Assessment of Secondary Sarcomas among Patients with Cancer of the Abdomen or Pelvis Who Received Combinations of Surgery, Radiation, and Chemotherapy vs Surgery Alone

Abstract

Importance: The association of radiation and chemotherapy with the development of secondary sarcoma is known, but the contemporary risk has not been well characterized for patients with cancers of the abdomen and pelvis. Objective: To compare the risk of secondary sarcoma among patients treated with combinations of surgery, radiation, or chemotherapy with patients treated with surgery alone and the general population. Design, Setting, and Participants: This population-based cohort study included 173580 patients in Ontario, Canada, with nonmetastatic cancer of the prostate, bladder, colon, rectum or anus, cervix, uterus, or testis. Patients were enrolled from January 1, 2002, to January 31, 2017. Data analysis was conducted from March 1, 2019, to January 31, 2020. Exposures: Treatment combinations of radiation, chemotherapy, and surgery. Main Outcome and Measures: Diagnosis of sarcoma based on histologic codes from the Ontario Cancer Registry. Time to sarcoma was compared using a cause-specific proportional hazard model. Results: Of 173580 patients, most were men (125080 [72.1%]), and the largest group was aged between 60 and 69 years (58346 [33.6%]). Most patients had genitourinary cancer (86235 [51.4%]) or colorectal cancer (69241 [39.9%]). Overall, 64301 (37.1%) received surgery alone, 51220 (29.5%) received radiation alone, 15624 (9.0%) were treated with radiation and chemotherapy, 15252 (8.8%) received radiation with surgery, and 11822 (6.8%) received all 3 treatments. A total of 332 patients (0.2%) had sarcomas develop during a median (interquartile range) follow-up of 5.7 (2.2-8.9) years. The incidence of sarcoma was 0.3% among those who underwent radiation alone (138 of 51220) and radiation with chemotherapy (40 of 15624), 0.2% among those who received radiation and surgery (36 of 15252) and all 3 modalities (25 of 11822), and 0.1% among those who received surgery with chemotherapy (13 of 14861) and surgery alone (80 of 64801). Compared with a reference group of patients who had surgery alone, the greatest risk of sarcoma was found among patients who underwent a combination of radiation and chemotherapy (cause-specific relative hazard [csRH], 4.07; 95% CI, 2.75-6.01; P