Bladder Cancer Diagnoses Research Articles

The emerging role of the androgen receptor in bladder cancer.

Men are three to four times more likely to get bladder cancer than women. The gender disparity characterizing bladder cancer diagnoses has been investigated. One hypothesis is that androgen receptor (AR) signaling is involved in the etiology and progression of this disease. Although bladder cancer is not typically described as an endocrine-related malignancy, it has become increasingly clear that AR signaling plays a role in bladder tumors. This review summarizes current findings regarding the role of the AR in bladder cancer. We discuss work demonstrating AR expression in bladder cancer and its role in promoting formation and progression of tumors. Additionally, we discuss the therapeutic potential of targeting the AR in this disease.

Bladder cancer in HIV-infected adults: an emerging concern?

IntroductionAs HIV-infected patients get older more non-AIDS-related malignancies are to be seen. Cancer now represents almost one third of all causes of deaths among HIV-infected patients [1]. Albeit bladder cancer is one of the most common malignancy worldwide [2], only 13 cases of bladder cancer in HIV-infected patients have been reported in the literature so far [3].Materials and MethodsWe conducted a monocentric study in our hospital. We selected all patients who were previously admitted (from 1998 to 2013) in our hospital with diagnoses of HIV and bladder cancer. The objective was to assess the prevalence and characteristics of bladder cancers in HIV-infected patients in our hospital. ResultsBased on our administrative HIV database (6353 patients), we found 15 patients (0.2%) with a bladder cancer. Patients’ characteristics are presented in Table 1. Patients were mostly men and heavy smokers. Their median nadir CD4 cell count was below 200 and most had a diagnosis of AIDS. A median time of 14 years was observed in those patients, between the diagnosis of HIV-infection and the occurrence of bladder cancer, although in patients much younger (median age 56) than those developing bladder cancer without HIV infection (71.1 years) [4]. Haematuria was the most frequent diagnosis circumstance in HIV-infected patients who had relatively preserved immune function on highly active antiretroviral therapy (HAART). Histopathology showed relatively advanced cancers at diagnosis with a high percentage of non transitional cell carcinoma (TCC) tumor and of TCC with squamous differentiation, suggesting a potential role for human papilloma virus (HPV) co-infection. Death rate was high in this population.ConclusionsBladder cancers in HIV-infected patients remain rare but occur in relatively young HIV-infected patients with a low CD4 nadir, presenting with haematuria, most of them being smokers, and have aggressive pathological features that are associated with severe outcomes.

Long-term Outcomes in Treatment of Invasive Bladder Cancer With Concomitant Boost and Accelerated Hyperfractionated Radiation Therapy

The aim of this study was to evaluate the long-term clinical efficacy and toxicity of concomitant boost and accelerated hyperfractionated radiation therapy (CBAHRT) in patients with invasive bladder cancer. Between October 1997 and September 2012, 334 patients with diagnoses of invasive bladder cancer were selected. These patients received CBAHRT as a bladder-conserving approach. The treatment consisted of a dose of 45 Gy/1.8 Gy to the whole pelvis with a daily concomitant boost of 1.5 Gy to the tumor. Total dose was 67.5 Gy in 5 weeks. A total of 32 patients (10.3%) had a diagnosis of stage T1, 202 (64.3%) were at stage T2, 46 (14.6%) were at stage T3a, 22 (7%) were at stage T3b, and 12 (3.8%) were at stage T4a. The follow-up period was 33.1 months (range, 4.3-223.3 months). Grade 3 late intestinal toxicity was observed in 9 patients (2.9%), whereas grade 3 late urinary toxicity was observed in 8 patients (2.5%). The median overall survival (OS) was 26.3 months (95% confidence interval [CI]: 21.4-31.2). The 5-, 10, and 15-year OS rates were 32.1% (standard error [SE], ± 0.027), 17.9% (SE, ± 0.025) and 12.5% (SE, ± 0.028), respectively. The median cause-specific survival (CSS) was 42.1 months (95% CI: 28.7-55.5). The 5-, 10-, and 15-year CSS rates were 43.2% (SE, ± 0.03), 30.3% (SE, ± 0.03), and 28% (SE, ± 0.04), respectively. The median relapse-free survival (RFS) was 111.8 months (95% CI: 99.6-124). The 5-, 10-, and 15-year RFS rates were 61.9% (SE, ± 0.03), 57.6% (SE, ± 0.04), and 48.2% (SE, ± 0.07), respectively. The CBAHRT technique demonstrated acceptable toxicity and local control rates in patients with invasive bladder cancer, and this therapy facilitated bladder conservation. In selected patients, the CBAHRT technique is a practical alternative treatment option with acceptable 5-, 10-, and 15-year results in patients undergoing cystectomy as well as concurrent chemoradiation therapy.

