was present in 2/51 (4%) cervical carcinomas, whereas weak GATA3 expression was present in 7/51 (14%) cervical, 6/74 (8%) head and neck cancers, and 2/83 (3%) lung carcinomas. Remaining 191 primary and 24 metastatic tumors were GATA3 negative. Therefore, specificity of GATA3 calculated on the basis of morphologic and immunophenotypic UC mimics from lung, cervix, head and neck was 92%. Our findings demonstrate high sensitivity and specificity of the GATA3 diagnostic marker, with not only maintained but increased expression in regional metastases.
Rachakonda PS, Hosen I, de Verdier PJ, et al. TERT promoter mutations in bladder cancer affect patient survival and disease recurrence through modification by a common polymorphism. Proc Natl Acad Sci U S A. 2013; 110(43):17426-31 [PubMed] Article available free on PMC after 22/04/2014 Related Publications
The telomerase reverse transcriptase (TERT) promoter, an important element of telomerase expression, has emerged as a target of cancer-specific mutations. Originally described in melanoma, the mutations in TERT promoter have been shown to be common in certain other tumor types that include glioblastoma, hepatocellular carcinoma, and bladder cancer. To fully define the occurrence and effect of the TERT promoter mutations, we investigated tumors from a well-characterized series of 327 patients with urothelial cell carcinoma of bladder. The somatic mutations, mainly at positions -124 and -146 bp from ATG start site that create binding motifs for E-twenty six/ternary complex factors (Ets/TCF), affected 65.4% of the tumors, with even distribution across different stages and grades. Our data showed that a common polymorphism rs2853669, within a preexisting Ets2 binding site in the TERT promoter, acts as a modifier of the effect of the mutations on survival and tumor recurrence. The patients with the mutations showed poor survival in the absence [hazard ratio (HR) 2.19, 95% confidence interval (CI) 1.02-4.70] but not in the presence (HR 0.42, 95% CI 0.18-1.01) of the variant allele of the polymorphism. The mutations in the absence of the variant allele were highly associated with the disease recurrence in patients with Tis, Ta, and T1 tumors (HR 1.85, 95% CI 1.11-3.08). The TERT promoter mutations are the most common somatic lesions in bladder cancer with clinical implications. The association of the mutations with patient survival and disease recurrence, subject to modification by a common polymorphism, can be a unique putative marker with individualized prognostic potential.
D'Souza AM, Phillips GS, Pohar KS, Zynger DL Clinicopathologic characteristics and overall survival in patients with bladder cancer involving the gastrointestinal tract. Virchows Arch. 2013; 463(6):811-8 [PubMed] Related Publications
Involvement of the gastrointestinal (GI) tract by bladder cancer is rare and documented in only a few case reports with no prognostic information available. The aim of this study was to clinicopathologically characterize patients with pathologically proven bladder cancer in the GI tract. We reviewed pathology reports from cystectomy patients at our institution from 2006 to 2011, identifying those with GI involvement at or after cystectomy. Overall survival (OS) was analyzed using Kaplan-Meier curves and Cox proportional hazard regression models. Twelve patients had surgical pathology specimens with GI involvement (anus, rectum, colon, and small bowel) at (n = 11) or within 4 months (n = 1) of cystectomy. These patients were noted to be pathologically staged inconsistently. GI involvement was a negative predictor of survival, with a 1.5-year OS of 25 versus 62 % without GI involvement (P < 0.001), similar to our pT4 patients (OS 26 %). In node-negative patients, there was a significantly worse 1.5-year OS with GI involvement compared to those without tumor in the GI tract (P = 0.005). We provide the first case series of patients with bladder cancer in the GI tract. GI involvement is a strong negative predictor of survival and behaves comparable to pT4 patients. However, we recommend that pathologists adhere to the current pT staging guidelines, in which GI involvement is not a criterion, until further research is conducted illustrating if and how it should be incorporated.
