Bladder Cancer In Men Research Articles

Highlights of This Issue

There is growing evidence suggesting that soy isoflavones play a protective role in the development of cancer. However, few epidemiological studies have investigated the association between soy isoflavone intake and bladder cancer. This prospective study in Japan detected a decreased risk of bladder cancer among men who had higher intakes of total soy and isoflavones, suggesting a protective effect of soy isoflavone intake against bladder cancer in men. This finding by Wada and colleagues on the potential benefit of consuming soy foods against bladder cancer is promising and warrants further studies.Americans living in rural communities face many challenges when it comes to receiving adequate cancer care. This has resulted in a growing disparity in mortality and incidence for certain cancers in rural areas when compared to their urban counterparts. In order to understand and improve cancer control in rural communities, the NCI conducted an assessment of the current state of research through a progressive series of portfolio analyses, meetings, and funding opportunity announcements. In this commentary, Kennedy and colleagues provide an overview of the NCI's vision for rural cancer control, and detail recommendations stemming from a recently held meeting to advance rural cancer control research. This commentary also serves as an introduction to the CEBP Focus on Rural Cancer Control, which contains three additional commentaries and six research articles.Human papillomavirus self-sampling is a promising method to improve cervical cancer screening coverage, but not all routine screening non-attenders accept self-sampling. Harder and colleagues investigated determinants of participating in self-sampling among 21,314 non-attenders in a Danish routine screening program who were invited to order a self-sampling test. Information on socio-demographic, health-related, and lifestyle characteristics were obtained from registries and questionnaires. Basic education, low income, non-Western origin, and being unmarried were associated with lower self-sampling participation. Women with prior schizophrenia and long-term screening non-attenders were less likely to participate. The study highlights that although self-sampling can increase cervical cancer screening coverage, certain population groups may remain unscreened.The use of alerts and reminders in the electronic health record has led to increased screening for a variety of conditions. However, implementation of screening recommendations for chronic hepatitis B among foreign-born persons at risk has been suboptimal. Chak and colleagues randomized patients at risk for chronic hepatitis B to receive an electronic medical alert reminding primary care physicians to screen for the virus during clinic visits. The study shows that electronic alerts increase screening for chronic hepatitis B—a condition known to cause liver cancer in affected patients. In the age of digital medicine, the study has broad implications for mass screening of patients at risk for this chronic viral infection.

The effect of androgen deprivation treatment on subsequent risk of bladder cancer diagnosis in male patients treated for prostate cancer.

Bladder cancer (BCa) is three-to-four times more common in men than in women. To explain this gender gap, several theories have been proposed, including the impact of androgen hormones. The aim of this study was to investigate the differential impact of androgen deprivation therapy (ADT) on subsequent risk of developing BCa in men with prostate cancer (PCa). A total of 196,914 patients diagnosed with histologically confirmed localized PCa between 2000 and 2009 were identified in the SEER-Medicare insurance program-linked database. Competing-risk regression analyses were performed to assess the risk of developing BCa adjusting for the risk of all-cause mortality. Univariable and multivariable competing-risk regression analyses were performed to test the effect of ADT on BCa incidence for each PCa treatment modality. Of the 196,914 individuals included in the study, 68,421 (34.7%) received ADT. Median (IQR) follow-up was 59 (29-95)months. Overall, a total of 2495 (1.3%) individuals developed BCa during follow-up. After stratification according to ADT, the 10-year cumulative incidence rate was 1.75% (95% CI 1.65-1.85). In the untreated group, the 10-year cumulative incidence rate was 1.99% (95% CI 1.83-2.15). In multivariable competing-risk regression, the use of ADT was not associated with BCa, after accounting for the risk of dying from any cause (p = 0.1). We failed to identify any impact of ADT on the risk of developing a subsequent BCa even after stratifying according to the type of treatment. Further studies are required to explain the gender gap in BCa incidence and outcomes.

Cancers in France in 2015 attributable to occupational exposures.

Recent and comprehensive estimates for the number of new cancer cases in France attributable to occupational exposures are lacking. To estimate the number of new cancer cases attributable to occupational exposures, using a newly developed methodology and the most recent data, for a comprehensive set of occupational carcinogens in France in 2015. Surveys among employees, the national labor force data, a cohort of agricultural workers, national monitoring of workers exposed to ionizing radiation and job-exposure matrix in France were used. The number and proportion of new cancer cases attributable to established occupational carcinogens (Group 1) was estimated using estimation of lifetime exposure and risk estimates from cohort studies. Cancer data were obtained from the French Cancer Registries Network. In France in 2015, an estimated 7905 new cancer cases, 7336 among men and 569 among women, were attributable to occupational exposures, representing 2.3% of all new cancer cases (3.9% and 0.4% among men and women respectively). Among men and women, lung cancer was impacted the most, followed by mesothelioma and bladder cancer in men, and by mesothelioma and ovary in women. These cancers contributed to 89% of the total cancers attributable to occupational carcinogens in men, and to 80% in women. The main contributing occupational agent was asbestos among men (45%) and women (60%). Currently, occupational exposures contribute to a substantial burden of cancer in France. Enhanced monitoring and implementation of protective labor policies could potentially prevent a large proportion of these cancers.

