Low unit response rates can increase bias and compromise study validity. Response rates have continued to fall over the past decade despite all efforts to increase participation. Many factors have been linked to reduced response, yet relatively few studies have employed multivariate approaches to identify characteristics that differentiate respondents from nonrespondents since it is hard to collect information on the latter. We aimed to assess factors contributing to enrollment of prostate cancer (PCa) patients. We combined data from the North Carolina-Louisiana (LA) PCa Project’s LA cohort, with additional sources such as US census tract and LA tumor registry data. We included specific analyses focusing on blacks, a group often identified as hard to enroll in health-related research. The ability to study the effect of Hurricane Katrina, which occurred amidst enrollment, as a potential determinant of nonresponse makes our study unique. Older age (≥ 70) for blacks (OR 0.65) and study phase with respect to Hurricane Katrina for both races (OR 0.59 for blacks, OR 0.48 for whites) were significant predictors of participation with lower odds. Neighborhood poverty for whites (OR 1.53) also was a significant predictor of participation, but with higher odds. Among blacks, residence in Orleans parish was associated with lower odds of participation (OR 0.33) before Katrina. The opposite occurred in whites, with lower odds (OR 0.43) after Katrina. Our results overall underscore the importance of tailoring enrollment approaches to specific target population characteristics to confront the challenges posed by nonresponse. Our results also show that recruitment-related factors may change when outside forces bring major alterations to a population's environment and demographics.