- Email: [email protected]
1160 SMOKING AND RISK OF UROTHELIAL CELL CARCINOMA OF THE BLADDER: RESULTS FROM A CONTEMPORARY, PROSPECTIVE COHORT STUDY
Vol. 183, No. 4, Supplement, Monday, May 31, 2010
THE JOURNAL OF UROLOGY姞
been hampered by its relatively low incidence in the population. Risk factors for the development of CaBl exist. Prediction tools that consider these risk factors are needed to estimate the risk of CaBl in the individual patient. We sought to use demographic and lifestyle information obtained from the PLCO trial to predict the risk of developing any and high-grade (HG) CaBl among PLCO participants. METHODS: 147,632 men and women aged 55-74 without a history of bladder cancer at time of randomization participated in the PLCO trial and had full baseline sociodemographic information, comorbidity data, and lifestyle information (e.g. smoking history). Cox proportional hazards regression was used to estimate the risks of any CaBl and of HG CaBl for a given risk profile. The entire cohort was randomly split into two-thirds for model development and one-third for model validation. Predictive accuracy was assessed by the concordance index statistic. RESULTS: Over a median follow-up of 9.2 years, incident bladder cancer cases were detected in 803 of 72,404 of men (277 HG BlCa) and 173 of 75,228 of women (51 HG BlCa). Among nonsmokers, the incidence of BlCa was 61.3 per 100,000 person years (py) and 14 per 100,000 py among men and women respectively. There was a 4 fold increase in incidence between the highest and lowest categories of smoking. Cox proportional hazards models on each of the two endpoints were developed based on age, gender, comorbidity, BMI, NSAID use, and smoking pack-years. Age, gender, and smoking were statistically significant predictors of cancer incidence (P ⬍ 0.05). In the test cohort, the concordance indices were 75.8% and 75.3%, for the “all CaBl” and high-grade CaBl models, respectively. CONCLUSIONS: Nomograms to predict the risk of BlCa and HG disease have been developed based on baseline patient information and smoking status. These models could be used to identify a cohort suitable for screening or chemoprevention. The risk of BlCa among non-smokers is very low and among these patients, sociodemographic factors failed to identify a high-risk population. Risk Factor White
All CaBl (ref)
Adv CaBl (ref)
African Amer
0.59*
0.88
Oth Race
0.44†
0.48
Age
1.07‡
1.07‡
Female
e449
1160 SMOKING AND RISK OF UROTHELIAL CELL CARCINOMA OF THE BLADDER: RESULTS FROM A CONTEMPORARY, PROSPECTIVE COHORT STUDY. James Hotaling*, Jonathan Wright, Michael Porter, Emily White, Seattle, WA INTRODUCTION AND OBJECTIVES: Cigarette smoking is one the leading causative factors associated with urothelial cell carcinoma of the bladder (UC). A number of case-control studies have investigated the relationship between both duration of current smoking and length of time from smoking cessation with UC. Fewer prospective cohort studies have been conducted on a contemporary population. Using a large prospective cohort, we explore the relationship between current and former smoking and risk of UC. METHODS: Participants in the VITamins And Lifestyle Study (VITAL) comprised the study population, which included 77,719 Washington State residents aged 50-76 years. Baseline self-administered questionnaires were completed in 2000-2002 on health history and cancer risk factors. Participants with prevalent UC were excluded. Incident UC cases were determined via linkage to the Surveillance, Epidemiology, and End Results (SEER) cancer registry through 2007. Smoking history was categorized as ever use (never, former, current); pack years smoked (quartiles of use for current and former smokers); and time since quitting in years (for former smokers). Multivariate cox regression was used to estimate the Hazard ratios (HR) for developing UC by smoking status controlling for age, gender and race. RESULTS: A total of 330 incident UC cases were identified. Of those without UC, 8% were current smokers and 44% were former smokers. The risk of UC was 2-fold higher (95% CI 1.5—2.6) for former smokers and 4-fold higher (95% CI 2.9 —5.8) for current smokers compared to those who never smoked. Both pack years of smoking and years since quitting were associated with the risk of developing UC (both pTrend ⬍ 0.01). Among former smokers, the 2-fold increased risk remained for all subsets of pack-years and years since quitting except for those with ⬍ 7.5 pack years of smoking. CONCLUSIONS: In a contemporary, large prospective cohort, we confirm the 2-4 fold increase risk of UC in smokers, with a dose dependent effect seen for pack years smoked. The increased risk of developing UC persisted for more than 20 years after quitting smoking. Former smokers with less than 7.5 pack-years of smoking had no increased risk of bladder cancer.
