Childhood Cancer Survivors Have Increased Rates of Late, Major Surgeries

Childhood cancer survivors have increased rates of undergoing late, major surgical procedures 5 or more years after diagnosis, according to data from the Childhood Cancer Survivor Study.

Among more than 25,000 survivors diagnosed with cancer from 1970 to 1999 when they were under age 21, the likelihood of having subsequent major surgery was 80% higher compared with a comparison group of about 5,000 siblings (adjusted rate ratio [aRR] 1.8, 95% CI 1.7-1.9), reported Brent Weil, MD, of Boston Children's Hospital and Harvard Medical School, and colleagues.

Their study in The Lancet Oncology showed that the cumulative burden of late, major surgical interventions was present across all anatomic systems. Moreover, many of these survivors (25.4%) underwent two or more surgical procedures.

"[W]e now know that childhood cancer survivors will more frequently receive major surgical interventions as they age when compared with the general population," the researchers wrote. "This outcome should be anticipated and disclosed to patients and families, especially when complex local control interventions are planned for primary cancer therapy. Childhood cancer survivors would benefit from regular healthcare evaluations aiming to anticipate impending surgical issues and to intervene early in the disease course when feasible."

In a commentary accompanying the study, Danny Youlden, PhD, of the Viertel Cancer Research Centre in Brisbane, Australia, and colleagues said it is not surprising that surgery is more common in survivors of childhood cancer considering that cytotoxic chemotherapy and radiotherapy at a young age can seriously impact developing organs and body systems.

"However, the magnitude of the risk found in this study is striking," they wrote.

The median age of the survivors at cancer diagnosis was 6.1 years, with a median age at last follow-up of 29.4 years for survivors, and 35.2 years for siblings. Median follow-up was 21.8 years for survivors and 27.0 years for siblings.

The primary outcome of a late, major surgical intervention was defined as any surgical operation likely to require general anesthesia, or monitored anesthesia care, occurring 5 or more years after the primary cancer diagnosis.

The 25,656 survivors in the study underwent a total of 28,202 late major surgical procedures compared with 4,110 for the 5,045 nearest-age siblings in the analysis. The 35-year mean cumulative counts (MCCs) of surgical interventions was 206.7 per 100 survivors and 128.9 per 100 siblings.

Additionally, the researchers found that the likelihood of late major surgical procedures was greater in female versus male survivors (aRR 1.4, 95% CI 1.4-1.5), as well as in survivors diagnosed in the 1990s compared with those diagnosed in the 1970s (aRR 1.4, 95% CI 1.3-1.5).

Survivors received late interventions more frequently than siblings in most anatomical regions or organ systems, with the largest increased risks seen in the following:

• Central nervous system (aRR 16.9, 95% CI 9.4-30.4)
• Endocrine (aRR 6.7, 95% 5.2-8.7)
• Cardiovascular (aRR 6.6, 95% CI 5.2-8.3)
• Respiratory (aRR 5.3, 95% CI 3.4-8.2)

The highest cumulative burdens of late, major surgical interventions were observed among survivors of Hodgkin lymphoma (35-year MCC of 333.3 per 100 survivors), Ewing sarcoma (322.9 per 100 survivors), and osteosarcoma (269.6 per 100 survivors), with an increased proportion of breast, endocrine, and cardiovascular surgeries seen in female Hodgkin lymphoma survivors.

The study also found an association between locoregional cancer therapy and increased late surgical interventions in pediatric childhood cancer survivors.

In their commentary, Youlden and colleagues said that while the study provides more information about the ongoing burden of childhood cancer, some key unknowns include the risk and range of effects in later survivor cohorts, reasons for higher risks of surgery in females, and the effect of different initial treatments among survivors.

"Large population-based studies of childhood cancer survivors, particularly those that use linked real-world data, will be required to answer these questions," the commentators suggested.

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