Patients who receive radiation or chemotherapy for nonmetastatic prostate or bladder cancer or other abdominal or pelvic malignancies are at increased risk for secondary sarcomas compared with those treated with surgery alone.

A combination of radiation and chemotherapy was associated with the greatest risk for sarcoma compared with surgery alone. In addition, the risk for secondary sarcomas is higher than the risk for sarcoma in the general population, a new study suggests.

“This study provides further evidence to support the association of radiotherapy with secondary sarcoma; the finding of an increase in risk with combination radiotherapy and chemotherapy, in particular, merits further study,” a team led by Robert K. Nam, MD, of Sunnybrook Health Science Centre, University of Toronto, Toronto, Ontario, Canada, wrote in a paper published in JAMA Network Open.

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The study included a population-based cohort of 173,580 patients in Ontario, Canada, who had nonmetastatic cancer of the prostate, bladder, colon, rectum or anus, cervix, uterus, or testis. Of these, 125,080 (72.1%) were men. Most patients had genitourinary cancers (86,235, 51.4%) and colorectal cancer (69,241, 39.9%).

The cohort consisted of 64,301 patients (37.1%) who underwent surgery alone, 51,220 (29.5%) who had radiation alone, 15,624 (9.0%) who received both radiation and chemotherapy, 15,252 (8.8%) who received radiation and surgery, and 11,822 (6.8%) who received all 3 treatments.

During a median follow-up time of 5.7 years, sarcomas developed in 332 patients (0.2%). The incidence of sarcomas was 0.3% among patients who had radiation therapy alone and radiation in addition to chemotherapy, 0.2% among those who received radiation and surgery and all 3 modalities, and 0.1% among patients who received both surgery with chemotherapy, Dr Nam’s team reported.

Compared with the surgery-only patients, patients who underwent a combination of radiation treatment and chemotherapy had a 4.0-fold increased risk of sarcoma, whereas those who received radiation alone, radiation with surgery, and all 3 modalities each had an approximately a 2.3-fold increased risk, the investigators reported.

Among patients with prostate cancer, those who received radiation alone and radiation plus surgery had a relative rate of sarcoma double that of patients who had surgery alone. The relative rate was not significantly elevated among patients who had radiation plus chemotherapy.

Compared with Ontario’s general population, patients treated with radiation had a 2.4-fold increased sarcoma rate compared with the general population (41.3 vs 17.2 events per 100,000 person-years), according to the investigators.

“In this cohort study, patients treated with radiation or chemotherapy for abdominopelvic cancers had an increased rate of sarcoma,” the authors concluded. “Although the absolute rate is low, patients and physicians should be aware of this increased risk of developing sarcoma.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Hird AE, Magee DE, Matta R, et al. Assessment of secondary sarcomas among patients with cancer of the abdomen or pelvis who received combinations of surgery, radiation, and chemotherapy vs surgery alone. Published online October 1, 2020. JAMA Netw Open. doi:10.1001/jamanetworkopen.2020.13929