Examining the Frequency of Late Anorectal Disease in Childhood Cancer Survivors After Pelvic Radiation

Survivors of childhood cancer who received ≥30 Gy of pelvic radiotherapy as treatment were at increased risk for late anorectal disease, according to the results of a Childhood Cancer Survivor study. Occurrence of this late anorectal disease had a detrimental impact on the well-being of these survivors.

“Clinicians who treat cancer survivors must be aware of late anorectal diseases, which warrant conscientious treatment and symptom reduction, and their impact on quality of life,” Arin L. Madenci, MD, MPH, of Boston Children’s Hospital, and colleagues wrote in Cancer.

The study included data from 25,530 survivors of childhood cancer diagnosed between 1970 and 1999, and 5,036 of their siblings. All participants were evaluated for late-onset anorectal disease defined as self-reported fistula-in-ano, anorectal stricture, or pathology/medical record-confirmed anorectal subsequent malignant neoplasms (SMN) 5 or more years after the primary cancer diagnosis.

The median age at cancer diagnosis was 6.1 years and the median follow-up from time of diagnosis was 22.5 years.

During follow-up, 394 survivors were diagnosed with late anorectal disease: 74% with fistula-in-ano, 29% had anorectal stricture, and 7% had anorectal SMN. Median age at diagnosis was 27 years. The 40-year cumulative incidence was 2.7%.

Diagnosed SMNs included adenocarcinoma (n=19), epithelial carcinoma (n=2), neuroendocrine carcinoma (n=1), and unspecified neoplasms (n=2).

“Among childhood cancer survivors, anorectal SMNs were rare, with a 45-year cumulative incidence rate less than 1%,” the researchers wrote. “Despite this, it is important to recognize that subsequent anorectal neoplasms may occur more frequently as survivors continue to age because of late effects of ionizing radiation, which is associated with an increased risk for SMNs even beyond the age of 40 years.”

During the same time, 84 siblings were diagnosed with anorectal disease: 87% had a fistula-in-ano, 27% had anorectal stricture, and 1% had anorectal primary cancer. Median age at diagnosis was 30 years. The 40-year cumulative incidence was also 2.7%.

Compared with their siblings, childhood cancer survivors had a 1.2-fold higher rate of late-onset anorectal disease, a nonsignificant difference.

Of the survivors with radiotherapy information available, 41% who developed anorectal SMNs had radiotherapy directed to the pelvis, 36% had indirect stray dose to the pelvis from adjacent or distant sites, and 23% did not receive radiotherapy. Median dose of radiation to the pelvis was 44 Gy. Among survivors, treatment with pelvic radiotherapy of 30 to 49.9 Gy (adjusted RR=1.6) or 50 Gy or greater (adjusted RR=5.4) was independently associated with late-onset anorectal disease.

Multivariable analysis showed that those survivors who developed late-onset anorectal disease had greater impairment in health-related quality of life compared with those without anorectal disease. They were significantly more likely to report depression, anxiety, and somatization.