Subsequent Bladder Cancer Research Articles

Methylcap-seq reveals novel DNA methylation markers for the diagnosis and recurrence prediction of bladder cancer in a Chinese population.

PurposeThere is a need to supplement or supplant the conventional diagnostic tools, namely, cystoscopy and B-type ultrasound, for bladder cancer (BC). We aimed to identify novel DNA methylation markers for BC through genome-wide profiling of BC cell lines and subsequent methylation-specific PCR (MSP) screening of clinical urine samples.Experimental DesignThe methyl-DNA binding domain (MBD) capture technique, methylCap/seq, was performed to screen for specific hypermethylated CpG islands in two BC cell lines (5637 and T24). The top one hundred hypermethylated targets were sequentially screened by MSP in urine samples to gradually narrow the target number and optimize the composition of the diagnostic panel. The diagnostic performance of the obtained panel was evaluated in different clinical scenarios.ResultsA total of 1,627 hypermethylated promoter targets in the BC cell lines was identified by Illumina sequencing. The top 104 hypermethylated targets were reduced to eight genes (VAX1, KCNV1, ECEL1, TMEM26, TAL1, PROX1, SLC6A20, and LMX1A) after the urine DNA screening in a small sample size of 8 normal control and 18 BC subjects. Validation in an independent sample of 212 BC patients enabled the optimization of five methylation targets, including VAX1, KCNV1, TAL1, PPOX1, and CFTR, which was obtained in our previous study, for BC diagnosis with a sensitivity and specificity of 88.68% and 87.25%, respectively. In addition, the methylation of VAX1 and LMX1A was found to be associated with BC recurrence.ConclusionsWe identified a promising diagnostic marker panel for early non-invasive detection and subsequent BC surveillance.

393 TIME INTERVAL AFTER PROSTATE RADIOTHERAPY AFFECTS THE GRADE AND HISTOLOGY OF SUBSEQUENT BLADDER CANCER RESULTS OF A SEER STUDY

You have accessJournal of UrologyUrothelial Cancer: Natural History & Pathophysiology/Marker1 Apr 2012393 TIME INTERVAL AFTER PROSTATE RADIOTHERAPY AFFECTS THE GRADE AND HISTOLOGY OF SUBSEQUENT BLADDER CANCER RESULTS OF A SEER STUDY Satyan Shah, Richard Hoffman, Trisha Fleet, Anthony Smith, and Charles Wiggins Satyan ShahSatyan Shah Albuquerque, NM More articles by this author , Richard HoffmanRichard Hoffman Albuquerque, NM More articles by this author , Trisha FleetTrisha Fleet Albuquerque, NM More articles by this author , Anthony SmithAnthony Smith Albuquerque, NM More articles by this author , and Charles WigginsCharles Wiggins Albuquerque, NM More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.457AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bladder cancer (BC) in the setting of prior prostate radiotherapy (XRT) is more often high grade. However, it is unclear whether the latency period following XRT influences pathologic features of subsequent BC. We used population-level data to determine the temporal association between XRT and occurrence of high-grade and variant histology BC. METHODS The SEER database was used to identify incident prostate cancer cases between 1990-2007 meeting the following criteria: 1) malignant behavior 2) age at diagnosis > 40 years 3) treatment with XRT as part of initial cancer-directed therapy 4) subsequent development of BC 1 or more years after diagnosis. Only cases histologically confirmed with active follow-up were considered. Cases were stratified into 3 groups, based on the time elapsed after XRT and before development of subsequent BC. Group 1 developed BC 1-4 years after XRT, Group 2 developed BC 5-9 years after XRT, and Group 3 developed BC 10 or more years after treatment. We compared the frequency of high-grade and variant histology BC in each group using chi-square analysis. Variant histology was defined as the following histological types: carcinosarcoma, small cell carcinoma, sarcomatoid, spindle cell carcinoma, or pseudosarcomatous transitional cell carcinoma. RESULTS A total of 1570 cases met the inclusion criteria with 761 in Group 1, 593 in Group 2, and 216 in Group 3. As more time elapsed after prostate XRT, subsequent BC was more frequently high grade (31.9% in Group 1 vs. 37.4% in Group 2 vs. 44.9% in Group 3, p=0.0001). Variant histology BC developed in only 15 of 1570 cases (0.9%). However, increasing time interval between prostate XRT and subsequent BC was also associated with increased frequency of variant histology (0.4% in Group 1 vs. 1.2% in Group 2 vs. 2.3% in Group 3, p=0.03). CONCLUSIONS Incident bladder cancers diagnosed following prostate radiotherapy were increasingly likely over time to be high grade and of variant histology. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e161 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Satyan Shah Albuquerque, NM More articles by this author Richard Hoffman Albuquerque, NM More articles by this author Trisha Fleet Albuquerque, NM More articles by this author Anthony Smith Albuquerque, NM More articles by this author Charles Wiggins Albuquerque, NM More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