Sternberg CN, Skoneczna IA, Castellano D, et al. Larotaxel with Cisplatin in the first-line treatment of locally advanced/metastatic urothelial tract or bladder cancer: a randomized, active-controlled, phase III trial (CILAB). Oncology. 2013; 85(4):208-15 [PubMed] Related Publications
BACKGROUND: This open-label, randomized phase III trial evaluated larotaxel/cisplatin versus gemcitabine/cisplatin as first-line treatment for locally advanced (T4b) or metastatic urothelial tract or bladder cancer. METHODS: Patients were randomized to larotaxel 50 mg/m(2) with cisplatin 75 mg/m(2) every 3 weeks (larotaxel/cisplatin) or gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 with cisplatin 70 mg/m(2) on day 1 every 4 weeks (gemcitabine/cisplatin). The primary endpoint was overall survival (OS). RESULTS: The trial was prematurely closed following the sponsor's decision to stop clinical development of larotaxel (n = 337 randomized). The larotaxel dose was reduced to 40 mg/m(2) and cisplatin to 60 mg/m(2) following a data monitoring committee safety review of the first 97 patients. At the time of analysis, the median OS was 13.7 months [95% confidence interval (CI) 11.2-17.1] with larotaxel/cisplatin and 14.3 months (95% CI 10.5 to not reached) with gemcitabine/cisplatin [hazard ratio (HR) 1.21; 95% CI 0.83-1.76; p = 0.33]. The median progression-free survival (PFS) was 5.6 months (95% CI 4.1-6.2) with larotaxel/cisplatin and 7.6 months (95% CI 6.6-9.1) with gemcitabine/cisplatin (HR 1.67; 95% CI 1.24-2.25). More myelosuppression was observed with gemcitabine/cisplatin. CONCLUSION: There was no difference in OS. Although the trial was closed prematurely, PFS appeared worse with larotaxel/cisplatin, suggesting that larotaxel/cisplatin does not improve outcomes versus cisplatin/gemcitabine.
Stanton ML, Xiao L, Czerniak BA, Guo CC Urothelial tumors of the urinary bladder in young patients: a clinicopathologic study of 59 cases. Arch Pathol Lab Med. 2013; 137(10):1337-41 [PubMed] Related Publications
CONTEXT: Urothelial tumors are rare in young patients. Because of their rarity, the natural history of the disease in young patients remains poorly understood. OBJECTIVE: To understand the pathologic and clinical features of urothelial tumors of the urinary bladder in young patients. DESIGN: We identified 59 young patients with urothelial tumors of the urinary bladder treated at our institution and analyzed the tumors' pathologic features and the patients' clinical outcomes. RESULTS: All patients were 30 years or younger, with a mean age of 23.5 years (range, 4-30). Thirty-eight patients (64%) were male, and 21 (36%) were female. Most tumors were noninvasive, papillary urothelial tumors (49 of 59; 83%), including papillary urothelial neoplasms of low malignant potential (7 of 49; 14%), low-grade papillary urothelial carcinomas (38 of 49; 78%), and high-grade papillary urothelial carcinomas (4 of 49; 8%). Only a few (n=10) of the urothelial tumors were invasive, invading the lamina propria (n=5; 50%), muscularis propria (n=4; 40%), or perivesical soft tissue (n=1; 10%). Clinical follow-up information was available for 41 patients (69%), with a mean follow-up time of 77 months. Of 31 patients with noninvasive papillary urothelial tumors, only 1 patient (3%) later developed an invasive urothelial carcinoma and died of the disease, and 30 of these patients (97%) were alive at the end of follow-up, although 10 (32%) had local tumor recurrences. In the 10 patients with invasive urothelial carcinomas, 3 patients (30%) died of the disease and 5 others (50%) were alive with metastases (the other 2 [20%] were alive with no recurrence). CONCLUSION: Urothelial tumors in young patients are mostly noninvasive, papillary carcinomas and have an excellent prognosis; however, a small subset of patients may present with high-grade invasive urothelial carcinomas that result in poor clinical outcomes.
Patel P, Reikie BA, Maxwell JP, et al. Long-term clinical outcome of inverted urothelial papilloma including cases with focal papillary pattern: is continuous surveillance necessary? Urology. 2013; 82(4):857-60 [PubMed] Related Publications
OBJECTIVE: To investigate the necessity for continuous cystoscopic surveillance of inverted papilloma (IP), including tumors exhibiting mixed morphology (IP with focal papillary architecture). METHODS: We retrieved all cases of de novo ("primary") IP, diagnosed in our institution during 10 years (from January 2000 to December 2009), from the information database. Patients with a history of urothelial carcinoma or concurrent urothelial carcinoma were excluded. Surveillance was performed by routine cystoscopy, and follow-up was obtained from our institutional and regional clinical and pathology databases. RESULTS: We identified 35 patients with IP, including 3 with focal papillary architecture. Mean patient age was 60 years (range, 26-88) with male-to-female ratio of 1.9:1. Most common tumor location was urinary bladder (86%), followed by urethra (14%). Focal papillary architecture was identified in 3 patients (aged 51, 52, and 78 years). Mean follow-up was 66 months (median 68; range, 11-132). Only 1 male patient (age 81) had a subsequent diagnosis of IP on follow-up cystoscopy at 9 months; no recurrence or progression was documented in the other patients diagnosed with IP. CONCLUSION: The absence of progression of IP on long-term follow-up in this study strongly argues against the need of continuous surveillance for patients in whom (1) strict diagnostic criteria are followed, (2) a complete resection can be ascertained, and (3) no previous or concurrent urothelial malignancies are documented. In this study, the 3 patients with IP showing focal papillary architecture had a benign course, similar to the previously documented cases.
