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Origins of the gender disparity in bladder cancer risk: a SEER analysis

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Origins of the gender disparity in bladder cancer risk: a SEER analysis

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Content ORIGINS OF THE GENDER DISPARITY IN BLADDER CANCER RISK:
A SEER ANALYSIS
by
Sichen Zhou
A Thesis Presented to the
FACULTY OF THE USC KECK SCHOOL OF MEDICINE
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(APPLIED BIOSTATISTICS AND EPIDEMIOLOGY)
August 2024
Copyright 2024 Sichen Zhou

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Acknowledgements
I would like to express my deepest gratitude to my committee chair and members, Dr.
Victoria Cortessis, Dr. Wendy Mack, and Dr. Anishka D’souza. Thank you for your invaluable
guidance, patience, and discipline throughout the process of completing this thesis. Your passion,
expertise, and insights have and will always inspire me to think critically and approach
challenges with curiosity and determination. I would also like to thank my professors and peers
for their inspiration and friendship that made my journey at USC truly incredible. Above all, I
would like to thank my parents for their unconditional love and support. Although we lived in
completely opposite time-zones, you have always been there to rid me of all doubts and provide
with me strength as I become who I am today. I miss you and I love you.

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Table of Contents
Acknowledgements.........................................................................................................................ii
List of Tables..................................................................................................................................iv
List of Figures..................................................................................................................................v
Abstract...........................................................................................................................................vi
Chapter 1: Introduction ...................................................................................................................1
Chapter 2: Methods .........................................................................................................................3
Data Source ...................................................................................................................3
Definition.......................................................................................................................3
Statistical Analysis.........................................................................................................5
Chapter 3: Results ...........................................................................................................................7
Overview .......................................................................................................................7
Covariates......................................................................................................................8
Temporal Trends..........................................................................................................11
Chapter 4: Discussion....................................................................................................................13
References......................................................................................................................................38

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List of Tables
Table 1. Incident Bladder Cancer of Any Histotype Diagnosed at Each Subsite and in the
Entire Bladder according to Demographic Factors, All Participants and Individual
Racial/Ethnic Groups, SEER+NPCR Reporting Area excluding North Dakota and
Wisconsin, 2001-2020...................................................................................................................18
Table 2. Incident Urothelial Carcinoma, Squamous Cell Carcinoma, Adenocarcinoma and
Small Cell Carcinoma of the Urinary Bladder Diagnosed at Specific Subsite and Entire
Bladder according to Age and Sex among all Participants, SEER+NPCR Reporting Area
excluding North Dakota and Wisconsin, 2001-2020 ....................................................................20
Table 3. Incident Bladder Cancer of Any Histotype Diagnosed at Each Subsite and in the
Entire Bladder according to Demographic Factors, All Participants and Individual
Racial/Ethnic Groups, SEER+NPCR Reporting Area excluding North Dakota and
Wisconsin, 2001-2020 ..................................................................................................................22
Table 4. Incident Urothelial Carcinoma Diagnosed at Specific Subsites and within the Entire
Bladder according to Demographic Factors, SEER+NPCR Reporting Area excluding North
Dakota and Wisconsin, 2001-2020................................................................................................26
Table 5. Incident Squamous Cell Carcinoma Diagnosed at Specific Subsites and within the
Entire Bladder according to Demographic Factors, SEER+NPCR Reporting Area excluding
North Dakota and Wisconsin, 2001-2020......................................................................................29
Table 6. Incident Adenocarcinoma Diagnosed at Specific Subsites and within the Entire
Bladder according to Demographic Factors, SEER+NPCR Reporting Area excluding North
Dakota and Wisconsin, 2001-2020................................................................................................32
Table 7. Incident Small Cell Carcinoma Diagnosed at Specific Subsites and within the Entire
Bladder according to Demographic Factors, SEER+NPCR Reporting Area excluding North
Dakota and Wisconsin, 2001-2020................................................................................................35

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List of Figures
Figure 1. Bladder Anatomy and ICD-O-3......................................................................................3
Figure 2. Age-Specific Incidence Rates (ASIR) of Bladder Cancer of Any Histotype
According to Bladder Subsite in Males (A) and Females (B) and Corresponding Ratios
of ASIR in Males to ASIR in Females (C); SEER+NPCR Reporting Area excluding North
Dakota and Wisconsin, 2001-2020..................................................................................................9
Figure 3. Incidence Rate Ratio Between Males and Females (IRRsex) Adjusted by Age
(A) and Relative Excess Risk due to Interaction Between older age and male sex
(RERIage-sex) (B) for all Histotypes Over the Progression Renal Pelvis, Ureter, Ureteric
Orifice, Body of Bladder, and Bladder Neck, Including the Entire Bladder and the
Urethra...........................................................................................................................................10
Figure 4. Age-Adjusted Incident Rate (AAIR) of Bladder Cancer of Any Histotype.
According to Subsite in Males (A) and Females (B) and Corresponding Incidence Rate
Ratio (IRR) between males and females (C); SEER+NPCR Reporting Area excluding
North Dakota and Wisconsin, every 5 years from 2001-2020.......................................................12

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Abstract
Background: Bladder cancer is one of the most prevalent cancers worldwide, and accounts for
approximately 80,000 incident malignancies in the US annually. Despite the urinary bladder
serving the same function in males and females, the incidence of bladder cancer is three to four
times greater in men than in women. This disparity remains unexplained even after considering
major demonstrated risk factors such as the history of tobacco smoking and occupational
exposures. We hypothesize that a significant proportion of the male excess in bladder cancer risk
is caused by urine retention due to benign prostatic hyperplasia (BPH). The combination of male
sex and older age serves as a proxy measure of BPH, which is not captured in cancer registry
data. Thus, the hypothesis anticipates that joint influences of these factors will result in a greaterthan-additive increase in bladder cancer incidence, especially in cancer diagnosed in regions of
the bladder subject to greater retention of urine.
Objective: This study characterized influences of year of diagnosis, biological sex, and age on
bladder cancer incidence according to race/ethnicity of participants and both histological type
and anatomical subsite of primary tumors diagnosed in the United States from 2001 to 2020.
Methods: Age-adjusted incidence rates (AAIRs), age-specific incidence rates (ASIRs), and
annual percent change (APC) were obtained using the Surveillance, Epidemiology, and End
Results (SEER) and the National Program of Cancer Registries (NPCR) combined datasets from
2001-2020. Multivariate negative binomial regression models were used to calculate point and
95% confidence interval (CI) estimates of incidence rate ratios (IRR) and relative excess risk due
to age-sex interaction (RERI) for all bladder cancer and for urothelial carcinoma, squamous cell
carcinoma, adenocarcinoma, and small cell carcinoma diagnosed within the entire bladder and at
individual subsites.

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Results: In both males and females, the AAIR per 100,000 person-years at risk was highest in
the body of the bladder (male: 32.44, 95% CI: 32.37, 32.50; female: 7.97, 95% CI:7.94, 8.00)
and lowest in the urethra (male: 0.23, 95%CI: 0.22, 0.23; female: 0.068, 95% CI: 0.065, 0.07). In
all racial/ethnic groups, ASIRs were greater at each successive age group and for males
compared to females. Bladder cancer incidence decreased somewhat between 2001 and 2020
(APC: -1.18, 95%CI: 0.22, 0.23). The IRRsex quantifies the ratio of incidence in males versus
females, accounting for age. Among all participants, we estimated the IRRsex for bladder cancer
of all histotypes at all subsites to be 3.51 (95%CI: 2.83, 4.36), indicating over three-fold risk in
males. We found IRRsex to be highest for tumors in the bladder neck (5.53, 95% CI: 4.42, 6.93),
followed by the body of the bladder (3.75, 95% CI: 3.00, 4.70), ureteric orifice (3.02, 95% CI:
2.13, 4.28), ureter (1.89, 95% CI: 1.51, 2.35), and renal pelvis (1.86, 95% CI: 1.56, 2.20). While
Non-Hispanic White participants had the highest incidence, clear IRRsex patterns of male excess
were evident in all racial/ethnic groups. Among histotypes, estimates of IRRsex varied most
between subsites for urothelial carcinoma; estimates of IRRsex differed less between subsites for
squamous cell carcinoma, adenocarcinoma, and small cell carcinoma. Values of the RERIagesex >0 identify a greater-than-additive influence of older age (>60 years) and male sex on bladder
cancer incidence. All calculable estimates of the RERIage-sex were substantially elevated, and
among all participants the estimate of the RERIage-sex for all bladder cancer diagnosed at all
subsites was 17.47 (95%CI: 7.40, 27.54).
Conclusion: Joint effects of male sex and older age on urothelial carcinoma incidence are far
greater than additive, and departures from additivity are larger for anatomic subsites of the
bladder expected to be in greatest contact with retained urine (i.e., the bladder neck and the body
of the bladder). These results accord with the possibility that a biologically and clinically

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significant portion of the male excess of bladder cancer is caused by retention of urine following
the development of BPH. Future research should evaluate the association between the risk of
bladder cancer and BPH directly.

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Chapter 1: Introduction
Bladder cancer represents a significant global health challenge with substantial incidence
and mortality rates. In 2020, bladder cancer was among the ten most common cancers worldwide
(Sung et al., 2021) and accounted for more than 80,000 new cases each year in the U.S. (Fang et
al., 2020). The urinary bladder is a hollow, muscular organ in the pelvic cavity that temporarily
stores urine drained from the kidneys until urination. It is lined by specialized urothelial cells,
which are constantly exposed to bladder carcinogens such as arylamine compounds (Yu et al.,
2002) contained in the urine. Over 90% of bladder cancer cases arise from these urothelial cells
(Saginala et al., 2020). This histotype of bladder cancer is referred to as urothelial carcinoma, or
transitional cell carcinoma. Squamous cell carcinoma, adenocarcinoma, small cell carcinoma,
and other minor variant subtypes account for most of the remaining cases.
Previous studies have shown that male sex, older age, non-Hispanic white race/ethnicity,
history of cigarette smoking, occupational exposure to certain chemicals, and a few genetic
susceptibility variants are major risk factors for bladder cancer (Fang et al., 2020; Sung et al.,
2021; Jubber et al., 2023). The risk of bladder cancer is elevated for older individuals, and agerelated risk rises notably at age over 50 years. Bladder cancer diagnosis is three to four times
higher in men than women. Non-Hispanic whites bear the highest burden of disease while nonHispanic Asians have the lowest incidence rates. The annual age-adjusted incidence rates of
bladder cancer in the US have been declining, potentially due to reduced smoking rates and
stringent workplace regulations (Jubber et al., 2023). Smoking tobacco and certain occupational
exposures are well-established risk factors for bladder cancer. However, the male excess in
bladder cancer risk is not explained by the higher prevalence of tobacco smoking and higher
prevalence of occupational exposures in men. Previous studies have demonstrated that even after

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controlling for smoking and occupational hazards, the gender disparity in bladder cancer
remained (Hartge at al., 1990 and Hemelt et al., 2009).
Some case-control and cohort studies have shown that benign prostatic hyperplasia
(BPH) is associated with an increased risk of bladder cancer in men (Dai et al., 2016). BPH is a
condition of nonmalignant enlargement of the prostate and is an age-associated disease that
occurs in a third of men aged over 50 years and more than 50% of men aged over 60 (Thorpe and
Neal, 2003). It has been suggested that the incomplete emptying of the bladder in BPH patients
may be responsible for damage in the lower urinary tract and that the retained urine may prolong
urothelial cell exposure to urinary carcinogens excreted in urine. However, the mechanism is not
fully understood. We extend this longstanding urogenous contact hypothesis of bladder cancer
etiology by proposing that a significant portion of the excess in male bladder cancer is caused by
retention of urine in the bladder due to BPH. The combination of male sex and older age serve as
a proxy measure of BPH, which is not captured in cancer registry data. We hypothesize that joint
influences of these factors will manifest as greater than additive influences of male sex and older
age on bladder cancer incidence, and that departures from additivity will be more pronounced for
cancer diagnosed in regions of the bladder subject to greater retention of urine. Results of this
study may provide further insight into mechanisms that underlie the gender disparity in bladder
cancer risk and may have implications for management of BPH as a novel strategy for
preventing bladder cancer.

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Chapter 2: Methods
Data Source
The study utilized a comprehensive database comprising data from the National Program
of Cancer Registries (NPCR) and the National Institutes of Health's (NIH) Surveillance,
Epidemiology, and End Results (SEER) Program, released June 2023. The combined database
includes cancer registry data from 50 states and the District of Columbia, which provides
information on more than 37 million cancer cases. Collectively these registries cover
approximately 97 percent of the U.S. population. SEER*Stat software (version 8.4.3) was used
to identify cases and obtain data from the NPCR and SEER Incidence - U.S. Cancer Statistics
Public Use Research Database, 2022 Submission (2001-2020).
Definitions
Bladder subsites were identified using ICD-O-3 site codes: renal pelvis (C64.9 Renal
pelvis, C65.9 Kidney, NOS), ureter (C66.9 Ureter), ureteric orifice (C67.6 Ureteric orifice), body
of the bladder (C67.0 Trigone of bladder, C67.1 Dome of bladder, C67.2 Lateral wall of bladder,
C67.3 Anterior wall of bladder, C67.4 Posterior wall of bladder, 67.8 Overlapping lesion of
bladder, and 67.9 Bladder, NOS), bladder neck (C67.5 Bladder neck), and urethra (C68.0
Urethra). Figure 1 provide the anatomy of the bladder with ICD-O-3 site codes. Two values of
bladder subsite were derived from these codes prior to analysis. First, ‘body of the bladder’ was
defined to include the 7 specified and unspecified regions of the bladder enumerated above,
based on medical oncologist and pathologist opinions regarding challenges inherent in
distinguishing between individual subsites within the body of the bladder. Also ‘entire bladder’
was defined by combining codes for all subsites. Cancers for which site was the kidney (C65.9
Kidney, NOS) were excluded if the histology was consistent with renal cell carcinoma rather

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than urothelial carcinoma, specifically 8020/3: Carcinoma, undifferentiated, NOS, 8140/3:
Adenocarcinoma, NOS, or 8260/3: Papillary adenocarcinoma, NOS.
Figure 1. Bladder Anatomy and ICD-O-3 (Spiessl et al., 2013).
Included malignancies were based on ICD-O-3 histology code, subdivided into the
following types (a) urothelial carcinoma (8020/3: Carcinoma, undifferentiated, NOS, 8050/:
Papillary carcinoma, NOS, 8052/3: Papillary squamous cell carcinoma, 8082/3:
Lymphoepithelial carcinoma, 8120/3: Transitional cell carcinoma, NOS, 8122/3: Transitional
cell carcinoma, spindle cell, 8130/3: Papillary transitional cell carcinoma, 8131/3: Transitional
cell carcinoma, micropapillary, 8490/3: Signet ring cell carcinoma, 8980/3: Carcinosarcoma,
NOS); (b) squamous cell carcinoma (8070/3: Squamous cell carcinoma, NOS, 8071/3:
Squamous cell carcinoma, keratinizing, NOS, 8072/3: Squamous cell carcinoma, large cell,
nonkeratinizing, NOS, 8074/3: Squamous cell carcinoma, spindle cell); (c) adenocarcinoma
(8140/3: Adenocarcinoma, NOS, 8260/3: Papillary adenocarcinoma, NOS); and (d) small cell
carcinoma (8013/3: Large cell neuroendocrine carcinoma, 8041/3: Small cell carcinoma, NOS,
8045/3: Combined small cell carcinoma, 8246/3: Neuroendocrine carcinoma, NOS). Tumors
with ambiguously scored histotypes (e.g. 8020/3: Carcinoma, undifferentiated, NOS) were
included as urothelial carcinoma, which was overwhelmingly the most common histology.