Lung, Bladder, and Kidney Cancer Mortality 40 Years After Arsenic Exposure Reduction.

Region II in northern Chile (population 442 570) experienced a sudden major increase in arsenic water concentrations in 1958 in the main city of Antofagasta, followed by a major reduction in exposure when an arsenic removal plant was installed in 1970. It provides a unique opportunity to study latency effects of exposure to arsenic, and this is the first study with mortality data up to 40 years after exposure reduction. We previously identified high mortality rates in Region II up to the year 2000. Here we present rate ratios (RRs) for Region II compared with all the rest of Chile from 2001 to 2010, and with unexposed Region V (population 1 539 852) for all years from 1950 to 2010. All statistical tests were one-sided. From 2001 to 2010, comparing Region II with the rest of Chile, lung and bladder mortality were still greatly elevated (RR = 3.38, 95% confidence interval [CI] = 3.19 to 3.58, P < .001 for lung cancer in men; RR = 2.41, 95% CI = 2.20 to 2.64, P < .001 for lung cancer in women; RR = 4.79, 95% CI = 4.20 to 5.46, P < .001 for bladder cancer in men; RR = 6.43, 95% CI = 5.49 to 7.54, P < .001 for bladder cancer in women). Kidney cancer mortality was also elevated (RR = 1.75, 95% CI = 1.49 to 2.05, P < .001 for men; RR = 2.09, 95% CI = 1.69 to 2.57, P < .001 for women). Earlier short latency acute myocardial infarction mortality increases had subsided. Lung, bladder, and kidney cancer mortality due to arsenic exposure have very long latencies, with increased risks manifesting 40 years after exposure reduction. Our findings suggest that arsenic in drinking water may involve one of the longest cancer latencies for a human carcinogen.

MP10-09 SUPPRESSED RECURRENT BLADDER CANCER AFTER ANDROGEN SUPPRESSION WITH ANDROGEN-DEPRIVATION THERAPY OR 5?-REDUCTASE INHIBITOR

You have accessJournal of UrologyBladder Cancer: Epidemiology & Evaluation II1 Apr 2017MP10-09 SUPPRESSED RECURRENT BLADDER CANCER AFTER ANDROGEN SUPPRESSION WITH ANDROGEN-DEPRIVATION THERAPY OR 5?-REDUCTASE INHIBITOR Masaki Shiota, Keijiro Kiyoshima, Akira Yokomizo, Ario Takeuchi, Eiji Kashiwagi, Ryosuke Takahashi, Junichi Inokuchi, Katsunori Tatsugami, and Masatoshi Eto Masaki ShiotaMasaki Shiota More articles by this author , Keijiro KiyoshimaKeijiro Kiyoshima More articles by this author , Akira YokomizoAkira Yokomizo More articles by this author , Ario TakeuchiArio Takeuchi More articles by this author , Eiji KashiwagiEiji Kashiwagi More articles by this author , Ryosuke TakahashiRyosuke Takahashi More articles by this author , Junichi InokuchiJunichi Inokuchi More articles by this author , Katsunori TatsugamiKatsunori Tatsugami More articles by this author , and Masatoshi EtoMasatoshi Eto More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.337AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES It has been suggested that androgen-suppression therapy (AST) may inhibit the occurrence of primary bladder cancer as well as intravesical recurrence of bladder cancer. This study aimed to reveal whether intravesical recurrence is affected by an inhibition of androgen signaling among men with non-muscle invasive bladder cancer. METHODS This study examined the intravesical recurrent rate among men treated with or without AST by androgen-deprivation therapy for prostate cancer or 5a-reductase inhibitor dutasteride for benign prostatic hyperplasia. RESULTS This study included 228 men with AST (n = 32) or without AST (n = 196). During the median follow-up period of 3.6 or 3.0 years, intravesical recurrence occurred in four (12.5%) or 59 (30.1%) of men with or without AST, respectively. On multivariate analysis, multiple tumor (hazard ration, HR = 1.82, p = 0.027), large tumor (HR = 2.13, p = 0.043) and ever smoking (HR = 2.45, p = 0.020) as well as the presence of AST (HR = 0.36, p = 0.024) were independent risk factors for intravesical recurrence (Fig. A). Notably, tumor progression to muscle-invasive bladder cancer occurred in six (3.1%) men without AST, while no case progressed to muscle-invasive bladder cancer in men with AST. CONCLUSIONS Our study suggested the possibility of AST for prophylactic use of intravesical recurrence of bladder cancer. Further explorations on the prophylactic effect of AST on bladder cancer pathogenesis are warranted. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e111 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Masaki Shiota More articles by this author Keijiro Kiyoshima More articles by this author Akira Yokomizo More articles by this author Ario Takeuchi More articles by this author Eiji Kashiwagi More articles by this author Ryosuke Takahashi More articles by this author Junichi Inokuchi More articles by this author Katsunori Tatsugami More articles by this author Masatoshi Eto More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Distribución municipal de la incidencia de los tumores más frecuentes en un área de elevada mortalidad por cáncer