Munari E, Fujita K, Faraj S, et al. Dysregulation of mammalian target of rapamycin pathway in upper tract urothelial carcinoma. Hum Pathol. 2013; 44(12):2668-76 [PubMed] Related Publications
Upper tract urothelial carcinoma (UTUC) accounts for 5% to 10% of all urothelial carcinomas. Despite many shared features, key clinical and molecular genetic differences between upper tract and bladder urothelial carcinomas are becoming apparent. We have previously demonstrated alterations of mammalian target of rapamycin (mTOR) pathway in bladder carcinoma with a potential impact on biological behavior. In the current study, we evaluated the expression status and prognostic significance of mTOR pathway members in UTUC. Archival formalin-fixed and paraffin-embedded tissues from 99 primary UTUCs were retrieved from one of the authors' institution. Tissue microarrays were constructed with triplicate tumor samples and paired nonneoplastic urothelium. Tissue microarrays were analyzed using immunohistochemistry for mTOR pathway members: PTEN, phos-AKT, phos-mTOR, phos-S6, phos-4EBP1, and related markers p27 and c-MYC; correlation with clinicopathologic parameters and outcome was performed. We found significantly lower expression of PTEN, phos-AKT, phos-mTOR, phos-S6, phos-4EBP1, p27, and c-MYC in UTUC compared with paired benign urothelium (P < .0005). We found a strong positive correlation between PTEN and phos-AKT. Moderate correlation was observed between phos-mTOR and phos-S6, PTEN and p27, phos-AKT and p27, phos-S6 and p27, phos-mTOR and c-MYC, phos-S6 and c-MYC, and p27 and c-MYC. None of the evaluated biomarkers were associated with increased hazard ratios for tumor recurrence or for cancer-specific mortality, when adjusting for relevant clinicopathologic variables. Dysregulation of the mTOR pathway was observed in UTUC compared with normal urothelium, implicating a potential pathogenic role in tumor development. In our cohort, expression of the evaluated biomarkers had no prognostic value.
Lima L, Severino PF, Silva M, et al. Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy. Br J Cancer. 2013; 109(8):2106-14 [PubMed] Article available free on PMC after 15/10/2014 Related Publications
BACKGROUND: High risk of recurrence/progression bladder tumours is treated with Bacillus Calmette-Guérin (BCG) immunotherapy after complete resection of the tumour. Approximately 75% of these tumours express the uncommon carbohydrate antigen sialyl-Tn (Tn), a surrogate biomarker of tumour aggressiveness. Such changes in the glycosylation of cell-surface proteins influence tumour microenvironment and immune responses that may modulate treatment outcome and the course of disease. The aim of this work is to determine the efficiency of BCG immunotherapy against tumours expressing sTn and sTn-related antigen sialyl-6-T (s6T). METHODS: In a retrospective design, 94 tumours from patients treated with BCG were screened for sTn and s6T expression. In vitro studies were conducted to determine the interaction of BCG with high-grade bladder cancer cell line overexpressing sTn. RESULTS: From the 94 cases evaluated, 36 had recurrence after BCG treatment (38.3%). Treatment outcome was influenced by age over 65 years (HR=2.668; (1.344-5.254); P=0.005), maintenance schedule (HR=0.480; (0.246-0.936); P=0.031) and multifocality (HR=2.065; (1.033-4.126); P=0.040). sTn or s6T expression was associated with BCG response (P=0.024; P<0.0001) and with increased recurrence-free survival (P=0.001). Multivariate analyses showed that sTn and/or s6T were independent predictive markers of recurrence after BCG immunotherapy (HR=0.296; (0.148-0.594); P=0.001). In vitro studies demonstrated higher adhesion and internalisation of the bacillus to cells expressing sTn, promoting cell death. CONCLUSION: s6T is described for the first time in bladder tumours. Our data strongly suggest that BCG immunotherapy is efficient against sTn- and s6T-positive tumours. Furthermore, sTn and s6T expression are independent predictive markers of BCG treatment response and may be useful in the identification of patients who could benefit more from this immunotherapy.
