- Email: [email protected]
PD57-01 HEMATURIA RISK INDEX - RISK OF UROTHELIAL MALIGNANCY IN PATIENTS WITH ASYMPTOMATIC MICROSCOPIC HEMATURIA
THE JOURNAL OF UROLOGYâ
e1120
CONCLUSIONS: Only a quarter of our respondents utilize FT in their practice with surgeon’s experience being the only independent predictor for utilizing FT. Majority of respondents though consider FT to be beneficial in prostate cancer management and would use it more often if provided more reliable and cost effective options. Over time, experience and accessibility to reliable methods to perform FT may lead to further utilization of this novel treatment strategy. Source of Funding: This research was funded by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research.
PD56-11 DEVELOPMENT OF CONVECTIVE WATER VAPOR ENERGY FOR TREATING LOCALIZED PROSTATE CANCER: FIRST-IN-MAN EARLY CLINICAL EXPERIENCES. Christopher Dixon*, Sleepy Hollow, NY; Ramon Rodriguez Lay, Panama City, Panama; Cesar Cabanas, Asuncion, Paraguay; Edwin Rijo, La Romana, Dominican Republic; Thayne Larson, Scottsdale, AZ INTRODUCTION AND OBJECTIVES: Earlier work has confirmed the unique thermodynamic properties of phase-change convective radiofrequency (RF) ablation using water vapor (steam) to conform to the anatomical zones of the prostate. The objective of this study was to assess in vivo treatment of prostate cancer and the early clinical effects using convective RF water vapor. METHODS: A total of 20 patients have been treated at 2 centers using the Reviv System and 6 have completed 6 month follow up biopsy. All patients had clinically localized prostate cancer as determined by biopsy, DRE, PSA and prostate MRI (non mp3). Treatment was performed using a urethral cooling catheter and a transperineal, ultrasound guided approach for needle placement and water vapor delivery. Several doses of thermal energy were tested depending on prostate size. Follow-up monitoring included serial, gadolinium enhanced MRIs performed preprocedure and at 1 week, 1, 3, and 6 months post-procedure and a surveillance biopsy at 6 months post-procedure. Standard AE reporting was used to evaluate clinical outcomes. RESULTS: 20 patients have been treated. 11 patients underwent hemiablation, 6 whole gland ablation (3 staged), 2 unilateral PZ treatment and 1 hemiablation with contralateral PZ ablation. Serial MRIs confirmed tissue ablation in all patients. Ablation was seen to the prostatic apex, capsular boundaries and the anterior zones of the prostate. Six-month surveillance biopsies have been completed on 6 patients. Four had completely negative biopsies for cancer and two had positive biopsies that were in untreated zones. Catheterization and adverse events will be reviewed. There has been no incontinence, bladder neck contractures or rectal injuries. CONCLUSIONS: The zonal anatomy of the prostate is ideal for phase change convective RF ablation using water vapor. The thermodynamics and physical principles validated by MRI indicate that effective ablation can be safely delivered anywhere in the prostate including the apex, capsular margins and anterior prostate. Partial, focal, zonal or whole gland ablation can be performed. These early and limited data confirm that effective tissue ablation to all areas of the prostate is feasible using convective thermal water vapor. Source of Funding: NxThera Inc. Maple Grove, Minnesota, USA
PD56-12 SURVEY OF ABDOMINAL ACCESS AND ASSOCIATED MORBIDITY FOR ROBOT-ASSISTED RADICAL PROSTATECTOMY (RARP)- DOES PALMER’S POINT WARRANT FURTHER AWARENESS AND STUDY? William K Johnston III*, Northville, MI; David Miller, Susan Linsell, Khurshid Ghani, Ann Arbor, MI
Vol. 197, No. 4S, Supplement, Monday, May 15, 2017
INTRODUCTION AND OBJECTIVES: Laparoscopic access for RARP is often initiated in the peri-umbilical location. Palmer’s Point, located in the left upper quadrant, has been reported as an alternative access site for pelvic laparoscopy to reduce morbidity, but not widely reported among urologists. Furthermore, there are no published articles specifically addressing vascular injuries during RARP access within the literature. To better understand surgeons’ preferences for access and its associated morbidity during RARP, we surveyed surgeons from two urological organizations. METHODS: An anonymous online questionnaire (Survey Monkey) consisting of 17 questions that assessed training, experience, and preferences for RARP was emailed in December 2014 and collected until February 2015 to members performing RARP of the Endourology Society (ES) and the Michigan Urological Society Improvement Collaborative (MUSIC). Surgeons