Bladder cancer incidence and mortality in patients treated with radiation for uterine cancer.

To estimate the effect of radiation therapy (RT) administered for uterine cancer (UtC) on bladder cancer (BC) incidence, tumour characteristics at presentation, and mortality. In this retrospective cohort study, records of 56 681 patients diagnosed with UtC as their first primary malignancy during 1980-2005 were obtained from the Surveillance, Epidemiology and End-Results (SEER) database. Follow-up for incident BC ended on 31 December 2008. Occurrences of BC diagnoses and BC deaths in patients with UtC managed with or without RT were summarised with counts and person-time incidence rates (counts divided by person-years of observation). Age adjustment of rates was performed by direct standardisation. Incident BC cases were described in terms of histological types, grades and stages. With a mean follow-up of 15 years, BC was diagnosed in 146 (0.93%) of 15 726 patients with UtC managed with RT, and in 197 (0.48%) of 40 955 patients with UtC managed without RT, with an age-adjusted rate ratio of 2.0 (95% confidence interval [CI] 1.6-2.5). Fatal BC occurred in 39 (0.25%) and 36 (0.09%) of patients with UtC managed with vs without RT, respectively, with an age-adjusted rate ratio of 2.9 (95% CI 1.8-4.6). Incident BC cases diagnosed in patients with UtC managed with vs without RT had similar distributions of histological types, grades, and stages. Use of RT for UtC is associated with increased BC incidence and mortality later in life. Heightened awareness should help identify women with new voiding symptoms or haematuria, all of which should be fully evaluated.

Developments and controversies in the management of noninvasive bladder cancer

To summarize recent developments and controversies in the diagnosis and management of nonmuscle invasive bladder cancer (NMIBC). The majority of incident bladder cancer diagnoses are noninvasive. The mainstay of diagnosis remains cystoscopy and transurethral resection, with enhanced optical techniques potentially improving detection of nascent disease. Intravesical chemotherapeutic and immunotherapeutic agents reduce the likelihood of recurrence and progression, with novel agents showing promise. The identification of variant histology with aggressive phenotypes permits identification of patients unlikely to respond to intravesical agents, in whom early cystectomy is advocated. Risk stratification of patients with NMIBC continues to improve and should be used to inform surveillance and treatment paradigms. Tobacco cessation may improve disease-specific endpoints and overall mortality. NMIBC encompasses a variety of tumors with heterogeneous natural histories, making clinical management challenging. Improved detection with novel technologies and optimization of existing treatment modalities hold promise of improving oncologic outcomes in the future.

Bladder Cancer in Males: A Comprehensive Review of Urothelial Carcinoma of the Bladder

Bladder cancer is the second most common genitourinary malignancy after prostate cancer. It is a disease most commonly encountered in the elderly, particularly males, and has several well-established risk factors, including smoking and occupational exposures to certain chemical carcinogens. Roughly 90% of all bladder cancers are urothelial in origin; that is, they arise from the epithelial lining of the bladder. The remainder, including squamous cell carcinoma and adenocarcincoma, are nonurothelial. This review will focus solely on bladder cancer of urothelial origin, commonly referred to as urothelial carcinoma (UC) of the bladder. Bladder cancer can be divided into three distinct clinical entities: nonmuscle-invasive bladder cancer (NMIBC), muscle-invasive bladder cancer (MIBC), and metastatic bladder cancer. Each entity calls for different management. NMIBC, which accounts for roughly 70% of bladder cancer diagnoses, usually can be managed with transurethral resection, intravesical chemotherapy/immunotherapy, and aggressive surveillance protocols to monitor for recurrence and progression. MIBC calls for radical cystectomy (RC) with urinary diversion and bilateral pelvic lymph node dissection. Although it is often underutilized, neoadjuvant chemotherapy with platinum-based regimens improves survival. Data on adjuvant chemotherapy are less robust, but it remains an option for those who are medically fit and considered to be at high risk for recurrence and progression. Bladder-preserving strategies, including partial cystectomy and trimodality therapy, can provide adequate cancer control in appropriately selected patients with MIBC. Stringent surveillance is required. Metastatic bladder cancer is often lethal and the standard of care remains platinum-based chemotherapy regimens. Renal insufficiency is a common comorbidity that prevents patients from receiving chemotherapy in all settings. Currently, there are no recommended second-line chemotherapy regimens. Given the high rate of recurrence and progression, better prognostic variables should help to identify those who should be targeted in clinical trials. As bladder cancer affects a large number of men every year and significantly contributes to healthcare expenditures, prompt diagnosis and appropriate management are critical.

