Also fewer side effects and better quality of life

Vaginal brachytherapy (VBT), where radiotherapy is given internally, is as effective as external beam radiotherapy (EBRT) in preventing local disease recurrence with similar rates of survival, but with significantly less toxicity and better quality of life, in patients with high-intermediate risk endometrial cancer. Wherever possible, VBT should replace EBRT and become the standard treatment for all patients with high-intermediate risk endometrial cancer after surgery, concludes an article published in this week’s edition of The Lancet.

Endometrial cancer is the most common gynaecological cancer in postmenopausal women in developed countries and, because of an aging population, incidence of the disease is increasing. About 80% of patients are diagnosed with stage 1 disease in which the initial treatment is usually surgery (removal of the uterus and ovaries). Radiotherapy (VBT or EBRT) is given after surgery to patients at high-intermediate risk as it lowers the likelihood of local disease recurrence from about 20% to 5%. However, the best adjuvant radiotherapy treatment option remains unclear and practices vary widely.

In 2002, the Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC-2) trial commenced to examine whether VBT is as effective as EBRT at preventing vaginal recurrence (the most frequent site of recurrence in patients with high-intermediate risk endometrial cancer), whilst monitoring occurrence of possible side effects and resulting quality of life.

427 patients were randomly assigned to EBRT (46 Gy in 23 fractions) or VBT (21 Gy high-dose rate in three fractions or 30 Gy low-dose rate). Quality of life was assessed using self-reported questionnaires completed at regular intervals after treatment for up to 5 years. Preliminary results showed that in the first 2 years after treatment patients who received EBRT experienced significantly more gastrointestinal toxic effects, especially diarrhoea, more often resulting in limitations to their daily activities and decreased social functioning.

In today’s study, the PORTEC team report the main trial results on efficacy, side-effects, and patient-reported quality of life, to establish the best adjuvant treatment option for patients with high-intermediate risk endometrial cancer.

Findings showed that at median follow-up of 45 months, very few vaginal recurrences occurred in either radiotherapy group (3 for VBT vs 4 for EBRT), showing VBT to be very effective in ensuring local disease control. Estimated 5-year vaginal recurrence rates were 1.8% after VBT and 1.6% after EBRT.

Additionally, there were no significant differences in 5-year locoregional (vaginal or pelvic or both) recurrence, and rates of overall (84.8% for VBT vs 79.6% for EBRT) and disease-free survival (82.7% vs 78.1% for EBRT) were similar.

Importantly, patients in the EBRT group experienced significantly higher rates of mild to moderate gastrointestinal adverse events than those in the VBT group at completion of radiotherapy (53.8% vs 12.6%). While the occurrence of adverse events did decrease in the EBRT group over time, rates remained significantly higher compared to VBT.

The authors say: “PORTEC-2 shows that patients at high-intermediate risk, about 30% of all patients with endometrial cancer, can be safely treated with vaginal brachytherapy alone, with fewer side-effects and improved quality of life. EBRT will thus be used only for the 15% of patients with high-risk or advanced disease.”

They conclude: “VBT should be the adjuvant treatment of choice for patients with endometrial carcinoma of high-intermediate risk.”

In an accompanying Comment, Henry Kitchener from the University of Manchester Academic Health Science Centre, Manchester, UK, and Melanie Powell from the Barts and London NHS Trust, London, UK agree with the recommendations of the trial authors and say that VBT should become the standard of care in these patients. They point out that: “VBT is not as widely available as is EBRT so patients might need to travel further for treatment, but VBT needs fewer treatments and has a better toxicity profile than does EBRT, and is associated with improved quality of life for a similar outcome.”

Source: Lancet