Bladder tumours following chemotherapy and radiotherapy for ovarian cancer: A case—control study

Abstract

A collaborative group of cancer registries and hospitals carried out a case-control study of tumours of the bladder in women who had previously been treated for ovarian cancer. A total of 63 cases of bladder tumours were identified, and 188 controls were selected matching for age, year of ovarian cancer diagnosis and survival time. Full details of the treatment for ovarian cancer were sought for both cases and for controls. The risk of bladder tumours was increased for patients who had been treated by radiotherapy alone (1.9; 95% confidence interval, 0.77-4.9), by chemotherapy alone (3.2; 0.97-10), and by chemotherapy and radiotherapy (5.2; 1.6-16), when comparison was made with patients treated only by surgery. Patients treated by chemotherapy were separated into 2 groups according to whether they had received cyclophosphamide. Among those who had, there was a clear increase in risk (approximately 4-fold) regardless of whether or not they had also received radiotherapy. For those who received only other drugs, risk was increased substantially among patients who had also been treated by radiation, as compared with patients treated by surgery alone, and those who had received radiotherapy only. Both melphalan and thiotepa were implicated as potential bladder carcinogens on the basis of these results. The estimated risk of bladder tumours due to cyclophosphamide was more than twice the risk following radiation to the bladder, and it appeared substantially earlier. For both agents, the risk continued to increase more than 10 years after treatment began.

Identification of Candidate Alkylator-Induced Cancer Susceptibility Genes by Whole Genome Scanning in Mice

“…In addition to the well-established link between alkylating agent exposure and t-MDS/AML in humans, it is now apparent that these drugs also increase the risk of secondary solid tumors such as lung adenocarcinoma (4), bladder carcinoma (49), and sarcoma (50). These observations provide additional validation of our ENU screen in mice and justify further study of these strains to understand the genetic basis of susceptibility to a broad range of alkylator-induced malignancies.…”

Molecular Mechanisms and Pathways in Bladder Cancer Development and Progression

“…Radiation Therapy: An increased risk for developing BC has been associated with radiation therapy to the pelvis for ovarian, 21 cervical, 22 and prostatic carcinomas. 23 BC tends to occur 5 to 10 years after radiation and is characteristically high grade and locally advanced at diagnosis.…”

Second Malignancies Among Elderly Survivors of Cancer

“…In particular, the risks for bladder, soft tissue, and bone cancers are substantially higher in women who received radiation, and these risks become most apparent Ն10 years following the initial radiation therapy [54,57]. The risk with chemotherapy in the development of second cancers is also apparent across all age groups.…”