ObjectiveTo describe the geographic distribution patterns of the municipal incidence of the most common tumours in the Huelva province (Spain) as compared to the estimated incidence for all of Spain. MethodsRelative risk (RR) was computed based on the conditional autoregressive model proposed by Besag, York and Mollié by applying the INLA tool to the cancer data for 2007-2011 for the following tumour locations: colon, rectum and anus (men and women); trachea, bronchia, and lungs, prostate and bladder in men; and breasts in women. The RR was presented in in choropleth and isopleth (with kriging interpolation) risk maps. ResultsRR for bladder cancer in men was greater than 1.0 in all municipalities, with confidence intervals over 1.0 in four municipalities; Madrid having a 1.56 RR (95%CI 1.30–1.67). For prostate cancer, a posteriori probabilities were below 0.1 in 68 of the 79 municipalities. For lung cancer, nine municipalities had confidence limits below 1.0, almost all of them in western Spain. For women, the RR for breast cancer was significantly higher in the capital of province area. The cancer incidence rates for the Huelva province were, in general, similar to those estimated for Spain, standing out bladder cancer in men (35% higher) and prostate cancer (30% lower). ConclusionsIn the Huelva province, there is a geographical municipal distribution of cancer incidence with well-defined patterns for some specific tumour locations, with overall incidence rates very similar to those in the rest of Spain.

EPIDEMIOLOGICAL ASPECTS THE INCIDENCE OF CANCER OF THE KIDNEY AND BLADDER IN PRIMORSKY KRAI

Urinary system cancer is a malignancy caused by environmental exposures, the prevalence of which directly depends on the impact of environmental and anthropogenic factors. The aim of the study was to assess the kidney and bladder cancer incidence in different ecological and bioclimatic zones of Primorsky Krai. Material and methods. The incidence of kidney and bladder cancers in Primorsky Krai for the period between 1994 and 2014 was analyzed. In assessing the risk of kedney and bladder cancers in bioclimatic zones (marine climate, marine to continental transition and continental climate), environmental problems of the territories of Primorsky Krai were classified using the following ranks: critical, stress-like, satisfactory, and relatively favorable. The risk assessment was conducted using the guidance on Human Health Risk Assessment for Environmental Impact Assessment. To calculate the environmental impact on risk of urinary system cancer, the information entropy analysis was used. Results. The territories with low, medium and high incidence of bladder and kidney cancers were identified. The high incidences of kidney and bladder cancers were registered in the territories with environmental problems ranked as critical and stress-like, affected by coal, mining and chemical industries, and in the territories with intensive use of chemical pesticides. The incidence of bladder cancer in men tended to rise from the continental bioclimatic zone to the coast in all ecological zones mainly due to differences in the structure of the bioclimate between the coast and continental areas of Primorsky Krai. The increased risk of urinary system cancer was shown to be associated with parameters, such as the quality of drinking water, total pollution of the environment, chemical composition of groundwater, and the sanitary condition of the soil. Conclusion. The environmental risk assessment and ranking of territories by risk allow the cancer prevention and control programs to be developed and the need for increased cancer screening in certain areas to be identified.

Years of life lost as a measure of cancer burden in Colombia, 1997-2012

There is hardly any information regarding years of life lost due to cancer in Colombia. To quantify total and average years of life lost due to cancer in Colombia, and to investigate changes in this burden between 1997 and 2012. We obtained sex-specific data on age distribution, remaining life expectancy, deaths due to specific cancers and total number of deaths from the Colombian Departamento Administrativo Nacional de Estadísticas. We calculated years of life lost based on each individual´s age at death and the remaining life expectancy at that age; as for average years of life, we divided these by the number of deaths due to specific cancers. The total number of cancer deaths increased by 33% between 1997 and 2012, comprising 15% of male and 20% of female deaths in the period 2010-2012. Total years of life lost due to cancer increased by 25.1% for males and 31.1% for females over the study period. The highest increases (>40%) were observed for colorectal, pancreas and kidney cancers in both sexes, for melanomas and bladder cancer in men, and for breast and ovarian cancer in women. Trends in average years of life lost were stable. Almost half (48-50%) of the years of life lost due to childhood cancers were due to leukemia. Cancer is an increasing health burden in Colombia. The high average years of life lost illustrate the poor prognosis of the disease compared to other countries. Primary prevention, early detection, and adequate and timely treatments are needed to change this situation.

Mincle, an Innate Immune Receptor, Is Expressed in Urothelial Cancer Cells of Papillomavirus-Associated Urothelial Tumors of Cattle.