The risk of bladder cancer in patients diagnosed with other primary neoplasms: Analysis of the SEER database

ObjectiveWe evaluated patients with history of previous malignancy to determine risk of an ensuing bladder cancer. Materials and methodsThe National Cancer Institute's Surveillance, Epidemiology, and End Results 9 registry database from 1973 to 1999 (SEER) was reviewed for patients with initial primary cancers in oral cavity and pharynx, colon and rectum, respiratory system, breast, prostate, testis, or penis. This group of patients was then examined to identify subsequent separate primary malignancies in the bladder. Comparison was made to the incidence of bladder cancer in the general population to determine a standardized incidence ratio (SIR). Additional analysis was performed based on age at diagnosis, stage, gender, race, and use of external beam radiation for treatment of initial cancer. ResultsA total of 7,289 (0.5%) of patients had a bladder cancer following their initial malignancy. Patients with prostate cancer had the largest increase in risk of bladder cancer with a SIR of 8.24, and all initial cancer groups had an elevated risk of bladder cancer relative to the general population. External beam radiation and non-White gender were associated with an increased risk of bladder cancer. Older age at diagnosis of the initial cancer correlated with a lower risk of subsequent bladder cancer. ConclusionsThis study suggests an increased risk of bladder cancer following a separate initial cancer. Lower threshold for working up those patients for bladder cancer may be warranted.

360 BLADDER CANCER PROGNOSIS IS WORSE IN THE SETTING OF PRIOR PROSTATE RADIOTHERAPY: RESULTS OF A POPULATION-BASED SEER STUDY

You have accessJournal of UrologyUrothelial Cancer: Markers + Natural History & Pathophysiology1 Apr 2011360 BLADDER CANCER PROGNOSIS IS WORSE IN THE SETTING OF PRIOR PROSTATE RADIOTHERAPY: RESULTS OF A POPULATION-BASED SEER STUDY Satyan Shah, Anthony Smith, and Charles Wiggins Satyan ShahSatyan Shah Albuquerque, NM More articles by this author , Anthony SmithAnthony Smith Albuquerque, NM More articles by this author , and Charles WigginsCharles Wiggins Albuquerque, NM More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.446AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Radiation therapy for prostate cancer is associated with an increased risk of subsequent bladder cancer. However, the natural history of radiation-induced bladder cancer is not well understood. Using SEER data, we characterized tumor grade and survival in bladder cancer patients with and without history of prior pelvic radiation therapy. METHODS The SEER database was used to identify incident bladder cancer cases between 1973–2007 meeting the following criteria: 1) male gender 2) histologically confirmed 3) active followup 4) malignant behavior and 5) age at diagnosis > 40 years. From these cases, 2 cohorts were created: 1) patients with no prior malignancy and no known radiation 2) patients with prior prostate cancer treated with definitive pelvic radiation. Because of the latency period associated with radiation-induced malignancies, the latter cohort was restricted to cases in which prostate cancer preceded bladder cancer diagnosis by more than 5 years. The 2 cohorts were compared in terms of distribution of high grade (SEER grades 3 and 4) vs. low grade (SEER grades 1 and 2) disease. In a further restricted analysis of only the high-grade cases in each cohort, we compared bladder cancer specific survival (BCSS). RESULTS A total of 110,914 cases of incident bladder cancer met the inclusion criteria. In 68,435 of these cases, bladder cancer was the only known malignancy (cohort 1). In 1,490 cases, there was a history of prior prostate cancer treated with radiation therapy (cohort 2). High-grade disease represented a larger percentage of cases in cohort 2 than cohort 1 (43% vs. 39%, p<0.001). Further analysis was restricted to the 27,166 total men with high-grade bladder cancer. The 5-year BCSS of patients with history of prior prostate cancer radiation therapy was significantly lower than patients without any prior malignancy (52% vs. 60%, p<0.001). In a multivariate Cox proportional hazards model adjusted for age, race, time period of diagnosis, and stage, patients with prior prostate cancer radiation therapy had a higher bladder cancer specific mortality with hazard ratio of 1.36 [95% CI 1.19 – 1.56]. CONCLUSIONS Radiation treatment for prostate cancer makes subsequent bladder cancer more likely to be high grade and lethal. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e146-e147 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Satyan Shah Albuquerque, NM More articles by this author Anthony Smith Albuquerque, NM More articles by this author Charles Wiggins Albuquerque, NM More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Bladder cancer after managing upper urinary tract transitional cell carcinoma: risk factors and survival

