Adding radiation to chemo not better for locally-advanced endometrial cancer

By Gene Emery

(Reuters Health) - 12/6/2019

Supplementing chemotherapy with radiation failed to improve relapse-free survival in patients with stage III or IVA endometrial carcinoma, according to a comparison of the two therapies in 707 volunteers.

Research published June 12 online in The New England Journal of Medicine produced Kaplan-Meier estimates at 60 months for 59% who received chemoradiotherapy versus 58% with chemotherapy alone (hazard ratio of 0.90 with a 90% confidence interval of 0.74 to 1.10).

"This study was designed to show that chemoradiotherapy was superior to systemic chemotherapy but the findings were that the combination arm was not superior," chief author Dr. Daniela Matei of Northwestern University in Chicago told Reuters Health in a telephone interview. "The hypothesis had been that, given together, they would control the disease better."

"This does push radiation to the back burner of treatment," said Dr. Matei, who estimated that 5,000 to 10,000 U.S. women have endometrial carcinoma at this stage. "The mainstay of treatment for these patients should be systemic chemotherapy."

The Matei team found a higher 5-year rate of distant recurrence with chemoradiotherapy but lower rates of vaginal recurrent and pelvic and paraaortic lymph-node recurrence.

Serious side effects of grade 3, 4 or 5 were slightly lower with chemoradiotherapy, with rates of 58% versus 63% in the chemotherapy-only group.

The study establishes "a new standard of care for this group of patients," Dr. Matei said. "We observed that patients receiving chemotherapy alone had a better quality of life compared to patients who received both chemotherapy and radiation," in part because chronic side effects were less of a problem.

And moving away from radiation "will save a lot of money," said Dr. Matei, who is the Diana Princess of Wales professor in cancer research at Northwestern.

The National Cancer Institute funded the trial.

All of the women in the GOG 258 trial had received a hysterectomy and bilateral salpingo-oophorectomy within 8 weeks before entering the trial, and no remaining tumor could be larger than 2 cm. Surgery to remove lymph nodes was done in 94% of the volunteers.

Radiation was planned for a total dose of 4,500 cGy in 25 fractions. Chemotherapy consisted of cisplatin, carboplatin, paclitaxel and granulocyte colony-stimulating factor. Median follow-up was 47 months.

Five-year vaginal recurrence rates were 2% with chemoradiotherapy versus 7% with chemotherapy alone. Pelvic and paraaortic lymph-node tumors recurred in 11% with combination treatment versus 20% with chemotherapy only.

"However, that didn't translate into a longer remission rate or longer survival rate," said Dr. Matei.

And when it came to distant recurrence, the rate was 27% in chemoradiotherapy patients versus 21% in the chemotherapy-only group.

Side effects rated grade 4 or higher occurred in 14% of the chemoradiation recipients and 30% in the chemotherapy-only group.

The two deaths attributed to treatment both occurred in the chemotherapy-only group.

"Although acute toxic effects were more common in the chemoradiotherapy group than in the chemotherapy-only group in our trial, most were low-grade and reversible on treatment discontinuation," the researchers said. "Chronic toxic effects included diarrhea, lymphedema, and musculoskeletal events and were more common with chemoradiotherapy."


N Engl J Med 2019

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