Introduction of a tobacco-screening initiative for those at risk for bladder cancer in a high volume urology clinic.

4540 Background: Tobacco use is causal or contributory in 50% of bladder cancer diagnoses. Continued use after diagnosis may negatively impact recurrence, progression, and mortality. Despite its relevance, tobacco screening was infrequently occurring in a regional urology clinic. We hypothesized that the clinic was fertile ground for a tobacco-screening initiative given the number of referrals for bladder cancer, hematuria, and other tobacco-related urologic conditions. Methods: An EMR-based tobacco-screening prompt was designed using the same informatics architecture and clinical reporting system used in primary care. The prompt was introduced for all new patient encounters beginning January 2010. We prospectively collected the proportion of patients asked about tobacco use, advised to quit, and assisted with smoking cessation. Results: For the two years ending December 2011, 4,617 patients were seen in urologic consultation; 31% (n = 1,444) were referred for tobacco-related urologic diagnoses, 36% (n = 518) of whom were referred for bladder cancer or hematuria. The tobacco-screening prompt was used 57% (n = 2,626) of the time. Attending physicians utilized the template in 17% of their encounters, resident physicians in 71%, and nurse practitioners in 97% (p < 0.001). 49% (n = 255) of those referred for bladder cancer or hematuria were screened for tobacco use. Active smokers comprised 21% (n = 558) of screened patients. Relative to former and never smokers, active smokers were more likely referred for bladder cancer or hematuria (p = 0.005). 40% (n = 225) of active smokers desired to quit. Those counseled by an attending physician were more likely ready to quit and trended toward a more intensive cessation program (p = 0.004 and p = 0.07, respectively). Conclusions: Our data suggest that urology clinics may be important sites for tobacco-screening initiatives, particularly for those with tobacco-related urologic diagnoses. Screening patients referred for bladder cancer or hematuria is likely high yield due to the increased proportion of active smokers. Given the disparate utilization of the prompt, identification of provider-level facilitators and barriers to tobacco screening is worthy of study.

Bridging the gender gap in bladder cancer diagnoses

Bridging the gender gap in bladder cancer diagnoses

Long-term therapy with thiazolidinediones and the risk of bladder cancer: A cohort study.

1503 Background: The US Food and Drug Administration and other regulatory agencies recently warned prescribers that use of pioglitazone, a thiazolidinedione (TZD), may increase the risk of bladder cancer. France and Germany removed the drug from their markets, although the rest of Europe did not. However, no information was available about the risk from alternative TZDs. We aimed to compare bladder cancer risk over time with use of TZDs relative to sulfonylureas (SUs), and between pioglitazone and rosiglitazone. Methods: We conducted a cohort study of patients with type 2 diabetes who initiated treatment with a TZD or SU using The Health Improvement Network (2000-2010), a UK general practitioner medical record database. Incident cancers within the database were identified. We computed hazard ratios (HRs) of bladder cancer for TZDs in comparison to the reference group of SU users. Results: There were 60 incident diagnoses of bladder cancer in the TZD cohort (n=18,459) and 137 in the SU cohort (n=41,396). There was no significant difference in bladder cancer risk between the cohorts (HR 0·93, [95% CI 0·68-1·29]), but most use was short-term use. In contrast, the risk of bladder cancer increased with increasing time since initiation of TZD versus SU therapy (HRs 1·15, 1·40, and 1·72 for 3-4, 4-5, and ≥ 5 years, respectively; P-trend=0·033). Bladder cancer risk also increased with increasing time since initiation of pioglitazone (P-trend<0·001) and rosiglitazone (P-trend=0·006). Direct comparison of pioglitazone to rosiglitazone did not demonstrate significant differences in cancer risk with increasing time since initiation (P-trend=0·12) or duration of therapy (P-trend=0·75). Conclusions: Long-term TZD therapy is associated with an increased risk of bladder cancer, which appears to be a class effect.