To identify independent risk factors for the development of bladder cancer after surgical management of upper urinary tract transitional cell carcinoma (UUT-TCC). Between January 1999 and December 2008, 154 patients were treated surgically for UUT-TCC at the Clinic of Urology, Clinical Center of Serbia. Patients with a previous history of bladder cancer and patients with concomitant bladder cancer were excluded from the study. In all, 92 patients were then available for evaluation. The median follow-up after surgery was 39.5 months. Univariate and multivariate analyses using the logistic regression model were performed. The intravesical disease-free rate and survival were calculated using the Kaplan-Meier method, and the log-rank test was used to determine statistical differences. In this study, 21.7% patients treated for UUT-TCC developed subsequent bladder tumors. Tumor multifocality was the only independent predictor associated with the development of subsequent bladder cancer (P = 0.028, RR = 3.52). Intravesical recurrence-free survival rates for these 92 patients at 1, 3, 5, and 7 years were 85.8, 80, 79.3, and 78.3%, respectively. Patients with tumors extending to multiple sites were significantly more likely to present subsequent intravesical recurrence (P = 0.006). The development of bladder cancer had no significant effect on the survival of patients who underwent surgical treatment of UUT-TCC, compared to patients without bladder cancer development (P = 0.660). Neither did the type of surgery mode affect patient survival (P = 0.245). This study is limited by biases associated with its retrospective design. The multiplicity of the UUT-TCC is an independent risk factor for the occurrence of bladder cancer.

Increasing Age and Treatment Modality Are Predictors for Subsequent Diagnosis of Bladder Cancer Following Prostate Cancer Diagnosis

To determine the effect of prostate cancer therapy (surgery or external beam irradiation, or both or none) on the actuarial incidence of subsequent bladder cancer. The Surveillance, Epidemiology, and End Results registry from 1973 to 2005 was analyzed. Treatment was stratified as radiotherapy, surgery, both surgery and adjuvant radiation, and neither modality. Brachytherapy was excluded. In all, 555,337 prostate carcinoma patients were identified; 124,141 patients were irradiated; 235,341 patients were treated surgically; 32,744 patients had both surgery and radiation; and 163,111 patients received neither modality. Bladder cancers were diagnosed in: 1,836 (1.48%) men who were irradiated (mean age, 69.4 years), 2,753 (1.09%) men who were treated surgically (mean age, 66.9 years); 683 (2.09%) men who received both modalities (mean age, 67.4 years), and 1,603 (0.98%) men who were treated with neither modality (mean age, 71.8 years). In each treatment cohort, Kaplan-Meier analyses showed that increasing age (by decade) was a significant predictor of developing bladder cancer (p < 0.0001). Incidence of bladder cancer was significantly different for either radiation or surgery alone versus no treatment, radiation versus surgery alone, and both surgery and radiation versus either modality alone (p < 0.0001). On multivariate analysis, age and irradiation were highly significant predictors of being diagnosed with bladder cancer. Following prostate cancer, increasing age and irradiation were highly significant predictors of being diagnosed with bladder cancer. While use of radiation increased the risk of bladder cancer compared to surgery alone or no treatment, the overall incidence of subsequent bladder cancer remained low. Routine bladder cancer surveillance is not warranted.