Ellis CL, Chang AG, Cimino-Mathews A, et al. GATA-3 immunohistochemistry in the differential diagnosis of adenocarcinoma of the urinary bladder. Am J Surg Pathol. 2013; 37(11):1756-60 [PubMed] Related Publications
GATA-3 is a newly described marker that labels urothelial and breast carcinoma. However, no prior study has evaluated the expression of GATA-3 in primary bladder adenocarcinoma. Tissue microarrays (TMAs) containing 46 primary bladder adenocarcinomas were constructed. They contained 19 signet ring cell (SRC) and 27 conventional adenocarcinomas. Three additional cases of SRC using routine sections were included resulting in a total of 22 SRCs. In addition, TMAs containing 32 primary gastric signet ring adenocarcinomas and 36 primary lobular breast carcinomas were evaluated. The TMAs were subjected to immunohistochemical analysis for GATA-3, with nuclear labeling scored by intensity and percentage labeling. Breast and urothelial TMAs were also labeled for estrogen receptor, progesterone receptor, and gross cystic duct fluid protein. Diffuse nuclear GATA-3 labeling was seen in 9/22 (41.0%) SRCs and in 2/27 (7.0%) conventional adenocarcinomas (P=0.01). Extracellular mucin production was seen in 12 SRCs. One of 12 (8.0%) SRCs with extracellular mucin was GATA-3 positive, and 8/10 SRCs without extracellular mucin was GATA-3 positive (P=0.005). No nuclear GATA-3 labeling was seen in any gastric signet ring carcinoma. Diffuse, moderate to strong nuclear GATA-3 labeling was seen in 36/36 (100%) primary lobular breast carcinomas. Nuclear GATA-3 labeling is a useful marker for primary adenocarcinomas of the urinary bladder with signet ring features and can be helpful in distinguishing primary signet ring carcinomas of the urinary bladder from gastric signet ring carcinomas. GATA-3 is rarely positive in bladder adenocarcinomas that lack signet ring features and in SRCs displaying extracellular mucin production.
Gan C, Patel A, Fowler S, et al. Snapshot of transurethral resection of bladder tumours in the United Kingdom Audit (STUKA). BJU Int. 2013; 112(7):930-5 [PubMed] Related Publications
OBJECTIVES: To determine the quality of transurethral resection of bladder tumour (TURBT) in the UK. To evaluate the utility of a novel 'snapshot' methodology in carrying out national audits. PATIENTS AND METHODS: Every consultant Urologist in the UK was asked to contribute details of their first patient with a new bladder cancer treated with TURBT after midnight of 31st January 2010. Responses were received from 192 consultants. RESULTS: The median (range) time from referral to first Urology appointment was 11 (0-161) days, and the median (range) time from first appointment to TURBT was 27 (1-588) days. In all, 12 (6.3%) patients underwent photodynamic diagnosis-assisted TURBT and 119 patients (61%) received a dose of Mitomycin C after TURBT. The rate of major complications was low, with five incidences (2.6%) of bladder perforation. There was no record of muscle present in resected specimens in 40 cases (20.8%) and resection was considered incomplete in 26 cases (13.5%). In all, 31 patients (16.1%) underwent early re-resection with residual tumour or carcinoma in situ detected in 17 cases, although no tumour was upstaged. Of the 37 patients classified with intermediate-risk non-muscle-invasive bladder cancer (NMIBC), there were nine recurrences (24.3%) at 3 months, and 13 recurrences (35.1%) at 1 year. Newly presenting MIBC managed with currently available treatments has a high mortality rate of 33.3% at 1 year. CONCLUSIONS: The quality of TURBT in the UK is high. Areas for improvement include the timeliness of diagnosis and treatment, and improved care of patients with intermediate-risk NMIBC and MIBC. The 'snapshot' methodology is promising but widening participation is a priority.
Ferreccio C, Yuan Y, Calle J, et al. Arsenic, tobacco smoke, and occupation: associations of multiple agents with lung and bladder cancer. Epidemiology. 2013; 24(6):898-905 [PubMed] Related Publications
BACKGROUND: Millions of people worldwide are exposed to arsenic in drinking water, and many are likely coexposed to other agents that could substantially increase their risks of arsenic-related cancer. METHODS: We performed a case-control study of multiple chemical exposures in 538 lung and bladder cancer cases and 640 controls in northern Chile, an area with formerly high drinking water arsenic concentrations. Detailed information was collected on lifetime arsenic exposure, smoking, secondhand smoke, and other known or suspected carcinogens, including asbestos, silica, and wood dust. RESULTS: Very high lung and bladder cancer odds ratios (ORs), and evidence of greater than additive effects, were seen in people exposed to arsenic concentrations >335 µg/L and who were tobacco smokers (OR = 16, 95% confidence interval = 6.5-40 for lung cancer; and OR = 23 [8.2-66] for bladder cancer; Rothman Synergy Indices = 4.0 [1.7-9.4] and 2.0 [0.92-4.5], respectively). Evidence of greater than additive effects were also seen in people coexposed to arsenic and secondhand tobacco smoke and several other known or suspected carcinogens, including asbestos, silica, and wood dust. CONCLUSIONS: These findings suggest that people coexposed to arsenic and other known or suspected carcinogens have very high risks of lung or bladder cancer.