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Cases aged 45 and above are included in the study since the incidence was rare for those
aged below 45 years. For the calculation of age-adjusted incidence rates, age was categorized
into 4 groups: 45-59 years, 60-69 years, 70-79 years, and 80+ years. Race/ethnicity of NonHispanic White (NHW), Non-Hispanic Black (NHB), Non-Hispanic American Indian/Alaska
Native (NHAIAN), Non-Hispanic Asian or Pacific Islander (NHAPI), Hispanic All Races (H),
Suppressed (North Dakota and Wisconsin), and Non-Hispanic Unknown Race were included in
the study. Due to small incident case counts, statistical analyses were not performed on the NonHispanic Unknown Race.
Statistical Analysis
For each histological type, age-adjusted incidence rates (AAIRs; per 100,000 cases and
age-adjusted to the 2000 US Standard Population [19 age groups - Census P25-1130]; Age
recode with < 1 year, 1-4 years, 5-9 years, ..., 85+ years), age-specific incidence rates (ASIRs),
annual percent changes (APCs), and counts according to sex (male, female) and race/ethnicity
were extracted using Rate Session in SEER*Stat. Tiwari modification was used for 95%
confidence intervals to improve efficiency since they have empirical coverage probabilities that
are less than or equal to their counterparts and ensures that the interval retain nominal level of
confidence (Tiwari et al., 2006). APCs were calculated fitting a weighted least squares regression
to the natural logarithm of the rates using calendar year as a regressor variable, where the weight
for the i
th year is the inverse of the estimate of the variance of the rate for i (Kim et al., 2000).
Temporal trends of age-adjusted and age-specific incidence rates and rate ratios between males
and females were graphically presented using Microsoft Excel 2024.
Sex- and age-stratum specific counts for each bladder cancer histotype and racial/ethnic
groups were captured using Rate Session in SEER*Stat. Incidence rate ratios comparing

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occurrence in males versus females with adjustment for 5-year categories of age (IRRsex) and
incidence rate ratios comparing occurrence in each of three older age groups (60-69 years, 70-79
years, ≥80 years) to occurrence at 45-59 years of age with adjustment for sex (IRRage) were
estimated using Stata software (version 18.0). The nbreg command was used to implement
regression analyses on stratum-specific incidence counts using the negative binomial model. The
dependent variable was number of cases, and the independent variables were sex and age
(categorized). Time at risk in the base population was represented in person-years and
represented in the regression model as a log offset. Negative binomial regression was used
instead of possession regression due to the overdispersion of the data. Relative excess risk due to
interaction (RERI) between male sex and older age was assessed using the reri nbreg command.
For these calculations, age was dichotomized into young age group (≤60 years) and older age
group (>60 years). Data were excluded from analysis if fewer than 16 cases were reported in a
single stratum, and tabular results for such strata were reported as not available (NA).

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Chapter 3: Results
Overview
From 2001 to 2020, a total of 1,473,902 incident urothelial carcinomas, squamous cell
carcinomas, adenocarcinomas, and small cell carcinomas of the urinary bladder diagnosed at the
primary sites renal pelvis, ureter, ureteric orifice, body of the bladder, bladder neck, and urethra
were identified in reporting areas of the SEER and NPCR registries and included in this study.
Table 1 provides case counts and key estimates of all incident bladder cancer diagnosed at each
subsite and in the entire bladder according to sex and racial/ethnic group. The male-to-female
ratio of all incident bladder cancer cases was approximately 3:1 (Nmale = 1,101,351, Nfemale =
372,551). Of all bladder cancer diagnoses, the majority were urothelial carcinoma (N =
1,432,556; 97.2%), followed by squamous cell carcinoma (N = 20,209; 1.4%), small cell
carcinoma (N = 12,281; 0.8%), and adenocarcinoma (N = 8,860; 0.6%). The age-adjusted
incidence rate (AAIR per 100,000 person-years) of all incident bladder cancer in males was the
highest in the body of the bladder (32.44, 95% CI: 32.37, 32.50) subsite, followed by the renal
pelvis (1.44), bladder neck (1.42), ureteric orifice (1.11), ureter (0.78), and urethra (0.23). For
females, the AAIR was highest in the body of the bladder (7.97, 95% CI:7.94, 8.00), followed by
renal pelvis (0.79), ureter (0.37), ureteric orifice (0.34), bladder neck (0.18), and urethra (0.07).
Among the racial/ethnic groups, non-Hispanic white (NH White) males and females had the
highest AAIRs for all bladder cancer (male: 41.4, 95% CI: 41.32, 41.48; female: 10.76, 95% CI:
10.73, 10.80). Table 2 provides these counts and estimates based on data from all participants for
all bladder cancer as well as bladder cancer of each histologic type. Tables 3-7 provide this
information based on data from individual racial/ethnic groups for bladder cancer of each
histologic type.

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Covariates
Sex
The age-adjusted incidence rate ratio comparting occurrence of bladder cancer of all
histotypes at all subsites between men and women (IRRsex) was 3.51 (95%CI: 2.83, 4.36) for all
participants. For all bladder cancer, the IRRsex was highest in the bladder neck (5.53, 95% CI:
4.42, 6.93), followed by body of the bladder (3.75, 95% CI: 3.00, 4.70), the ureteric orifice (3.02,
95% CI: 2.13, 4.28), the ureter (1.89, 95% CI: 1.51, 2.35), and the renal pelvis (1.86, 95% CI:
1.56, 2.20) after adjusting for age (Table 1, Figure 3A). Table 2 further displays the IRR between
age groups (IRRage) adjusted by sex and IRRsex adjusted by age groups in urothelial carcinoma,
squamous cell carcinoma, adenocarcinoma, and small cell carcinoma individually. The pattern in
IRR between men and women by subsites was profound in urothelial carcinoma. The IRRsex in
all participants with urothelial carcinoma was 3.60 (95%CI: 2.89, 4.49) in the entire bladder;
specifically, the highest in the bladder neck (5.74, 95% CI: 4.59, 7.17) and the lowest in the renal
pelvis (1.86, 95% CI: 1.56, 2.22). The IRRsex in all participants with squamous cell carcinoma
diagnosed at all subsites was 1.30 (95%CI: 1.03, 1.64); IRRsex of adenocarcinoma was 1.73
(95%CI: 1.27, 2.36); and 3.57 (95%CI: 2.88, 4.43) for small cell carcinoma. IRRsex of a few
subsites in squamous cell carcinoma, adenocarcinoma, and small cell carcinoma could not be
calculated due to small numbers, thus a distinct pattern in IRRsex according to subsites was not
fully investigated for these histotypes.
Age
Estimates of the IRR comparing age groups reveal notably higher incidence rates with
older age. Specifically, compared to those in the baseline group 45-59 years of age, after
adjusting for sex estimates of IRR are 3.75 (95%CI: 2.74, 5.11) for those 60-69 years of age;

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8.06 (95%CI: 5.91, 5.11) for those 70-79 years of age; and 11.98 (95%CI: 8.78, 16.35) for those
80 years of age or older. A similar pattern of more elevated IRR in successively older age groups
is observed across all histotypes, subsites, and racial/ethnic groups. Figure 2 displays the age
specific incidence rates (ASIRs) of all bladder cancer at each subsite for 5-year age groups,
separately for males (panel A) and females (panel B). ASIRs for both sexes increase with age
and peak at 80-84 or ≥85 years for each subsite.
Figure 2. Age-Specific Incidence Rates (ASIR) of Bladder Cancer of Any Histotype According to Bladder Subsite
in Males (A) and Females (B) and Corresponding Ratios of ASIR in Males to ASIR in Females (C); SEER+NPCR
Reporting Area excluding North Dakota and Wisconsin, 2001-2020.
0
50
100
150
200
250
300
350
<49
years
50-54
years
55-59
years
60-64
years
65-69
years
70-74
years
75-79
years
80-84
years
85+
years
Incidence rate (per 100,000)
(B) ASIR of Bladder Cancer of Any Histotype in
Females
C64.9, 65.9 Renal pelvis/Kidney, NOS C66.9-Ureter
C67.0-67.4, 67.8, 67.9- Body of bladder C67.5-Bladder neck
C67.6-Ureteric orifice C68.0-Urethra

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For each 5-year age group, the ratio between ASIRs of males and females is highest for
tumors of the bladder neck, followed by body of the bladder, ureteric orifice and ureter or renal
pelvis. For urethra, values of the ratio are similar to values for uretic orifice in younger age
groups (<64 years) but exceed values for body of bladder in highest age groups (≥70-74 years).
The male-to-female ratio between ASIRs corresponding to the bladder neck, body of bladder,
urethra and ureteric orifice generally increased as age progresses, while ratios for ureter and
renal pelvis are approximately constant across age groups (Figure 2C).
Age and Sex Interaction
Values of the RERIage-sex exceeding the null value, zero, identify greater than additive
apparent influences of male sex and age >60 years on incidence of bladder cancer. Among all
participants the estimate was 17.47 (95%CI: 7.40, 27.54) for bladder cancer of any histotype
within the entire bladder (Figure 4, Tables 1-2). The excess risk was highest for tumors
diagnosed in the bladder neck and lowest for those in the renal pelvis (Figure 3B).

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Figure 3. Incidence Rate Ratio Between Males and Females (IRRsex) Adjusted by Age (A) and Relative Excess Risk
due to Interaction Between older age and male sex (RERIage-sex) (B) for all Histotypes over the Progression Renal
Pelvis, Ureter, Ureteric Orifice, Body of Bladder, and Bladder Neck, Including the Entire Bladder and the Urethra.
Temporal Trends
Estimates of annual percent change (APC) in age-adjusted rates reveal overall declines in
incidence of all bladder cancer over the calendar period 2001-2020 in both males and females
(APC male: -1.18, 95%CI: -1.435, -0.936; APC female: -1.18, 95%CI: -1.435, -0.936) (Tables 1
and 2). Additionally, the AAIR of bladder cancer of any histotype diagnosed at each subsite has
gradually decreased from 2001 to 2020 for both males and females (Figure 4A and B). The maleto-female ratio between the AAIRs of any histotype bladder cancer estimated for successive 5-

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year intervals of calendar year reveal that the ratio is highest for bladder neck and lowest for
renal pelvis throughout the study period (Figure 4C). Despite a discernable temporal decrease in
the ratio for bladder neck tumors and slight increase for urethral tumors, ratios of AAIR between
males and females remained relatively stable for each subsite over the study period.
Figure 4. Age-Adjusted Incident Rate (AAIR) of Bladder Cancer of Any Histotype According to Subsite in Males
(A) and Females(B) and Corresponding Incidence Rate Ratio (IRR) between males and females (C); SEER+NPCR
Reporting Area excluding North Dakota and Wisconsin, every 5 years from 2001-2020.
0
5
10
15
20
25
30
35
40
2001-2005 2006-2010 2011-2015 2016-2020
Incidence Rate (per 100,000)
(B) AAIR of Bladder Cancer of Any Histotype in all
Females
C64.9, 65.9 Renal pelvis/Kidney, NOS C66.9-Ureter
C67.0-67.4, 67.8, 67.9- Body of bladder C67.5-Bladder neck
C67.6-Ureteric orifice C68.0-Urethra

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Chapter 4: Discussion
Bladder cancer accounts for approximately 4.7% of all new cancer cases and is one of the
most common cancers in the United States, with a higher disease burden among men than
women (Antoni et al., 2017). This study utilized data from the SEER and NPCR combined
registries in the US to investigate the incidence of bladder cancer according to age, sex,
race/ethnicity, histological type, and anatomical site, and to understand potential factors leading
to the gender disparity in bladder cancer risk. The excess risk of bladder cancer in males was
most pronounced in subsites in the lower urinary tract (i.e., the bladder neck and body of the
bladder), where the bladder urothelium's contact with urinary carcinogenic compounds is likely
to be most prolonged if the bladder retains urine, in particular due to the presence of BPH.
Despite racial differences in bladder cancer risk, the male excess risk in the bladder neck was
found in all racial/ethnic groups. The results for demographic factors and tumor histology are
consistent with established patterns of bladder cancer incidence, while novel results for anatomic
subsite of the bladder and assessment of statistical interaction between measures of sex accord
with the postulated role of BPH or some factor that may prolong urine retention. Thus, this study
provides new insight into bladder cancer etiology that may have implications for novel
preventive strategies involving mitigation of BPH.
Higher age-adjusted incidence rates of bladder cancer in males (37.1 per 100,000 personyears) compared to females (9.7 per 100,000 person-years) across all subsites and racial/ethnic
groups, and a male-to-female ratio of 3.51 were found in this study. These results align with the
four times higher risk in males reported in existing literature (Saginala et al., 2020). The risk of
bladder cancer is substantially elevated at higher ages for both males and females, with the agespecific incidence rate (ASIR) being much higher for participants over the age of 60. This trend