were also asked to share their personal experience with a vascular event or bowel injury during RARP. RESULTS: Questionnaires were answered by 111 surgeons in total (ES, n¼71 and MUSIC, n¼40) with an estimated total response rate of 5.5% In total, 77% reported prior experience with the Veress needle method before exposure to RARP and 71% of respondents primarily use the Veress needle for RARP, with 73% reporting access primarily at the peri-umbilical location. A personal experience with a vascular or a bowel injury during veress needle insertion was reported in 18% and 9% of surgeons, respectively; furthermore 26% of respondents were personally aware of at least 1 death or life-threatening event among colleagues (5% reported 3 or more). The majority (56%) of respondents were unaware of Palmer’s Point, while among the minority aware of Palmer’s Point, only 33% reported ever using this location. CONCLUSIONS: In this survey, surgeons most commonly access the abdomen at the peri-umbilical location with a Veress needle for RARP with the majority not aware or utilizing Palmer’s Point. Nearly 1 in 5 surgeons reported a personal experience with a vascular injury and over 1 in 4 reported a death or life-threatning injury among colleagues during access for RARP. Palmer’s Point, located away from major vasculature, may reduce the morbidity of access for RARP and warrants further awareness and study, Source of Funding: None
Bladder Cancer: Epidemiology & Evaluation III Podium 57 Monday, May 15, 2017
1:00 PM-3:00 PM
PD57-01 HEMATURIA RISK INDEX - RISK OF UROTHELIAL MALIGNANCY IN PATIENTS WITH ASYMPTOMATIC MICROSCOPIC HEMATURIA Ronald Loo*, Casey Ng, Jeff Slezak, Steven Jacobsen, Pasadena, CA INTRODUCTION AND OBJECTIVES: To determine the incidence and predictors for malignancy in patients who undergo workup for microscopic hematuria. METHODS: We conducted a prospective cohort study of patients undergoing evaluation for asymptomatic microscopic hematuria from January 2009 to July 2016 in an integrated managed care organization in Southern California. Patients’ accompanying diagnoses and baseline cohort characteristics were determined and identified using our comprehensive electronic health record system. Cancers indicated in the workup were validated by chart review. Additional cancers documented in the institutional cancer registry through July 2015 were included if diagnosed within 1 year of initial workup. Bivariate associations were assessed using the chi-square test; multivariable logistic
THE JOURNAL OF UROLOGYâ
Vol. 197, No. 4S, Supplement, Monday, May 15, 2017
e1121
regression was used to build a predictive risk model and create a hematuria risk index. RESULTS: Within a cohort of 6417 patients with microscopic hematuria, a total of 177 (2.8%) were diagnosed with a neoplasm. On multivariate analysis, age between 50-59 (OR¼1.96, 2 points), age over 60 (OR¼5.21, 4 points), history of gross hematuria (OR¼3.15, 3 points), current or past smoking history (OR¼1.51, 1 point), male gender (OR¼2.57, 2 points), >25 red blood cell per high power field (OR¼2.94, 2 points), Non-Hispanic Black (OR¼1.73, 1 point), and Non-Hispanic White (OR¼2.31, 2 points) were all significant predictors of malignancy. A modified Hematuria Risk Index (0 to 14 points) was developed from these factors, which demonstrated an improved area under the receiver operating characteristic curve of 0.841 compared to our previous model at 0.807. We observed natural breaks in the scores that grouped the patients into low (0-4 points, 41.7%), moderate (5-9 points, 49.0%), and high-risk of cancer (10-14 points, 9.2%). Malignancy was found in 0.4%, 2.5% and 15.0% of patients from the low, moderate and high-risk groups, respectively. CONCLUSIONS: Advance age, history of gross hematuria, current or past smoking history, male gender, >25 red blood cell per high power field, and certain ethnic groups are significant predictors for malignancy in the setting of microscopic hematuria. Classification of patients into low, moderate and high-risk groups will improve patient counseling and will hopefully reduce the need for invasive endoscopy and ionizing radiation exposure for patients within the low-risk category. Source of Funding: none