BackgroundMincle, macrophage-inducible C-type lectin, is a member of C-type lectin receptors. It plays an important role in anti-mycobacterial and anti-fungal immunity. Furthermore it senses dead cells through its primary ligand SAP130.Materials and FindingsWe examined ten urothelial tumors of the urinary bladder of cattle. Eight of them expressed E5 cDNA of bovine papillomaviruses type 2 (BPV-2) and type 13 (BPV-13) that belong to Deltapapillomavirus genus. Two of them were not examined for detection of E5 cDNA. Mincle expression appeared to occur in urothelial neoplastic cells only. No mincle expression was detected in urothelial cells from healthy cattle. Mincle expression was characterized by a membranous pattern in papillary urothelial cancers; isolated and/or clustered urothelial cells showing a strong cytoplasmic immunoreactivity were primarily seen in invasive urothelial cancers.ConclusionThis is the first study about the expression of mincle in veterinary oncology and the first report which describes the expression of functional mincle receptor in neoplastic cells in medical literature. As it has been shown that urothelial cancer cells have the ability to function as antigen-presenting cells (APCs), it is conceivable that mincle expression is involved in the presentation of cancer cell antigens to cells of the immune system. Furthermore, since expression of mincle contributes to the control of Mycobacterium bovis BCG infection, this study has exciting clinical implications in comparative medicine keeping in mind that Bacillus Calmette-Guérin (BCG) immunotherapy is currently the most effective treatment of non-muscle invasive bladder cancer in man. Mincle expression in urothelial tumor cells warrants further study to better understand the role, if any, of this receptor in bladder cancer. Future studies will provide insights in the role of mincle receptor of urothelial cancer cells in antitumor immunotherapy.

Bladder cancer and occupational exposure to diesel and gasoline engine emissions among Canadian men.

The International Agency for Research on Cancer has classified diesel exhaust as a carcinogen based on lung cancer evidence; however, few studies have investigated the effect of engine emissions on bladder cancer. The purpose of this study was to investigate the association between occupational exposure to diesel and gasoline emissions and bladder cancer in men using data from the Canadian National Enhanced Cancer Surveillance System; a population‐based case–control study. This analysis included 658 bladder cancer cases and 1360 controls with information on lifetime occupational histories and a large number of possible cancer risk factors. A job‐exposure matrix for engine emissions was supplemented by expert review to assign values for each job across three dimensions of exposure: concentration, frequency, and reliability. Odds ratios (OR) and their corresponding 95% confidence intervals were estimated using logistic regression. Relative to unexposed, men ever exposed to high concentrations of diesel emissions were at an increased risk of bladder cancer (OR = 1.64, 0.87–3.08), but this result was not significant, and those with >10 years of exposure to diesel emissions at high concentrations had a greater than twofold increase in risk (OR = 2.45, 1.04–5.74). Increased risk of bladder cancer was also observed with >30% of work time exposed to gasoline engine emissions (OR = 1.59, 1.04–2.43) relative to the unexposed, but only among men that had never been exposed to diesel emissions. Taken together, our findings support the hypothesis that exposure to high concentrations of diesel engine emissions may increase the risk of bladder cancer.

Abstract A27: Association between diabetes pharmacotherapies and bladder cancer: A Medicare epidemiologic study

Abstract Background: Patients with type two diabetes mellitus (T2DM) have an increased risk of bladder cancer; they are also commonly treated with pioglitizone and angiotensin receptor blockers (ARBs), medications associated with an increased cancer risk in some studies. This study aimed to further explore the relationship between these medications and bladder cancer in an older population with higher baseline risk of this cancer and common exposure to these drugs. We examine the risk associated with exposure to the individual drug/drug class, and risk associated with exposure to both to assess for a potential cancer promoting interaction. Methods: Using a 40% Medicare random sample denominator and corresponding inpatient, outpatient (2004-2012) and prescription (2006-2012) claims, we studied fee-for-service beneficiaries age 67 and older. We identified pharmacotherapeutically treated diabetics (2006 to 2011) defined as patients filling one or more prescription for an oral hypoglycemic drug. Individual-level, time varying exposure to all oral and injectable hyopglycemics as well as ARBs and ACE-Is was calculated as count of drug-specific daily doses; daily doses were derived empirically as the median daily dose (MDDs) for this population. Cox proportional hazards models, adjusted for patient characteristics, comorbidities and diabetes complications, were used to examine the risk of incident bladder cancer associated with cumulative observed exposure to pioglitazone and ARBs. To address possible indication bias for the exposures of interest, we also estimated risk associated ACE-I exposure and non-pioglitazone TZD exposure, substitutes for the exposures of interest not suspected of increasing cancer risk. Interaction terms estimated the effect of exposure to ARBs with pioglitazone and ARBs with non-pioglitazone TZD. Secondary models repeated main models stratified on gender due to the higher baseline risk of bladder cancer in men. Results: Overall, we identified 1,161,443 diabetics, 62.5% female, 10.7% black, 9.8% Hispanic. Mean age at the beginning of follow-up was 75.1 years (SD 7.5); 18.9% had evidence of current or past tobacco use. Mean follow time was 42.2 months (SD 26.4). Overall, 20.2% of the cohort used some pioglitazone (mean exposure 642 MDDs); 31.7% used some ARB (Mean exposure 745 MDDs); 10.4% used some non-pioglitazone TZD (mean exposure 503 MDDs); 59.1% used some ACE-I (mean exposure 855 MDDs). 8.0% used both pioglitazone and ARBs; 13.2% used both pioglitazone and ACE-I; 4.1% used non-pioglitazone TZD and ARB; and 6.8% used non-pioglitazone TZD and ACE-I. In total, 5,874 bladder cancers were identified, 69% amongst men, an incidence of 0.28/1000 PY in men and 0.07/1000 PY in women. Compared to no observed exposure, the risk of bladder cancer associated with each additional year of exposure at median daily dose was: 0.97 (95% CI 0.89, 1.06) for pioglitazone, 1.04 (95% CI 0.97, 1.12) for ARBs; 0.99 (95% CI 0.95, 1.03) for ACE-Is and 0.98 (95% CI 0.86, 1.12) for non- pioglitizone TZDs. The risk of bladder cancer associated with each additional year of exposure to both pioglitizone and ARB was 0.97 (95% CI 0.91, 1.04); for pioglitazone and ACE-I, 1.01 (95% CI 0.98, 1.03); for non-pioglitazone TZD and ARB, 0.99 (95% CI 0.91, 1.08); and for non-pioglitazone TZD and ACE-I, 0.99 (95% CI 0.93, 1.04). Results did not differ when stratified by sex. Conclusions: We found no increased risk of bladder cancer associated with pioglitizone use, ARB use or exposure to both over an average observation time of 3.5 years. While the findings of this observational study should be confirmed in a prospective trial of longer duration, overall the results should reassure diabetics and their clinicians using these products to minimize the substantial health risks associated with diabetes. Citation Format: Jeremy Smith, Rebecca Zaha, Todd A. Mackenzie, Margaret R. Karagas, Nancy E. Morden. Association between diabetes pharmacotherapies and bladder cancer: A Medicare epidemiologic study. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A27.

