Risk of Secondary Malignancies in Ovarian Cancer Survivors: 54,305 Patients Analyzed With 40 Years of Follow-up

Abstract

Survivors of ovarian cancer are at risk of developing a secondary malignancy (SM). We sought to evaluate the risk of developing SM, stratified by treatment modality and site of SM.Standardized incidence ratios (SIR, observed-to-expected [O/E] ratio) and absolute excess risk of SM, were assessed in 54,305 patients diagnosed with ovarian cancer as a first malignancy between 1975 and 2016 in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Follow-up was available through 2016. Importantly, the SIRs take into account age at diagnosis, race, year of diagnosis and patient-years at risk. Non-melanoma skin cancers were not counted as SM. SIRs were also evaluated for patients according to latency from their initial diagnosis.Of 54,305 patients diagnosed with ovarian cancer, 1,010 received radiation therapy (RT) alone, 35,842 received chemotherapy (CT) alone, and 1,035 were treated with chemotherapy and radiation (CRT). 16,418 patients received neither CT or RT. Overall, 3,981 patients (7.3%) developed SM, which was more than the endemic rate [O/E 1.13 (95% CI 1.09- 1.16); P < 0.05]. Patients who received any RT (RT+CRT) had an increased risk of SM compared to those who didn't [O/E 1.42 (95% CI 1.24- 1.61) vs O/E 1.11 (95% CI 1.08- 1.15), respectively; P < 0.05] which included an excess risk of 4.82 bladder cancers per 10,000 patient-years at risk. Patients who received any CT (CT+CRT) had a similar risk of developing SM compared to those not treated with CT [O/E 1.11 (95% CI 1.07- 1.16) vs O/E 1.14 (95% CI 1.09- 1.12), respectively; P < 0.05]. Those who received any CT had an excess risk of 4.1 cases of leukemia per 10,000 patient-years at risk compared to those who did not receive CT. When stratified into treatment groups (No CT/RT, RT alone, CT alone, CRT), the CRT group had higher rates of SM than the no CT/RT and CT groups [O/E 1.56 (95% CI 1.25- 1.93)]. There was no statistically significant difference in the SM rate between the RT group and no CT/RT group [O/E 1.35 (95% CI 1.14- 1.57) vs O/E 1.13 (95% CI 1.07- 1.18), respectively]. The CT and CRT groups had an increased risk of leukemia compared to the no CT/RT group (P < 0.05). The CT only group had a lower risk of developing lung cancer than the no CT/RT group (P < 0.05). The excess risk of developing a solid tumor was greatest at latencies of 10-20 years. The excess risk of developing leukemia was greatest at latencies up to 10 years.This is the largest study to examine the risk of SM in patients with ovarian cancer and has the longest follow-up. The risk of SM was increased after having ovarian cancer and varied with treatment modality. Patients treated with any RT had higher rates of SM than those not treated with RT. Importantly, CT did not result in an increased excess risk of solid tumor SM, only in an increased excess risk of leukemia. These results may help inform SM screening protocols for women with ovarian cancer.A.C. Casper: None. M.W. Parsons: None. J. Chipman: None. L.M. Burt: ARRO executive committee. G. Suneja: Research Grant; National Institutes of Health. Honoraria; National Comprehensive Cancer Network. Travel Expenses; National Comprehensive Cancer Network, Radiation Oncology Institute, American Board of Radiology; Radiation Oncology Institute, National Comprehensive Cancer Network, ASTRO.K.A. Maurer: None. D.K. Gaffney: Research Grant; NCI. Consultant; NCI. run meetings; NCI.