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Skin cancer
Source: Late Effects of Treatment for Childhood Cancer (PDQ®)–Health Professional Version, National Cancer Institute.
Source updated: April 14, 2025 · Captured 2026-09-09.
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Context: Subsequent Neoplasms / Therapy-Related Solid SNs
Keratinocyte carcinomas (KCs) (i.e., basal cell carcinomas [BCCs] and squamous cell carcinomas [SCCs], also called nonmelanoma skin cancers [NMSCs]) are one of the most common SNs among childhood cancer survivors and show a strong association with radiation therapy.[4,82,83] Adherence to sun protection behaviors can reduce exposure to UV radiation that may exacerbate risk.
The CCSS performed a randomized, controlled, comparative effectiveness trial to test methods to improve early detection of skin cancer among survivors of childhood cancer at high risk after radiation therapy exposure. Participants were randomly assigned to the experimental arm, which included print materials in combination with mHealth strategies (text messages and use of the Advancing Survivors’ Knowledge website), or the control arm. Screening rates improved by 1.5-fold in the experimental arm. Rates of physician skin examination increased from baseline to 12 months, and rates of self-examination increased from baseline to 18 months in all three intervention groups. However, the increase in rates did not differ between the intervention groups.[84]
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Evidence (excess risk of KCs):
An updated analysis of the CCSS confirmed an increased risk of KCs in participants with histories of radiation therapy. Compared with participants who did not receive radiation therapy, CCSS participants treated with radiation therapy had a 4.5-fold increased risk of KCs (95% CI, 3.5–5.9).[83]
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An updated analysis of the CCSS confirmed an increased risk of KCs in participants with histories of radiation therapy. Compared with participants who did not receive radiation therapy, CCSS participants treated with radiation therapy had a 4.5-fold increased risk of KCs (95% CI, 3.5–5.9).[83]
The risk of KCs increased with higher radiation therapy doses. Per 10 Gy of radiation therapy at the KC site, the RR was similar for head/neck (1.0; 95% CI, 1.0–1.1) and extremity sites (1.0; 95% CI, 0.7–1.3). The RR was slightly higher for trunk sites (1.1; 95% CI, 1.0–1.3).
An updated analysis of the CCSS confirmed an increased risk of KCs in participants with histories of radiation therapy. Compared with participants who did not receive radiation therapy, CCSS participants treated with radiation therapy had a 4.5-fold increased risk of KCs (95% CI, 3.5–5.9).[83]
Allogeneic and autologous HSCT were associated with an increased risk of KCs (RR for allogeneic HSCT, 3.4; 95% CI, 2.4–4.8 and RR for autologous HSCT, 2.3; 95% CI, 1.2–4.2).
In 5,843 childhood cancer survivors in the DCOG-LATER cohort, investigators found that childhood cancer survivors had a 30-fold increased risk of developing BCCs.[30]
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In 5,843 childhood cancer survivors in the DCOG-LATER cohort, investigators found that childhood cancer survivors had a 30-fold increased risk of developing BCCs.[30]
After a first BCC diagnosis, 46.7% of patients developed additional BCCs.
In 5,843 childhood cancer survivors in the DCOG-LATER cohort, investigators found that childhood cancer survivors had a 30-fold increased risk of developing BCCs.[30]
BCC risk was associated with any radiation therapy to the relevant radiation field (site of BCC) (HR, 14.32) and with estimated percentage of exposed skin surface area (26%–75%: HR, 1.99; 76%–100%: HR, 2.16 vs. 1%–25% exposed; Ptrend among exposed = .002).
In 5,843 childhood cancer survivors in the DCOG-LATER cohort, investigators found that childhood cancer survivors had a 30-fold increased risk of developing BCCs.[30]
BCC risk was not associated with prescribed radiation dose and likelihood of sun-exposed skin area.
In 5,843 childhood cancer survivors in the DCOG-LATER cohort, investigators found that childhood cancer survivors had a 30-fold increased risk of developing BCCs.[30]
Of all chemotherapy groups examined, only vinca alkaloids increased the BCC risk (HR, 1.54).
The occurrence of a KC as the first SN has been reported to identify a population at high risk of a future invasive malignant SN.[7]
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The occurrence of a KC as the first SN has been reported to identify a population at high risk of a future invasive malignant SN.[7]
CCSS investigators observed a cumulative incidence of a malignant neoplasm of 20.3% (95% CI, 13.0%–27.6%) at 15 years among radiation-exposed survivors who developed a KC as a first SN, compared with 10.7% (95% CI, 7.2%–14.2%) among survivors whose first SN was an invasive malignancy.
Malignant melanoma has also been reported as an SN in childhood cancer survivor cohorts, although at a much lower incidence than NMSCs.
Risk factors for malignant melanoma identified among these studies include the following:[85]
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Radiation therapy (>40 Gy).
Alkylating agents.
Bleomycin.
Evidence (excess risk of melanoma):
Investigators assessed the incidence, risk factors, and outcomes for patients with melanoma in the CCSS cohort (n = 25,716).[85]
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Investigators assessed the incidence, risk factors, and outcomes for patients with melanoma in the CCSS cohort (n = 25,716).[85]
There were 160 survivors (median attained age, 33 years) who developed 177 melanomas (110 invasive, 62 in situ cutaneous, 5 ocular).
Investigators assessed the incidence, risk factors, and outcomes for patients with melanoma in the CCSS cohort (n = 25,716).[85]
The 40-year cumulative incidence was 1.1% for all participants and 1.5% for those who received cumulative radiation doses of 40 Gy or higher. The standard incidence ratios were 2.0 when compared with the general population.
Investigators assessed the incidence, risk factors, and outcomes for patients with melanoma in the CCSS cohort (n = 25,716).[85]
An increase in cutaneous melanomas was associated with a cumulative radiation dose of 40 Gy or higher to the site of the melanoma (HR, 2.0), cumulative cyclophosphamide equivalent dose of 20,000 mg/m2 or higher (HR, 1.9), and bleomycin exposure (HR, 2.2).
Investigators assessed the incidence, risk factors, and outcomes for patients with melanoma in the CCSS cohort (n = 25,716).[85]
The presence of an invasive melanoma was associated with a twofold risk of death.
A systematic review that included data from 19 original studies (total N = 151,575 survivors; median follow-up of 13 years) observed an incidence of 10.8 cases of malignant melanoma per 100,000 childhood cancer survivors per year.[86]
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A systematic review that included data from 19 original studies (total N = 151,575 survivors; median follow-up of 13 years) observed an incidence of 10.8 cases of malignant melanoma per 100,000 childhood cancer survivors per year.[86]
Melanomas most frequently developed in survivors of Hodgkin lymphoma, hereditary retinoblastoma, soft tissue sarcoma, and gonadal tumors. However, the relatively small number of survivors represented in the relevant studies preclude assessment of melanoma risk among other types of childhood cancer.
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