Lower Urinary Tract Symptoms and Risk of Bladder Cancer in Men: Results From the Health Professionals Follow-up Study

To understand the association between lower urinary tract symptoms (LUTS) and risk of bladder cancer in a large cohort of men. Using data from the Health Professionals Follow-up Study, we examined risk of bladder cancer in relation to severity of LUTS among 30,183 men. During the follow-up period from 1996 until 2010, 476 newly diagnosed cases of bladder cancer occurred. The Cox proportional hazards regression was used to adjust for potential confounders. Among men with severe LUTS, risk of bladder cancer was 64% higher (relative risk [RR], 1.64; 95% confidence interval [CI], 0.87-3.08) compared with men who reported no LUTS. Subjects with both voiding and storage dysfunction had a significantly higher risk of bladder cancer (RR, 1.60; 95% CI, 1.00-2.56). Among individual urinary symptoms, urinary hesitancy was strongly associated with bladder cancer; those who experienced urinary hesitancy at least 50% of the time had more than twice the risk of bladder cancer (RR, 2.21; 95% CI, 1.29-3.78). Our findings suggest that LUTS, especially urinary hesitancy, are associated with the development of bladder cancer in men.

Pioglitazone and bladder cancer risk: a multipopulation pooled, cumulative exposure analysis.

The evidence on the association between pioglitazone use and bladder cancer is contradictory, with many studies subject to allocation bias. The aim of our study was to examine the effect of exposure to pioglitazone on bladder cancer risk internationally across several cohorts. The potential for allocation bias was minimised by focusing on the cumulative effect of pioglitazone as the primary endpoint using a time-dependent approach. Prescription, cancer and mortality data from people with type 2 diabetes were obtained from six populations across the world (British Columbia, Finland, Manchester, Rotterdam, Scotland and the UK Clinical Practice Research Datalink). A discrete time failure analysis using Poisson regression was applied separately to data from each centre to model the effect of cumulative drug exposure on bladder cancer incidence, with time-dependent adjustment for ever use of pioglitazone. These were then pooled using fixed and random effects meta-regression. Data were collated on 1.01 million persons over 5.9 million person-years. There were 3,248 cases of incident bladder cancer, with 117 exposed cases and a median follow-up duration of 4.0 to 7.4 years. Overall, there was no evidence for any association between cumulative exposure to pioglitazone and bladder cancer in men (rate ratio [RR] per 100 days of cumulative exposure, 1.01; 95% CI 0.97, 1.06) or women (RR 1.04; 95% CI 0.97, 1.11) after adjustment for age, calendar year, diabetes duration, smoking and any ever use of pioglitazone. No association was observed between rosiglitazone and bladder cancer in men (RR 1.01; 95% CI 0.98, 1.03) or women (RR 1.00; 95% CI 0.94, 1.07). The cumulative use of pioglitazone or rosiglitazone was not associated with the incidence of bladder cancer in this large, pooled multipopulation analysis.

Bladder Cancer: The Hormonal Dependence Enigma and a New Hormonal Player.

