Reduced Long-Term Survival and Increased Risk of Secondary Cancer in Younger Women After External Pelvic Radiation for Early-Stage Endometrial Cancer
In a study reported in Journal of Clinical Oncology, Mathias Onrud, MD, of Norwegian Radium Hospital, Oslo University Hospital, and colleagues assessed outcomes in the follow-up of the Norwegian Radium Hospital trial to determine long-term effects of external beam radiation therapy in the adjuvant treatment of early-stage endometrial cancer. They found no survival benefit of external pelvic radiation, with pelvic radiation decreasing survival and increasing risk of secondary cancer in women aged < 60 years at diagnosis.
Study Details
In the Norwegian Radium Hospital trial, which enrolled patients between 1968 and 1974, 568 patients with stage I endometrial cancer underwent abdominal hysterectomy and bilateral salpingo-oopherectomy. Patients were then randomly assigned to receive either vaginal radium brachytherapy followed by external beam radiation therapy (n = 288) or brachytherapy alone (control group, n = 280). Patients in the control group and the external beam radiation therapy group had median ages of 59 and 60 years, 98% of both groups had tumor confined to the uterine corpus, and all patients were white. The groups were well balanced for other baseline characteristics. Although there was no difference in the distribution of histologic grade between age groups, a greater proportion of women aged > 60 years had tumors of deep myometrial infiltration.
Overall Survival Outcomes
No patients were lost to follow-up. By the end of follow-up, 7.9% of patients were still alive. After median follow-up of 20.5 years (range 0–43.4 years), there was no significant difference in median overall survival between the external beam radiation therapy and control group (20.50 vs 20.48 years, hazard ratio [HR] = 1.13, P = .0186). Analysis by age at diagnosis showed that patients aged < 60 years had a significantly higher mortality rate after external beam radiation therapy than the control group (HR = 1.36, P = .013). The difference in survival was most evident after 20 years of follow-up. There was no difference in overall mortality among women older than 60 years (HR = 0.91, P = .45).
Risk of Secondary Cancers
In total, 30.5% of patients in the external beam radiation therapy group were diagnosed with a secondary cancer compared with 24.5% in the control group (HR = 1.42, 95% confidence interval [CI] = 1.01–2.00). Median time to secondary cancer was 15.0 years. Among women aged < 60 years at diagnosis, external beam radiation therapy was associated with a doubling of risk for secondary cancer (HR = 2.02, P = .002); in this age group, secondary cancer developed in 39.7% of patients in the external beam radiation therapy group and 25.6% of the control group. In women aged > 60 years, there was no significant difference in risk between treatment arms (HR = 0.81, 95% CI = 0.45–1.43). The proportions of colorectal and anal cancers and cancers of the bladder, vulva, and the skin were higher in the external beam radiation therapy group than in the control group; fewer cases of breast cancer were detected in the external beam radiation therapy group.
The investigators concluded: “[T]here was no survival benefit after [external beam radiation therapy] in early-stage endometrial cancer. On the contrary, younger women experience decreased survival, and the incidence of secondary cancers increased after long-term follow-up. Prolonged post-treatment surveillance should be considered after [external beam radiation therapy] with respect to secondary cancers.”
The corresponding author for this study is Kristina Lindemann, MD, PhD, of Norwegian Radium Hospital, Oslo University Hospital.
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