Trends in the Hidden Burden of Cancer in an Autopsy-Based Study Over 66 Years in Japan.

Importance: Conventional cancer statistics account only for individuals with a clinical diagnosis, overlooking potentially large numbers of undetected malignant neoplasms. Autopsy-based studies offer a unique opportunity to estimate the burden of cancer, including latent tumors. Objective: To evaluate long-term trends and characteristics of cancers using a nationwide autopsy registry in Japan. Design, Setting, and Participants: This cohort study of hospital-based autopsies over a 66-year period (1958-2023) obtained data from the Annual of the Pathological Autopsy Cases in Japan (APAC-J), a nationwide database maintained by the Japanese Society of Pathology. Latent cancers, defined as malignant neoplasms undiagnosed during life but discovered at autopsy, were analyzed based on International Statistical Classification of Diseases, Tenth Revision and International Classification of Diseases for Oncology, Third Edition. All autopsies recorded in APAC-J were included. The data were analyzed between May 7 and August 2, 2025. Main Outcomes and Measures: The main outcome was the proportion of total, multiple, and latent cancers by year, age group, and sex based on trends in latent cancer detection; metastatic status of latent cancers; and the enrichment ratio in autopsy, a novel metric comparing cancer prevalence in autopsies with national mortality statistics. Results: From 1958 to 2023, 1 486 557 autopsies were registered in APAC-J (mean age based on available age group data, 59.1 years; 62.5% male), with 55.2% including cancer diagnoses. The proportion of multiple primary cancers increased from 1.8% (420 of 22 989) in 1974 to 14.4% (957 of 6661) in 2023. The enrichment ratio in autopsy was elevated in adolescents (aged 15-19 years), young adults (aged 20-24 years), and adults aged 80 years or older. Since 1986, 36 133 latent cancers were found in 34 174 of 811 159 autopsies (4.2%). The detection rate of latent cancers increased from 1.7% (683 of 39 839) in 1986 to 7.4% (493 of 6661) in 2023. Latent prostate cancer at age 75 to 79 years was identified in 4.5% (corresponding to a 2017-2021 prevalence of 656.2 per 100 000 population), 6.9-fold higher than the clinical incidence, whereas latent thyroid cancer at age 50 to 54 years showed substantially larger excesses (0.9% of men and 1.7% of women, representing 94.5-fold and 60.7-fold higher prevalences, respectively). Overall, metastases were present in 7.3% of latent cancers (2649 of 36 133). Conclusions and Relevance: This cohort study of autopsies across Japan found a substantial reservoir of undiagnosed cancer, including some with metastatic potential. These findings highlight the persistent value of autopsy for assessing cancer burden and underscore the need to refine approaches for early detection while minimizing overdiagnosis.