Dear Editor, Bladder cancer is considered to be a hormonal-independent malignancy. However, an increasing number of studies show that sex hormonesmight have an important role in the etiology or progression of specific urothelial carcinoma subtypes. The most important indication that bladder cancer might be influenced by sex hormone is that the incidence and risk of developing bladder cancer in men is notably greater comparing to women, even when established risk factors such as smoking, occupational exposure, and urinary tract infection are counterbalanced between the sexes. The effect of sex hormones in bladder tissues is documented during pregnancy and menopause where the bladder undergoes dramatic changes in structure, function, histology, and gene expression. Bladder tissues are shown to express androgen, estrogen, and progesterone receptors. Additionally, in animal models, estrogens are shown to inhibit and androgens to promote bladder cancer development even when carcinogenetic substances are used such as N-butyl-N-(4hydroylbutyl)nitrosamine [1]. Another indication of the hormonal contribution in bladder cancer development is the relatively lower risk of parous women to develop this malignancy compared to the nulliparous females. A human bladder tumor cell line, R198, was shown to develop under the effect of androgens while it regressed under the presence of estrogen [2]. Finally, there is also the report of a man who developed endometriosis of urinary bladder, after 5 years treatment with estrogen therapy for prostate cancer [3]. The lesion regressed after estrogen withdrawal, indicating a metaplasia potential of the urothelium under extreme changes of hormonal environment. Under these circumstances, we would like to report our experience of a 65-year-old woman treated for breast cancer who developed urothelial carcinoma at the trigone of the urinary bladder, 1 year after the onset of adjuvant hormonal therapy with third-generation non-steroidal aromatase inhibitor. The patient underwent modified radical mastectomy with ipsilateral axillary lymphadenectomy 4 years ago and subsequently chemotherapy (FEC and docetaxel) and radiotherapy. Three months after the onset of aromatase inhibitor treatment, the patient claimed to have aggravated hirsutism of both arms and no hair growth on the parietal skull following a pattern of androgenetic alopecia. A year since the onset of adjuvant hormonal therapy, a papillary protrusion was detected at the trigone of the urinary bladder. The histological report showed a non-muscle invasive low-grade papillary urothelial carcinoma, grade 1 by WHO-ISUP. One and a half year later, the patient was found to have bladder cancer relapse with the same histological urothelial tumor and the same androgenetic effects of the adjuvant hormonal therapy. The current hypothesis we propose is that the excessive androgen environment produced by the aromatase inhibitor in a postmenopausal woman with lack of the counterbalancing hormones (estrogen and progesterone) could contribute to the development of bladder cancer. There are some hypotheses which try to explain the hormonal dependence of bladder cancer and especially of the trigone of the urinary bladder. The trigone and the prostate have the same embryologic endodermic origin. This hypothesis is supported by the finding that the tumor cells of R198 cell line have some similar characteristics with human prostatic carcinomas [2]. Additionally, one of the ways that K. Ntzeros (*) :G. Louka Department of Urology, Hospital of Korinthos, Korinthos, Greece e-mail: konstantinos.ntzeros@gmail.com

Does occupational exposure to solvents and pesticides in association with glutathione S-transferase A1, M1, P1, and T1 polymorphisms increase the risk of bladder cancer? The Belgrade case-control study.

ObjectiveWe investigated the role of the glutathione S-transferase A1, M1, P1 and T1 gene polymorphisms and potential effect modification by occupational exposure to different chemicals in Serbian bladder cancer male patients.Patients and MethodsA hospital-based case-control study of bladder cancer in men comprised 143 histologically confirmed cases and 114 age-matched male controls. Deletion polymorphism of glutathione S-transferase M1 and T1 was identified by polymerase chain reaction method. Single nucleotide polymorphism of glutathione S-transferase A1 and P1 was identified by restriction fragment length polymorphism method. As a measure of effect size, odds ratio (OR) with corresponding 95% confidence interval (95%CI) was calculated.ResultsThe glutathione S-transferase A1, T1 and P1 genotypes did not contribute independently toward the risk of bladder cancer, while the glutathione S-transferase M1-null genotype was overrepresented among cases (OR = 2.1, 95% CI = 1.1–4.2, p = 0.032). The most pronounced effect regarding occupational exposure to solvents and glutathione S-transferase genotype on bladder cancer risk was observed for the low activity glutathione S-transferase A1 genotype (OR = 9.2, 95% CI = 2.4–34.7, p = 0.001). The glutathione S-transferase M1-null genotype also enhanced the risk of bladder cancer among subjects exposed to solvents (OR = 6,5, 95% CI = 2.1–19.7, p = 0.001). The risk of bladder cancer development was 5.3–fold elevated among glutathione S-transferase T1-active patients exposed to solvents in comparison with glutathione S-transferase T1-active unexposed patients (95% CI = 1.9–15.1, p = 0.002). Moreover, men with glutathione S-transferase T1-active genotype exposed to pesticides exhibited 4.5 times higher risk in comparison with unexposed glutathione S-transferase T1-active subjects (95% CI = 0.9–22.5, p = 0.067).ConclusionNull or low-activity genotypes of the glutathione S-transferase A1, T1, and P1 did not contribute independently towards the risk of bladder cancer in males. However, in association with occupational exposure, low activity glutathione S-transferase A1 and glutathione S-transferase M1-null as well as glutathione S-transferase T1-active genotypes increase individual susceptibility to bladder cancer.

Metabolic syndrome and cancer: holistic or reductionist?

