Childhood cancer survivors at higher long-term risk for major surgery

In a study that compared survivors with their siblings, the 35-year mean cumulative count of major surgical interventions at least five years after diagnosis was 206.7 per 100 versus 128.9 per 100, respectively.

Childhood cancer survivors are at higher risk for major surgery five or more years after their initial diagnosis, a recent study found.

Researchers evaluated data from the Childhood Cancer Survivor Study (CCSS), a U.S. retrospective cohort study of five-year survivors of childhood cancer, and a comparison group of nearest-age siblings of survivors selected by simple random sampling. The primary outcome was any self-reported late major surgical intervention (defined as any operation requiring anesthesia) that occurred at least five years after the primary cancer diagnosis. The goal of the study was to estimate the cumulative burden of late major surgical interventions among childhood cancer survivors and to examine associations between specific childhood cancer treatments and the late surgical interventions. The results were published May 11 by The Lancet Oncology.

A total of 25,656 cancer survivors diagnosed between Jan. 1, 1970, and Dec. 31, 1999 (13,721 male, 11,935 female), were included in the study, with 5,045 nearest-age siblings included as a comparator group. Median follow-up for survivors was 21.8 years (interquartile range [IQR], 16.5 to 28.4 years), and median age at diagnosis was 6.1 years (IQR, 3.0 to 12.4 years). Survivors had 28,202 late major surgical interventions versus 4,110 among siblings. The 35-year mean cumulative count (MCC) of late major surgical interventions was 206.7 per 100 survivors (95% CI, 202.7 to 210.8 per 100 survivors) and 128.9 per 100 siblings (95% CI, 123.0 to 134.7 per 100 siblings). Late major surgical intervention was more likely in survivors than in siblings (adjusted rate ratio [RR], 1.8; 95% CI, 1.7 to 1.9) and in female versus male survivors (adjusted RR, 1.4; 95% CI, 1.4 to 1.5).

Survivors whose cancer was diagnosed in the 1990s were more likely to have late surgery than those diagnosed in the 1970s (adjusted RR, 1.4; 95% CI, 1.3 to 1.5). The cumulative burdens of late major surgical intervention were highest in those who had had Hodgkin lymphoma (35-year MCC, 333.3 [95% CI, 320.1 to 346.6] per 100 survivors), Ewing sarcoma (35-year MCC, 322.9 [95% CI, 294.5 to 351.3] per 100 survivors), and osteosarcoma (35-year MCC, 269.6 [95% CI, 250.1 to 289.2] per 100 survivors). Locoregional surgery or radiotherapy cancer treatment was associated with late surgical intervention in the same body region or organ system.

The authors noted that the CCSS was not population-based and that late surgical intervention was self-reported, among other limitations. “In conclusion, this study demonstrates a newly understood chronic late effect of paediatric cancer therapy comprising a significant burden of late, major surgical interventions. The need for late surgery should be anticipated and inform the education of parents and caregivers of paediatric patients with cancer at the time of diagnosis and treatment,” the authors wrote. “Childhood cancer survivors should have regular health-care evaluations that anticipate surgical issues and treat them early in the disease course.”

The authors of an accompanying comment said that while it's not surprising to find a higher risk for late surgery in childhood cancer survivors than in their siblings, the magnitude of risk demonstrated in the current study is striking and the results are an important contribution to the overall picture of the burden of childhood cancer over a patient's lifetime.

“Future research should build on what the CCSS has already achieved and continues to achieve. Key unknowns include the risk and range of late effects among more recent survivor cohorts, reasons for the higher risk of late surgery among female survivors compared with male survivors, variations in outcomes across subgroups of childhood cancer survivors who might be disadvantaged due to race, economic circumstances, geography, or access to services, and the impact of diverse types of initial treatment,” the comment authors wrote. “Large population-based studies of childhood cancer survivors, particularly those that use linked real-world data, will be required to answer these questions.”