PD57-02 CHARACTERIZATION OF UROTHELIAL CANCER CIRCULATING TUMOR CELLS WITH A NOVEL SELECTION-FREE METHOD Heather Chalfin*, Max Kates, Emma van der Toom, Stephanie Glavaris, James Verdone, Noah Hahn, Kenneth Pienta, Michael Gorin, Trinity Bivalacqua, Baltimore, MD INTRODUCTION AND OBJECTIVES: The majority of work performed to date investigating circulating tumor cells (CTCs) as biomarkers of urothelial carcinoma (UC) has utilized the CellSearch test (Jansen Diagnostics, Raritan, NJ). One factor limiting the sensitivity of this assay is its reliance on positive selection of CTCs expressing the cell surface protein EpCAM. In this study, we used a novel selectionfree method to enumerate and characterize CTCs in patients with UC across a range of stages. METHODS: Blood samples from 38 patients (9 controls, 8 with non-muscle invasive bladder cancer [NMIBC], 12 with muscle-invasive bladder cancer [MIBC] and 9 with metastatic UC) were processed with the AccuCyte-CyteFinder system (RareCyte, Inc., Seattle, WA). Slides were stained for the white blood cell (WBC) markers CD45 and CD66b, and the epithelial markers EpCAM and pan-cytokeratin (CK). CTCs were defined as nucleated cells positive for CK but negative for the WBC markers. Separately, the more restrictive CellSearch definition was also applied, with the additional requirement of EpCAM positivity. The Kruskal-Wallis ANOVA test was used to compare CTC counts between cancer stage groups. RESULTS: CTCs were detected in 2/8 (25%) patients with NMIBC, 7/12 (58%) with MIBC, and 6/9 (67%) with metastatic disease. No CTCs were found in any control. Comparing CTC counts between groups, the only statistically significant comparison was between controls and patients with metastatic UC (p¼0.009, Fig 1A). Using EpCAM positivity as a requirement for defining a CTC, no CTCs were detected in any patient with NMIBC, and only 2 (17%) patients with MIBC (Fig 1B). CTCs tended to be larger in patients with metastatic UC (Fig 2). CONCLUSIONS: CTCs were detected at all UC stages and exhibited phenotypic diversity for cell size and EpCAM expression. EpCAM negative CTCs that would be missed with the CellSearch test were detected in patients with NMIBC and MIBC.
Source of Funding: This work is supported by NCI grant nos. U54CA143803, CA163124, CA093900, CA143055 to K.J.P as well as the Prostate Cancer Foundation, the Patrick C. Walsh Fund, and a gift from the Stutt family. E.E.vdT is supported by the Cure for Cancer Foundation. H.J.C. is supported by the Urology Care Foundation’s Resident Research Award. T.J.B. received funding from the Greenberg bladder cancer institute.
PD57-03 ASSESSMENT OF THE ECOLOGICAL ASSOCIATION BETWEEN TOBACCO SMOKING EXPOSURE AND BLADDER CANCER INCIDENCE OVER THE PAST HALF-CENTURY IN THE UNITED STATES Thomas Seisen*, Stuart R. Lipsitz, Joaquim Bellmunt, Boston, MA; Mani Menon, Detroit, MI; Nicolas von Landenberg, Philipp Gild, Boston, ^ t, Paris, France; Toni K. Choueiri, Quoc-Dien Trinh, MA; Morgan Roupre Maxine Sun, Boston, MA INTRODUCTION AND OBJECTIVES: Tobacco smoking is recognized as the most established risk factor for bladder cancer. As such, we aimed to assess the ecological association between tobacco smoking prevalence and bladder cancer incidence in the US over the past half-century, and to contrast it with that observed for lung cancer, which represents the most established tobacco-related malignancy. METHODS: The annual overall tobacco smoking prevalence rates were extracted from the Report of the Surgeon General (19501978) and the Center for Disease Control website for the years 19531983. The overall age-adjusted incidence rates of bladder and lung cancers were derived from the Surveillance, Epidemiology, and End Results database for the years 1983-2013 (30-year time-lag). All analyses were stratified according to gender. Weighted least square regression models were used to assess the bladder and lung cancer incidence rate differences (IRD) and the proportion of changes in incidence of each malignancy related to tobacco smoking prevalence variations. Additional comparisons between the associations of tobacco smoking prevalence with bladder vs. lung cancer incidence rates were performed using a Wald test. RESULTS: The associations between tobacco smoking prevalence and bladder cancer incidence were not significant in the overall (IRD¼+0.04; 95%CI: from -0.14 to +0.22; P¼0.631), men (IRD¼+0.07;
e1120
CONCLUSIONS: Only a quarter of our respondents utilize FT in their practice with surgeon’s experience being the only independent predictor for utilizing FT. Majority of respondents though consider FT to be beneficial in prostate cancer management and would use it more often if provided more reliable and cost effective options. Over time, experience and accessibility to reliable methods to perform FT may lead to further utilization of this novel treatment strategy. Source of Funding: This research was funded by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research.
