Risk of Secondary Sarcoma Among Patients Treated for Cancers of the Abdomen and Pelvis with Surgery, Radiation or Chemotherapy: A Population-Based Cohort Study

Abstract

Background: The causal association between radiation and chemotherapy treatment and the development of secondary sarcoma is well known, but the contemporary risk has not been well characterized for patients with cancers of the abdomen and pelvis. Methods: We conducted a population–based retrospective cohort study examining the risk of sarcoma among patients with localized cancer of the prostate, bladder, colorectal, cervical, uterine, and testis between 2002–2016. The primary outcome was the development of sarcoma. Cox proportional hazard analysis was used to estimate the risk of sarcoma after treatment combinations with radiation, chemotherapy, or surgery. Findings: We identified 173,580 patients. Most patients had genitourinary (51∙4%) or colorectal cancer (39∙9%). Overall, 332 (0∙2%) sarcomas developed over a median of 5∙7 years (IQR: 2∙2–8∙9). Compared to a reference group of patients who had surgery alone, the greatest risk for sarcoma was found for patients who underwent a combination of radiation and chemotherapy (HR=4∙1,95%CI:2∙8–6∙0,p<0∙001). This was followed by patients who had radiation alone (HR=2∙4,95%CI:1∙8–3∙1,p<0∙001), radiation with surgery (HR=2∙3,95%CI:1∙6–3∙5,p<0∙001), and all three modalities (HR=2∙3,95%CI:1∙4–3∙6,p<0∙001). The standardized incidence ratio for sarcoma among patients treated with radiation compared to the general population was 2∙4 (95%CI:1∙6–3∙7). The annual number of cases of sarcoma increased from 2009 (15 per 100,000 persons) to 2016 (32 per 100,000 persons), but the annual rate did not change over time. Interpretation: Patients treated with radiation and chemotherapy for abdominopelvic cancers had an increased risk of sarcoma. The number of cases is increasing per year due to longer survival from the treatment of the initial cancer. Funding Statement: This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long–Term Care. This study also received funding from the Ajmera Family Chair in Urologic Oncology awarded to RKN. Declaration of Interests: GSK has acted as a consultant for Merck, Roche, Janssen and Ferring and received honoraria for lectures on behalf of Biosyent, Merck, Roche and Theralase. SH reports receiving grants from Astellas Pharma Canada, Allergan, AMI, Boston Scientific, and Pfizer all outside the submitted work. All other authors have no conflicts of interest to declare. Ethics Approval Statement: The study was approved by the Sunnybrook Research Ethics Board.