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emphasizes the possibility that novel measures for primary prevention or early detection
strategies might be most efficiently targeted to older.
The interaction between sex and age presents a particularly intriguing aspect of bladder
cancer epidemiology. The study found a statistically significantly greater than additive
interaction between apparent influences of older age (>60 years) and male sex for bladder cancer
of any histotype at each subsite. This interaction, quantified as the relative excess risk due to
interaction (RERI), was most pronounced in the bladder neck and least in the renal pelvis. The
highest RERI in the bladder neck suggests that older men are at exceptionally high risk for
cancer in this subsite, necessitating heightened vigilance in this demographic. This finding
coincides with previous studies on the association between benign prostatic hyperplasia (BPH)
and bladder cancer, where older males with BPH are at higher risk (Dai et al., 2016). Because the
age-sex interaction captures joint effects of these variables, which together are risk factors for
BPH, these results accord with a causal link between BPH and bladder cancer. A possible
explanation is that the incomplete emptying of the bladder in older males with BPH results in
prolonged exposure of bladder urothelium to urinary carcinogens (Jacobsen et al., 1995).
A striking finding of this study is the pattern in the incidence rate ratio (IRR) between
sexes, adjusted by age, when considering anatomical subsites of bladder cancer. This ratio
measure of excess incidence in men was found to be the highest in the bladder neck (5.53, 95%
CI: 4.42, 6.93) and the body of the bladder (3.75, 95% CI: 3.00, 4.7), which belong to the lower
urinary tract, and the weakest in the renal pelvis (1.86, 95% CI: 1.56, 2.20) and ureter (1.89, 95%
CI: 1.51, 2.35), which belong to the upper urinary tract. The elevated male-to-female risk in the
lower urinary tract could be due to the same reasoning that BPH prolongs urothelium contact
with carcinogens predominantly at sites in the lower tract. One study hints that the poor

15
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15
prognosis of bladder neck cancer may be due to the distinct anatomy of the subsite, but the
causative mechanisms are yet to be investigated (Xiao et al., 2015). The aggravated risk from the
interaction between the male sex and older age, in addition to the high IRR between men and
women in the lower urinary tract, suggests that biological factors unique to males, possibly
related to anatomy, hormonal changes, genetic predispositions, or prolonged exposure to
carcinogens, synergize to elevate the risk substantially. Analyses stratified by sex revealed that
the IRR between older age and younger age was higher in males than in females. This finding
further emphasizes that as men age, their risk of developing bladder cancer increases more
steeply compared to women, in particular in the lower bladder. In addition to influences of BPH
at older ages, this steep increase in older men could also be related to cumulative lifestyle risks
and potentially less frequent engagement in preventive healthcare measures.
Racial/ethnic differences in bladder cancer incidence have been reported previously
(Wang, Chang, & Li, 2018), and similar findings were observed in this study when bladder
cancer was stratified by histotype. In urothelial carcinoma and small cell carcinoma, AAIRs were
highest for non-Hispanic Whites, approximately two times those of non-Hispanic Blacks, nonHispanic American Indians/Alaska Natives, and Hispanics; AAIRs were lowest in non-Hispanic
Asians/Pacific Islanders. In adenocarcinoma and squamous cell carcinoma, AAIRs of nonHispanic Blacks were higher compared to other racial/ethnic groups. These disparities highlight
the need for further research into the genetic, environmental, and socioeconomic factors
contributing to the disparate incidence rates among specific racial/ethnic groups.
Overall, bladder cancer incidence declined from 2001 to 2020, as previously reported.
This pattern may reflect declines in smoking prevalence 20 to 30 years ago (Antoni et al., 2017).
This likely reflects the impact of public health efforts such as smoking cessation programs and

16
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improved occupational safety standards. The annual percent change (APC) showed a consistent
decrease in both males and females, suggesting that these measures have been effective across
the board. However, the persistence of high male-to-female ratios in incidence rates across all
subsites implicates factors other than tobacco smoking in the ongoing sex disparity in risk, and
indicates that targeted prevention strategies for men, especially older men, are needed.
A great strength of this study was the use of population-based incidence data
representative of most regions of the United States, with nearly complete ascertainment of newly
diagnosed cancers accompanied by demographic information. Moreover, tumors were
characterized by expert histopathology and subsite of the bladder where they occurred. There are
a few limitations to this study. While the SEER and NPCR databases cover registries of 50 states
in the US and provide the most comprehensive data on cancer, some ethnicities and histotypes
had a limited number of patients. Consequently, we lacked statistical power for analyzing IRR
and RERI in these groups. The inclusion of tumors with ambiguous histotypes (e.g., Carcinoma,
undifferentiated, NOS) among urothelial carcinomas may have introduced a slight degree of
information bias. Several variables of key importance to the hypothesis were not available in the
SEER and NPCR data resources. Consequently, data used in the analysis did not include either
direct measures of BPH or several important covariates, including history of smoking tobacco,
an important risk factor in males and females, other sources of exposure to arylamine compounds
that have historically been more prevalent in males, or parity which has more recently been
proposed as a preventive factor in females. Misclassification of BPH by the combination of male
sex and older age may have attenuated estimates of effect size estimated in this work. Our
inability to address possible confounding by the remaining covariates may have distorted
estimates of effect size in directions and to degrees that remain undetermined. However, it seems

17
17
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unlikely that such confounding would have spuriously created the dramatically different
estimates of IRRsex and RERI observed between anatomic subsites. Finally, this study did not
distinguish muscle-invasive bladder cancer from non-muscle invasive bladder cancer, the latter
accounting for 75% of newly diagnosed bladder cancer characterized by high recurrence rate.
Future studies that distinguish between muscle invasive and non-muscle invasive forms of
bladder cancer may provide additional insight into the gender disparity.
In conclusion, this study provides a nuanced understanding of the sex and age dynamics
in bladder cancer incidence specified by histology, anatomical subsite, and race/ethnicity. The
findings underscore the possibility that new strategies for targeted prevention, early detection,
and intervention may address the specific needs of high-risk populations, particularly older men.
Future research should aim to elucidate the mechanisms underlying the observed sex and age
interactions as the basis of innovative approaches to mitigate these risks. Additionally, an indepth analysis of bladder cancer incidence and survival in the lower urinary tract, specifically the
bladder walls and bladder neck, is needed. The history of BPH could be measured to further test
the hypothesis. Continued efforts to promote healthy behaviors, enhance screening programs,
and ensure equitable access to healthcare will be vital in sustaining the positive trends observed
and improving outcomes for all individuals affected by bladder cancer.

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Table 1. Incident Bladder Cancer of Any Histotype Diagnosed at Each Subsite and in the Entire Bladder according to Demographic Factors, All Participants and
Individual Racial/Ethnic Groups, SEER+NPCR Reporting Area excluding North Dakota and Wisconsin, 2001-2020
Renal Pelvis Ureter Ureteric OriPice Body of Bladder Bladder neck Entire Bladder Urethra
All Participants
N, male 42,651 22,794 33,708 962,147 33,354 1,101,351 6,697
N, female 30,128 14,154 13,077 305,696 6,938 372,551 2,558
AAIR, male 1.44
(1.426, 1.453)
0.778
(0.768, 0.788)
1.108
(1.096, 1.12)
32.437
(32.371, 32.503)
1.142
(1.13, 1.155)
37.133
(37.062, 37)
0.229
(0.223, 0.234)
AAIR,
female
0.787
(0.778, 0.796)
0.368
(0.362, 0.374)
0.344
(0.338, 0.35)
7.973
(7.944, 8.002)
0.181
(0.177, 0.185)
9.721
(9.689, 9.752)
0.068
(0.065, 0.07)
APC, male -1.417*
(-1.836, -0.996)
-0.785*
(-1.08, -0.49)
-3.892*
(-4.491, -3.289)
-1.056*
(-1.299, -0.812)
-1.779*
(-2.199, -1.357)
-1.179*
(-1.433, -0.924)
-1.919*
(-2.407, -1.429)
APC, female -1.133*
(-1.627, -0.636)
-0.631*
(-0.994, -0.267)
-3.838*
(-4.415, -3.256)
-1.086*
(-1.323, -0.848)
-1.407*
(-1.941, -0.871)
-1.186*
(-1.435, -0.936)
-2.242*
(-3.044, -1.433)
IRR sex 1.86 (1.56, 2.20) 1.89 (1.51, 2.35) 3.02 (2.13, 4.28) 3.75 (3.00, 4.70) 5.53 (4.42, 6.93) 3.51 (2.83, 4.36) 2.25 (1.60, 3.17)
RERI age-sex 5.78 (0.036, 11.20) 9.01 (0.92, 17.10) 8.81 (2.39, 15.23) 18.72 (7.95, 29.50) 33.11 (12.5, 54.29) 17.47 (7.40, 27.54) 6.56 (1.71, 6.98)
Non-Hispanic White
N, male 35,361 19,685 29,521 829,179 28,369 947,474 5,359
N, female 24,912 11,816 11,423 254,730 5,641 310,173 1,651
AAIR, male 1.55 0.864 1.272 36.22 1.256 41.4 0.238
AAIR,
female
0.855 0.403 0.404 8.848 0.195 10.764 0.058
IRR sex 1.82 (1.74, 1.91) 2.12 (2.07, 2.17) 3.13 (2.91, 3.38) 3.95 (3.58, 4.36) 6.06 (5.47, 6.71) 3.72 (3.42, 4.05) 3.83 (3.17, 4.62)
RERI age-sex 6.18 (-4.63, 17.00) 11.58 (-4.24,
27.41)
8.81 (2.39, 15.23) 17.61 (1.52, 33.71) 35.26 (-0.76, 71.3) 16.69 (0.96, 32.43) 17.37 (-1.12,
35.85)
Non-Hispanic Black
N, male 2,324 751 1,055 43,744 1,868 50,470 728
N, female 1,858 675 475 21,814 623 26,057 612
AAIR, male 0.851 0.301 0.391 17.239 0.749 19.81 0.279
AAIR,
female
0.5 0.184 0.126 5.894 0.166 7.028 0.157
IRR sex 1.72 (1.52, 1.95) 1.66 (1.48, 1.86) 3.30 (2.93, 3.71) 2.94 (2.89, 3.01) 4.39 (3.98, 4.84) 2.83 (2.79, 2.88) 1.73 (1.30, 2.30)
RERI age-sex 2.16 (-2.36, 6.70) 6.81 (-3.91, 17.54) 9.77 (0.57, 18.98) 12.60 (-0.83, 25.8) 20.29 (1.01, 39.57) 11.39 (-0.53,
23.32)
3.13 (0.59, 4.75)
Non-Hispanic American Indian/Alaska Native
N, male 142 57 88 2,886 95 18,982 25
N, female 90 52 33 891 24 1098 8
AAIR, male 0.804 0.329 0.489 17.637 0.644 20.059 0.157
AAIR,
female
0.464 0.265 0.155 4.27 0.118 5.312 NA
IRR sex 1.75 (1.26, 2.43) 1.35 (0.85, 2.15) NA 4.02 (3.71, 4.36) NA 3.72 (3.46, 4.01) NA

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19
19
RERI age-sex NA NA NA 19.19 (-0.22, 38.6) NA 18.14 (-0.52,
36.81)
NA
Non-Hispanic Asian or PaciPic Islander
N, male 1,034 680 515 16,031 616 18,982 106
N, female 844 547 214 4,994 135 6,805 71
AAIR, male 0.886 0.586 0.424 13.766 0.536 16.289 0.091
AAIR,
female
0.561 0.363 0.135 3.256 0.09 4.449 0.044
IRR sex 1.62 (1.47, 1.79) 1.67 (1.48, 1.89) 3.10 (2.60, 3.68) 4.24 (4.09, 3.39) 6.02 (4.91, 7.37) 3.67 (3.56, 3.78) 1.91 (1.26, 2.87)
RERI age-sex 5.49 (-6.31, 17.29) 8.29 (-7.33, 23.91) 10.60 (-0.67, 21.9) 26.42 (-4.94,
57.78)
43.04 (-17.62,
103.7)
22.44 (-4.76,
49.64)
NA
Hispanic (All Races)
N, male 2,544 999 1,313 39,673 1,407 46,271 335
N, female 1,630 672 480 13,518 310 16,766 156
AAIR, male 1.112 0.455 0.537 17.641 0.635 20.53 0.149
AAIR,
female
0.563 0.237 0.157 4.507 0.103 5.617 0.05
IRR sex 1.98 (1.85, 2.12) 2.00 (1.80, 2.22) 3.35 (3.00, 3.76) 3.69 (3.33, 4.08) 5.82 (5.08, 6.68) 3.47 (3.20, 3.76) 2.36 (1.90, 2.93)
RERI age-sex 9.43 (-7.20, 26.07) 14.37 (-8.02,
36.77)
14.82 (1.03, 28.63) 23.50 (-1.92, 48.9) 41.41 (-4.46, 87.3) 22.12 (-2.42,
46.66)
12.65 (-0.22,
25.52)
Suppressed (North Dakota and Wisconsin)
N, male 1,111 554 1,050 22,901 853 26,594 125
N, female 716 358 387 7,199 172 8,882 50
AAIR, male 1.699 0.856 1.558 35.114 1.324 40.743 0.193
AAIR,
female
0.861 0.43 0.48 8.771 0.207 10.812 0.062
IRR sex 2.01 (1.81, 2.23) 1.92 (1.66, 2.22) 3.17 (2.80, 3.60) 3.81 (3.51, 4.14) 6.25 (5.19, 7.53) 3.62 (3.42, 3.85) NA
RERI age-sex 8.47 (-7.07, 24.01) 8.56 (-6.36, 23.48) 10.26 (2.28, 18.25) 19.10 (0.28, 37.92) 51.16 (-9.0, 111.3) 18.17 (-0.19,
36.54)
NA
Non-Hispanic Unknown Race
N, male 135 59 166 7,733 146 8,267 19
N, female 66 16 37 2,550 33 2,770 10
N – number of incident cases; AAIR – age-adjusted incidence rate (incident cases/100,000 person years at risk); APC – annual percent change in AAIR in the period
2001-2020; IRR – incidence rate ratio (IRR age, per 10 years of age, adjusted by sex; IRR sex, male versus female, adjusted by age); RERI age-sex – relative excess risk due
to interaction between older age (>60 years old) and male sex, parentheses identify 95% conPidence intervals

