High risk of metastatic recurrence among young cancer patients

A new study of adolescents and young adults (AYAs) with seven common cancers reveals that nearly one in ten patients diagnosed with non-metastatic disease later develop metastatic recurrence — a condition associated with significantly worse survival outcomes. Metastasis is when cancer cells spread from the initial or primary site to other parts of the body. It comes with significantly worse survival outcomes.

UC Davis Comprehensive Cancer Center scientists led the research. The findings highlight the urgent need to identify and address survivorship needs for young cancer survivors.

“As treatments improve survival, young patients with cancer face unique challenges,” said Ann Brunson, UC Davis research analyst and the study’s lead author. “Our research deepens understanding of survivorship and the impact of metastatic recurrence, using statewide data to reveal trends and guide future studies.”

The research, based on data from more than 48,000 AYAs in California, was published in JAMA Oncology on November 26. It is the first study of its kind to examine metastatic disease in this population.

Researchers analyzed data from the California Cancer Registry linked with statewide health care records from the California Department of Health Care Access and Information (HCAI). The study group included AYAs aged 15–39 diagnosed with cancer between 2006 and 2018, with follow-up through the end of 2020. Metastatic recurrence was identified by specific diagnosis codes HCAI or cancer cause of death.

The median follow-up time was 6.7 years and the median age at diagnosis was 33. Most patients were non-Hispanic white (48%) or Hispanic (32%), lived in high socioeconomic status neighborhoods (43%) and had private or military insurance (76%).

High rates of metastatic disease and recurrence

Among the 48,406 AYAs studied, 9.2% had metastatic disease at diagnosis while 9.5% developed metastatic recurrence later.  AYAs with colorectal cancer (44.2%) and sarcoma (41.7%) had the highest overall proportion of metastatic disease, followed by patients with breast (23.9%), cervical (23.6%) and testicular (21.6%) cancers.

For AYAs initially diagnosed with nonmetastatic disease, the five-year cumulative incidence of metastatic recurrence was highest for those with:

• Sarcoma (24.5%)
• Colorectal cancer (21.8%)
• Cervical cancer (16.3%)
• Breast cancer (14.7%) 

Cervical cancer had particularly high recurrence rates across all stages, with stage 3 patients experiencing a cumulative incidence of 41.7%.

The study also found that recurrence rates varied over time. Cervical cancer recurrence increased from 12.7% in 2006-2009 to 20.4% in 2015-2018, while colorectal cancer and melanoma saw declines. Notably, stage 1 cervical cancer showed the most pronounced increase, while stage 3 melanoma had a significant decrease in recurrence.

Survival after metastatic recurrence was worse than survival for those diagnosed with metastatic disease initially, except in testicular and thyroid cancers. Breast cancer patients with metastatic recurrence had nearly a threefold increased hazard of death (HR=2.87), while cervical (HR=2.10), melanoma (HR=1.61), sarcoma (HR=1.57), and colorectal cancer (HR=1.53) patients also faced significantly higher hazards of death.

To make sure their method for detecting metastatic recurrence was accurate, the researchers compared their findings to Kaiser Permanente Northern California and found an overall concordance rate of 96.9% when they accounted for patients who were never completely disease-free.

“These findings highlight the significant burden of metastatic recurrence among adolescents and young adults and the need for tailored survivorship care,” said Theresa Keegan, the study’s senior author. “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.”