(ref)
(ref)
Male
3.80‡
5.51‡
Fam Hx Cancer
1.03
0.96
Fam Hx Blad Ca
0.81
1.41
Unk Fam Hx Blad Ca
1.08
1.03
No Comorbidities
0.80*
0.97
1161
One Comorbidity
0.97
1.00
0.25-10 pack-years
1.57†
1.33
EARLY DIAGNOSIS OF BLADDER CANCER IN HIGH-RISK POPULATIONS WITH URINE-BASED TUMOR MARKER TESTS – INTERIM DATA OF THE PROSPECTIVE STUDY UROSCREEN
10-20 pack-years
1.74†
1.78*
20-30 pack-years
2.70‡
2.94‡
30-40 pack-years
2.55‡
3.11‡
40-50 pack-years
3.08‡
3.51‡
50-60 pack-years
3.49‡
4.45‡
⬎ 60 pack-years
4.13‡
4.53‡
Use of Aspr
1.09
1.19
BMI ⬎ 30
0.97
0.91
Table 1:
Estimated relative risks for all bladder cancer and for high grade bladder cancer in Cox proportional hazards models.
* ⫽ p ⬍ 0.05, † ⫽ p ⬍ 0.01, ‡ ⫽ p ⬍ 0.0001.
Source of Funding: None
Source of Funding: None
Gerhard Feil*, Karl-Dietrich Sievert, Tu¨bingen, Germany; Michael Nasterlack, Ludwigshafen, Germany; Gabriele Leng, Leverkusen, Germany; Georg Johnen, Bochum, Germany; Se´verine Huber, Tu¨bingen, Germany; Beate Pesch, Dirk Taeger, Bochum, Germany; Bernd Scheuermann, Friedhelm Eberle, Thomas Mayer, Ludwigshafen, Germany; Heike Bontrup, Bochum, Germany; Martin Pelster, Leverkusen, Germany; Harald Wellha¨ußer, Heidelberg, Germany; Kay-Gerald Bierfreund, Christian Bayer, Christian Wiens, Leverkusen, Germany; Matthias Kluckert, Heidelberg, Germany; Thomas Bru¨ning, Bochum, Germany; Arnulf Stenzl, Tu¨bingen, Germany INTRODUCTION AND OBJECTIVES: UroScreen is a prospective study for early diagnosis of bladder cancer in 1,772 chemical workers with former exposure to aromatic amines. The aim of the study is to assess the predictive values of the urine-based tumor marker tests UroVysion, and NMP22 and of the apoptotic marker survivin for bladder cancer screening. Interim results from observations between September 2003 and September 2009 are presented.
THE JOURNAL OF UROLOGY姞
been hampered by its relatively low incidence in the population. Risk factors for the development of CaBl exist. Prediction tools that consider these risk factors are needed to estimate the risk of CaBl in the individual patient. We sought to use demographic and lifestyle information obtained from the PLCO trial to predict the risk of developing any and high-grade (HG) CaBl among PLCO participants. METHODS: 147,632 men and women aged 55-74 without a history of bladder cancer at time of randomization participated in the PLCO trial and had full baseline sociodemographic information, comorbidity data, and lifestyle information (e.g. smoking history). Cox proportional hazards regression was used to estimate the risks of any CaBl and of HG CaBl for a given risk profile. The entire cohort was randomly split into two-thirds for model development and one-third for model validation. Predictive accuracy was assessed by the concordance index statistic. RESULTS: Over a median follow-up of 9.2 years, incident bladder cancer cases were detected in 803 of 72,404 of men (277 HG BlCa) and 173 of 75,228 of women (51 HG BlCa). Among nonsmokers, the incidence of BlCa was 61.3 per 100,000 person years (py) and 14 per 100,000 py among men and women respectively. There was a 4 fold increase in incidence between the highest and lowest categories of smoking. Cox proportional hazards models on each of the two endpoints were developed based on age, gender, comorbidity, BMI, NSAID use, and smoking pack-years. Age, gender, and smoking were statistically significant predictors of cancer incidence (P ⬍ 0.05). In the test cohort, the concordance indices were 75.8% and 75.3%, for the “all CaBl” and high-grade CaBl models, respectively. CONCLUSIONS: Nomograms to predict the risk of BlCa and HG disease have been developed based on baseline patient information and smoking status. These models could be used to identify a cohort suitable for screening or chemoprevention. The risk of BlCa among non-smokers is very low and among these patients, sociodemographic factors failed to identify a high-risk population. Risk Factor White
All CaBl (ref)
Adv CaBl (ref)
African Amer
0.59*
0.88
Oth Race
0.44†
0.48
Age
1.07‡
1.07‡
Female
e449