Metabolic syndrome has become a major public health problem worldwide and represents a common clinical condition in countries with a high incidence of obesity and western dietary patterns. Metabolic syndrome associates with common cancers at many sites, including liver, colorectal, and bladder cancers in men, and endometrial, pancreatic, breast post-menopausal, and colorectal cancers in women. However, the role played by each single component of the syndrome on cancer risk is still unclear. For endometrial cancer, obesity and/or high circumference waist explain all the risk associated with the full metabolic syndrome, while for post-menopausal breast cancer, the risk conveyed by metabolic syndrome appears to be greater than its parts, as no single component explains the full risk associated with the syndrome. Future research should cover other avenues in order to elucidate the complexity of biological processes linking metabolic syndrome and cancer.

The kidney as a new target for antidiabetic drugs: SGLT2 inhibitors

A novel class of antidiabetic drugs - SGLT2 (Na(+) /glucose cotransporter type 2) inhibitors - target renal reabsorption of glucose and promote normal glucose levels, independent of insulin production or its action at receptors. We review this new mechanistic approach and the reported efficacy and safety of clinical testing of lead compounds. Information was obtained from various bibliographic sources, including PubMed and others, on the basic science and the clinical trials of SGLT2 inhibitors. The information was then summarized and evaluated from the perspective of contribution to a fuller understanding of the potential and current status of the lead clinical candidates. Diabetes mellitus is a spectrum of disorders that involves inadequate insulin function resulting in adverse health sequelae due to acute and chronic hyperglycaemia. Current antidiabetic pharmacotherapy primarily addresses either insulin production at the pancreatic β-cells or insulin action at insulin receptors. These drugs have less than full clinical effectiveness and sometimes therapy-limiting adverse effects. The third major component of glucose balance, namely elimination, has not been a significant therapeutic target to date. SGLT2 inhibitors are a novel approach. A sufficient number of clinical trials have been conducted on sufficiently chemically diverse SGLT2 inhibitors to reasonably conclude that they have efficacy (HbA1c reductions of 0·4-1%), and thus far, the majority of adverse effects have been mild and transitory or treatable, with the caveat of possible association with increased risk of breast cancer in women and bladder cancer in men.

Is sparing the prostate still considered radical cystectomy? The case against prostate-sparing cystectomy for bladder cancer

Radical cystoprostatectomy with bilateral pelvic lymphadenectomy and urinary diversion remains the gold standard therapy for localized bladder cancer in men.1 The procedure has been refined over several decades with the current application of nerve-sparing techniques.2,3 Unfortunately, the procedure carries significant risks of urinary and sexual dysfunction resulting in bladder-sparing approaches being popularized for selected early invasive bladder cancers. More recently, some authors have suggested that prostate-sparing cystectomy may be appropriate in selected men to improve postoperative sexual and urinary function.4–6 They propose that leaving the prostate, or part of it, intact will result in less damage to pelvic innervation and better preservation of sexual function and urinary sphincter control in cases of orthotopic diversion. These potential functional improvements must be weighed against any risks for oncologic outcomes. One potential oncologic pitfall is the assumption that the prostate does not harbour transitional cell carcinoma (TCC) of the bladder. The incidence of occult prostatic involvement with TCC in patients undergoing radical cystectomy ranges between 20% and 48%,7–9 raising significant concern about sparing the prostate. In a large study, Pettus and colleagues10 concluded that patients with tumours involving the trigone and bladder neck or associated carcinoma in situ of the bladder should be considered at high risk for developing prostatic urethral carcinoma. Moreover, the absence of these factors did not conclusively rule out the presence of carcinoma in the prostatic urethra. Another significant risk is the potential for prostatic adenocarcinoma. Many argue that prostate cancer is not a major problem in this population, since men undergoing cystectomy for invasive bladder cancer are often elderly, with a poor prognosis for their bladder cancer. However, prostate-sparing surgery is usually offered to men whose pelvic disease is not advanced and in whom sexual function is normal, thus younger men. It is precisely in these younger men with early forms of invasive bladder cancer that occult prostate cancer could pose problems in the future. Occult prostate cancer has a reported incidence of 23% to 47% in men undergoing radical cystectomy. Furthermore, about 50% of these cancers are potentially significant based on histologic criteria.11–14 Revelo and colleagues11 detected that 41% of cases had unsuspected prostatic cancer, of which 48% were clinically significant and 16% were extracapsular. Of importance, 60% involved the apex, including 79% of significant cases, suggesting that recommending apical sparing as a compromise could potentially be equally hazardous. These findings were confirmed by another study in which 27% of patients undergoing cystectomy for invasive TCC of the bladder were found to have prostatic carcinoma (PCa), with 33% involving the apex of the prostate.15 The authors suggested that the high likelihood of apical prostate cancer requires careful excision of the apical margins. Kablain and colleagues13 previously reported that 38% of patients undergoing cystectomy for bladder cancer and who harbour prostate carcinoma had a distinct apical predominance of the tumours. In a recent study, Hautmann and colleagues16 addressed the probability of overlooking clinically significant prostate cancer using sextant biopsy. They analyzed specimens from 133 consecutive patients undergoing cystoprostatectomy for bladder cancer. Patients were included in the study if they had serum prostate-specific antigen (PSA) 25%. Systematic sextant biopsy was performed in the operating room immediately following cystoprostatectomy and prostates were subsequently step-sectioned (3 mm). The threshold defined to distinguish between significant and insignificant cancer was 0.5 cm3. Incidental prostatic cancer was found in 58 of the 133 bladder cancer patients (44%), with presence of significant cancer in many. Sextant biopsy detected 7 cancers, including 4 of 47 (9%) that were insignificant and 3 of 11 (27%) that were significant. Thus, sextant biopsy missed 8 (73%) of 11 of significant prostate cancers. These data suggest that despite careful screening for prostate cancer for cystoprostatectomy patients, it remains regularly overlooked in a significant proportion of clinically relevant cases. In a recent prospective study by Saad and colleagues,17 425 men had radical cystoprostatectomy for invasive bladder cancer and entire mounted prostates were step-sectioned at 2 to 3 mm intervals. Of 425 cases examined, there was histological evidence of prostatic adenocarcinoma in 90 cases (21.2%). Prostatic TCC was found in 66 patients (15.6%). There was also significant benign prostatic hyperplasia in 175 (41.2%). They concluded that the marginal reported functional advantage of prostate-sparing cystectomy is not worth the potential oncological risks. In a prospective study, Koraitim and colleagues18 studied urinary continence and voiding differences between men undergoing classic radical cystoprostatectomy and men with prostate-sparing cystectomy. They found no statistical difference between both groups with respect to urinary continence, but found a significant difference in peak flow rate. They concluded that preservation of prostatic apex may present an element obstructing the evacuation of ileal bladders.

