Metastatic Recurrence: A Concerning Burden Facing Young Patients

Although modern therapeutic advances have positively transformed the prognostic outlook for adolescent and young adult patients with cancer, a recent population-based study has illustrated the ongoing burden and prognostic implications of metastatic recurrence in this group across multiple tumor types, signaling the need for continued care throughout cancer survivorship.^1,2

The retrospective study in JAMA Oncology observed that among over 44,000 adolescent and young adult patients with cancer who presented with nonmetastatic disease between 2006 and 2018, nearly a quarter of patients with sarcoma (cumulative incidence [CMI], 24.5%; 95% CI, 22.6%–26.6%) experienced metastatic recurrence within 5 years, the highest proportion among the patient subgroups examined. Likewise, the 5-year CMI was 21.8% (95% CI, 20.3%–23.4%) among those with colorectal cancer, 16.3% (95% CI, 15.0%–17.6%) among those with cervical cancer, and 14.7% (95% CI, 14.0%–15.4%) among those with breast cancer.

CMI of metastatic recurrence generally increased with stage at diagnosis. Across all stage 3 cancers except for thyroid, the 5-year CMI was higher than 30%, suggesting increased vulnerability of metastatic recurrence in more advanced disease.

Additionally, temporal trends in 5-year CMI were observed in select cancers. In cervical cancer, 5-year CMI increased by 12.7% between 2006 and 2009, jumping to a 20.4% increase between 2015 and 2018. Conversely, for colorectal cancer, 5-year CMI decreased by 24.4% and 19.2% in the respective time periods; melanoma also saw a similar decrease.

Critically, metastatic recurrence has significant prognostic implications. In this cohort, patients who experienced metastatic recurrence had higher hazards of death compared with those who presented with metastatic disease at diagnosis in all cancers except for testicular and thyroid.

“These findings highlight the significant burden of metastatic recurrence among adolescents and young adults and the need for tailored survivorship care,” said Theresa Keegan, PhD, MS, University of California Davis Health and senior author, in a news release.² “Understanding these patterns helps us identify inequities and evaluate how well our efforts are working to prevent, detect[,] and treat both early and metastatic disease.”

Patient Characteristics

Data for the cohort examined in this study were derived from the California Cancer Registry linked with statewide health care records from the California Department of Health Care Access and Information.

The cohort included 48,406 patients aged 15 to 39 years old who were diagnosed with cancer between 2006 and 2018. The median age at diagnosis was 33.0 years (IQR, 28.0–37.0), a minority (9.2%) presented with metastatic disease, and 9.5% experienced metastatic recurrence. An array of malignancies was represented in the cohort, including sarcoma, colorectal, cervical, breast, melanoma, testicular, and thyroid cancers.

Implications: Caring for Cancer Survivors

This study aimed to characterize a critical gap in the literature: clinical outcomes following metastatic recurrence, particularly among adolescents and young adults who carry the risk of early mortality.

In a corresponding editorial in JAMA Oncology, Amy Berkman, MD of St. Jude Children’s Research Hospital and colleagues wrote that the study’s “findings largely parallel trends in metastatic recurrent disease incidence and mortality among populations with broader age ranges, with some notable exceptions.”³

The findings give rise to not only future investigations into the mechanisms driving these patterns, but also development of future treatment strategies and efforts to provide ongoing supportive care at all stages of cancer survivorship.

REFERENCES

1. Brunson A, Wun T, Abrahão R, et al. Metastatic recurrence among adolescents and young adults with cancer. JAMA Oncol. Published online November 26, 2025. doi:10.1001/jamaoncol.2025.4971

2. High risk of metastatic recurrence among young cancer patients. News release. University of California Davis. November 26, 2025. Accessed December 3, 2025. https://tinyurl.com/bdhdkjf3

3. Berkman A, Roth M, Livingston JA. Metastatic Recurrence in Adolescent and Young Adult Cancer—Key Drivers of Early Mortality. JAMA Oncol. Published online November 26, 2025. doi:10.1001/jamaoncol.2025.4926