Prostate cancer managed with active surveillance: role of anatomic MR imaging and MR spectroscopic imaging

urothelial carcinoma. There are a variety of reasons for false-negative diagnoses of ureteral and bladder cancer during MDCTurography. Early-enhanced thin-section MDCT of a full bladder with urine can decrease the number of false negatives bladder studies. This “bladder -wall phase “, obtained 60 seconds after contrast injection has superior accuracy for detection of small lesions in comparison with the excretory phase alone (bladder fully distended by opacified urine), as used by the authors. However small flat tumors that do not appear as filling defects and carcinoma in situ tumors, are almost impossible to be detected by MDCT-urography. For this reason, although not a perfect test, cystocopy remains the reference standard procedure in the investigation of hematuria.

The impact of a bladder cancer diagnosis on smoking behavior: An opportunity to improve care.

4570 Background: Cigarette smoking is causal in 30-50% of bladder cancer diagnoses. Smoking after diagnosis results in decreased recurrence and progression-free survival. Little is known about the smoking history, awareness of the risks of continued smoking, and success with quitting among patients with incident bladder cancer. Methods: A random sample of bladder cancer survivors was obtained from the California Cancer Registry. Subjects were surveyed regarding tobacco history, beliefs regarding risk factors, and physician influence on smoking. Four cohorts were created: never smokers, former smokers (quit smoking prior to diagnosis), and active smokers (smoking at time of diagnosis). Active smokers were classified as continued smokers (still smoking at time of survey) and quit smokers. Cohorts were compared using contingency tables and multivariate analysis. Results: Of 153 patients surveyed, 77% of respondents were male. Mean age was 69.2 years. 23% were never smokers, 59% former smokers, and 18% were active smokers at diagnosis. 39% of active smokers continued to smoke after diagnosis. Quit smokers were more likely than former or continued smokers to endorse tobacco use as a risk factor for their bladder cancer (94% vs. 44% vs. 82%, respectively, p<0.001), with 82% indicating that their urologist was the source of this knowledge. 88% of quit smokers indicated that the diagnosis of bladder cancer was responsible for their successful cessation and 71% cited the advice of the urologist. There were no differences between the quit smokers and the continued smokers in age at diagnosis, packs per day, or total pack years. Continued smokers started smoking at a younger age than quit smokers [mean 14.1 vs. 19.4, p=0.003] and had smoked for more years [mean 53.3 vs 37.1, p=0.002]. Conclusions: Most patients with incident bladder cancer are active or former smokers. Patients who continue smoking after diagnosis demonstrate lower smoking health literacy compared with those who quit smoking. Urologists play an important role in educating their patients with bladder cancer. Patient education and smoking cessation efforts aimed at newly diagnosed bladder cancer patients could improve overall and disease-specific survival. No significant financial relationships to disclose.

Impact of Previous Radiotherapy for Prostate Cancer on Clinical Outcomes of Patients With Bladder Cancer

The impact of prostate cancer radiotherapy on the biological behavior of bladder cancer remains unclear. We compared the outcomes of patients with bladder cancer previously treated for prostate cancer with radiotherapy vs other treatment modalities. We identified 144 patients diagnosed with bladder cancer between January 1992 and June 2007 with a previous prostate cancer diagnosis. Clinicopathological data and outcomes were compared between patients with irradiated (brachytherapy and/or external beam radiation therapy 83) and nonirradiated (androgen deprivation therapy, radical prostatectomy and/or surveillance 61) disease. Median time between prostate and bladder cancer diagnoses was longer in the irradiated vs nonirradiated group (59 months, IQR 25 to 88, vs 24 months, IQR 2 to 87, p = 0.007). Patients in the irradiated group presented with higher tumor grade (high 92% vs 77%, p = 0.016) and had progression to higher stage disease (muscle invasive 70% vs 43%, p = 0.001) than those in the nonirradiated group. Of the patients undergoing cystectomy those previously treated with radiation had a numerically higher rate of nonorgan confined disease (75% vs 56% for nonirradiated, p = 0.1). Among all patients with bladder cancer 5-year cancer specific survival was 73% (95% CI 59-87) for irradiated vs 83% (95% CI 71-95) for nonirradiated (p = 0.07). Median followup was 53 months (IQR 24 to 75). More time elapsed between prostate and bladder cancer diagnoses for patients treated with radiation, and these patients also presented with more advanced disease. Future studies are needed to further establish clinical differences in bladder cancer between irradiated and nonirradiated cases, and whether biological differences exist.

