Metastatic Recurrence Among Adolescents and Young Adults With Cancer.

[IMPORTANCE] Despite treatment advances, metastatic recurrence continues to be a leading cause of morbidity and mortality. Empirical data on the incidence and survival after metastatic recurrence remain limited, as cancer registries historically do not collect data on recurrence.

[OBJECTIVE] To estimate the cumulative incidence (CMI) of metastatic recurrence among adolescents and young adults diagnosed with earlier-stage disease and compare survival to those with metastatic disease at diagnosis.

[DESIGN, SETTING, PARTICIPANTS] This was a retrospective cohort study of adolescents and young adults aged 15 to 39 years who were diagnosed with nonmetastatic cancers from 2006 to 2018. Adolescents and young adults were identified from the California Cancer Registry linked with statewide hospitalization, emergency department, and ambulatory surgery encounters from the California Department of Health Care Access and Information. Data were analyzed from December 2023 to June 2025.

[EXPOSURES] Cancer types, including melanoma, sarcoma, and breast, cervical, colorectal, testicular, and thyroid cancers.

[MAIN OUTCOMES AND MEASURES] Metastatic recurrence was identified using International Classification of Diseases, Ninth Revision, Clinical Modification, and Tenth Revision, Clinical Modification, metastatic disease codes at least 6 months after cancer diagnosis or from an underlying cancer cause of death. Follow-up was through December 31, 2020.

[RESULTS] Of a total of 48 406 adolescents and young adults (median [IQR] age at diagnosis, 33.0 [28.0-37.0] years; 67.4% female), 9.2% had metastatic disease at diagnosis, and 9.5% had metastatic recurrence. Among 43 935 adolescents and young adults who presented with nonmetastatic disease, the 5-year CMI of metastatic recurrences was highest among patients with sarcoma (24.5%; 95% CI, 22.6%-26.6%) and colorectal cancer (21.8%; 95% CI, 20.3%-23.4%) and intermediate for cervical (16.3%; 95% CI, 15.0%-17.6%) and breast (14.7%; 95% CI, 14.0%-15.4%) cancers. The CMI for metastatic recurrence increased with increasing stage at diagnosis, with 5-year CMIs higher than 30% for all stage III cancers (except thyroid). The 5-year CMI of metastatic recurrence also increased over time for cervical cancer (2006-2009: 12.7% [95% CI, 10.8%-14.8%]; 2015-2018: 20.4% [95% CI, 17.5%-23.6%]) and decreased for colorectal cancer (2006-2009: 24.4% [95% CI, 21.3%-27.6%]; 2015-2018: 19.2% [95% CI, 16.4%-22.2%]). Survival after metastatic recurrence was worse than metastatic disease at diagnosis for all cancer types, except for testicular and thyroid cancers.

[CONCLUSIONS AND RELEVANCE] The findings from this cohort study highlight the overall burden of metastatic disease in adolescents and young adults, expanding the knowledge of metastatic recurrences that help improve care for adolescent and young adult survivors throughout the cancer survivorship spectrum.