腎盂尿管癌の臨床的検討

We retrospectively reviewed 107 patients of upper urinary tract carcinoma to determine the overall outcome, prognostic factors, frequency of subsequent bladder cancer and role of adjuvant therapy. 107 patients of upper urinary tract carcinoma, who underwent surgical treatment at Sumitomo Hospital between January 1992 and June 2007 were reviewed. The Kaplan-Meier method and Cox's proportional hazard model were used. Five-year disease specific survival, progression free survival and bladder recurrence free rates in all patients were 88.1%, 51.2% and 64.9% respectively. Multivariate analysis revealed squamous differentiation to be the most important prognostic factor. Five-year disease specific survival in locally advanced upper urinary tract carcinoma treated with adjuvant chemoradiation was 74.0%, which was not statistically different from it without chemoradiation. Our series suggests that the adjuvant chemoradiation does not improve the outcome in patients with locally advanced upper urinary tract carcinoma.

Radiation Therapy for Prostate Cancer Increases Subsequent Risk of Bladder and Rectal Cancer: A Population Based Cohort Study

Pre-prostate specific antigen era series demonstrated an increased risk of bladder cancer and rectal cancer in men who received radiotherapy for prostate cancer. We estimated the risk of secondary bladder cancer and rectal cancer after prostate radiotherapy using a contemporary population based cohort. We identified 243,082 men in the Surveillance, Epidemiology and End Results database who underwent radical prostatectomy or radiotherapy for prostate cancer between 1988 and 2003. We estimated the incidence rate, standardized incidence ratio and age adjusted incidence rate ratio of subsequent bladder cancer and rectal cancer associated with radical prostatectomy, external beam radiotherapy, brachytherapy, and a combination of external beam radiotherapy and brachytherapy. The relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively. Compared to the general United States population the standardized incidence ratio for bladder cancer developing after radical prostatectomy, external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy was 0.99, 1.42, 1.10 and 1.39, respectively. The relative risk of rectal cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.26, 1.08 and 1.21, respectively. The standardized incidence ratio for rectal cancer developing after radical prostatectomy, external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy was 0.91, 0.99, 0.68 and 0.86, respectively. Men who receive radiotherapy for localized prostate cancer have an increased risk of bladder cancer compared to patients undergoing radical prostatectomy and compared to the general population. The risk of rectal cancer is increased in patients who receive external beam radiotherapy compared to radical prostatectomy. Patients should be counseled appropriately regarding these risks.

Is there evidence for a multidisciplinary follow-up after urological cancer? An evaluation of subsequent cancers

Follow-up after cancer treatment has been focussing on the detection of local recurrence or metastatic disease of the primary cancer. Subsequent independent malignancies arising during follow-up have not been considered as relevant. Our study evaluated the risk of independent cancers following the diagnosis of primary urological cancer. From 1990 to 1998 data from 4,119 patients with a minimum follow-up of 5 years were collected. A total of 1,835 patients had primary prostate cancer, 1,269 and 1,015 patients had primary bladder and renal cell cancer, respectively. The most common subsequent malignancies in males were prostate cancer followed by lung and colon cancer. Breast and colon cancer were the most frequently detected subsequent cancers in females. The age correlated comparison of diagnosed and expected cancer in men with primary prostate cancer revealed an increase in relative risk for bladder, kidney and rectal cancer of 3.75, 2.03 and 1.32-fold, respectively. In men with primary bladder cancer the relation for prostate, kidney and lung cancer was 4.05, 2.51 and 2.13-fold, respectively; for females the relation for kidney cancer was 4.55-fold. In men with primary kidney cancer subsequent rectal, prostate and bladder cancer showed a 4.38, 2.91 and 2.48-fold increase, respectively. These data suggest an increase in relative risk for subsequent urologic and non-urologic cancer during follow-up. Clinicians involved in oncological follow-up need to be aware of this finding. To which degree a follow-up scheme, not solely focussing on the primary urological malignancy could improve survival needs to be evaluated in further studies.

