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Radiotherapy for rectal cancer linked to risk for later malignant gynecological neoplasms

JAMA Network Open
Reuters Health - 08/01/2021 - Women who receive radiotherapy for rectal cancer may be at an increased risk of uterine and ovarian cancer, a new study suggests.

In an analysis of information from the SEER database on more than 20,000 female patients diagnosed with rectal cancer, researchers found the treatment was associated with a three-fold increased risk of subsequent uterine cancer and a two-fold increased risk of ovarian cancer, according to the report published in JAMA Network Open.

"In our analysis, we assessed the dynamic risk and incidence of SGMN (second gynecological malignant neoplasms)," write the authors, led Xu Guan of the National Center/Cancer Hospital, Chinese Academy of Sciences and Peking Union Medical College in Beijing.

"The highest radiotherapy-associated risk for developing ovarian cancer was found after a latency of more than 20 years, but for cancer of the uterine corpus, the highest risk was found within five to 10 years," they write. "This finding suggests that long-term follow-up may be warranted for the detection of ovarian cancer after radiotherapy, but follow-up for cancer of the uterine corpus should be considered in the early latency."

To explore whether radiotherapy treatment for rectal cancer might increase the risk of gynecologic malignancies, the researchers turned to information from the Surveillance, Epidemiology and End Results (SEER) database gathered between January 1, 1973 and December 31, 2015. Female patients diagnosed with either rectal cancer or rectosigmoid cancer were included in the analysis.

Exclusion criteria included patients in whom rectal cancer was not their first primary cancer, patients who were aged younger than 20 years, patients with distant stage, patients who survived less than five years after rectal cancer diagnosis, patients who did not undergo surgery, and patients with missing data on radiotherapy, surgery, age, tumor stage, race, survival status or follow-up information.

The researchers identified 20,142 women who fit their criteria, with 14,832 (65.7%) who did not receive radiotherapy and 5,310 (34.3%) who received the treatment. Median follow-up was 140 months. After a latency of five years, 176 patients (1.2%) in the no-radiotherapy group and 144 patients (2.7%) in the radiotherapy group developed SGMN.

The cumulative incidence of combined SGMNs was 2.16% after rectal cancer diagnosis; the incidences were 1.53% in patients with no radiotherapy and 4.53% in patients receiving radiotherapy. In organ-specific analyses, the cumulative incidences of cancer of the uterine corpus, ovarian cancer, and other SGMNs were significantly higher in the radiotherapy group than the no-radiotherapy group, including cancer of the uterine corpus (1.00% vs 2.80%), ovarian cancer (0.29% vs 0.98%), and other SGMNs (0.20% vs 0.62%), but no difference was observed for cervical cancer.

In subgroup analysis, the adjusted relative risk of additional risk for combined SGMNs was 2.82. An increased risk was also observed for cancer of the uterine corpus (RR, 3.19), ovarian cancer (RR, 2.26), and other SGMNs (RR, 2.72).

The authors were unavailable to comment before press time.

"The work is a very elegant population-based study with appropriate latency selection and sound statistical approach," said Dr. Zahra Ghiassi-Nejad, an assistant professor in the department of radiation oncology at the Icahn School of Medicine at Mount Sinai in New York.

"Previously the question of secondary gynecologic malignancy following radiotherapy for rectal cancer had not been adequately addressed," Dr. Ghiassi-Nejad said in an email. "Given the findings of increased risk of SGMN, radiation oncologists should adequately counsel patients on this increased cumulative risk and be mindful of adequate gyn follow up to address symptoms and hopefully diagnose these secondary malignancy cases as early as possible."

The new study has limitations, said Dr. Susannah Ellsworth, a radiation oncologist at the UPMC Hillman Cancer Center.

"The SEER database doesn't give tremendously granular information," Dr. Ellsworth said, adding that there are many factors that might affect the ultimate findings.

For example, she said, there may be differences between patients who receive radiotherapy and those who do not. "Patients who undergo operative management may be fundamentally different from those who require radiation," she added. "Also, you wouldn't know how many women in one group versus the other had a hysterectomy."

"I would caution against using this data to make any kind of treatment decision," Dr. Ellsworth said. "I see this as a hypothesis generating study."

SOURCE: https://bit.ly/3hXcKFg JAMA Network Open, online January 8, 2021.

By Linda Carroll

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