Adjuvant Pelvic Radiotherapy Appropriate Treatment for Early-Stage Endometrial Cancers

Results from a recent study did not demonstrate the superiority of vaginal cuff brachytherapy plus chemotherapy (VCB/C) over pelvic radiation therapy in patients with early-stage endometrial cancer (J Clin Oncol. 2019 Apr 17. Epub ahead of print).

“Studying the effect of adjuvant systemic chemotherapy in serous tumors is important, because this histologic subgroup is associated with an increase in intra-abdominal and systemic metastases and a disproportionate number of deaths,” according to Marcus E. Randall, MD, Department of Radiation Medicine, University of Kentucky, Lexington, and colleagues.

“Better outcomes with adjuvant therapy that includes chemotherapy have been documented in some series, whereas others have failed to identify a favorable impact,” they added.

Thus, Dr Randall and his co-investigators conducted the open-label, phase 3 GOG-0249 trial to

compare the effects of VCB/C versus pelvic radiation therapy on recurrence-free survival (RFS) in women with high-risk, early-stage endometrial cancer.

Patients were eligible for inclusion if they had stage I endometrioid with Gynecologic Oncology Group protocol 33–based high-intermediate-risk criteria, stage II disease, or stage I to II serous or clear cell tumors. A total of 601 patients (median age, 63 years) were recruited, 74% of whom had stage I disease (histologies included endometrioid in 71%, serous in 15%, and clear cell in 5%).

Patients were randomized to receive pelvic radiation therapy (45 to 50.4 Gy over 5 weeks) or VCB followed by paclitaxel 175 mg/m2 (3 hours) plus carboplatin (area under the curve, 6) every 21 days for 3 cycles.

The primary end point was to determine whether VCB/C increased RFS compared with pelvic radiation therapy in patients with high-intermediate and high-risk, early-stage endometrial cancer.

After a median follow-up of 53 months, the 60-month RFS was the same (0.76; 95% CI, 0.70-0.81) for each of the treatment arms (hazard ratio, 0.92; 90% confidence limit, 0.69-1.23). The OS rates at 60 months were 0.87 (95% CI, 0.83-0.91) with pelvic radiation therapy and 0.85 (95% CI, 0.81-0.90) with VCB/C (hazard ratio, 1.04; 90% confidence limit, 0.71-1.52).

Although pelvic and para-aortic nodal recurrences were more frequent with VCB/C than with radiotherapy (9% vs 4%, respectively), vaginal and distant recurrence rates were similar between the arms.

“There was no heterogeneity of treatment effect with respect to RFS or overall survival among clinical or pathologic variables evaluated,” Dr Randall and colleagues said.

Ultimately, the study did not demonstrate the superiority of VCB/C over pelvic radiation therapy; acute toxicity was greater with VCB/C than with radiotherapy, and late toxicity was similar between both treatment arms.

“Pelvic RT [radiation therapy] alone remains an effective, well-tolerated, and appropriate adjuvant treatment in high-risk early-stage endometrial carcinomas of all histologies,” Dr Randall et al concluded.—Hina Khaliq