As reported in the Journal of Clinical Oncology by Larissa A. Meyer, MD, MPH, and colleagues, ASCO has endorsed the recently published American Society for Radiation Oncology (ASTRO) guideline on postoperative radiation therapy for endometrial cancer.¹ The ASCO clinical practice guideline endorsement panel was co-chaired by Dr. Meyer, of The University of Texas MD Anderson Cancer Center, and Alexi Wright, MD, MPH, of Dana-Farber Cancer Institute. The ASTRO guideline was reported by Klopp et al in Practical Radiation Oncology in 2014.²

“The endorsement represents common ground as we work collaboratively with our radiation oncology colleagues to care for women with endometrial cancer,” Dr. Meyer told The ASCO Post. “It highlights areas of mutual agreement as well as areas where further research needs to be done to optimize evidence-based medical care.”

Key recommendations of the ­ASTRO guideline with qualifying statements by the ASCO endorsement panel, in italics, are reproduced below.

No Additional Therapy

Which patients with endometrioid endometrial cancer require no additional therapy after hysterectomy?

Following total abdominal hysterectomy with or without node dissection, no radiation therapy is a reasonable option for patients with cancer of any grade without residual disease in the hysterectomy specimen, despite positive biopsy (despite a positive prehysterectomy biopsy of any grade).

Following total abdominal hysterectomy with or without node dissection, no radiation therapy is a reasonable option for patients with grade 1 or 2 cancers with either no invasion or < 50% myometrial invasion.

Vaginal cuff brachytherapy may be considered in patients with negative node dissection with grade 3 tumor without myometrial invasion.

Vaginal cuff brachytherapy may be considered in patients with negative node dissection with grade 1 or 2 tumors with < 50% myometrial invasion and higher-risk features, such as age > 60 years or lymphovascular space invasion.

Vaginal Cuff Irradiation

Which patients with endometrioid endometrial cancer should receive vaginal cuff irradiation?

Vaginal cuff brachytherapy is as effective as pelvic radiation at preventing vaginal recurrence for patients with grade 1 or 2 tumors with ≥ 50% myometrial invasion or grade 3 tumors with < 50% myometrial ­invasion.

Vaginal cuff brachytherapy is preferred to pelvic radiation in patients with the above risk factors, particularly in patients who have had comprehensive nodal assessment.

External-Beam Radiation

Which patients should receive postoperative external-beam radiation?

Patients with grade 3 cancer with ≥ 50% myometrial invasion or cervical stroma invasion of any grade may benefit from pelvic radiation to reduce the risk of pelvic recurrence.

Patients with grade 1 or 2 tumors with ≥ 50% myometrial invasion may also benefit from pelvic radiation to reduce pelvic recurrence if other risk factors are present, such as age > 60 years or lymphovascular space invasion. Vaginal brachytherapy may be a better option for patients with these features, especially if surgical staging was adequate and nodes were ­negative.

The best available evidence at this time suggests that reasonable options for adjuvant treatment of patients with positive nodes or involved uterine serosa, ovaries/fallopian tubes, vagina, bladder, or rectum include external-beam radiation therapy, as well as adjuvant chemotherapy. The best evidence for this population supports the use of chemotherapy, but consideration of external-beam radiation therapy is reasonable.

Chemotherapy without external-beam radiation may be considered for some patients with positive nodes or involved uterine serosa, ovaries/fallopian tubes, vagina, bladder, or rectum based on pathologic risk factors for pelvic recurrence.

Radiation therapy without chemotherapy may be considered for some patients with positive nodes or involved uterine serosa, ovaries/fallopian tubes, vagina, bladder, or rectum based on pathologic risk factors for pelvic recurrence. Patients receiving chemotherapy seem to have improved survival compared with radiation therapy alone.

Brachytherapy Plus External-Beam Radiotherapy

When should brachytherapy be used in addition to external-beam radiation?

Prospective data are lacking to validate the use of vaginal brachytherapy after pelvic radiation, and most retrospective studies show no evidence of benefit, albeit with small patient numbers. Use of vaginal brachytherapy in patients also undergoing pelvic external-beam radiation is not generally warranted, unless risk factors for vaginal recurrence are present.

Radiotherapy Plus Chemotherapy

How should radiation therapy and chemotherapy be integrated in the management of stage I to III endometrioid endometrial cancer?

The best available evidence suggests that concurrent chemoradiation followed by adjuvant chemotherapy is indicated for patients with positive nodes or involved uterine serosa, ovaries/fallopian tubes, vagina, bladder, or rectum. Evidence regarding concurrent chemoradiation is limited at this time, and this recommendation is based on expert opinion; we anticipate level 1 evidence from upcoming prospective randomized clinical trials (GOG 0258 and PORTEC-3). Chemotherapy may also be considered in certain patients with high-risk early-stage endometrial cancer, and clinical trials addressing this question are underway.

Alternative sequencing strategies with external-beam radiation and chemotherapy are also acceptable. Prospective trials have examined sequential radiation therapy and chemotherapy. Evidence supporting sandwich-type therapy is currently limited.  ■

Disclosure: Dr. Meyer has received travel and accommodation support from AstraZeneca. Dr. Wright reported no potential conflicts of interest. For full disclosures of the other authors, visit jco.ascopubs.org.

References

1. Meyer LA, Bohlke K, Powell MA, et al: Postoperative radiation therapy for endometrial cancer: American Society of Clinical Oncology clinical practice guideline endorsement of the American Society for Radiation Oncology evidence-based guideline. J Clin Oncol 33:2908-2913, 2015.

2. Klopp A, Smith BD, Alektiar K, et al: The role of postoperative radiation therapy for endometrial cancer: Executive summary of an American Society for Radiation Oncology evidence-based guideline. Pract Radiat Oncol 4:137-144, 2014.