Second primary cancer after treatment for cervical cancer. Late effects after radiotherapy

Using data from the population-based Danish Cancer Registry, the relative risk (RR) of second primary cancer was assessed among 24,970 women with invasive cervical cancer (1943-1982) and 19,470 women with carcinoma in situ of the cervix. The analysis was stratified according to treatment with (+) and without (-) radiation. For all second primaries combined, a RR+ = 1.1 (95% confidence interval (CI) = 1.06-1.18) and a RR- = 1.3 (95% CI = 1.13-1.40) was observed after invasive cervical cancers and a RR+ = 3.5 (95% CI = 1.4-7.2) and RR- = 1.1 (95% CI = 0.7-1.6) following in situ cancer. The small overall excess of second primary cancer is accounted for by an increase of some cancers such as lung, bladder, and a concurrent decrease in others such as breast. Although not statistically different from nonirradiated, the RR increased with time since treatment among irradiated invasive cervical cancer patients in organs close to and at intermediate distance from the cervix, reaching a maximum after 30 or more years of follow-up (RR = 1.9; 95% CI = 1.4-2.5). Altogether, for these sites an excess of 64 cases per 10,000 women per year were attributable to radiation among survivors of 30+ years. The highest risks among long-term survivors were observed for the following: other genital organs (RR = 5.8; 95% CI = 1.8-13.0) bladder (RR = 5.5; 95% CI = 2.8-9.5), connective tissue (RR = 3.3; 95% CI = 0.4-12.0), stomach (RR = 2.5; 95% CI = 1.1-4.7) and rectum (RR = 2.4; 95% CI = 1.1-4.6). A significant deficit of risk for breast cancer (RR = 0.7, 95% CI = 0.6-0.8) was observed for 10+ years, may be attributable to the effect of ovarian ablation by radiotherapy. It is speculated that the same effect also may explain the observed deficits of brain tumors (RR = 0.6; 95% CI = 0.4-1.0) and skin melanomas (RR = 0.6; 95% CI = 0.3-1.0). It is concluded that cancers attributable to radiation, apart from acute nonlymphocytic leukemias, tend to appear late (10 or more years after radiotherapy), and that the risk remains elevated for more than 30 years.