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Table 2. Incident Urothelial Carcinoma, Squamous Cell Carcinoma, Adenocarcinoma and Small Cell Carcinoma of the Urinary Bladder Diagnosed at SpeciPic Subsite
and Entire Bladder according to Age and Sex among all Participants, SEER+NPCR Reporting Area excluding North Dakota and Wisconsin, 2001-2020
Renal Pelvis Ureter Ureteric OriPice Body of Bladder Bladder neck Entire Bladder Urethra
Urothelial Carcinoma
N, male 41,069 22,237 33,468 942,103 32,368 1,075,846 4,601
N, female 28,909 13,713 12,974 293,528 6,566 356,710 1,020
AAIR, male 1.387
(1.373, 1.4)
0.758
(0.748, 0.769)
1.099
(1.087, 1.111)
31.754
(31.689, 31.819)
1.108
(1.095, 1.12)
36.266
(36.196, 36)
0.16
(0.156, 0.165)
AAIR, female 0.755
(0.746, 0.764)
0.356
(0.35, 0.362)
0.341
(0.335, 0.347)
7.654
(7.626, 7.626)
0.171
(0.167, 0.167)
9.304
(9.273, 9.335)
0.027
(0.025, 0.028)
APC, male -1.412*
(-1.83, -0.993)
-0.809*
(-1.102, -0.515)
-3.885*
(-4.482, -3.284)
-1.080*
(-1.325, -0.835)
-1.838*
(-2.27, -1.405)
-1.206*
(-1.461, -0.949)
-2.819*
(-3.403, -2.232)
APC, female -1.129*
(-1.602, -0.654)
-0.685*
(-1.048, -0.32)
-3.877*
(-4.473, -3.277)
-1.105*
(-1.356, -0.853)
-1.392*
(-1.944, -0.836)
-1.203*
(-1.465, -0.941)
-2.316*
(-3.511, -1.107)
IRR age
45-59 years
60-69 years
70-79 years
80+ years
1
3.75 (2.94, 4.80)
9.10 (7.12, 11.62)
14.26 (11.03,
18.43)
1
4.79 (3.47, 6.61)
12.18 (8.79, 16.88)
18.57 (13.28,
25.98)
1
3.33 (2.05, 5.42)
6.08 (3.74, 9.90)
7.85 (4.76, 12.95)
1
3.70 (2.68, 5.10)
7.84 (5.68, 10.81)
11.69 (8.47,
16.14)
1
3.75 (2.74, 5.15)
8.70 (6.36, 11.91)
14.15 (10.24,
19.57)
1
3.75 (2.74, 5.11)
8.06 (5.91, 10.99)
11.98 (8.78,
16.35)
1
2.96 (1.84, 4.77)
6.68 (4.13, 10.80)
13.33 (7.56,
23.53)
IRR sex 1.86 (1.56, 2.22) 1.89 (1.51, 2.38) 3.02 (2.13, 4.28) 3.84 (3.06, 4.83) 5.74 (4.59, 7.17) 3.60 (2.89, 4.49) 3.30 (2.30, 4.72)
RERI age-sex 5.81 (0.22, 11.41) 9.21 (0.813, 17.60) 9.31 (1.99, 16.62) 19.48 (8.22,
30.74)
35.91 (13.43,
58.4)
18.29 (7.68,
28.90)
12.81 (1.24,
24.37)
Squamous Cell Carcinoma
N, male 867 280 83 7,430 272 10,522 1,590
N, female 711 229 48 7,652 191 9,687 856
AAIR, male 0.029
(0.027, 0.031)
0.01
(0.009, 0.011)
0.003
(0.002, 0.004)
0.254
(0.248, 0.26)
0.01
(0.009, 0.011)
0.356
(0.349, 0.363)
0.051
(0.048, 0.054)
AAIR, female 0.019
(0.017, 0.02)
0.006
(0.005, 0.007)
0.001
(0.001, 0.002)
0.201
(0.197, 0.206)
0.005
(0.004, 0.006)
0.255
(0.25, 0.26)
0.023
(0.021, 0.024)
APC, male -2.900*
(-4.11, -1.674)
NA NA -2.116*
(-2.616, -1.614)
NA -1.847*
(-2.266, -1.427)
0.375
(-0.734, 1.497)
APC, female -2.003*
(-3.497, -0.487)
NA NA -1.216*
(-1.671, -0.759)
NA -1.301*
(-1.753, -0.848)
-1.584*
(-2.919, -0.231)
IRR age
45-59 years
60-69 years
70-79 years
80+ years
1
3.11 (2.62, 3.72)
7.33 (6.23, 8.34)
10.74 (8.82,
13.09)
1
3.53 (2.40, 5.19)
11.52 (8.13, 16.32)
19.51 (13.35,
28.51)
NA 1
2.63 (1.92, 3.60)
5.31 (3.90, 7.22)
9.89 (7.18, 13.63)
1
2.26 (1.31, 3.90)
7.16 (4.28, 12.00)
13.71 (8.02,
23.42)
1
2.57 (1.84, 3.59)
5.45 (3.89, 7.65)
9.11 (6.47, 12.83)
1
2.03 (1.28, 3.22)
3.68 (2.32, 5.85)
4.97 (2.87, 8.59)
IRR sex 1.50 (1.33, 1.68) 1.65 (1.33, 2.04) NA 1.10 (0.89, 1.37) 1.78 (1.24, 2.56) 1.30 (1.03, 1.64) 2.33 (1.63, 3.33)
RERI age-sex 1.28 (-2.72, 5.29) 7.04 (-7.12, 21.09) NA 0.93 (-1.49, 3.36) 6.46 (-3.14, 16.07) 1.89 (-0.59, 4.37) 2.98 (-0.37, 6.33)
Adenocarcinoma

21
21
21
N, male 245 105 67 4,446 321 5,593 410
N, female 155 99 26 2,207 123 3,267 657
AAIR, male 0.008
(0.007, 0.009)
0.003
(0.003, 0.004)
0.002
(0.002, 0.003)
0.15
(0.146, 0.155)
0.011
(0.01, 0.013)
0.189
(0.184, 0.0194)
0.014
(0.013, 0.016)
AAIR, female 0.004
(0.004, 0.005)
0.003
(0.002, 0.003)
0.001
(0, 0.001)
0.058
(0.056, 0.061)
0.003
(0.003, 0.004)
0.086
(0.084, 0.09)
0.017
(0.016, 0.019)
APC, male NA NA NA -2.963*
(-3.653, -2.267)
NA -2.714*
(-3.355, -2.068)
NA
APC, female NA NA NA -2.675*
(-3.502, -1.841)
NA -2.877*
(-3.47, -2.281)
-3.213*
(-4.597, -1.808)
IRR age
45-59 years
60-69 years
70-79 years
80+ years
1
2.73 (1.94, 3.85)
5.87 (4.25, 8.11)
-
1
-
2.18 (1.44, 3.31)
-
NA 1
2.85 (2.04, 3.98)
5.41 (3.87, 7.56)
8.32 (5.77, 12.00)
1
1.23 (0.40, 3.77)
2.43 (0.77, 7.68)
4.72 (0.99, 22.57)
1
2.66 (1.75, 4.05)
5.03 (3.30, 7.66)
8.08 (5.11, 12.77)
1
2.49 (0.74, 8.35)
3.05 (0.87, 10.75)
5.20 (1.39, 19.39)
IRR sex 1.96 (1.51, 2.54) 1.12 (0.75, 1.70) NA 2.14 (1.67, 2.75) 2.28 (0.84, 6.19) 1.73 (1.27, 2.36) 0.35 (0.14, 0.88)
RERI age-sex 2.98 (-1.76, 7.71) NA NA 4.73 (1.04, 8.41) 3.03 (0.16, 5.91) 3.87 (0.76, 6.98) -0.27 (-2.42, 1.88)
Small cell carcinoma
N, male 470 173 90 8,169 393 9,391 96
N, female 356 113 29 2,309 58 2,890 25
AAIR, male 0.016
(0.014, 0.017)
0.006
(0.005, 0.007)
0.003
(0.002, 0.004)
0.279
(0.271, 0.285)
0.014
(0.013, 0.015)
0.321
(0.315, 0.328)
0.003
(0.003, 0.004)
AAIR, female 0.01
(0.009, 0.011)
0.003
(0.002, 0.004)
0.001
(0.001, 0.001)
0.06
(0.058, 0.063)
0.001
(0.001, 0.002)
0.076
(0.073, 0.079)
0.003
(0.003, 0.004)
APC, male NA NA NA 4.002*
(3.096, 4.915)
NA 3.763*
(2.917, 4.615)
NA
APC, female NA NA NA 3.616*
(2.644, 4.598)
NA 3.556*
(2.786, 4.332)
NA
IRR age
45-59 years
60-69 years
70-79 years
80+ years
1
2.69 (2.07, 3.51)
7.01 (5.50, 8.93)
10.59 (7.64,
13.44)
1
-
3.02 (1.99, 4.57)
4.07 (2.52, 6.57)
1
-
2.68 (1.44, 5.00)
-
1
4.32 (3.18, 5.86)
9.95 (7.38, 13.42)
16.70 (12.23,
22.79)
1
3.87 (2.42, 6.21)
16.42 (10.78,
25.01)
29.34 (18.67,
46.1)
1
4.13 (3.05, 5.61)
9.19 (6.86, 12.32)
16.18 (11.87,
22.08)
1
-
-
2.87 (1.59, 5.19)
IRR sex 1.63 (1.37, 1.93) 1.87 (1.34, 2.63) NA 3.69 (2.96, 4.60) NA 3.57 (2.88, 4.43) NA
RERI age-sex 4.39 (-3.38, 12.16) NA NA 24.63 (6.58,
42.68)
NA 22.15 (6.23,
38.06)
NA
N – number of incident cases; AAIR – age-adjusted incidence rate (incident cases/100,000 person years at risk); APC – annual percent change in AAIR in the period
2001-2020; IRR – incidence rate ratio (IRR age, per 10 years of age, adjusted by sex; IRR sex, male versus female, adjusted by age); RERI age-sex – relative excess risk due
to interaction between older age (>60 years old) and male sex, parentheses identify 95% conPidence intervals

22
22
22
Table 3. Incident Bladder Cancer of Any Histotype Diagnosed at Each Subsite and in the Entire Bladder according to Demographic Factors, All Participants and
Individual Racial/Ethnic Groups, SEER+NPCR Reporting Area excluding North Dakota and Wisconsin, 2001-2020
Renal Pelvis Ureter Ureteric OriPice Body of Bladder Bladder neck Entire Bladder Urethra
All Participants
N, male 42,651 22,794 33,708 962,147 33,354 1,101,351 6,697
N, female 30,128 14,154 13,077 305,696 6,938 372,551 2,558
AAIR, male 1.44
(1.426, 1.453)
0.778
(0.768, 0.788)
1.108
(1.096, 1.12)
32.437
(32.371, 32.503)
1.142
(1.13, 1.155)
37.133
(37.062, 37)
0.229
(0.223, 0.234)
AAIR,
female
0.787
(0.778, 0.796)
0.368
(0.362, 0.374)
0.344
(0.338, 0.35)
7.973
(7.944, 8.002)
0.181
(0.177, 0.185)
9.721
(9.689, 9.752)
0.068
(0.065, 0.07)
IRR age, males
45-59 years
60-69 years
70-79 years
80+ years
1
3.59 (2.50, 5.15)
8.02 (5.60, 11.49)
12.37 (8.48, 18.05)
1
4.60 (2.86, 7.39)
11.27 (7.02, 18.07)
18.26 (11.14, 29.93)
1
3.46 (1.81, 6.59)
6.21 (3.07, 11.84)
8.46 (4.19, 16.66)
1
3.87 (2.48, 6.04)
8.68 (5.56, 13.56)
13.14 (8.41,
20.53)
1
3.73 (2.40, 5.79)
9.32 (6.01, 14.44)
15.62 (9.87,
24.71)
1
3.86 (2.49, 6.00)
8.65 (5.57, 13.45)
13.02 (8.38, 20.24)
1
2.83 (1.77, 4.53)
6.53 (4.08, 10.43)
12.17 (7.38,
20.07)
IRR age, female
45-59 years
60-69 years
70-79 years
80+ years
1
3.98 (2.95, 5.38)
10.21 (7.58, 13.76)
16.26 (11.89,
26.15)
1
4.97 (3.27, 7.56)
12.66 (8.35, 19.21)
18.79 (12.17, 29.04)
1
3.17 (1.53, 6.58)
5.95 (2.87, 12.33)
7.42 (3.51, 15.26)
1
3.49 (2.23, 5.45)
6.99 (4.48, 10.91)
10.29 (6.59,
16.07)
1
3.62 (2.32, 5.66)
7.60 (4.88, 11.84)
11.87 (7.55,
18.67)
1
3.57 (2.35, 5.42)
7.34 (4.84, 11.15)
10.80 (7.11, 16.42)
1
2.33 (1.08, 5.01)
3.68 (1.71, 7.93)
5.33 (2.07, 13.73)
IRR sex 1.86 (1.56, 2.20) 1.89 (1.51, 2.35) 3.02 (2.13, 4.28) 3.75 (3.00, 4.70) 5.53 (4.42, 6.93) 3.51 (2.83, 4.36) 2.25 (1.60, 3.17)
RERI age-sex 5.78 (0.036, 11.20) 9.01 (0.92, 17.10) 8.81 (2.39, 15.23) 18.72 (7.95,
29.50)
33.11 (12.5,
54.29)
17.47 (7.40, 27.54) 6.56 (1.71, 6.98)
Non-Hispanic White
N, male 35,361 19,685 29,521 829,179 28,369 947,474 5,359
N, female 24,912 11,816 11,423 254,730 5,641 310,173 1,651
AAIR, male 1.55 0.864 1.272 36.22 1.256 41.4 0.238
AAIR,
female
0.855 0.403 0.404 8.848 0.195 10.764 0.058
IRR age, males
45-59 years
60-69 years
70-79 years
80+ years
1
3.62 (3.50, 3.76)
8.53 (8.25, 8.82)
12.87 (12.38,
13.38)
1
5.00 (4.74, 5.27)
12.90 (12.26, 13.56)
18.80 (17.75, 19.90)
1
3.18 (3.07, 3.30)
6.06 (5.86, 6.27)
7.39 (7.08, 7.72)
1
3.80 (3.77, 3.83)
8.33 (8.27, 8.39)
11.98 (12.0,
12.08)
1
3.95 (3.79, 4.12)
9.66 (9.28, 10.05)
15.07 (14.4,
15.77)
1
3.79 (3.76, 3.82)
8.35 (8.29, 8.40)
12.03 (11.93,
12.12)
1
3.33 (3.03, 3.66)
8.38 (7.67, 9.15)
15.1(13.68,
16.67)
IRR age, female
45-59 years
60-69 years
70-79 years
80+ years
1
3.91 (3.73, 4.11)
10.08 (9.63, 10.55)
15.01 (14.28,
15.77)
1
4.44 (4.13, 4.78)
11.43 (10.67, 12.24)
16.21 (15.04, 17.46)
1
2.88 (2.72, 3.04)
4.85 (4.58, 5.12)
5.54 (5.17, 5.94)
1
3.19 (3.14, 3.23)
6.16 (6.09, 6.24)
8.22 (8.10, 8.34)
1
3.25 (2.96, 3.57)
6.94 (6.35, 7.58)
10.12 (9.16,
11.17)
1
3.24 (3.20, 3.28)
6.46 (6.39, 6.54)
8.71 (8.60, 8.83)
1
2.84 (2.43, 3.32)
4.98 (4.27, 5.80)
7.57 (6.36, 9.02)

