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Limitations in the imputation strategy to handle missing nativity data in the Surveillance, Epidemiology, and End Results program

We recognize the innovative approach of Montealegre et al in studying cancer disparities between foreign-born and US-born ethnic minorities. In the past, this type of analysis has been plagued by data limitations. Among these, birthplace information collected by cancer registries is incomplete and this deficiency does not occur randomly. This is because birthplace information is often secured from death certificates. In other words, those with a known birthplace are disproportionately deceased whereas those without birthplace information tend to be cancer survivors. As such, in this study, the stage of disease at diagnosis and ethnicity subcategory used in the logistic regression model to determine a birth in the United States or a foreign birth reflect data disproportionately derived from deceased cases with a known birthplace, whereas the imputation is performed on a completely different group of patients, mostly cancer survivors. Thus the “missing at random” assumption that allows for the use of multiple imputation is of complex interpretation. Moreover, the authors then use the results of that imputed birthplace to study survival. However, both stage and Hispanic ethnicity are strongly associated with survival, which may raise questions about the validity of this survival analysis. In the Surveillance, Epidemiology, and End Results (SEER) program, patients have their birthplace recorded based on the information in their medical records at the time of diagnosis. However, not all the medical records contain this information. When patients die, there is an additional report of birthplace coming from the death certificate. SEER registries will collect this additional information and that is why birthplace data are more complete for deceased than for living individuals. SEER requires annual data submissions from all participating registries. These submissions include both newly diagnosed cancer cases but also updated information (such as birthplace) on cancer cases from the previous submissions. Thus, by analyzing data regarding 2 different submissions of SEER data, we can analyze the distributions of nativity for the existing cases at 2 different points in time. It follows that one can compare the proportions of US-born and foreignborn individuals in a later submission among all cases with unknown birthplace in an earlier submission to the corresponding proportions of nativity obtained from the multiple imputation procedures that Montealegre et al propose. For this purpose, we requested and analyzed a data set from SEER that was restricted to Hispanic cases diagnosed from 1995 through 2004 and who were reported in 2 different submissions: the 2006 (earlier) submission and the 2012 (later) submission. A total of 53,531 cases among Hispanics were reported in both submissions (5812 cervical cancer cases, 28,346 prostate cancer cases, and 19,373 colorectal cancer cases). Of these, a total of 2345 cases (112 cases of cervical cancer, 1403 cases of prostate cancer, and 830 cases of colorectal cancer) had an unknown birthplace in the 2006 submission but their birthplace became available in the 2012 submission (of whom 43 cervical cancer, 534 prostate cancer and 207 colorectal cancer cases, were found to be foreign-born). The proportions of unknown birthplaces allocated for foreign-born and US-born cases using the imputation developed by Montealegre et al were 12% and 88%, respectively, for cervical cancer; 14% and 86%, respectively, for prostate cancer; and 10% and 90%, respectively, for colorectal cancer. Based on observed data, our findings were significantly different. For cervical cancer, the observed data showed that 38% of cases were foreign-born and 62% were US-born (95% confidence interval [95% CI], 30%-48% and 52%-70%, respectively). For prostate cancer, we found 38% of cases were foreign-born (95% CI, 36%-41%) and 62% were US-born (95% CI, 59%-64%). Finally, for colorectal cancer cases, we determined that 25% were foreign-born (95% CI, 22%-28%) and 75% were US-born (95% CI, 72%-80%). The 2345 analyzed cases (those with an unknown birthplace in the 2006 submission but a known birthplace in the 2012 submission) were significantly older than the remaining cancer cases with an unknown birthplace in both submissions. This was expected given that between the 2 points in time, older individuals are more likely to die and birthplaces will be recovered from the death certificates of deceased subjects. However, in the total group with known birthplace in both 2006 and 2012, the foreign-born cases were significantly younger than the US-born cancer cases. This suggests that the observed proportions in our analysis are an overestimate of the US-born and an underestimate of the foreign-born cases, and therefore the differences between the proportions as estimated by Montealegre et al and the real proportions are even greater than those reported here. Overall, these results strongly suggest that the proportions of nativity obtained from multiple imputations are