Previous radiation exposure is a well-known risk factor for angiosarcomas. The direct oncogenic effects of ionizing radiation and prolonged cellular stimulation during repair of tissue damage resulting from radiation-induced ischaemic change are thought to play a role in the development of angiosarcoma [13
]. Other factors that have been linked to angiosarcomas include: chronic lymphoedema and chemical exposure such as arsenic, thorium dioxide and vinyl chloride. None of the reported cases had a history of exposure to the above-mentioned chemicals.
Cahan et al
] proposed that radiation-induced sarcoma may occur in a previously irradiated area within a latent period of as long as 7 years. Although the association of angiosarcoma with radiation exposure has been described previously [15
], only three out of 10 reported cases of prostate angiosarcoma had previous radiation exposure where PSA levels were within normal range or undetectable [9
Only one of these three cases involved a recurrent adenocarcinoma of the prostate [12
]. In the case report by Lee et al
], it was thought to be a malignant transformation within a pre-existing teratoma lesion; therefore, it is not clear whether post-radiation angiosarcoma stems from a dedifferentiated prostate cancer or signifies instead a second mesenchymal neoplasm. The estimated lifetime risk of developing post-irradiation sarcoma at any site with long-term follow-up appears to be 0.03% to 0.8% [17
Huang et al
] reported an enhanced risk of soft-tissue sarcomas after adjuvant radiotherapy among patients with breast cancer in Surveillance of Epidemiology and End Results (SEER) data. This risk was especially increased for angiosarcomas and peak incidence was reported 5–10 years after the radiation therapy [18
]. A concurrent lymphoedema, secondary to breast cancer treatment, was thought to be a potential confounder in this association [19
]. A similar association between radiotherapy and subsequent angiosarcomas has also been reported in the gynaecological cancer literature [19
]. Kim et al
] found 66 reported cases of radiation-associated angiosarcoma where the most common indication for radiation therapy was breast cancer (44%), followed by gynaecological cancer (21%). Kim et al
] also reported that 85% of radiation-associated angiosarcomas were detected in the skin with a median latency period of 8 years. In the same study, the median age at diagnosis was 65 years and median survival was 12 months [21
Another large population-based cohort study evaluating the risk of angiosarcoma among all patients with cancer found an increased risk of truncal angiosarcoma among women with breast and gynaecological cancers [19
]. This study did not find a strong relationship with radiotherapy, age or male gender. Although ionizing radiation is a well documented aetiology for angiosarcoma, Müller et al
] found no increased risk of secondary malignancy in the literature from the mid-1980s to 2007 after adjustment for age and follow-up duration; however, they reported an enhanced number of secondary cancers of the bladder, rectum, lung and sarcoma after prostate irradiation.
Moon et al
] reported enhanced risk of second primary cancer of the bladder, rectum, gastrointestinal tract, brain and lung, lymphoma and leukaemia among patients with prostate cancer 5 years after radiation therapy as compared with those who did not receive radiation in SEER data. In the same study, men who received radiation therapy in the form of radioactive implants or isotopes did not have an increased risk of a second primary cancer [23
]. In this large cohort study, no enhanced risk of prostate angiosarcoma was reported.