Misclassification of primary liver cancer in the Life Span Study of atomic bomb survivors

Primary liver cancer is difficult to diagnose accurately at death, due to metastases from nearby organs and to concomitant diseases, such as chronic hepatitis and cirrhosis. Trends in diagnostic accuracy could affect radiation risk estimates for incident liver cancer by altering background rates or by impacting risk modification by sex and age. We quantified the potential impact of death-certificate inaccuracies on radiation risk estimates for liver cancer in the Life Span Study of atomic bomb survivors. True-positive and false-negative rates were obtained from a previous study that compared death-certificate causes of death with those based on pathological review, from 1958 to 1987. We assumed various scenarios for misclassification rates after 1987. We obtained estimated true positives and estimated false negatives by stratified sampling from binomial distributions with probabilities given by the true-positive and false-negative rates, respectively. Poisson regression methods were applied to highly stratified person-year tables of corrected case counts and accrued person years. During the study period (1958-2009), there were 1,885 cases of liver cancer, which included 383 death-certificate-only (DCO) cases; 1,283 cases with chronic liver disease as the underlying cause of death; and 150 DCO cases of pancreatic cancer among 105,444 study participants. Across the range of scenarios considered, radiation risk estimates based on corrected case counts were attenuated, on average, by 13-30%. Our results indicated that radiation risk estimates for liver cancer were potentially sensitive to death-certificate inaccuracies. Additional data are needed to inform misclassification rates in recent years.