The American Society for Clinical Oncology (ASCO) Endorsement Panel has endorsed postoperative radiotherapy guidelines for patients with endometrial cancer published by the American Society for Radiation Oncology (ASTRO).

The ASCO endorsement described the guidelines as “clear, thorough, and based on the most relevant scientific evidence.”1

Endometrial cancer is not uncommon among American women, with approximately 50,000 diagnoses and 9,300 deaths in the United States expected this year.2

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Despite its prevalence, consensus was lacking on optimal adjuvant treatment of the disease. Last year, to address this lack of consensus, ASTRO published an evidence-based guideline on the use of postoperative radiation therapy in women who undergo surgery for endometrial cancer. ASTRO recognized that data from existing prospective clinical trials contributed to ambiguity in treatment decision-making, both due to features of trial design and specific disease factors, such as the low recurrence rates in early stage disease.3

Five Key Questions Addressed in ASTRO Guideline

With the ASCO endorsement this month, a review of the ASTRO recommendations is timely. In essence, ASTRO sought to answer five important questions surrounding postoperative adjuvant therapy for women with stage 1 to 4 endometrioid endometrial cancer:

  1. Which patients require no additional therapy after hysterectomy?
  2. Which patients should receive vaginal cuff brachytherapy?
  3. Which women with early stage and which women with stage 3-4A disease should receive postoperative EBRT?
  4. Should brachytherapy be used in addition to EBRT?
  5. How should radiation therapy and chemotherapy be integrated in the management of stage 1-3 endometrial cancer?

To answer the first question, the guidelines recognize that EBRT does not convey a survival benefit for women with early stage disease. Although it may reduce recurrence, the lack of survival benefit plus the morbidity associated with EBRT recommend against its use.

Thus, ASTRO specifies that adjuvant radiation therapy is not necessary for women without residual disease in hysterectomy samples despite a positive biopsy or for women with grade 1 or 2 cancers without or with less than 50% invasion of the myometrium.

Of note, the ASCO endorsement adds “despite a positive prehysterectomy biopsy of any grade. For women with more negative disease factors, ASTRO specifies that vaginal cuff brachytherapy, not EBRT, may be beneficial for women with node-negative, grade 3 tumors without myometrial invasion or for women with node-negative, grade 1 or 2 tumors with less than 50% myometrial invasion accompanied by high-risk features, including being older than 60 or having lymphovascular invasion.

RELATED: In Patients with Endometrial Cancer, Radiation Therapy with Concurrent Paclitaxel After Surgery is Effective

To answer the second question, both ASTRO and ASCO agree that vaginal cuff brachytherapy is preferred over EBRT for locoregional control in high-intermediate risk disease, particularly for patients who have undergone comprehensive nodal assessment.

Data from the PORTEC-2 trial, which directly compared the two modalities, show that vaginal cuff brachytherapy is as effective as pelvic radiation for prevention of vaginal recurrence in patients with grade 1 or 2 tumors with 50% or more myometrial invasion or grade 3 tumors with less than 50% myometrial invasion.

Disease-free and overall survival rates were similar, but vaginal brachytherapy had less associated acute toxicity.1,3

The data supporting use of vaginal brachytherapy after EBRT (question 4) are weak, and there are no prospective data to validate this practice. Sequential EBRT and vaginal brachytherapy is not generally recommended, unless risk factors for vaginal recurrence are present.

Who should receive postoperative EBRT (question 3)? As noted, it provides no survival benefit in early stage disease, and is not recommended.

ASTRO states that postoperative EBRT may reduce the risk of pelvic recurrence in women with grade 3 disease and 50% or more myometrial invasion or cervical stroma invasion, as well as women with grade 1 or 2 disease, 50% or more myometrial invasion and high-risk features.

As reinforced in the ASCO endorsement, vaginal brachytherapy may be a preferred option for the latter group of women with stage 1 or 2 disease.