Second malignancies following testicular cancer, ovarian cancer and Hodgkin's disease: an international collaborative study among cancer registries.

Eleven population-based cancer registries tabulated second cancers among 133,411 patients diagnosed with testicular cancer, ovarian cancer or Hodgkin's disease between 1945 and 1984. Overall, 3,157 second cancers were observed, as compared with 2,420 expected at least one year after the first cancer. Survivors of testicular and ovarian cancer experienced 30% and 20% more cancers respectively than the general population comparison group, and patients previously diagnosed with Hodgkin's disease had an 80% excess of cancer. No information was available either on treatment for the first cancer, or other risk factors. However, temporal patterns in the risk of specific second cancers were analysed, with particular reference to the possible role of therapy for the first cancer. Leukaemia of the acute or non-lymphatic type, which has been previously linked to alkylating agent therapy, occurred in excess following all 3 first cancers, as did non-Hodgkin's lymphoma (overall relative risks of 6.1 and 1.8 respectively, with considerably higher relative risks following Hodgkin's disease). Other cancers for which important and plausibly therapy-induced excesses occurred were lung cancer following Hodgkin's disease (relative risk 1.9), breast cancer following Hodgkin's disease (relative risk 1.4) and bladder cancer following ovarian cancer and Hodgkin's disease (relative risks 1.7 and 2.2 in women, respectively). Rarer sites at which striking excesses occurred were the salivary gland, thyroid, bone and connective tissue. There were smaller, but clear excesses for cancers of the rectum and colon following ovarian cancer and testicular cancer, skin cancer following Hodgkin's disease, and kidney cancer following ovarian cancer. Overdiagnosis, misclassification of metastases and confounding by other risk factors were all considered as explanations of observed excesses. Nonetheless, it appeared that there are clear excess risks for cancers other than acute leukaemia which must be ascribed to therapy for the first cancer, especially in view of the possible under-reporting in registry material. Case-control studies are under way to provide information on the role of specific aspects of therapy.