Abstract
Bladder cancer is one of the top ten most common cancers in the U.S., and one of the most expensive to treat.
Most cases (75%) are non-muscle-invasive bladder cancer (NMIBC) with high rates of recurrence (70%) and
progression (25%). While prognostic factors remain largely unknown, the success of Bacillus Calmette-Guerin
(BCG), an intravesical immunotherapy as the most effective therapy for NMIBC for over four decades,
highlights the potential of the inflammatory and immune environments in determining treatment response and
prognosis. Given the median age of bladder cancer diagnosis is 73 years, patients are commonly faced with
age-related loss of muscle mass (sarcopenia), increase of fat accumulation (obesity), or both (sarcopenic
obesity), which are all characterized by chronic inflammation and altered immune responses. These body
composition phenotypes are associated with tumor progression and increased mortality. Thus, we hypothesize
that body composition at diagnosis may shape the host inflammatory and immune milieu and impact bladder
cancer prognosis. This hypothesis will be tested in the Bladder Cancer Epidemiology, Wellness, and Lifestyle
Study (Be-Well; R01 CA172855, MPI: Kwan/Tang/Kushi) of newly diagnosed NMIBC patients from 2015-2019
at Kaiser Permanente, one of the largest prospective cohort studies of NMIBC, with 1,472 patients enrolled
with rich patient, clinical, and biospecimen data to examine genetic and lifestyle factors in prognosis and
survival. We propose to conduct a full investigation of body composition, inflammation, and immunity
in bladder cancer outcomes in Be-Well to determine how adiposity, muscle, and inflammatory and
immune biomarkers at diagnosis can identify NMIBC patients at high risk for treatment failure and/or
disease recurrence and progression. Our aims are: 1) to determine the association of computed
tomography (CT)-derived body composition phenotypes (sarcopenia, adiposity, myosteatosis) with NMIBC
recurrence (first and multiple) and progression; 2) to determine the association of body composition with BCG
immunotherapy outcomes including adverse events and treatment failure; 3) to examine the association of
circulating inflammatory and immune biomarkers with body composition and BCG outcomes and NMIBC
prognosis; 4) explore if the addition of body composition measures and inflammatory and immune biomarkers
improves the performance of current risk stratification models for NMIBC patients. Given the common clinical
use of CT, body composition measures could be readily incorporated into the current clinicopathological factor-
based risk stratification system to improve the clinical care of NMIBC.