23
23
23
IRR sex 1.82 (1.74, 1.91) 2.12 (2.07, 2.17) 3.13 (2.91, 3.38) 3.95 (3.58, 4.36) 6.06 (5.47, 6.71) 3.72 (3.42, 4.05) 3.83 (3.17, 4.62)
RERI age-sex 6.18 (-4.63, 17.00) 11.58 (-4.24, 27.41) 8.81 (2.39, 15.23) 17.61 (1.52,
33.71)
35.26 (-0.76, 71.3) 16.69 (0.96, 32.43) 17.37 (-1.12,
35.85)
Non-Hispanic Black
N, male 2,324 751 1,055 43,744 1,868 50,470 728
N, female 1,858 675 475 21,814 623 26,057 612
AAIR, male 0.851 0.301 0.391 17.239 0.749 19.81 0.279
AAIR,
female
0.5 0.184 0.126 5.894 0.166 7.028 0.157
IRR age, males
45-59 years
60-69 years
70-79 years
80+ years
1
3.13 (2.81, 3.49)
5.51 (4.92, 6.17)
5.92 (4.97, 7.05)
1
4.20 (3.39, 5.20)
9.30 (7.53, 11.48)
14.92 (11.45, 19.44)
1
2.95 (2.51, 3.48)
5.55 (4.69, 6.56)
6.76 (5.28, 8.64)
1
3.82 (3.72, 3.93)
7.53 (7.33, 7.74)
11.15 (10.7,
11.56)
1
3.71 (3.24, 4.24)
8.38 (7.34, 9.55)
12.28 (10.34,
14.6)
1
3.74 (3.65, 3.84)
7.37 (7.19, 7.56)
10.79 (10.43,
11.15)
1
2.73 (2.24, 3.34)
5.02 (4.08, 6.16)
8.83 (6.75, 11.54)
IRR age, female
45-59 years
60-69 years
70-79 years
80+ years
1
3.30 (2.85, 3.86)
6.71 (5.85, 7.69)
10.07 (8.54, 11.97)
1
5.24 (4.02, 6.84)
12.17 (9.43, 15.71)
14.42 (10.59, 19.62)
1
3.64 (2.77, 4.80)
5.69 (4.29, 7.55)
9.76 (6.99, 13.62)
1
3.69 (3.53, 3.85)
7.77 (7.46, 8.10)
11.3 (10.74,
11.87)
1
3.08 (2.42, 3.92)
6.29 (4.98, 7.94)
8.33 (6.20, 11.18)
1
3.58 (3.44, 3.72)
7.45 (7.18, 7.73)
10.72 (10.24,
11.22)
1
1.89 (1.54, 2.32)
2.81 (2.27, 3.49)
2.57 (1.82, 3.63)
IRR sex 1.72 (1.52, 1.95) 1.66 (1.48, 1.86) 3.30 (2.93, 3.71) 2.94 (2.89, 3.01) 4.39 (3.98, 4.84) 2.83 (2.79, 2.88) 1.73 (1.30, 2.30)
RERI age-sex 2.16 (-2.36, 6.70) 6.81 (-3.91, 17.54) 9.77 (0.57, 18.98) 12.60 (-0.83, 25.8) 20.29 (1.01,
39.57)
11.39 (-0.53,
23.32)
3.13 (0.59, 4.75)
Non-Hispanic American Indian/Alaska Native
N, male 142 57 88 2,886 95 18,982 25
N, female 90 52 33 891 24 1,098 <16
AAIR, male 0.804 0.329 0.489 17.637 0.644 20.059 0.157
AAIR,
female
0.464 0.265 0.155 4.27 0.118 5.312 NA
IRR age, males
45-59 years
60-69 years
70-79 years
80+ years
NA NA NA NA NA 1
3.51 (3.18, 3.87)
7.55 (6.85, 8.33)
12.06 (10.58,
13.74)
NA
IRR age, female
45-59 years
60-69 years
70-79 years
80+ years
NA NA NA NA NA 1
3.76 (3.16, 4.49)
6.78 (5.67, 8.11)
11.00 (8.80, 13.75)
NA
IRR sex 1.75 (1.26, 2.43) 1.35 (0.85, 2.15) NA 4.02 (3.71, 4.36) NA 3.72 (3.46, 4.01) NA

24
24
24
RERI age-sex NA NA NA 19.19 (-0.22, 38.6) NA 18.14 (-0.52,
36.81)
NA
Non-Hispanic Asian or PaciPic Islander
N, male 1,034 680 515 16,031 616 18,982 106
N, female 844 547 214 4,994 135 6,805 71
AAIR, male 0.886 0.586 0.424 13.766 0.536 16.289 0.091
AAIR,
female
0.561 0.363 0.135 3.256 0.09 4.449 0.044
IRR age, males
45-59 years
60-69 years
70-79 years
80+ years
1
4.37 (3.58, 5.34)
11.04 (9.12, 13.37)
15.92 (12.59,
20.14)
1
6.34 (4.84, 8.31)
15.72 (12.11, 20.41)
22.33 (16.40, 30.41)
1
3.09 (2.39, 3.99)
6.87 (5.36, 8.81)
9.75 (7.05, 13.50)
1
3.97 (3.78, 4.17)
9.31 (8.87, 9.77)
15.76(14.87,
16.70)
1
3.66 (2.82, 4.76)
10.90 (8.56,
13.89) 16.55
(12.33, 22.2)
1
4.01 (3.83, 4.20)
9.53 (9.12, 9.96)
15.74 (14.92,
16.60)
1
-
2.66 (1.58, 4.50)
-
IRR age, female
45-59 years
60-69 years
70-79 years
80+ years
1
4.26 (3.49, 5.42)
11.69 (9.32, 14.65)
18.23 (14.05,
23.66)
1
5.70 (4.14, 7.85)
14.81 (10.92, 20.08)
23.21 (16.46, 32.73)
1
2.86 (1.92, 4.28)
5.60 (3.78, 8.31)
8.85 (5.44, 14.41)
1
3.76 (3.43, 4.13)
8.28 (7.57, 9.06)
15.09 (13.62,
16.7)
1
3.18 (1.76, 5.75)
9.18 (5.34, 15.78)
20.04 (11.1,
36.21)
1
3.86 (3.56, 4.18)
8.85 (8.20, 9.56)
15.55 (14.23,
17.00)
1
2.76 (1.42, 5.37)
4.93 (2,54, 9.59)
-
IRR sex 1.62 (1.47, 1.79) 1.67 (1.48, 1.89) 3.10 (2.60, 3.68) 4.24 (4.09, 3.39) 6.02 (4.91, 7.37) 3.67 (3.56, 3.78) 1.91 (1.26, 2.87)
RERI age-sex 5.49 (-6.31, 17.29) 8.29 (-7.33, 23.91) 10.60 (-0.67, 21.9) 26.42 (-4.94,
57.78)
43.04 (-17.62,
103.7)
22.44 (-4.76,
49.64)
NA
Hispanic (All Races)
N, male 2,544 999 1,313 39,673 1,407 46,271 335
N, female 1,630 672 480 13,518 310 16,766 156
AAIR, male 1.112 0.455 0.537 17.641 0.635 20.53 0.149
AAIR,
female
0.563 0.237 0.157 4.507 0.103 5.617 0.05
IRR age, males
45-59 years
60-69 years
70-79 years
80+ years
1
4.41 (3.91, 4.97)
11.12 (9.92, 12.48)
16.78 (14.52,
19.38)
1
6.34 (5.17, 7.77)
15.16 (12.42, 18.50)
25.09 (19.81, 31.78)
1
4.15 (3.56, 4.83)
8.24 (7.06, 9.61)
9.81 (7.88, 12.21)
1
4.79 (4.65, 4.94)
11.8 (11.45,
12.15)
18.07 (17.4,
18.75)
1
4.10 (3.46, 8.85)
12.3 (10.55, 14.4)
17.48(14.34, 21.3)
1
4.75 (4.61, 4.88)
11.69 (11.37,
12.01)
17.79 (17.19,
18.41)
1
3.83 (2.77, 5.31)
9.85 (7.22, 13.43)
16.85 (11.51,
24.68)
IRR age, female
45-59 years
60-69 years
70-79 years
80+ years
1
4.66 (3.93, 5.52)
12.27 (10.48,
14.39)
21.47 (17.95,
25.68)
1
5.74 (4.32, 7.64)
16.41 (12.56, 21.43)
24.13 (17.78, 32.75)
1
4.16 (3.16, 5.49)
8.16 (6.22, 10.70)
12.07 (8.66,
16.81)
1
3.82 (3.62, 4.03)
8.13 (7.73, 8.57)
12.8 (12.05,
13.63)
1
3.83 (2.67 5.49)
8.70 (6.17, 12.26)
12.59 (8.27,
19.15)
1
3.94 (3.76, 4.14)
8.64 (8.25, 9.05)
13.66 (12.92,
14.44)
1
3.59 (2.33, 5.55)
5.48 (3.49, 8.59)
-

25
25
25
IRR sex 1.98 (1.85, 2.12) 2.00 (1.80, 2.22) 3.35 (3.00, 3.76) 3.69 (3.33, 4.08) 5.82 (5.08, 6.68) 3.47 (3.20, 3.76) 2.36 (1.90, 2.93)
RERI age-sex 9.43 (-7.20, 26.07) 14.37 (-8.02, 36.77) 14.82 (1.03,
28.63)
23.50 (-1.92, 48.9) 41.41 (-4.46, 87.3) 22.12 (-2.42,
46.66)
12.65 (-0.22,
25.52)
Suppressed (North Dakota and Wisconsin)
N, male 1,111 554 1,050 22,901 853 26,594 125
N, female 716 358 387 7,199 172 8,882 50
AAIR, male 1.699 0.856 1.558 35.114 1.324 40.743 0.193
AAIR,
female
0.861 0.43 0.48 8.771 0.207 10.812 0.062
IRR age, males
45-59 years
60-69 years
70-79 years
80+ years
1
3.01 (2.49, 3.65)
7.46 (6.24, 8.92)
11.47 (9.29, 14.17)
1
3.63 (2.74, 4.83)
9.20 (7.05, 12.02)
14.41 (10.59, 19.60)
1
3.83 (3.20, 4.59)
6.16 (5.13, 7.40)
7.93 (6.29, 10.01)
1
3.85 (3.68, 4.02)
9.01 (8.64, 9.40)
13.2 (12.57,
13.87)
1
3.81 (3.01, 4.82)
9.11 (7.28, 11.39)
17.13 (17.36,
22.0)
1
3.80 (3.65, 3.96)
8.81 (8.47, 9.15)
12.99 (12.42,
13.60)
1
3.78 (2.08, 6.85)
9.46 (5.40, 16.59)
11.84 (5.98,
23.44)
IRR age, female
45-59 years
60-69 years
70-79 years
80+ years
1
4.82 (3.54, 6.58)
13.13 (9.83, 17.53)
19.37 (14.18,
26.45)
1
4.37 (2.87, 6.64)
12.28 (8.33, 18.11)
17.65 (11.59, 26.92)
1
3.16 (2.29, 4.37)
6.60 (4.86, 8.95)
6.87 (4.72, 10.01)
1
3.48 (3.21, 3.77)
7.05 (6.53, 7.61)
9.68 (8.88, 10.56)
1
5.26 (2.95, 8.38)
9.23 (5.24, 13.29)
15.51 (8.42,
28.56)
1
3.57 (3.32, 3.84)
7.48 (6.98, 8.01)
10.26 (9.48, 11.10)
NA
IRR sex 2.01 (1.81, 2.23) 1.92 (1.66, 2.22) 3.17 (2.80, 3.60) 3.81 (3.51, 4.14) 6.25 (5.19, 7.53) 3.62 (3.42, 3.85) NA
RERI age-sex 8.47 (-7.07, 24.01) 8.56 (-6.36, 23.48) 10.26 (2.28,
18.25)
19.10 (0.28,
37.92)
51.16 (-9.0, 111.3) 18.17 (-0.19,
36.54)
NA
Non-Hispanic Unknown Race
N, male 135 68 166 7,733 146 8,267 19
N, female 78 34 65 2,550 33 2,770 10
N – number of incident cases; AAIR – age-adjusted incidence rate (incident cases/100,000 person years at risk); IRR – incidence rate ratio (IRR age, per 10 years of age,
adjusted by sex; IRR sex, male versus female, adjusted by age); RERI age-sex – relative excess risk due to interaction between older age (>60 years old) and male sex,
parentheses identify 95% conPidence intervals. NA – statistic cannot be calculated.