Should photodynamic diagnosis be standard practice for bladder cancer?

Bladder cancer (BC) is a frequently common disease with the highest lifetime treatment costs per patient of all cancers [1]. With an estimated 70,980 new diagnoses of BC and approximately 14,330 BC...

Incidence and pathological features of incidental prostate cancer and clinical significance thereof

To investigate the morbidity and pathological features of incidental prostate cancer and their clinical significance. 1483 prostate specimens obtained during operation, including transurethral resection of prostate (TURP) and total resection of the prostate, for the diagnoses of benign prostatic hypertrophy (BPH) or bladder cancer between January 1999 and August 2005 underwent pathological examination and 34beta12 and p63 immunohistochemical staining so as to detect incidental prostate cancer. The volume of incidental prostate cancer was calculated by the image analysis system. The clinical data were analyzed retrospectively. Comparison between the clinical and pathological feature of incidental prostate cancer was made. 53 cases of incidental prostate cancer, with the Gleason scores from 2 (1+1) to 9 (4+5) and the volumes from 0.18 to 1440.00 mm(3) were detected. The morbidity of incidental prostate cancer was 3.6%. The volume of 47 cases (88.7%) were less than 0.5 cm(3) as the threshold of insignificant cancer, and the volumes of 6 cases (11.3%) were more than 0.5 cm(3). All incidental prostate cancers of clinical significance were detected in the TURP samples. Among the incidental prostate cancers found in the TURP samples 20% were clinically significant cancers. The clinically significant incidental cancers were located in the central or transitional zone with the Gleason scores of 3 + 4 (2 cases), 4 + 2 (1 case), or 4 + 5 (3 cases). These clinically significant cancers were of diffuse distribution, and their preoperative clinical features were negative in palpation/image examination, elevation of serum PSA, and negative in puncture examination. Nowadays, the morbidity of incidental prostate cancer is lower than that of 1980s'. Among the incidental cancers 11.3% were of clinical significance. That the preoperative clinical examination cannot find these clinical significant cancers is partially caused by the pathological features of these tumors.

Sensitivity and specificity of antiproliferative factor, heparin-binding epidermal growth factor–like growth factor, and epidermal growth factor as urine markers for interstitial cystitis

We previously determined that the urine of interstitial cystitis (IC) patients specifically contains a factor (antiproliferative factor [APF]) that inhibits primary bladder epithelial cell proliferation, and that it has significantly decreased levels of heparin-binding epidermal growth factor–like growth factor (HB-EGF) and increased levels of epidermal growth factor (EGF) compared with urine from asymptomatic controls and patients with bacterial cystitis. We sought to confirm the specificity of these findings for IC using a larger patient population, including control patients with a variety of urogenital disorders. Clean catch urine specimens were collected from 219 symptomatic IC patients, 113 asymptomatic controls without bladder disease, and 211 patients with various urogenital diseases including acute bacterial cystitis, vulvovaginitis, chronic nonbacterial prostatitis, overactive bladder, hematuria, stress incontinence, neurogenic bladder, benign prostatic hyperplasia, bladder or pelvic pain without voiding symptoms, bladder cancer, prostate cancer, or miscellaneous diagnoses including anatomic disorders. APF activity was determined by 3H-thymidine incorporation into primary normal adult human bladder epithelial cells. HB-EGF and EGF levels were determined by enzyme-linked immunosorbent assay. APF activity was present significantly more often in IC than control urine specimens ( P <0.005 for IC vs any control group; sensitivity = 94%, specificity = 95%, P <10 −82 for IC vs all controls). HB-EGF levels were also significantly lower and EGF levels significantly higher in IC urine than in specimens from controls ( P <10 −84 and P <10 −36, respectively). These findings confirm the utility of APF, HB-EGF, and EGF as markers for IC. Understanding the reasons for altered levels of these markers may lead to understanding the pathogenesis of this disorder.