PD56-11 DEVELOPMENT OF CONVECTIVE WATER VAPOR ENERGY FOR TREATING LOCALIZED PROSTATE CANCER: FIRST-IN-MAN EARLY CLINICAL EXPERIENCES. Christopher Dixon*, Sleepy Hollow, NY; Ramon Rodriguez Lay, Panama City, Panama; Cesar Cabanas, Asuncion, Paraguay; Edwin Rijo, La Romana, Dominican Republic; Thayne Larson, Scottsdale, AZ INTRODUCTION AND OBJECTIVES: Earlier work has confirmed the unique thermodynamic properties of phase-change convective radiofrequency (RF) ablation using water vapor (steam) to conform to the anatomical zones of the prostate. The objective of this study was to assess in vivo treatment of prostate cancer and the early clinical effects using convective RF water vapor. METHODS: A total of 20 patients have been treated at 2 centers using the Reviv System and 6 have completed 6 month follow up biopsy. All patients had clinically localized prostate cancer as determined by biopsy, DRE, PSA and prostate MRI (non mp3). Treatment was performed using a urethral cooling catheter and a transperineal, ultrasound guided approach for needle placement and water vapor delivery. Several doses of thermal energy were tested depending on prostate size. Follow-up monitoring included serial, gadolinium enhanced MRIs performed preprocedure and at 1 week, 1, 3, and 6 months post-procedure and a surveillance biopsy at 6 months post-procedure. Standard AE reporting was used to evaluate clinical outcomes. RESULTS: 20 patients have been treated. 11 patients underwent hemiablation, 6 whole gland ablation (3 staged), 2 unilateral PZ treatment and 1 hemiablation with contralateral PZ ablation. Serial MRIs confirmed tissue ablation in all patients. Ablation was seen to the prostatic apex, capsular boundaries and the anterior zones of the prostate. Six-month surveillance biopsies have been completed on 6 patients. Four had completely negative biopsies for cancer and two had positive biopsies that were in untreated zones. Catheterization and adverse events will be reviewed. There has been no incontinence, bladder neck contractures or rectal injuries. CONCLUSIONS: The zonal anatomy of the prostate is ideal for phase change convective RF ablation using water vapor. The thermodynamics and physical principles validated by MRI indicate that effective ablation can be safely delivered anywhere in the prostate including the apex, capsular margins and anterior prostate. Partial, focal, zonal or whole gland ablation can be performed. These early and limited data confirm that effective tissue ablation to all areas of the prostate is feasible using convective thermal water vapor. Source of Funding: NxThera Inc. Maple Grove, Minnesota, USA
PD56-12 SURVEY OF ABDOMINAL ACCESS AND ASSOCIATED MORBIDITY FOR ROBOT-ASSISTED RADICAL PROSTATECTOMY (RARP)- DOES PALMER’S POINT WARRANT FURTHER AWARENESS AND STUDY? William K Johnston III*, Northville, MI; David Miller, Susan Linsell, Khurshid Ghani, Ann Arbor, MI
Vol. 197, No. 4S, Supplement, Monday, May 15, 2017
INTRODUCTION AND OBJECTIVES: Laparoscopic access for RARP is often initiated in the peri-umbilical location. Palmer’s Point, located in the left upper quadrant, has been reported as an alternative access site for pelvic laparoscopy to reduce morbidity, but not widely reported among urologists. Furthermore, there are no published articles specifically addressing vascular injuries during RARP access within the literature. To better understand surgeons’ preferences for access and its associated morbidity during RARP, we surveyed surgeons from two urological organizations. METHODS: An anonymous online questionnaire (Survey Monkey) consisting of 17 questions that assessed training, experience, and preferences for RARP was emailed in December 2014 and collected until February 2015 to members performing RARP of the Endourology Society (ES) and the Michigan Urological Society Improvement Collaborative (MUSIC). Surgeons were also asked to share their personal experience with a vascular event or bowel injury during RARP. RESULTS: Questionnaires were answered by 111 surgeons in total (ES, n¼71 and MUSIC, n¼40) with an estimated total response rate of 5.5% In total, 77% reported prior experience with the Veress