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

## TL;DR

A 66-year autopsy study in Japan reveals a significant number of undiagnosed cancers, including metastatic cases, highlighting the hidden cancer burden and the value of autopsies in cancer epidemiology.

## Contribution

The study introduces the 'enrichment ratio in autopsy' metric and reveals a growing number of undiagnosed metastatic cancers in Japan over six decades.

## Key findings

- Latent prostate cancer detection rates were 6.9-fold higher than clinical cases in Japan.
- Latent thyroid cancer prevalence was up to 60.7-fold higher than clinical incidence in women aged 50-54.
- Metastatic latent cancers increased over time, comprising 7.3% of all latent cancer cases.

## Abstract

What is the estimated cancer burden in Japan based on nationwide autopsy data over 6 decades?

In this cohort study of 1 486 557 autopsies performed between 1958 and 2023, 36 133 latent cancers were found. Detection rates increased, with latent prostate and thyroid cancers 6.9-fold and 60-fold more frequent than clinical cases; metastatic latent cancers made up 7.3% of cases and have been increasing in number.

These findings suggest that a small reservoir of undiagnosed, metastasis-competent cancers may increase with increasing longevity and underscore the value of autopsy for cancer epidemiology and early detection.

This cohort study evaluates the long-term trends and characteristics of latent cancers based on nationwide autopsy registry data in Japan.

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.

To evaluate long-term trends and characteristics of cancers using a nationwide autopsy registry in Japan.

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.

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.

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).

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.