Benign prostatic hyperplasia is a significant risk factor for bladder cancer in diabetic patients: a population-based cohort study using the National Health Insurance in Taiwan

BackgroundDiabetic patients have a higher risk of bladder cancer and benign prostatic hyperplasia (BPH). Theoretically, BPH patients may have an increased risk of bladder cancer because residual urine in the bladder surely increases the contact time between urinary excreted carcinogens and the urothelium. However, whether BPH increases bladder cancer risk in patients with type 2 diabetes has not been studied.MethodsThe reimbursement databases of all Taiwanese diabetic patients under oral anti-diabetic agents or insulin from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2006 and a total of 547584 men with type 2 diabetes were followed up for bladder cancer incidence until the end of 2009. Incidences of bladder cancer for BPH by status and by duration were calculated and adjusted hazard ratios (95% confidence intervals) were estimated by Cox regression. The effects of diabetes duration and medications used for diabetic control in relation with bladder cancer risk were also evaluated by Cox regression in BPH men.ResultsThe incidences were 258.77 and 69.34 per 100,000 person-years for patients with and without BPH, respectively, adjusted hazard ratio 1.794 (1.572, 2.047). For BPH patients, those who underwent surgical procedures for BPH had a higher incidence than those who did not (355.45 vs. 250.09 per 100,000 person-years), respective adjusted hazard ratios: 2.459 (1.946, 3.109) and 1.709 (1.492, 1.958). The significantly higher risk could be demonstrated for BPH of any duration: respective adjusted hazard ratios 1.750 (1.430, 1.605), 1.844 (1.543, 2.203), 2.011 (1.680, 2.406) and 1.605 (1.341, 1.921) for BPH <1, 1–3, 3–5 and ≥5 years versus patients without BPH. Sensitivity analyses for patients aged ≥60 years and after excluding BPH patients with surgical procedures or without surgical procedures, respectively, yielded similar results. In BPH men, diabetes duration was not significantly related with bladder cancer; but metformin was consistently associated with a significantly lower risk, with adjusted hazard ratio of 0.719 (0.590, 0.875) for all ages and 0.742 (0.604, 0.912) for age ≥60 years.ConclusionsBPH is a significant risk factor for bladder cancer in men with type 2 diabetes. Metformin may protect against bladder cancer in BPH men.

Quality of life after radical cystectomy for bladder cancer in men with an ileal conduit or continent urinary diversion: A comparative study

Aim:To investigate quality of life (QoL) domains with three forms of urinary diversions, including ileal conduit, MAINZ pouch, and orthotopic ileal neobladder after radical cystectomy in men with muscle-invasive bladder cancer.Materials and Methods:In a prospective study, 149 men underwent radical cystectomy and urinary diversion (70 ileal conduit, 16 MAINZ pouch, and 63 orthotopic ileal neobladder). Different domains of QoL, including general and physical conditions, psychological status, social status, sexual life, diversion-related symptoms, and satisfaction with the treatment were assessed using an author constructed questionnaire. Assessment was performed at three months postoperatively.Results:In questions addressing psychological status, social status, and sexual life, patients with continent diversion had a more favorable outcome (P = 0.002, P = 0.01, and P = 0.002, respectively). The rate of erectile dysfunction did not differ significantly between the three groups (P = 0.21). The rate and global satisfaction was higher with the MAINZ pouch (68.7%) and ileal neobladder (76.2%) as compared with the ileal conduit group (52.8%) (P = 0.002).Conclusion:Continent urinary diversion after radical cystectomy provides better results in terms of QoL as compared with ileal conduit diversion.