1160 SMOKING AND RISK OF UROTHELIAL CELL CARCINOMA OF THE BLADDER: RESULTS FROM A CONTEMPORARY, PROSPECTIVE COHORT STUDY. James Hotaling*, Jonathan Wright, Michael Porter, Emily White, Seattle, WA INTRODUCTION AND OBJECTIVES: Cigarette smoking is one the leading causative factors associated with urothelial cell carcinoma of the bladder (UC). A number of case-control studies have investigated the relationship between both duration of current smoking and length of time from smoking cessation with UC. Fewer prospective cohort studies have been conducted on a contemporary population. Using a large prospective cohort, we explore the relationship between current and former smoking and risk of UC. METHODS: Participants in the VITamins And Lifestyle Study (VITAL) comprised the study population, which included 77,719 Washington State residents aged 50-76 years. Baseline self-administered questionnaires were completed in 2000-2002 on health history and cancer risk factors. Participants with prevalent UC were excluded. Incident UC cases were determined via linkage to the Surveillance, Epidemiology, and End Results (SEER) cancer registry through 2007. Smoking history was categorized as ever use (never, former, current); pack years smoked (quartiles of use for current and former smokers); and time since quitting in years (for former smokers). Multivariate cox regression was used to estimate the Hazard ratios (HR) for developing UC by smoking status controlling for age, gender and race. RESULTS: A total of 330 incident UC cases were identified. Of those without UC, 8% were current smokers and 44% were former smokers. The risk of UC was 2-fold higher (95% CI 1.5—2.6) for former smokers and 4-fold higher (95% CI 2.9 —5.8) for current smokers compared to those who never smoked. Both pack years of smoking and years since quitting were associated with the risk of developing UC (both pTrend ⬍ 0.01). Among former smokers, the 2-fold increased risk remained for all subsets of pack-years and years since quitting except for those with ⬍ 7.5 pack years of smoking. CONCLUSIONS: In a contemporary, large prospective cohort, we confirm the 2-4 fold increase risk of UC in smokers, with a dose dependent effect seen for pack years smoked. The increased risk of developing UC persisted for more than 20 years after quitting smoking. Former smokers with less than 7.5 pack-years of smoking had no increased risk of bladder cancer.
(ref)
(ref)
Male
3.80‡
5.51‡
Fam Hx Cancer
1.03
0.96
Fam Hx Blad Ca
0.81
1.41
Unk Fam Hx Blad Ca
1.08
1.03
No Comorbidities
0.80*
0.97
1161
One Comorbidity
0.97
1.00
0.25-10 pack-years
1.57†
1.33
EARLY DIAGNOSIS OF BLADDER CANCER IN HIGH-RISK POPULATIONS WITH URINE-BASED TUMOR MARKER TESTS – INTERIM DATA OF THE PROSPECTIVE STUDY UROSCREEN
10-20 pack-years
1.74†
1.78*
20-30 pack-years
2.70‡
2.94‡
30-40 pack-years
2.55‡
3.11‡
40-50 pack-years
3.08‡
3.51‡
50-60 pack-years
3.49‡
4.45‡
⬎ 60 pack-years
4.13‡
4.53‡
Use of Aspr
1.09
1.19
BMI ⬎ 30
0.97
0.91
Table 1:
Estimated relative risks for all bladder cancer and for high grade bladder cancer in Cox proportional hazards models.
* ⫽ p ⬍ 0.05, † ⫽ p ⬍ 0.01, ‡ ⫽ p ⬍ 0.0001.
Source of Funding: None
Source of Funding: None
Gerhard Feil*, Karl-Dietrich Sievert, Tu¨bingen, Germany; Michael Nasterlack, Ludwigshafen, Germany; Gabriele Leng, Leverkusen, Germany; Georg Johnen, Bochum, Germany; Se´verine Huber, Tu¨bingen, Germany; Beate Pesch, Dirk Taeger, Bochum, Germany; Bernd Scheuermann, Friedhelm Eberle, Thomas Mayer, Ludwigshafen, Germany; Heike Bontrup, Bochum, Germany; Martin Pelster, Leverkusen, Germany; Harald Wellha¨ußer, Heidelberg, Germany; Kay-Gerald Bierfreund, Christian Bayer, Christian Wiens, Leverkusen, Germany; Matthias Kluckert, Heidelberg, Germany; Thomas Bru¨ning, Bochum, Germany; Arnulf Stenzl, Tu¨bingen, Germany INTRODUCTION AND OBJECTIVES: UroScreen is a prospective study for early diagnosis of bladder cancer in 1,772 chemical workers with former exposure to aromatic amines. The aim of the study is to assess the predictive values of the urine-based tumor marker tests UroVysion, and NMP22 and of the apoptotic marker survivin for bladder cancer screening. Interim results from observations between September 2003 and September 2009 are presented.