Bladder Cancer Risk Following Primary and Adjuvant External Beam Radiation for Prostate Cancer

Purpose Increased rates of secondary bladder malignancies have been reported after external beam radiation therapy (EBRT) for gynecological malignancies with relative risks of 2 to 4. This study was designed to determine if there was an increase in bladder cancer after EBRT for prostate cancer. Materials and Methods We retrospectively reviewed the Mayo Clinic Cancer Registry for patients who received EBRT for prostate cancer (1980 to 1998). Patients diagnosed with bladder cancer were identified. Comparative incidence rates were obtained from the national Surveillance, Epidemiology and End Results database. Subset analysis included patients treated with adjuvant radiation and those residing locally. Medical histories of patients with bladder cancer were reviewed. Results A total of 1,743 patients received EBRT for prostate cancer at our institution. In more than 12,353 man-years of followup no increase in bladder cancer risk was encountered. Subset analysis of men who received adjuvant radiation demonstrated that the relative risk of bladder cancer was increased but was not statistically significant. When the analysis was restricted to patients residing in the local area, the number of patients in whom subsequent bladder cancer developed was similar to Surveillance, Epidemiology and End Results rates. However, in the adjuvant radiation subset there was a statistically significant increase in subsequent bladder cancer. Patients in whom bladder cancer develops after EBRT often present with low grade disease but many have recurrence and progression. Conclusions This retrospective review suggests there is not evidence of increased risk of bladder cancer after radiation therapy, assuming unbiased followup and complete ascertainment of cases. The natural history of bladder cancer in this population does not seem to be altered by a history of radiation.

RISK FACTORS FOR INTRAVESICAL RECURRENCE FOLLOWING SURGICAL MANAGEMENT OF TRANSITIONAL CELL CARCINOMA OF THE UPPER URINARY TRACT

To identify risk factors for developing subsequent bladder cancer in patients undergoing surgical management of transitional cell carcinoma (TCC) of the upper urinary tract.This study included 177 patients who were diagnosed as having clinically localized upper urinary tract TCC and thereafter underwent nephroureterectomy after exclusion of those with a previous and/or concurrent history of bladder cancer. Univariate and multivariate analyses using both the logistic regression model and the Cox proportional hazards model were carried out in these 177 patients to determine the risk factors for intravesical recurrence after nephroureterectomy.Of the 177 patients, 63 (35.6%) developed recurrent bladder cancer after a median interval of 7.5 months. Intravesical recurrence-free survival rates for these 177 patients at 1, 3, and 5 years were 75.7%, 63.7%, and 54.1%, respectively. Univariate analyses showed that patients with low-stage tumors and those with multifocal tumors were likely to undergo subsequent intravesical recurrence; however, there was no significant impact of other factors on subsequent intravesical recurrence, including age, tumor side, tumor location, surgical modality, operation time, management of the distal ureter, tumor grade, lymph node metastasis, microvascular invasion, lymphatic invasion, and margin status. Furthermore, pathologic stage and tumor multifocality were identified as independent predictors for the development of recurrent bladder cancer by multivariate analyses.The incidence of intravesical recurrence after nephroureterectomy for upper urinary tract TCC is comparatively high. It could be important to perform careful follow-up targeting intravesical recurrence for such patients after nephroureterectomy, particularly those with low-stage tumors and/or multifocal tumors.

Bladder cancer following upper tract urothelial carcinoma

Upper tract urothelial carcinoma (UTUC) is uncommon relative to primary bladder transitional cell carcinoma, with notable differences at the genetic, molecular and clinical levels. A variety of management options with similar oncologic outcomes are available for UTUC. Regardless of upper tract treatment modality, recurrence in the bladder consistently occurs in 20–50% of patients, thus presenting a significant clinical challenge. The initial intravesical relapse typically occurs within the first 2 years following upper tract therapy, but the risk is lifelong and repeat episodes are common. The identification of variables that allow accurate risk stratification of UTUC patients with regards to future bladder relapse is crucial. Unfortunately, to date, no variables have been identified that can reliably predict such bladder recurrences. A history of bladder cancer prior to UTUC resection and upper tract tumor multifocality are frequently reported clinical risk factors. Candidate molecular markers, such as E-cadherin, also hold promise for improving patient risk stratification. The impact of bladder recurrences on patient survival is still poorly defined. The risk of progression to invasive bladder disease is not well documented but appears to be an infrequent event. This article highlights important recent observations and key current issues regarding UTUC and subsequent bladder cancer. In addition, we suggest a bladder surveillance regimen following UTUC and provide recommendations for managing patients with intravesical recurrences.

