Mortality risk persists beyond 30 years following Wilms’ tumor diagnosis

Survivors of Wilms’ tumors are at substantially increased risk for premature mortality 30 to 50 years following their diagnosis, according to an analysis of the British Childhood Cancer Survivor study.

Subsequent neoplasms and cardiac problems accounted for 75% of all excess deaths by 50 years after diagnosis.

“Although Wilms’ tumor is increasingly curable, survivors are at risk for a range of treatment-related, long-term adverse health and social outcomes,” Michael Hawkins, DPhil, professor of epidemiology and director of the Centre for Childhood Cancer Survivor Studies at the School of Health and Population Sciences of University of Birmingham, in Birmingham, U.K., and colleagues wrote.

Although previous studies have evaluated long-term outcomes among survivors of Wilms’ tumor, none have evaluated risks beyond 30 years. Hawkins and colleagues aimed to investigate the risks for adverse outcomes up to 50 years after Wilms’ tumor diagnosis. Specifically, researchers evaluated cause-specific mortality, risk for subsequent primary neoplasms, risk for adverse pregnancy outcomes, health status, smoking and alcohol consumption, educational attainment, marriage status and health services use.

The British Childhood Cancer Survivor Study included a cohort of 1,441 long-term Wilms’ tumor survivors from the population-based National Registry of Childhood Tumors. Patients in the cohort were diagnosed between 1940 and 1991, aged 15 years or younger at the time of diagnosis and were disease free for 5 years or more.

Median follow-up was 26.9 years.

During the observation period, 10% (n = 146) of the cohort died, 2% (n = 31) emigrated and 88% (n = 1,264) were alive at the exit date.

Eighty-two percent of the survivors (n = 756) received abdominal radiotherapy.

Overall, there were fivefold more deaths among survivors than expected (standardized mortality ratio [SMR] = 5.4; 95% CI, 4.6-6.4), which equated to 30.7 additional deaths (absolute excess risk [AER] = 30.7; 95% CI, 24.6-36.8) per 10,000 patient years.

Cause-specific mortality was highest for subsequent primary neoplasms (SMR = 7.3; 95% CI, 5.3-9.8) and cardiac diseases (SMR = 10.1; 95% CI, 6.5-14.9).

Subsequent primary neoplasms accounted for 32% of all excess deaths (AER = 9.8; 955 CI, 6.4-13.1), whereas Wilms’ tumor recurrence accounted for 21% (AER = 6.4; 95% CI, 3.9-9) and cardiac causes accounted for 19% (AER = 5.8; 95% CI, 3.3-8.3). From 30 years after diagnosis, subsequent primary neoplasms accounted for 50% of excess deaths (AER = 53.8; 95% CI, 30.2-77.4) and cardiac disease accounted for 25% (AER = 27; 95% CI, 10.3-43.7)

Most deaths from recurrence occurred between years 5 and 14 (n = 22 of 25) post-diagnosis. Three recurrence deaths occurred between 15 and 24 years after diagnosis, and no other deaths from recurrence occurred after year 25.

Cumulative risk of death from all causes, excluding recurrence, increased substantially, from 5.4% at 30 years following diagnosis to 22.7% 50 years following diagnosis.

The cumulative risk for developing a subsequent primary neoplasm was 3.7% (95% CI, 2.7-50) 30 years after diagnosis, which increased to 16.4% (95% CI, 10.7-23.2) 50 years after diagnosis.

Of all subsequent primary neoplasm observed, more than 40% developed beyond 30 years after diagnosis of Wilms’ tumor.

Subsequent primary neoplasms most commonly occurred in digestive sites (n = 17), and all patients who developed digestive neoplasms had received abdominal radiotherapy.

Researchers sent study participants a questionnaire to assess additional outcomes. In total,

941 survivors (70.5%) returned the questionnaire.

There were 412 pregnancies by 184 women. Of women who received abdominal irradiation, 32% of pregnancies resulted in low birth weight, 35% in preterm delivery and 22% in miscarriage.

Long-term survivors who had received abdominal radiotherapy were at increased risk for giving birth to a low-birth-weight baby (OR = 3.3; 95% CI, 2.2-4.9) and giving birth preterm (OR = 3.1; 95% CI, 2.1-4.7).

Survivors used health services more than the general population. Notably, long-term survivors were more likely to be hospitalized as in inpatient at least once in the past year (OR = 2; 95% CI, 2.6-2.6) and to attend hospital outpatients at least once in the past 3 months (OR = 2.6; 95% CI, 2.2-3.1).

Long-term survivors appeared less likely than the general population to be regular smokers (OR = 0.7, 95% CI, 0.6-0.9), consume alcohol (OR = 0.7, 95% CI, 0.6-0.9) or consume harmful amounts of alcohol (OR = 0.5, 95% CI, 0.3-0.7). Male survivors also were less likely to be married (OR = 0.7; 95% CI, 0.5-0.9).

Survivors did not differ from the general population with regard to education level.

Overall, radiation receipt plays a role in the risk for these outcomes, according to the researchers.

“The proportion of patients with Wilms’ tumor who were exposed to radiotherapy has reduced substantially in recent decades because of initiatives such as the SIP WT 2001 clinical trial, which sought to reduce late effects,” the researchers wrote. “However, the majority of current survivors, 30 years or more from diagnosis, received radiotherapy. Surveillance of this group should focus on subsequent primary neoplasms, in particular, bowel and breast cancers, and cardiac conditions.” – by Nick Andrews

Disclosure: The researchers report no relevant financial disclosures.