26
26
26
Table 4. Incident Urothelial Carcinoma Diagnosed at SpeciPic Subsites and within the Entire Bladder according to Demographic Factors, SEER+NPCR Reporting Area,
2001-2020
Renal Pelvis Ureter Uretic OriPice Body of Bladder Bladder neck Entire Bladder Urethra
All Participants
N, male 41,069 22,237 33,468 942,103 32,368 1,075,846 4,601
N, female 28,909 13,713 12,974 293,528 6,566 356,710 1,020
AAIR, male 1.387
(1.373, 1.4)
0.758
(0.748, 0.769)
1.099
(1.087, 1.111)
31.754
(31.689, 31.819)
1.108
(1.095, 1.12)
36.266
(36.196, 36)
0.16
(0.156, 0.165)
AAIR,
female
0.755
(0.746, 0.764)
0.356
(0.35, 0.362)
0.341
(0.335, 0.347)
7.654
(7.626, 7.626)
0.171
(0.167, 0.167)
9.304
(9.273, 9.335)
0.027
(0.025, 0.028)
IRR age
45-59 years
60-69 years
70-79 years
80+ years
1
3.75 (2.94, 4.80)
9.10 (7.12, 11.62)
14.26 (11.03,
18.43)
1
4.79 (3.47, 6.61)
12.18 (8.79, 16.88)
18.57 (13.28,
25.98)
1
3.33 (2.05, 5.42)
6.08 (3.74, 9.90)
7.85 (4.76, 12.95)
1
3.70 (2.68, 5.10)
7.84 (5.68, 10.81)
11.69 (8.47, 16.14)
1
3.75 (2.74, 5.15)
8.70 (6.36, 11.91)
14.15 (10.24,
19.57)
1
3.75 (2.74, 5.11)
8.06 (5.91, 10.99)
11.98 (8.78, 16.35)
1
2.96 (1.84, 4.77)
6.68 (4.13, 10.80)
13.33 (7.56, 23.53)
IRR sex 1.86 (1.56, 2.22) 1.89 (1.51, 2.38) 3.02 (2.13, 4.28) 3.84 (3.06, 4.83) 5.74 (4.59, 7.17) 3.60 (2.89, 4.49) 3.30 (2.30, 4.72)
RERI age-sex 5.81 (0.22, 11.41) 9.21 (0.81, 17.60) 9.31 (1.99, 16.62) 19.48 (8.22, 30.74) 35.91 (13.43,
58.39)
18.29 (7.68, 28.90) 12.81 (1.24, 24.37)
Non-Hispanic White
N, male 34,143 19,222 29,310 812,932 27,583 927,026 3,836
N, female 23,954 11,464 11,337 245,445 5,382 298,300 718
AAIR, male 1.496
(1.48, 1.512)
0.843
(0.831, 0.855)
1.263
(1.248, 1.278)
35.502
(35.424, 35.581)
1.22
(1.205, 1.235)
40.496
(40.413, 41)
0.172
(0.166, 0.177)
AAIR,
female
0.821
(0.811, 0.832)
0.391
(0.384, 0.398)
0.402
(0.394, 0.409)
8.524
(8.49, 8.559)
0.186
(0.181, 0.191)
10.348
(10.311, 10.386)
0.025
(0.023, 0.027)
IRR age
45-59 years
60-69 years
70-79 years
80+ years
1
3.79 (3.54, 4.05)
9.32 (8.72, 9.95)
14.02 (13.1, 15.0)
1
4.82 (4.62, 5.04)
12.38 (11.89,
12.91)
17.84 (17.04,
18.68)
1
3.02 (2.72, 3.36)
5.42 (4.87, 6.02)
6.41 (5.75, 7.15)
1
3.48 (3.03, 4.00)
7.15 (6.22, 8.22)
9.90 (8.61, 11.38)
1
3.65 (3.20, 4.16)
8.36 (7.33, 9.53)
12.61 (11.03,
14.41)
1
3.51 (2.12, 3.95)
7.35 (6.53, 8.27)
10.23 (9.09, 11.51)
1
3.78 (2.80, 5.12)
9.23 (6.83, 12.47)
16.52 (12.15,
22.46)
IRR sex 1.83 (1.75, 1.92) 2.14 (2.08, 2.19) 3.13 (2.90, 3.38) 4.02 (3.64, 4.43) 6.20 (5.65, 6.79) 3.78 (3.48, 4.11) 6.26 (5.09, 7.71)
RERI age-sex 6.34 (-4.72, 17.40) 11.77 (-4.21,
27.74)
8.75 (2.40, 15.10) 18.02 (1.66, 34.38) 36.33 (-0.58,
73.24)
17.11 (1.08, 33.13) 43.04 (-7.10,
93.18)
Non-Hispanic Black
N, male 2,182 718 1,042 42,022 1,759 48,088 365
N, female 1,740 649 467 20,265 536 23,839 182
AAIR, male 0.801
(0.766, 0.837)
0.288
(0.266, 0.311)
0.386
(0.361, 0.411)
16.556
(16.388, 16.725)
0.705
(0.67, 0.74)
18.884
(18.705, 19.064)
0.149
(0.133, 0.166)
AAIR,
female
0.469
(0.447, 0.492)
0.177
(0.164, 0.191)
0.124
(0.113, 0.136)
5.482
(5.406, 5.559)
0.144
(0.132, 0.157)
6.443
(6.36, 6.526)
0.046
(0.04, 0.054)

27
27
27
IRR age
45-59 years
60-69 years
70-79 years
80+ years
1
3.25 (2.73, 3.89)
6.17 (5.16, 7.37)
8.18 (6.73, 9.95)
1
4.59 (3.87, 5.44)
10.58 (8.97, 12.48)
14.25 (11.61,
17.50)
1
3.11 (2.71, 3.58)
5.51 (4.77, 6.36)
7.56 (6.21, 9.21)
1
3.84 (3.72, 3.96)
7.78 (7.53, 8.03)
11.39 (10.99,
11.81)
1
3.69 (3.26, 4.17)
8.29 (7.35, 9.35)
11.67 (9.99, 13.64)
1
3.78 (3.68, 3.89)
7.65 (7.43, 7.88)
11.10 (10.74,
11.48)
1
2.96 (1.84, 4.77)
6.68 (4.13, 10.80)
13.33 (7.56, 23.53)
IRR sex 1.73 (1.51, 1.97) 1.66 (1.48, 1.86) 3.22 (2.94, 3.74) 3.05 (2.98, 3.12) 4.86 (4.38, 5.41) 2.96 (2.90, 3.02) 2.28 (1.80, 2.91)
RERI age-sex 2.19 (-2.71, 7.09) 6.79 (-3.94, 17.53) 9.69 (0.61, 18.77) 13.62 (-0.60,
27.84)
26.06 (0.67, 51.45) 12.69 (-0.59,
25.97)
8.37 (0.65, 16.10)
Non-Hispanic American Indian/Alaska Native
N, male 137 57 86 2,799 93 3,189 17
N, female 86 50 33 828 23 1,025 5
AAIR, male 0.778
(0.643, 0.932)
0.329
(0.244, 0.432)
0.48
(0.378, 0.6)
17.101
(16.42, 17.801)
0.631
(0.5, 0.781)
19.425
(18.7, 20.168)
0.106
(0.06, 0.172)
AAIR,
female
0.444
(0.353, 0.55)
0.256
(0.188, 0.34)
0.155
(0.105, 0.219)
3.981
(3.705, 4.271)
0.113
(0.071, 0.171)
4.974
(4.664, 5.298)
NA
IRR age
45-59 years
60-69 years
70-79 years
80+ years
1
3.29 (2.13, 5.10)
6.79 (4.37, 10.56)
-
1
-
2.17 (1.15, 4.09)
-
1
3.38 (1.93, 5.93)
5.31 (2.90, 9.72)
-
1
3.45 (3.14, 3.78)
7.14 (6.50, 7.84)
11.87 (10.5, 13.42)
1
-
2.39 (1.45, 3.95)
-
1
3.58 (3.28, 3.91)
7.43 (6.80, 8.11)
12.00 (10.7, 13.46)
NA
IRR sex 1.73 (1.23, 2.42) 1.33 (0.69, 2.59) NA 4.23 (3.89, 4.60) NA 3.88 (3.60, 4.19) NA
RERI age-sex NA NA NA 20.76 (-0.64,
42.16)
NA 19.49 (-0.90,
39.89)
NA
Non-Hispanic Asian or PaciPic Islander
N, male 980 664 511 15,648 598 18,481 80
N, female 803 526 212 4,815 129 6,518 33
AAIR, male 0.842
(0.788, 0.898)
0.572
(0.528, 0.618)
0.421
(0.384, 0.46)
13.434
(13.217, 13.654)
0.518
(0.476, 0.562)
15.858
(15.622, 16.096)
0.071
(0.056, 0.089)
AAIR,
female
0.534
(0.487, 0.573)
0.349
(0.32, 0.381)
0.134
(0.116, 0.153)
3.137
(3.048, 3.228)
0.086
(0.071, 0.102)
4.261
(4.157, 4)
0.021
(0.015, 0.03)
IRR age
45-59 years
60-69 years
70-79 years
80+ years
1
4.34 (3.70, 5.08)
11.46 (9.86, 13.31)
17.18 (14.38,
20.53)
1
6.02 (4.89, 7.42)
15.36 (12.57,
18.77)
23.12 (18.34,
29.14)
1
3.02 (2.43, 3.76)
6.50 (5.26, 8.02)
9.33 (7.10, 12.25)
1
3.93 (3.76, 4.11)
9.05 (8.67, 9.45)
15.54 (14.77,
16.36)
1
3.60 (2.83, 4.58)
10.30 (8.23, 12.89)
17.62 (13.53,
22.94)
1
3.98 (3.82, 4.14)
9.36 (9.00, 9.73)
15.7 (15.00, 16.46)
1
-
3.41 (1.85, 6.28)
-
IRR sex 1.62 (1.46, 1.79) 1.71 (1.51, 1.93) 3.10 (2.61, 3.70) 4.28 (4.13, 4.44) 6.17 (5.01, 7.59) 3.73 (3.61, 3.84) NA
RERI age-sex 5.29 (-6.57, 17.14) 8.83 (-7.55, 25.20) 10.58 (-0.40,
21.56)
26.71 (-4.71,
58.13)
42.79 (-17.79,
103.37)
22.95 (-4.75,
50.65)
NA
Hispanic (All Races)
N, male 2,422 975 1,308 38,590 1,361 44,861 205

28
28
28
N, female 1,558 644 475 4,815 296 15,750 63
AAIR, male 1.064
(1.019, 1.11)
0.444
(0.415, 0.474)
0.535
(0.504, 0.567)
17.172
(16.99, 17.355)
0.613
(0.579, 0.649)
19.927
(19.731, 20.124)
0.071
(0.056, 0.089)
AAIR,
female
0.54
(-.513, 0.568)
0.227
(0.21, 0.246)
0.155
(0.141, 0.17)
4.239
(4.164, 4.315)
0.099
(0.088, 0.111)
5.28
(5.196, 5)
0.02
(0.015,0.025)
IRR age
45-59 years
60-69 years
70-79 years
80+ years
1
4.63 (4.18, 5.12)
11.96 (10.87,
13.17)
19.35 (17.36,
21.70)
1
6.23 (5.27, 7.38)
15.67 (13.32,
18.43)
24.19 (19.99,
29.27)
1
4.16 (3.64, 4.76)
8.22 (7.18, 9.40)
10.42 (8.68, 12.50)
1
4.30 (3.71, 4.97)
9.85 (8.52, 11.40)
15.14 (13.07,
17.54)
1
4.10 (3.51, 4.78)
11.90 (10.3, 13.75)
16.21 (13.49,
19.49)
1
4.38 (3.90, 4.90)
10.20 (9.10, 11.43)
15.66 (13.95,
17.58)
1
7.61 (4.68, 12.39)
18.83 (11.69,
30.35)
41.36 (24.34,
70.30)
IRR sex 1.97 (1.84, 2.11) 2.03 (1.82, 2.27) 3.37 (3.01, 3.77) 3.81 (3.44, 4.23) 5.87 (5.11, 6.75) 3.57 (3.30, 3.88) 3.75 (2.61, 5.39)
RERI age-sex 9.78 (-7.66, 27.22) 15.29 (-7.16,
37.74)
14.80 (1.01, 28.60) 24.62 (-1.66,
50.90)
42.46 (-4.84,
89.76)
23.31 (-2.24,
48.87)
NA
Suppressed (North Dakota and Wisconsin)
N, male 1078 536 1,045 22,445 832 26,020 84
N, female 694 347 386 6,942 267 8,552 16
AAIR, male 1.646
(1.548, 1.749)
0.828
(0.758, 0.902)
1.55
(1.456, 1.648)
34.411
(33.956, 34.87)
1.29
(1.203, 1.382)
39.856
(39.367, 40)
0.132
(0.105, 0.164)
AAIR,
female
0.832
(0.77, 0.897)
0.417
(0.374, 0.464)
0.479
(0.432, 0.531)
8.464
(8.263, 8.669)
0.201
(0.171, 0.235)
10.411
(10.188, 10.638)
0.018
(0.01, 0.031)
IRR age
45-59 years
60-69 years
70-79 years
80+ years
1
3.42 (2.83, 4.12)
8.86 (7.33, 10.71)
13.24 (10.82,
16.19)
1
3.82 (3.01, 4.85)
10.17 (8.15, 12.70)
15.60 (12.15,
20.02)
1
3.65 (3.12, 4.27)
6.25 (5.34, 7.31)
7.57 (6.21, 9.23)
1
3.69 (3.28, 4.15)
8.08 (7.19, 9.08)
11.48 (10.19,
12.93)
1
4.03 (3.23, 5.02)
9.07 (7.34, 11.20)
16.61 (13.16,
20.98)
1
3.72 (3.42, 4.04)
8.25 (7.60, 8.96)
11.78 (10.80,
12.84)
1
-
2.79 (1.60, 4.89)
-
IRR sex 2.03 (1.78, 2.31) 1.93 (1.66, 2.24) 3.17 (2.80, 3.59) 3.87 (3.56, 4.20) 6.28 (5.20, 7.58) 3.68 (3.47, 3.90) NA
RERI age-sex 8.17 (-7.21, 23.56) 8.73 (-6.60, 24.07) 10.23 (2.31, 18.14) 19.52 (0.37, 38.67) 49.40 (-8.71,
107.51)
18.60 (-0.14,
37.35)
NA
Non-Hispanic Unknown Race
N, male 127 65 166 7,667 142 8,181 14
N, female 74 33 64 2,519 33 2,726 3
N – number of incident cases; AAIR – age-adjusted incidence rate (incident cases/100,000 person years at risk); IRR – incidence rate ratio (IRR age, per 10 years of age,
adjusted by sex; IRR sex, male versus female, adjusted by age); RERI age-sex – relative excess risk due to interaction between older age (>60 years old) and male sex,
parentheses identify 95% conPidence intervals. NA – statistic cannot be calculated.