needle method before exposure to RARP and 71% of respondents primarily use the Veress needle for RARP, with 73% reporting access primarily at the peri-umbilical location. A personal experience with a vascular or a bowel injury during veress needle insertion was reported in 18% and 9% of surgeons, respectively; furthermore 26% of respondents were personally aware of at least 1 death or life-threatening event among colleagues (5% reported 3 or more). The majority (56%) of respondents were unaware of Palmer’s Point, while among the minority aware of Palmer’s Point, only 33% reported ever using this location. CONCLUSIONS: In this survey, surgeons most commonly access the abdomen at the peri-umbilical location with a Veress needle for RARP with the majority not aware or utilizing Palmer’s Point. Nearly 1 in 5 surgeons reported a personal experience with a vascular injury and over 1 in 4 reported a death or life-threatning injury among colleagues during access for RARP. Palmer’s Point, located away from major vasculature, may reduce the morbidity of access for RARP and warrants further awareness and study, Source of Funding: None
Bladder Cancer: Epidemiology & Evaluation III Podium 57 Monday, May 15, 2017
1:00 PM-3:00 PM
PD57-01 HEMATURIA RISK INDEX - RISK OF UROTHELIAL MALIGNANCY IN PATIENTS WITH ASYMPTOMATIC MICROSCOPIC HEMATURIA Ronald Loo*, Casey Ng, Jeff Slezak, Steven Jacobsen, Pasadena, CA INTRODUCTION AND OBJECTIVES: To determine the incidence and predictors for malignancy in patients who undergo workup for microscopic hematuria. METHODS: We conducted a prospective cohort study of patients undergoing evaluation for asymptomatic microscopic hematuria from January 2009 to July 2016 in an integrated managed care organization in Southern California. Patients’ accompanying diagnoses and baseline cohort characteristics were determined and identified using our comprehensive electronic health record system. Cancers indicated in the workup were validated by chart review. Additional cancers documented in the institutional cancer registry through July 2015 were included if diagnosed within 1 year of initial workup. Bivariate associations were assessed using the chi-square test; multivariable logistic
THE JOURNAL OF UROLOGYâ
Vol. 197, No. 4S, Supplement, Monday, May 15, 2017
e1121
regression was used to build a predictive risk model and create a hematuria risk index. RESULTS: Within a cohort of 6417 patients with microscopic hematuria, a total of 177 (2.8%) were diagnosed with a neoplasm. On multivariate analysis, age between 50-59 (OR¼1.96, 2 points), age over 60 (OR¼5.21, 4 points), history of gross hematuria (OR¼3.15, 3 points), current or past smoking history (OR¼1.51, 1 point), male gender (OR¼2.57, 2 points), >25 red blood cell per high power field (OR¼2.94, 2 points), Non-Hispanic Black (OR¼1.73, 1 point), and Non-Hispanic White (OR¼2.31, 2 points) were all significant predictors of malignancy. A modified Hematuria Risk Index (0 to 14 points) was developed from these factors, which demonstrated an improved area under the receiver operating characteristic curve of 0.841 compared to our previous model at 0.807. We observed natural breaks in the scores that grouped the patients into low (0-4 points, 41.7%), moderate (5-9 points, 49.0%), and high-risk of cancer (10-14 points, 9.2%). Malignancy was found in 0.4%, 2.5% and 15.0% of patients from the low, moderate and high-risk groups, respectively. CONCLUSIONS: Advance age, history of gross hematuria, current or past smoking history, male gender, >25 red blood cell per high power field, and certain ethnic groups are significant predictors for malignancy in the setting of microscopic hematuria. Classification of patients into low, moderate and high-risk groups will improve patient counseling and will hopefully reduce the need for invasive endoscopy and ionizing radiation exposure for patients within the low-risk category. Source of Funding: none
