ABSTRACT
PURPOSE: The interaction between sources of industrial byproducts and environmental pollutants (IBP/EP) and the prevalence of urothelial carcinoma (UC) in surrounding communities has been infrequently explored. The purpose of this research is to identify microregional UC hotspots and associated industrial and environmental risk factors. MATERIALS AND METHODS: We retrospectively queried a multi-institutional database for UC patients diagnosed between 2008 and 2018. Addresses were geocoded and used to perform hotspot analysis on the census block level. Demographic and clinicopathological characteristics, census data and proximity to sources of IBP/EP were compared between patients who did vs did not reside in a hotspot. Associations were tested using multilevel logistic regression models using 95% confidence intervals. RESULTS: A total of 5,080 patients met inclusion criteria and 148 (2.9%) were identified as living in 1 of 3 UC hotspots. In univariate analyses, race, tobacco and alcohol use, household income, IBP/EP exposure and proximity to traffic, industrial discharge and airports were significantly associated with UC hotspots. Multivariable analysis demonstrated that polycyclic aromatic hydrocarbon exposure (OR: 48.09, p ≤0.001) and proximity to high-density traffic (OR: >999, p ≤0.001) increased the odds of living in a hotspot. Patients living in a hotspot were significantly less likely to be white (OR: 0.06, p ≤0.001) or tobacco users (OR: 0.39, p=0.031) on multivariate analysis. CONCLUSIONS: Spatially related clusters of UC may be associated with locoregional environmental exposures rather than tobacco exposure and may also be correlated with socioeconomic disparities. Geospatial analysis can help to identify at-risk populations, offering the opportunity to better focus preventive and diagnostic interventions.
Subject(s)
Carcinoma, Transitional Cell/epidemiology , Disease Hotspot , Environmental Exposure/adverse effects , Social Factors , Urinary Bladder Neoplasms/epidemiology , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Pennsylvania/epidemiology , Retrospective StudiesABSTRACT
PURPOSE: Sipuleucel-T, an autologous cellular immunotherapy, was investigated in a randomized, double-blind, controlled trial to determine its biologic activity in androgen-dependent prostate cancer (ADPC). EXPERIMENTAL DESIGN: Patients with prostate cancer detectable by serum prostate-specific antigen (PSA) following radical prostatectomy received 3 to 4 months of androgen suppression therapy, and were then randomized (2:1) to receive sipuleucel-T (n = 117) or control (n = 59). The primary endpoint was time to biochemical failure (BF) defined as serum PSA ≥ 3.0 ng/mL. PSA doubling time (PSADT), time to distant failure, immune response, and safety were also evaluated. RESULTS: Median time to BF was 18.0 months for sipuleucel-T and 15.4 months for control (HR = 0.936, P = 0.737). Sipuleucel-T patients had a 48% increase in PSADT following testosterone recovery (155 vs. 105 days, P = 0.038). With only 16% of patients having developed distant failure, the treatment effect favored sipuleucel-T (HR = 0.728, P = 0.421). The most frequent adverse events in sipuleucel-T patients were fatigue, chills, and pyrexia. Immune responses to the immunizing antigen were greater in sipuleucel-T patients at Weeks 4 and 13 (P < 0.001, all) and were sustained prior to boosting as measured in a subset of patients a median of 22.6 months (range: 14.3-67.3 months) following randomization. CONCLUSIONS: No significant difference in time to BF could be shown. The finding of increased PSADT in the sipuleucel-T arm is consistent with its biologic activity in ADPC. Long-term follow-up will be necessary to determine if clinically important events, such as distant failure, are affected by therapy. Treatment was generally well tolerated.