29
29
29
Table 5. Incident Squamous Cell Carcinoma Diagnosed at SpeciPic Subsites and within the Entire Bladder according to Demographic Factors, SEER+NPCR Reporting
Area, 2001-2020
Renal Pelvis Ureter Uretic OriPice Body of Bladder Bladder neck Entire Bladder Urethra
All Participants
N, male 867 280 83 7,430 272 10,522 1,590
N, female 711 229 48 7,652 191 9,687 856
AAIR, male 0.029
(0.027, 0.031)
0.01
(0.009, 0.011)
0.003
(0.002, 0.004)
0.254
(0.248, 0.26)
0.01
(0.009, 0.011)
0.356
(0.349, 0.363)
0.051
(0.048, 0.054)
AAIR, female 0.019
(0.017, 0.02)
0.006
(0.005, 0.007)
0.001
(0.001, 0.002)
0.201
(0.197, 0.206)
0.005
(0.004, 0.006)
0.255
(0.25, 0.26)
0.023
(0.021, 0.024)
IRR age
45-59 years
60-69 years
70-79 years
80+ years
1
3.11 (2.62, 3.72)
7.33 (6.23, 8.34)
10.74 (8.82,
13.09)
1
3.53 (2.40, 5.19)
11.52 (8.13, 16.32)
19.51 (13.35,
28.51)
NA 1
2.63 (1.92, 3.60)
5.31 (3.90, 7.22)
9.89 (7.18, 13.63)
1
2.26 (1.31, 3.90)
7.16 (4.28, 12.00)
13.71 (8.02, 23.42)
1
2.57 (1.84, 3.59)
5.45 (3.89, 7.65)
9.11 (6.47, 12.83)
1
2.03 (1.28, 3.22)
3.68 (2.32, 5.85)
4.97 (2.87, 8.59)
IRR sex 1.50 (1.33, 1.68) 1.65 (1.33, 2.04) NA 1.10 (0.89, 1.37) 1.78 (1.24, 2.56) 1.30 (1.03, 1.64) 2.33 (1.63, 3.33)
RERI age-sex 1.28 (-2.72, 5.29) 7.04 (-7.12, 21.09) NA 0.93 (-1.49, 3.36) 6.46 (-3.14, 16.07) 1.89 (-0.59, 4.37) 2.98 (-0.37, 6.33)
Non-Hispanic White
N, male 661 239 71 5,911 224 8,257 1,151
N, female 567 178 42 5,837 144 7,385 617
AAIR, male 0.029
(0.027, 0.031)
0.011
(0.009, 0.012)
0.003
(0.003, 0.004)
0.262
(0.255, 0.269)
0.01
(0.009, 0.012)
0.365
(0.357, 0.373)
0.05
(0.047, 0.053)
AAIR, female 0.02
(0.018, 0.021)
0.006
(0.005, 0.007)
0.001
(0.001, 0.002)
0.205
(0.199, 0.21)
0.005
(0.004, 0.006)
0.259
(0.253, 0.265)
0.022
(0.02, 0.024)
IRR age
45-59 years
60-69 years
70-79 years
80+ years
1
3.16 (2.60, 3.83)
7.77 (6.49, 9.30)
11.15 (9.06,
13.73)
1
3.53 (2.40, 5.19)
11.52 (8.13, 16.33)
19.51 (13.35,
28.51)
NA 1
2.54 (2.22, 2.90)
5.83 (5.11, 6.66)
9.64 (8.42, 11.04)
1
2.26 (1.31, 3.90)
7.16 (4.28, 12.00)
13.71 (8.02, 23.42)
1
2.57 (2.37, 2.78)
5.84 (5.41, 6.30)
9.38 (8.65, 10.17)
1
2.28 (1.86, 2.78)
4.14 (3.38, 5.06)
5.58 (4.43, 7.02)
IRR sex 1.46 (1.29, 1.65) 1.65 (1.33, 2.04) NA 1.30 (1.18, 1.42) 1.78 (1.24, 2.56) 1.43 (1.35, 1.51) 2.28 (1.97, 2.65)
RERI age-sex 2.51 (-4.09, 9.11) 7.04 (-7.12, 21.09) NA 2.16 (-2.56, 6.89) 6.46 (-3.14, 16.07) 2.47 (-2.59, 7.53) 2.72 (-2.04, 7.48)
Non-Hispanic Black
N, male 66 < < 799 29 1,200 287
N, female 59 < < 998 35 1,255 146
AAIR, male 0.023
(0.018, 0.03)
NA NA 0.329
(0.305, 0.354)
0.013
(0.009, 0.019)
0.472
(0.444, 0.501)
0.1
(0.088, 0.112)
AAIR, female 0.016
(0.012, 0.02)
NA NA 0.267
(0.25, 0.284)
0.009
(0.006, 0.012)
0.334
(0.316, 0.354)
0.038
(0.032, 0.045)
IRR age

30
30
30
45
-59 years
60
-69 years
70
-79 years
80+ years
1
3.27 (1.76, 6.05)
4.67 (2.39, 9.19) -
NA NA
1
2.53 (1.97, 3.24)
5.86 (4.58, 7.50)
9.08 (6.94, 11.88)
NA
1
2.42 (2.01, 2.92)
5.13 (4.26, 6.17)
7.81 (6.34, 9.61)
1
1.97 (1.54, 2.53)
3.42 (2.65, 4.43)
4.60 (2.89, 7.31)
IRR sex 1.31 (0.67, 2.57) NA NA 1.16 (0.96, 1.39) NA 1.40 (1.22, 1.60) 2.80 (2.23, 3.51)
RERI age
-sex NA NA NA 1.98 (
-1.87, 5.83) NA 2.39 (
-1.37, 6.16) 4.08 (0.49, 7.68)
Non
-Hispanic American Indian/Alaska Native
N, male
<
<
< 29
< 37
<
N, female
<
<
< 40
< 42
<
AAIR, male NA NA NA 0.187
(0.12, 0.274)
NA 0.231
(0.158, 0.325)
NA
AAIR, female NA NA NA 0.173
(0.122, 0.238)
NA 0.184
(0.131, 0.251)
NA
IRR age
45
-59 years
60
-69 years
70
-79 years
80+ years
NA NA NA NA NA NA NA
IRR sex NA NA NA NA NA NA NA
RERI age
-sex NA NA NA NA NA NA NA
Non
-Hispanic Asian or PaciPic Islander
N, male 34
<
< 125
< 190 18
N, female 25
<
< 85
< 142 17
AAIR, male 0.028
(0.019, 0.04)
NA NA 0.114
(0.094, 0.137)
NA 0.168
(0.144, 0.195)
0.013
(0.008, 0.021)
AAIR, female 0.016
(0.012, 0.02)
NA NA 0.057
(0.046, 0.071)
NA 0.094
(0.079, 0.111)
0.011
(0.006, 0.017)
IRR age
45
-59 years
60
-69 years
70
-79 years
80+ years
NA NA NA
1-
3.06 (1.84, 5.08)
5.85 (3.21, 10.69)
NA
1
3.57 (2.24, 5.71)
10.36 (6.64, 16.18)
17.15 (10.43, 28.18)
NA
IRR sex NA NA NA 1.78 (1.10, 2.90) NA 1.64 (1.26, 2.15) NA
RERI age
-sex NA NA NA NA NA NA NA
Hispanic (All Races)
N, male 84
<
< 393
< 595 97
N, female 25 21
< 497
< 618 51
AAIR, male 0.033
(0.026, 0.042)
NA NA 0.173
(0.155, 0.192)
NA 0.251
(0.23, 0.274)
0.036
(0.028, 0.044)
AAIR, female 0.017
(0.011, 0.025)
0.007
(0.005, 0.011)
NA 0.168
(0.153, 0.184)
NA 0.208
(0191, 0.225)
0.017
(0.013, 0.023)
IRR age
45
-59 years NA NA NA
1 NA
1
1

31
31
31
60-69 years
70-79 years
80+ years
3.48 (2.82, 4.29)
8.41 (6.89, 10.27)
16.66 (13.23,
20.98)
3.16 (2.66, 3.75)
7.27 (6.16, 8.57)
13.49 (11.08, 16.43)
2.11 (1.29, 3.44)
3.54 (2.10, 5.96)
-
IRR sex NA NA NA 1.05 (0.09, 1.21) NA 1.28 (1.13, 1.44) NA
RERI age-sex NA NA NA 0.42 (-7.15, 8.00) NA 0.66 (-6.47, 7.79) NA
Suppressed (North Dakota and Wisconsin)
N, male 19 < < 175 < 216 28
N, female < < < 155 < 219 22
AAIR, male 0.03
(0.018, 0.047)
NA NA 0.236
(0.2, 0.277)
NA 0.329
(0.286, 0.376)
0.041
(0.027, 0.059)
AAIR, female NA NA NA 0.207
(0.176, 0.241)
NA 0.262
(0.228, 0.301)
0.029
(0.018, 0.044)
IRR age
45-59 years
60-69 years
70-79 years
80+ years
NA NA NA 1
2.61 (1.82, 3.73)
4.72 (3.32, 6.70)
8.83 (5.95, 13.09)
NA 1
2.71 (1.99, 3.68)
4.97 (3.69, 6.70)
8.87 (6.32, 12.45)
NA
IRR sex NA NA NA 1.19 (0.92, 1.54) NA 1.29 (1.04, 1.60) NA
RERI age-sex NA NA NA -0.78 (-5.56, 3.99) NA 0.46 (-4.05, 4.97) NA
Non-Hispanic Unknown Race
N, male < < < 18 < 27 <
N, female < < < 20 < 26 <
N – number of incident cases; AAIR – age-adjusted incidence rate (incident cases/100,000 person years at risk); IRR – incidence rate ratio (IRR age, per 10 years of age,
adjusted by sex; IRR sex, male versus female, adjusted by age); RERI age-sex – relative excess risk due to interaction between older age (>60 years old) and male sex,
parentheses identify 95% conPidence intervals. < – statistic not displayed due to less than 16 cases; NA – statistic cannot be calculated.

32
32
32
Table 6. Incident Adenocarcinoma Diagnosed at SpeciPic Subsites and within the Entire Bladder according to Demographic Factors, SEER+NPCR Reporting Area,
2001-2020
Renal Pelvis Ureter Uretic OriPice Body of Bladder Bladder neck Entire Bladder Urethra
All Participants
N, male 245 105 67 4,446 321 5,593 410
N, female 155 99 26 2,207 123 3,267 657
AAIR, male 0.008
(0.007, 0.009)
0.003
(0.003, 0.004)
0.002
(0.002, 0.003)
0.15
(0.146, 0.155)
0.011
(0.01, 0.013)
0.189
(0.184, 0.0194)
0.014
(0.013, 0.016)
AAIR, female 0.004
(0.004, 0.005)
0.003
(0.002, 0.003)
0.001
(0, 0.001)
0.058
(0.056, 0.061)
0.003
(0.003, 0.004)
0.086
(0.084, 0.09)
0.017
(0.016, 0.019)
IRR age
45-59 years
60-69 years
70-79 years
80+ years
1
2.73 (1.94, 3.85)
5.87 (4.25, 8.11)
-
1
-
2.18 (1.44, 3.31)
-
NA 1
2.85 (2.04, 3.98)
5.41 (3.87, 7.56)
8.32 (5.77, 12.00)
1
1.23 (0.40, 3.77)
2.43 (0.77, 7.68)
4.72 (0.99, 22.57)
1
2.66 (1.75, 4.05)
5.03 (3.30, 7.66)
8.08 (5.11, 12.77)
1
2.49 (0.74, 8.35)
3.05 (0.87, 10.75)
5.20 (1.39, 19.39)
IRR sex 1.96 (1.51, 2.54) 1.12 (0.75, 1.70) NA 2.14 (1.67, 2.75) 2.28 (0.84, 6.19) 1.73 (1.27, 2.36) 0.35 (0.14, 0.88)
RERI age-sex 2.98 (-1.76, 7.71) NA NA 4.73 (1.04, 8.41) 3.03 (0.16, 5.91) 3.87 (0.76, 6.98) -0.27 (-2.42, 1.88)
Non-Hispanic White
N, male 192 74 58 3,327 228 4,175 296
N, female 119 79 21 1,564 69 2,150 298
AAIR, male 0.008
(0.007, 0.01)
0.003
(0.002, 0.004)
0.003
(0.002, 0.003)
0.147
(0.0142, 0.152)
0.01
(0.009, 0.012)
0.185
(0.179, 0.191)
0.013
(0.012, 0.015)
AAIR, female 0.004
(0.004, 0.005)
0.003
(0.002, 0.003)
0.001
(0, 0.001)
0.055
(0.052, 0.058)
0.002
(0.002, 0.003)
0.076
(0.073, 0.079)
0.07
(0.016, 0.019)
IRR age
45-59 years
60-69 years
70-79 years
80+ years
1
2.73 (1.94, 3.85)
5.87 (4.25, 8.11)
-
1
-
2.18 (1.44, 3.31)
-
NA 1
2.79 (2.27, 3.43)
5.73 (4.67, 7.04)
8.58 (3.92, 18.77)
1
3.97 (2.42, 6.53)
9.44 (5.86, 15.22)
23.97 (14.45, 39.77)
1
2.85 (2.16, 3.76)
5.61 (4.25, 7.39)
8.34 (6.29, 11.06)
1
3.07 (1.47, 6.42)
4.12 (1.95, 8.71)
8.58 (3.92, 18.77)
IRR sex 1.96 (1.51, 2.54) 1.12 (0.75, 1.70) NA 2.66 (2.30, 3.08) 3.03 (2.12, 4.35) 2.38 (1.95, 2.90) 1.10 (0.63, 1.91)
RERI age-sex 2.98 (-1.76, 7.71) NA NA 8.62 (-0.17, 17.41) NA 7.53 (0.08, 14.98) 2.93 (-0.48, 6.33)
Non-Hispanic Black
N, male 32 16 5 551 57 725 64
N, female 25 < < 353 46 716 279
AAIR, male 0.011
(0.007, 0.015)
0.006
(0.003, 0.01)
NA 0.203
(0.0185, 0.222)
0.021
(0.016, 0.028)
0.269
(0.248, 0.291)
0.026
(0.019, 0.033)
AAIR, female 0.006
(0.004, 0.01)
NA NA 0.092
(0.082, 0.102)
0.012
(0.008, 0.016)
0.184
(0.171, 0.199)
0.07
(0.062, 0.079)
IRR age
45-59 years
60-69 years
70-79 years
80+ years
NA NA NA 1
2.51 (2.11, 3.00)
3.93 (3.26, 4.73)
5.98 (4.65, 7.69)
1
2.56 (1.30, 5.01)
4.96 (2.51, 9.82)
-
1
2.31 (1.96, 2.71)
3.50 (2.95, 4.14)
4.88 (3.92, 6.08)
1
1.89 (1.41, 2.53)
2.36 (1.71, 3.26)
2.58 (1.58, 4.21)