PD57-02 CHARACTERIZATION OF UROTHELIAL CANCER CIRCULATING TUMOR CELLS WITH A NOVEL SELECTION-FREE METHOD Heather Chalfin*, Max Kates, Emma van der Toom, Stephanie Glavaris, James Verdone, Noah Hahn, Kenneth Pienta, Michael Gorin, Trinity Bivalacqua, Baltimore, MD INTRODUCTION AND OBJECTIVES: The majority of work performed to date investigating circulating tumor cells (CTCs) as biomarkers of urothelial carcinoma (UC) has utilized the CellSearch test (Jansen Diagnostics, Raritan, NJ). One factor limiting the sensitivity of this assay is its reliance on positive selection of CTCs expressing the cell surface protein EpCAM. In this study, we used a novel selectionfree method to enumerate and characterize CTCs in patients with UC across a range of stages. METHODS: Blood samples from 38 patients (9 controls, 8 with non-muscle invasive bladder cancer [NMIBC], 12 with muscle-invasive bladder cancer [MIBC] and 9 with metastatic UC) were processed with the AccuCyte-CyteFinder system (RareCyte, Inc., Seattle, WA). Slides were stained for the white blood cell (WBC) markers CD45 and CD66b, and the epithelial markers EpCAM and pan-cytokeratin (CK). CTCs were defined as nucleated cells positive for CK but negative for the WBC markers. Separately, the more restrictive CellSearch definition was also applied, with the additional requirement of EpCAM positivity. The Kruskal-Wallis ANOVA test was used to compare CTC counts between cancer stage groups. RESULTS: CTCs were detected in 2/8 (25%) patients with NMIBC, 7/12 (58%) with MIBC, and 6/9 (67%) with metastatic disease. No CTCs were found in any control. Comparing CTC counts between groups, the only statistically significant comparison was between controls and patients with metastatic UC (p¼0.009, Fig 1A). Using EpCAM positivity as a requirement for defining a CTC, no CTCs were detected in any patient with NMIBC, and only 2 (17%) patients with MIBC (Fig 1B). CTCs tended to be larger in patients with metastatic UC (Fig 2). CONCLUSIONS: CTCs were detected at all UC stages and exhibited phenotypic diversity for cell size and EpCAM expression. EpCAM negative CTCs that would be missed with the CellSearch test were detected in patients with NMIBC and MIBC.
Source of Funding: This work is supported by NCI grant nos. U54CA143803, CA163124, CA093900, CA143055 to K.J.P as well as the Prostate Cancer Foundation, the Patrick C. Walsh Fund, and a gift from the Stutt family. E.E.vdT is supported by the Cure for Cancer Foundation. H.J.C. is supported by the Urology Care Foundation’s Resident Research Award. T.J.B. received funding from the Greenberg bladder cancer institute.
PD57-03 ASSESSMENT OF THE ECOLOGICAL ASSOCIATION BETWEEN TOBACCO SMOKING EXPOSURE AND BLADDER CANCER INCIDENCE OVER THE PAST HALF-CENTURY IN THE UNITED STATES Thomas Seisen*, Stuart R. Lipsitz, Joaquim Bellmunt, Boston, MA; Mani Menon, Detroit, MI; Nicolas von Landenberg, Philipp Gild, Boston, ^ t, Paris, France; Toni K. Choueiri, Quoc-Dien Trinh, MA; Morgan Roupre Maxine Sun, Boston, MA INTRODUCTION AND OBJECTIVES: Tobacco smoking is recognized as the most established risk factor for bladder cancer. As such, we aimed to assess the ecological association between tobacco smoking prevalence and bladder cancer incidence in the US over the past half-century, and to contrast it with that observed for lung cancer, which represents the most established tobacco-related malignancy. METHODS: The annual overall tobacco smoking prevalence rates were extracted from the Report of the Surgeon General (19501978) and the Center for Disease Control website for the years 19531983. The overall age-adjusted incidence rates of bladder and lung cancers were derived from the Surveillance, Epidemiology, and End Results database for the years 1983-2013 (30-year time-lag). All analyses were stratified according to gender. Weighted least square regression models were used to assess the bladder and lung cancer incidence rate differences (IRD) and the proportion of changes in incidence of each malignancy related to tobacco smoking prevalence variations. Additional comparisons between the associations of tobacco smoking prevalence with bladder vs. lung cancer incidence rates were performed using a Wald test. RESULTS: The associations between tobacco smoking prevalence and bladder cancer incidence were not significant in the overall (IRD¼+0.04; 95%CI: from -0.14 to +0.22; P¼0.631), men (IRD¼+0.07;