Medical Center

Endometrial Cancer
Women with endometrial cancer of high-intermediate risk, who comprise about 30% of the patient population, can be safely treated with vaginal brachytherapy (VBT) after surgery instead of undergoing external beam radiation therapy (EBRT). Both approaches offer similar control of recurrences and have a similar impact on survival, but VBT is associated with “significantly better” quality of life and fewer gastrointestinal (GI) adverse effects.

These are the conclusions of the Postoperative Radiation Therapy for Endometrial Carcinoma 2 (PORTEC-2) study, which has just been published in The Lancet. The results were reported at last year’s annual meeting of the American Society of Clinical Oncology, when 1 commentator predicted that they would significantly influence clinical practice.

“Vaginal brachytherapy should be the adjuvant treatment of choice for patients with endometrial carcinoma of high-intermediate risk,” write the study authors, headed by Remi Nout, MD, from Leiden University Medical Center in the Netherlands.

An accompanying editorial agrees with the investigators’ recommendation and extends it a little further. Editorialists Henry Kitchener, MD, from the University of Manchester, United Kingdom, and Melanie Powel, MD, from the London National Health Service Trust, United Kingdom, write, “VBT should become the standard of care for women with endometrial cancer of intermediate and high-intermediate risk.”

“We believe the results of PORTEC-2 are reliable and clinically important,” the editorialists add.

VBT requires fewer treatments and has a better toxicity profile than EBRT and is associated with improved quality of life for a similar outcome, they comment. However, because it is not as widely available as EBRT, patients may have to travel further for treatment, they add.

But what about women with high-risk or advanced endometrial cancer? The study authors suggest that these women, who comprise about 15% of the patient population, should be treated with EBRT. However, the editorialists point out that this question is being addressed in ongoing trials, including the PORTEC-3 study (which they are both involved in), which is comparing EBRT alone with chemoradiation followed by chemotherapy.

Noninferiority Randomized Trial

PORTEC-2 was an open-label, noninferiority trial carried out across 19 radiation oncology centers in the Netherlands. It involved 427 women with stage 1 or 2A endometrial cancer with features of high-intermediate risk who were randomized to receive either VBT (21-Gy high dose in 3 fractions, delivered 1 week apart, or 30-Gy low-dose rate) or EBRT (46 Gy in 23 fractions, delivered 5 times per week).

At a median follow-up of 45 months, few vaginal recurrences occurred in both treatment groups, the study authors note. There were 4 events among 183 patients in the EBRT group and 2 of 183 in the VBT group, giving estimated 5-year recurrence rates of 1.9% and 1.5%, respectively.

These estimated 5-year recurrence rates are “convincingly low and almost identical in both treatment groups,” the editorialists comment. Without radiotherapy, vaginal recurrence would occur in about 10% to 14% of cases, they point out.

Vaginal recurrence is the most frequent site of disease recurrence in patients with endometrial carcinoma of high-intermediate risk, the study authors comment, adding that VBT is “very effective in ensuring local control.”

Both groups also had similar disease-free and overall survival rates.

However, there were significant differences in toxicity, with more GI toxicity seen after EBRT than after VBT.

Patients assigned to VBT reported few GI symptoms, the study authors note, and no increase in symptoms after treatment ended, whereas the patients who had EBRT reported GI symptoms during and immediately after radiation and also an increase in symptoms after treatment ended. Grade 1 and 2 GI toxic effects were reported by 53.8% of patients receiving EBRT and 12.6% of patients receiving VBT, whereas late grade 3 GI toxic effects were reported by 4 patients (2%) receiving EBRT and 1 patient (<1%) receiving VBT and required surgery for bowel obstruction due to adhesions or fibrosis.

The editorialists also note that previously reported quality-of-life data from this PORTEC-2 trial showed that VBT was associated with lower symptom scores for diarrhea and fecal leakage than was EBRT, allowing for improved social functioning and reduced restriction on daily activities (J Clin Oncol. 2009;27:3547-3556).

“Toxic effects of therapy and how these affect quality of life is, for some patients, the most important factor in acceptance of treatment,” the editorialists comment. “By delivery of highly localized vaginal radiation, VBT reduces short-term and long-term morbidity.”

The PORTEC-2 study was funded by the Dutch Cancer Society. The study authors have disclosed no relevant financial relationships. Both editorialists report that they are on the trial management group for the ongoing PORTEC-3 trial.