Risk Factors for Intravesical Recurrence After Surgical Management of Transitional Cell Carcinoma of the Upper Urinary Tract

To identify risk factors for developing subsequent bladder cancer in patients undergoing surgical management of transitional cell carcinoma (TCC) of the upper urinary tract. This study included 177 patients who were diagnosed as having clinically localized upper urinary tract TCC and thereafter underwent nephroureterectomy after exclusion of those with a previous and/or concurrent history of bladder cancer. Univariate and multivariate analyses using both the logistic regression model and the Cox proportional hazards model were carried out in these 177 patients to determine the risk factors for intravesical recurrence after nephroureterectomy. Of the 177 patients, 63 (35.6%) developed recurrent bladder cancer after a median interval of 7.5 months. Intravesical recurrence-free survival rates for these 177 patients at 1, 3, and 5 years were 75.7%, 63.7%, and 54.1%, respectively. Univariate analyses showed that patients with low-stage tumors and those with multifocal tumors were likely to undergo subsequent intravesical recurrence; however, there was no significant impact of other factors on subsequent intravesical recurrence, including age, tumor side, tumor location, surgical modality, operation time, management of the distal ureter, tumor grade, lymph node metastasis, microvascular invasion, lymphatic invasion, and margin status. Furthermore, pathologic stage and tumor multifocality were identified as independent predictors for the development of recurrent bladder cancer by multivariate analyses. The incidence of intravesical recurrence after nephroureterectomy for upper urinary tract TCC is comparatively high. It could be important to perform careful follow-up targeting intravesical recurrence for such patients after nephroureterectomy, particularly those with low-stage tumors and/or multifocal tumors.

A Prospective Cohort Study of Bladder Cancer Risk in Relation to Active Cigarette Smoking and Household Exposure to Secondhand Cigarette Smoke

Active cigarette smoking is a major risk factor for bladder cancer. Secondhand exposure to cigarette smoke may also contribute to bladder carcinogenesis. The authors conducted a prospective cohort study to examine the influence of both active smoking and household exposure to secondhand smoke (SHS) on subsequent bladder cancer risk. The study population included persons from two cohorts established from private censuses conducted in Washington County, Maryland, in 1963 (n = 45,749; 93 cases) and 1975 (n = 48,172; 172 cases). Poisson regression models were fitted to estimate the relative risk of bladder cancer associated with active and passive smoke exposure in the two cohorts (referent category: never smokers who did not live with any smokers). Current smokers had an elevated risk of bladder cancer in both the 1963 cohort (relative risk (RR) = 2.7, 95% confidence limits (CL): 1.6, 4.7) and the 1975 cohort (RR = 2.6, 95% CL: 1.7, 3.9) after adjustment for age, education, and marital status. Among nonsmoking women, current household SHS exposure was associated with bladder cancer risk in the 1963 cohort (RR = 2.3, 95% CL: 1.0, 5.4) but not in the 1975 cohort (RR = 0.9, 95% CL: 0.4, 2.3). This study further solidifies the evidence that active smoking is causally associated with bladder cancer. Additional studies are needed to determine whether passive smoking is a risk factor for bladder cancer.

Protective Effects of Plasma Carotenoids on the Risk of Bladder Cancer

We examined the associations between plasma micronutrients and bladder cancer risk, and evaluated the combined effects of carotenoid and cigarette smoke. We performed a case-control study in 242 patients with bladder cancer and 204 healthy controls at Memorial Sloan-Kettering Cancer Center from 1993 to 1997. Epidemiological data and blood specimens were collected on 84 cases and 173 controls. Plasma micronutrients, including lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, beta-carotene, retinol, alpha-tocopherol and gamma-tocopherol, were determined by high performance liquid chromatography. The logistic regression model was used to estimate the effects from carotenoid, tocopherol and retinol on the risk of bladder cancer. Based on quartiles of plasma micronutrient levels and continuous variables, adjusted ORs were estimated for bladder cancer after controlling for potential confounders, including patient age, sex, education and pack-years of smoking. When using plasma levels of micronutrients as continuous variables, the adjusted OR was 0.22 (95% CI 0.05 to 0.92) for alpha-carotene, 0.42 (95% CI 0.18 to 1.00) for lutein, 0.16 (95% CI 0.02 to 1.06) for zeaxanthin, 0.94 (95% CI 0.89 to 0.99) for lycopene and 0.90 (95% CI 0.81 to 1.00) for beta-cryptoxanthin. The adjusted OR for the joint effect of plasma carotenoids and tobacco smoking was 6.22 (95% CI 1.87 to 20.8) in smokers with lower lutein and 5.18 (95% CI 1.57 to 17.1) in smokers with lower zeaxanthin. Our results show protective effects of carotenoids on bladder cancer. They suggest that bladder cancer may be a preventable disease through nutritional intervention, especially in smokers.

