# Excess mortality in young cancer survivors compared with the general population in Italy: a retrospective study from the Italian population-based cohort of adolescents and young adult cancer survivors

**Authors:** Paolo Giorgi Rossi, Francesco Marinelli, Pamela Mancuso, Lucia Mangone, Massimo Vicentini, Isabella Bisceglia, Alice Bernasconi, Laura Botta, Annalisa Trama

PMC · DOI: 10.3389/fonc.2025.1580953 · 2025-07-30

## TL;DR

Young cancer survivors in Italy face seven times higher mortality than the general population, with cancer and non-cancer deaths both contributing significantly.

## Contribution

This study quantifies the long-term excess mortality in young cancer survivors compared to the general population in Italy using a large population-based cohort.

## Key findings

- AYA cancer survivors had a 7.0-fold higher all-cause mortality compared to the general population.
- Excess mortality was highest in the first 5–10 years post-diagnosis and decreased over time.
- Non-cancer mortality remained elevated even 30 years after diagnosis, nearly equaling cancer-related deaths.

## Abstract

Adolescents and young adults (AYA) cancer survivors experience increased morbidity and mortality from second cancers, cardiovascular, infectious, kidney, and other chronic diseases. We aim to calculate all-causes cancer and non-cancer excess mortality of young cancer survivors compared to the general population.

The AYA cohort includes cancer patients diagnosed between 1976 and 2013 and alive at 5 years after diagnosis in 30 population-based Cancer Registries and followed up until 31 December 2019. The standardised mortality ratios (SMRs) and absolute excess risks (AERs) per 100,000 for person-years were calculated.

58,387 5-year survivors were followed up for 427,130 person-years; the median follow-up time was 5.7 years beyond the 5th year after diagnosis. During this time, 4,194 (7.2%) had died by the end of 2019, and only 1.6% were lost to follow-up. Compared with the general population, AYA survivors had higher mortality, overall, the SMR for all-cause mortality was 7.0 (95%CI: 6.8-7.2). The excess of mortality was higher in the first period after diagnosis (5–10 years), SMR 12.8 (95%CI 12.3-13.3), then it decreased, reaching an SMR of 2.2 (95%CI 1.6-3.2) after 30 years.

The excess mortality is mostly due to the malignancy of the primary tumour, but an about 2-fold excess of mortality is also appreciable for non-cancer causes. Young adult cancer survivors face a sevenfold increase in all-cause mortality compared to the general population, with a notable rise in both cancer-related and non-cancer deaths. Thirty years post-diagnosis, the excess risk from cancer and non-cancer causes becomes nearly equal.

## Linked entities

- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Genes:** GATA3 (GATA binding protein 3) [NCBI Gene 2625] {aka HDR, HDRS}, ARID1A (AT-rich interaction domain 1A) [NCBI Gene 8289] {aka B120, BAF250, BAF250a, BM029, C1orf4, CSS2}, PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) [NCBI Gene 5290] {aka CCM4, CLAPO, CLOVE, CWS5, HMH, MCAP}
- **Diseases:** Breast cancer (MESH:D001943), intracranial and intraspinal neoplasms (MESH:D001932), head and neck tumours (MESH:D006258), Thyroid and other endocrine gland tumours (MESH:D004701), respiratory conditions (MESH:D012131), melanoma (MESH:D008545), sarcoma (MESH:D012509), thyroid cancer (MESH:D013964), death (MESH:D003643), endocrine resistance (MESH:D004700), CNS (MESH:D002493), Germ cell and trophoblastic cancer (MESH:D009373), gliomas (MESH:D005910), gonadal carcinomas (MESH:D006058), leukaemia (MESH:D015458), cervix (MESH:D002577), and thyroid (MESH:D013966), Leukemia (MESH:D007938), second cancers (MESH:D016609), Cancers (MESH:D009369), thymic cancers (MESH:D013953), thyroid diseases (MESH:D013959), infections (MESH:D007239), toxicity (MESH:D064420), testicular cancer (MESH:D013736), Lymphomas (MESH:D008223), trophoblastic tumours (MESH:D014328), Hodgkin Lymphoma (MESH:D006689), cardiovascular, infectious, kidney, and other chronic diseases (MESH:D051436), adrenal abnormalities (MESH:D000224), CNS neoplasms (MESH:D016543)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12343270/full.md

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Source: https://tomesphere.com/paper/PMC12343270