33
33
33
IRR sex NA NA NA 2.19 (1.89, 2.53) 1.03 (0.53, 1.98) 1.33 (1.17, 1.53) 0.26 (0.16, 0.44)
RERI age
-sex NA NA NA 3.72 (0.16, 7.27) NA 1.60 (
-0.11, 3.31) NA
Non
-Hispanic American Indian/Alaska Native
N, male
<
<
< 27
< 34
<
N, female
<
<
<
<
< 19
<
AAIR, male NA NA NA 0.154 (0.098,
0.229)
NA 0.201 (0.135,
0.286)
NA
AAIR, female NA NA NA NA NA 0.085 (0.05, 0.133) NA
IRR age
45
-59 years
60
-69 years
70
-79 years
80+ years
NA NA NA NA NA NA NA
IRR sex NA NA NA NA NA NA NA
RERI age
-sex NA NA NA NA NA NA NA
Non
-Hispanic Asian or PaciPic Islander
N, male
<
<
< 106
< 130
<
N, female
<
<
< 61
< 89 21
AAIR, male NA NA NA 0.086 (0.07, 0.105) NA 0.108 (0.089,
0.129)
NA
AAIR, female NA NA NA 0.039 (0.03, 0.05) NA 0.056 (0.045,
0.070)
0.012 (0.008,
0.019)
IRR age
45
-59 years
60
-69 years
70
-79 years
80+ years
NA NA NA
1
4.29 (2.32, 7.92)
10.08 (5.58, 18.22) -
NA
1
3.00 (1.98, 4.55)
7.19 (4.85, 10.66) -
NA
IRR sex NA NA NA NA NA 1.89 (1.37, 2.61) NA
RERI age
-sex NA NA NA NA NA 4.20 (0.43, 8.83) NA
Hispanic (All Races)
N, male
<
<
< 305 16 362 27
N, female
<
<
< 165
< 222 40
AAIR, male NA NA NA 0.124 (0.109, 0.14) 0.009 (0.005, 0.014) 0.151 (0.134,
0.168)
0.012 (0.008,
0.018)
AAIR, female NA NA NA 0.052 (0.044,
0.061)
NA 0.07 (0.061, 0.080) 0.012 (0.009,
0.017)
IRR age
45
-59 years
60
-69 years
70
-79 years
80+ years
NA NA NA
1
4.09 (3.10, 5.38)
7.41 (5.60, 9.81)
11.19 (7.81, 16.03)
NA
1
3.76 (2.95, 4.81)
6.98 (5.45, 8.94)
10.86 (7.92, 14.90)
NA
IRR sex NA NA NA 2.22 (1.79, 2.75) NA 1.88 (1.55, 2.27) NA
RERI age
-sex NA NA NA 6.34 (
-0.68, 13.37) NA 5.15 (
-0.65, 10.94) NA

34
34
34
Suppressed (North Dakota and Wisconsin)
N, male < < < 101 < 131 <
N, female < < < 41 < 58 <
AAIR, male NA NA NA 0.159 (0.129,
0.193)
NA 0.207 (0.172,
0.246)
NA
AAIR, female NA NA NA 0.05 (0.035, 0.068) NA 0.072 (0.054,
0.094)
NA
IRR age
45-59 years
60-69 years
70-79 years
80+ years
NA NA NA 1
-
2.88 (1.65, 5.02)
-
NA 1
3.09 (1.70, 5.64)
8.94 (5.15, 15.49)
12.59 (6.55, 24.19)
NA
IRR sex NA NA NA NA NA NA NA
RERI age-sex NA NA NA NA NA NA NA
Non-Hispanic Unknown Race
N, male < < < 29 < 36 <
N, female < < < < < 13 <
N – number of incident cases; AAIR – age-adjusted incidence rate (incident cases/100,000 person years at risk); IRR – incidence rate ratio (IRR age, per 10 years of age,
adjusted by sex; IRR sex, male versus female, adjusted by age); RERI age-sex – relative excess risk due to interaction between older age (>60 years old) and male sex,
parentheses identify 95% conPidence intervals. < – statistic not displayed due to less than 16 cases; NA – statistic cannot be calculated.

35
35
35
Table 7. Incident Small Cell Carcinoma Diagnosed at SpeciPic Subsites and within the Entire Bladder according to Demographic Factors, SEER+NPCR Reporting Area,
2001-2020
Renal Pelvis Ureter Uretic OriPice Body of Bladder Bladder neck Entire Bladder Urethra
All Participants
N, male 470 173 90 8,169 393 9,391 96
N, female 356 113 29 2,309 58 2,890 25
AAIR, male 0.016
(0.014, 0.017)
0.006
(0.005, 0.007)
0.003
(0.002, 0.004)
0.279
(0.271, 0.285)
0.014
(0.013, 0.015)
0.321
(0.315, 0.328)
0.003
(0.003, 0.004)
AAIR, female 0.01
(0.009, 0.011)
0.003
(0.002, 0.004)
0.001
(0.001, 0.001)
0.06
(0.058, 0.063)
0.001
(0.001, 0.002)
0.076
(0.073, 0.079)
0.003
(0.003, 0.004)
IRR age
45-59 years
60-69 years
70-79 years
80+ years
1
2.69 (2.07, 3.51)
7.01 (5.50, 8.93)
10.59 (7.64, 13.44)
1
-
3.02 (1.99,
4.57)
4.07 (2.52,
6.57)
1
-
2.68 (1.44, 5.00)
-
1
4.32 (3.18, 5.86)
9.95 (7.38, 13.42)
16.70 (12.23,
22.79)
1
3.87 (2.42, 6.21)
16.42 (10.78, 25.01)
29.34 (18.67, 46.10)
1
4.13 (3.05, 5.61)
9.19 (6.86, 12.32)
16.18 (11.87, 22.08)
1
-
-
2.87 (1.59,
5.19)
IRR sex 1.63 (1.37, 1.93) 1.87 (1.34,
2.63)
NA 3.69 (2.96, 4.60) NA 3.57 (2.88, 4.43) NA
RERI age-sex 4.39 (-3.38, 12.16) NA NA 24.63 (6.58, 42.68) NA 22.15 (6.23, 38.06) NA
Non-Hispanic White
N, male 365 150 82 7,009 334 8,016 76
N, female 273 95 23 1,884 46 2,339 18
AAIR, male 0.016
(0.015, 0.018)
0.007
(0.006, 0.008)
0.004
(0.003, 0.005)
0.308
(0.301, 0.316)
0.015
(0.014, 0.017)
0.353
(0.346, 0.361)
0.001
(0, 0.001)
AAIR, female 0.01
(0.009, 0.011)
0.003
(0.003, 0.004)
0.001
(0.001, 0.001)
0.064
(0.062, 0.068)
0.001
(0.001, 0.002)
0.081
(0.078, 0.084)
0.001
(0, 0.001)
IRR age
45-59 years
60-69 years
70-79 years
80+ years
1
2.69 (2.07, 3.51)
7.01 (5.50, 8.93)
10.59 (7.64, 13.44)
1
-
3.02 (1.99,
4.57)
4.07 (2.52,
6.57)
1
-
2.68 (1.44, 5.00)
-
1
4.17 (3.87, 4.50)
9.36 (8.71, 10.06)
14.46 (13.32,
15.69)
1
3.87 (2.42, 6.21)
16.42 (10.78, 25.01)
29.34 (18.67, 46.10)
1
4.03 (3.76, 4.33)
9.44 (8.83, 10.09)
14.65 (13.58, 15.80)
1
-
-
2.87 (1.59,
5.19)
IRR sex 1.63 (1.37, 1.93) 1.87 (1.34,
2.63)
NA 4.56 (4.31, 4.83) NA 4.21 (4.00, 4.43) NA
RERI age-sex NA NA NA 28.07 (-1.68,
57.83)
NA 25.62 (-2.40, 53.66) NA
Non-Hispanic Black
N, male 44 < < 373 23 458 <
N, female 35 < < 198 < 248 <
AAIR, male 0.016 (0.011, 0.022) NA NA 0.152 (0.136,
0.169)
0.01 (0.006, 0.015) 0.185 (0.168, 0.204) NA

36
36
36
AAIR, female 0.009 (0.006, 0.013) NA NA 0.054 (0.047,
0.062)
NA 0.067 (0.058, 0.076) NA
IRR age
45
-59 years
60
-69 years
70
-79 years
80+ years
NA NA NA
1
4.85 (3.74, 6.29)
9.17 (7.05, 11.91)
15.59 (11.39,
21.33)
NA
1
4.55 (3.62, 5.72)
8.56 (6.80, 10.79)
13.32 (10.01, 17.73)
NA
IRR sex NA NA NA 2.74 (2.27, 3.31) NA 2.96 (2.27, 3.19) NA
RERI age
-sex NA NA NA 15.42 (
-1.66,
32.50)
NA 12.88 (0.42, 25.34) NA
Non
-Hispanic American Indian/Alaska Native
N, male
<
<
< 31
< 33
<
N, female
<
<
<
<
<
<
<
AAIR, male NA NA NA 0.195 (0.126,
0.283)
NA 0.202 (0.133, 0.181) NA
AAIR, female NA NA NA NA NA NA NA
IRR age
45
-59 years
60
-69 years
70
-79 years
80+ years
NA NA NA NA NA NA NA
IRR sex NA NA NA NA NA NA NA
RERI age
-sex NA NA NA NA NA NA NA
Non
-Hispanic Asian or PaciPic Islander
N, male 19
<
< 152
< 181
<
N, female
<
<
< 33
< 56
<
AAIR, male 0.015 (0.009, 0.024) NA NA 0.131 (0.111,
0.155)
NA 0.156 (0.133, 0.181) NA
AAIR, female NA NA NA 0.011 (0.015,
0.031)
NA 0.037 (0.028, 0.048) NA
IRR age
45
-59 years
60
-69 years
70
-79 years
80+ years
NA NA NA
1
3.58 (2.17, 5.90)
8.33 (5.16, 13.45)
17.42 (10.06,
30.15)
NA
1
3.89 (2.44, 6.18)
8.11 (5.14, 12.79)
19.36 (11.67, 32.12)
NA
IRR sex NA NA NA NA NA 3.84 (2.22, 6.65) NA
RERI age
-sex NA NA NA NA NA NA NA
Hispanic (All Races)
N, male 30
<
< 385 21 453
<
N, female 23
<
< 142
< 177
<

37
37
37
AAIR, male 0.012 (0.008, 0.017) NA NA 0.173 (0.155,
0.192)
0.01 (0.006, 0.015) 0.201 (0.182, 0.222) NA
AAIR, female 0.007 (0.005, 0.011) NA NA 0.048 (0.041,
0.057)
NA 0.06 (0.051, 0.069) NA
IRR age
45-59 years
60-69 years
70-79 years
80+ years
NA NA NA
1
4.85 (3.70, 6.36)
10.21 (7.81, 13.35)
23.28 (12.23,
22.79)
NA 1
4.49 (3.51, 5.74)
9.65 (7.57, 12.29)
22.70 (17.33, 29.72)
NA
IRR sex NA NA NA 3.51 (2.84, 4.33) NA 3.40 (2.81, 4.11) NA
RERI age-sex NA NA NA 27.31 (-11.91,
66.53)
NA 26.51 (-11.33, 64.35) NA
Suppressed (North Dakota and Wisconsin)
N, male < < < 200 < 227 <
N, female < < < 41 < 53 <
AAIR, male NA NA NA 0.308 (0.266,
0.354)
NA 0.352 (0.307, 0.401) NA
AAIR, female NA NA NA 0.051 (0.036, 0.07) NA 0.066 (0.049, 0.087) NA
IRR age
45-59 years
60-69 years
70-79 years
80+ years
NA NA
NA
1
4.90 (2.93, 8.17)
13.00 (8.00, 21.12)
19.78 (11.44,
34.18)
NA 1
4.84 (2.96, 7.91)
12.85 (8.07, 20.44)
21.89 (13.11, 36.56)
NA
IRR sex NA NA NA 5.09 (3.00, 8.62) NA 4.46 (2.75, 7.21) NA
RERI age-sex NA NA NA NA NA NA NA
Non-Hispanic Unknown Race
N, male < < < 19 23 < <
N, female < < < < < < <
N – number of incident cases; AAIR – age-adjusted incidence rate (incident cases/100,000 person years at risk); IRR – incidence rate ratio (IRR age, per 10 years of age,
adjusted by sex; IRR sex, male versus female, adjusted by age); RERI age-sex – relative excess risk due to interaction between older age (>60 years old) and male sex,
parentheses identify 95% conPidence intervals. < – statistic not displayed due to less than 16 cases; NA – statistic cannot be calculated.

38
38
38
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Abstract (if available)

Abstract Background: Bladder cancer is a prevalent cancer in the US, with men experiencing three to four times higher incidence than women.

Objective: This study examines how histological type, anatomical site, age, and race/ethnicity influence gender disparities in bladder cancer incidence in the US from 2001 to 2020.

Methods: Age-adjusted incidence rates (AAIRs), age-specific incidence rates (ASIRs), and annual percent change (APC) were obtained from SEER and NPCR datasets (2001-2020). Multivariate negative binomial regression models estimated incidence rate ratios (IRR), relative excess risk due to interaction (RERI), and 95% confidence intervals (CIs).

Results: The highest AAIR was in the bladder body (men: 32.44; women: 7.97) and the lowest in the urethra (men: 0.23; women: 0.068). Older males have a higher risk. Bladder cancer incidence decreased (APC: -1.18). The IRR between genders was 3.51, highest in the bladder neck (5.53) and lowest in the renal pelvis (1.86). Non-Hispanic White participants had the highest risk, with similar IRR patterns across all racial/ethnic groups. The interaction between older age and male sex was significant (RERI: 17.47).

Conclusion: The combined effects of male sex and older age on urothelial carcinoma incidence are substantially greater than additive, with the largest deviations from additivity observed in bladder regions most exposed to retained urine. Findings suggest urine retention due to benign prostatic hyperplasia (BPH) may significantly contribute to the higher incidence of bladder cancer in men. Future research should evaluate the direct association between bladder cancer risk and BPH.

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Asset Metadata

Creator Zhou, Sichen (author)

Core Title Origins of the gender disparity in bladder cancer risk: a SEER analysis

School Keck School of Medicine

Degree Master of Science

Degree Program Applied Biostatistics and Epidemiology

Degree Conferral Date 2024-08

Publication Date 07/16/2024

Defense Date 07/16/2024

Publisher Los Angeles, California (original), University of Southern California (original), University of Southern California. Libraries (digital)

Tag bladder cancer,Epidemiology,incidence,negative binomial regression,seer,urothelial carcinoma

Format theses (aat)

Language English

Contributor Electronically uploaded by the author (provenance)

Advisor Cortessis, Victoria (committee chair), D'Souza, Anishka (committee member), Mack, Wendy (committee member)

Creator Email stellazhouzsc@outlook.com,zhousich@usc.edu

Permanent Link (DOI) https://doi.org/10.25549/usctheses-oUC113997X5Y

Unique identifier UC113997X5Y

Identifier etd-ZhouSichen-13251.pdf (filename)

Legacy Identifier etd-ZhouSichen-13251

Document Type Thesis

Format theses (aat)

Rights Zhou, Sichen

Internet Media Type application/pdf

Type texts

Source 20240718-usctheses-batch-1184 (batch), University of Southern California (contributing entity), University of Southern California Dissertations and Theses (collection)

Access Conditions The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright.

Repository Name University of Southern California Digital Library

Repository Location USC Digital Library, University of Southern California, University Park Campus MC 2810, 3434 South Grand Avenue, 2nd Floor, Los Angeles, California 90089-2810, USA

Repository Email cisadmin@lib.usc.edu