Upper urinary tract cancer: Prognostic factors for bladder tumours development and systemic relapse

14560 Background: Transitional cell carcinomas (TCC) of the renal pelvis and ureter are relatively uncommon. An important characteristic of TCC is multifocality throughout the all urinary tract simultaneously and/or subsequently. To clarify the association between UTTCC and bladder tumors, we retrospectively analysed 86 patients with UTTCC in order to evaluate prognostic factors for recurrence and to identify risk factors for development of bladder cancers. Methods: All 86 upper tract transitional cell carcinoma patients (pts) were treated surgically between January 1988 and July 2005. Median age was 69 years (range: 34–91). We observed a male predominance (71%) and 78% of patients were heavy smokers. Forty-five (52.3%) patients had a diagnosis of bladder transitional carcinoma. The median age of this group of patients was 70 range 40–87). In fifteen cases (17%), bladder tumour occurred first than upper tract neoplasia; in 14 patients bladder and upper tract tumours were synchronous. Results: Median survival was 97 months; 49 (57%) patients are alive and 43 are disease-free. Grading, stage T, lympho-vascular invasion and squamous differentiation were significant prognostic factors for systemic relapse (p &lt; 0.05). Twenty-eight pts (32.5%) developed subsequent transitional bladder cancer after a median time of 12 months; multifocality of primitive tumours was significant predictive factor. Invasive UTTCC were less likely associated with bladder cancer. We observed that superficial bladder cancer developed more frequently in pts with well differentiated (G1–2) primitive cancer (90% of cases), without lympho-vascular invasion and with history of heavy smoke exposition. Conclusions: In our study, T, N and G confirmed to be the most important prognostic factors for systemic relapse. Lympho-vascular invasion highly predicts metastasis. Our analysis highlights that upper urinary tract cancers seem to have different history and different pattern of association with bladder tumours, according to specific prognostic factors. The development of recurrent superficial bladder cancer is more frequently associated with small well differentiated multifocal upper tract tumours.Therefore follow-up should be oriented according to these characteristics. No significant financial relationships to disclose.

Risk Factors for Subsequent Bladder Cancer Recurrence following Radical Surgery for Upper Urinary Tract Urothelial Cancer

Purpose: The purpose of this study was to determine the clinical and pathological risk factors for subsequent bladder recurrence for the patients suffering with transitional cell carcinoma in the upper urinary tract (UUT-TCC) following radical surgery, and these factors should allow more accurate prediction of the disease outcome. Materials and Methods: Between 1995 and 2004, a total of 71 patients underwent total nephroureterectomy for UUT-TCC. Patients with con- comitant or previous bladder tumor or a follow-up period of less than 1 year were excluded in this study. Univarariate and multivariate analysis by Coxs proportional hazards model was used to determine the inde- pendent risk factors for intravesical tumor recurrence. Results: Fifteen out of 71 patients (21.1%) experienced subsequent intra- vesical tumor recurrence during a mean follow-up period of 16.5 months (range: 3-28). On univariate analysis, tumor size, multiplicity, stage and grade were significantly correlated with subsequent intravesical tumor recurrence. On the multivariate analysis, tumor stage and multiplicity had a statistically significant impact on the risk of subsequent intravesical tumor recurrence. Conclusions: Tumor stage and multiplicity are important factors for subsequent intravesical tumor recurrence in the patients who suffer with UUT-TCC following surgery. Therefore, closer follow-up might necessary for patients with multiple foci and high stage UUT-TCC for the early detection of subsequent intravesical tumor recurrences. (Korean J Urol 2006;47:1035-1040) ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ

BLADDER CANCER RISK FOLLOWING PRIMARY AND ADJUVANT EXTERNAL BEAM RADIATION FOR PROSTATE CANCER

Increased rates of secondary bladder malignancies have been reported after external beam radiation therapy (EBRT) for gynecological malignancies with relative risks of 2 to 4. This study was designed to determine if there was an increase in bladder cancer after EBRT for prostate cancer. We retrospectively reviewed the Mayo Clinic Cancer Registry for patients who received EBRT for prostate cancer (1980 to 1998). Patients diagnosed with bladder cancer were identified. Comparative incidence rates were obtained from the national Surveillance, Epidemiology and End Results database. Subset analysis included patients treated with adjuvant radiation and those residing locally. Medical histories of patients with bladder cancer were reviewed. A total of 1,743 patients received EBRT for prostate cancer at our institution. In more than 12,353 man-years of followup no increase in bladder cancer risk was encountered. Subset analysis of men who received adjuvant radiation demonstrated that the relative risk of bladder cancer was increased but was not statistically significant. When the analysis was restricted to patients residing in the local area, the number of patients in whom subsequent bladder cancer developed was similar to Surveillance, Epidemiology and End Results rates. However, in the adjuvant radiation subset there was a statistically significant increase in subsequent bladder cancer. Patients in whom bladder cancer develops after EBRT often present with low grade disease but many have recurrence and progression. This retrospective review suggests there is not evidence of increased risk of bladder cancer after radiation therapy, assuming unbiased followup and complete ascertainment of cases. The natural history of bladder cancer in this population does not seem to be altered by a history of radiation.

Clinical analysis of 174 cases of primary ureteral carcinoma

To analyse the clinicopathological features and discuss the diagnosis, therapy and prognosis of primary ureteral carcinoma. One hundred and seventy four cases of primary ureteral carcinoma diagnosed pathologically between January 1971 and July 2002 in our institution were followed up and retrospectively studied. The incidence of primary ureteral carcinoma was increasing during the last 30 years. The mean age of occurrence was 63.7 years. The most useful methods of detecting tumors preoperatively were retrograde urogram, CT, magnetic resonance urography and ureteroscopy, with positive percentage of 87.8% (86/98), 96.0% (48/50), 95.8% (23/24), 87.0% (20/23) respectively. 131 (75.3%) cases underwent nephroureterectomy with a cuff of bladder. 171 (98.3%) cases were transitional cell carcinoma. T(a-2) and G(1, 2) tumors account for 70% of all respectively. The 5 year and 10 year survival rates were 53.1% (52/98) and 30.5% (18/59) respectively. The subsequent bladder cancer occurred in 38 cases (23.8%), and the subsequent contralateral ureteral carcinoma occurred in 6 cases (3.8%). The prognosis of primary ureteral carcinoma is poor. Tumor stage and grade are both the prognostic factors. Precise preoperative diagnosis and more effective adjuvant therapy may improve the prognosis.

Risk of bladder cancer following external beam radiation for prostate cancer

Abstract Introduction: Increased rates of secondary malignancies of the bladder have been reported after external beam radiation therapy (EBRT) for gynecologic malignancies with relative risks varying from 3–57. This study will determine if there is increased risk of subsequent bladder cancer for men treated with EBRT for prostate cancer from 1970–1999. Methods: We retrospectively reviewed the Mayo Clinic Cancer Registry for patients who received EBRT for prostate cancer, and isolated a cohort of patients with 10,000 man-years of follow-up after radiation. Medical histories of patients who developed subsequent bladder cancer were reviewed. Comparative cancer incidence rates were obtained from the SEER database (2000). Results: Of 3700 patients treated with EBRT for prostate cancer from 1970–1999, 806 patients (with 10,002 follow-up years) were randomly selected. 26 developed a subsequent bladder cancer. 20 sporadic cases of TCC were expected in a similarly aged population without radiation (from SEER data). Our data demonstrates the relative risk of developing a subsequent bladder cancer is 1.3 (CI 0.85–1.91) which is elevated but not statistically significant. Conclusions: This retrospective review shows the risk of bladder cancer in men who received radiation for prostate cancer is slightly higher than expected in a non-irradiated population. It is, however, lower than the risk reported in the gynecologic literature. Both radiation cystitis and bladder tumors can present with hematuria and irritative voiding. Urologists should be vigilant in evaluation of this subset of patients at increased risk for vesical neoplasms.