Updated Recommendations from ASTRO for the Adjuvant Treatment of Endometrial Cancer

Guidelines released by the American Society for Radiation Oncology touched on several recommendations for different types of adjuvant radiotherapy treatments in endometrial cancer, including vaginal brachytherapy (VBT) and external beam radiotherapy (EBRT), as well as challenges with sequencing radiotherapy and chemotherapy.

The task force that drafted the recommendations was comprised of multidisciplinary experts in the oncology field, including radiation oncologists, medical oncologists, and gynecologic oncologists, as well as a radiation oncology resident and, patient representative. The guidelines were reviewed by 16 official peer reviewers in total.

The guidelines were shaped by a systemic search through the Ovid MEDLINE database the focused on English publications ranging from January 2000 and January 2015 to August 2021. To be included, the publication needed to feature adult patients 18 years and over who were diagnosed with stage I to IVA non-metastatic endometrial carcinoma. Retrospective studies needed to be more recent to showcase modern treatment techniques. Literature reviews were required to include 25 or more patients.

The guidelines focused on the adjuvant management of endometrial cancer with an emphasis on the changing impact of uterine risk factors and disease stage, surgical staging procedures, and molecular profiling on treatment.

The Role of Adjuvant Radiotherapy in Endometrioid Carcinoma

Patients diagnosed with early-stage, low-grade endometrial cancer are known to have a favorable prognosis and low odds of disease recurrence. Due to this, the guidelines do not recommend the use of radiotherapy in the absence of uterine risk factors among those with FIGO stage IA, grade 1/2 endometrioid carcinoma. As VBT is thought to be well tolerated with low odds of clinically significant acute and chronic morbidity, it has been recommended as a treatment for patients with myoinvasive FIGO IA, grade 1/2 disease with uterine risk factor of recurrence.

Although rare, FIGO stage IA, grade 1/2 substantial lymphovascular space involvement (LVSI), EBRT can be considered as an option to reduce the chances of locoregional recurrence—specifically when surgical nodal staging is not performed. Moreover, those with grade 3 endometrioid carcinoma minus myoinvasion or residual disease in the hysterectomy biopsy specimen can receive treatment with or without VBT.

High-Risk Endometrial Cancer Histologies and Radiotherapy

High-risk histologies, despite being featured in a handful of trials, have not been included in randomized controlled trials assessing the role of radiotherapy; in particular, the studies have not focused on early -stage high-risk histologies. When high-risk histologies were included, the studies were often too underpowered to draw specific conclusions. After considering this lack of clinical research, experts stated that VBT plus or minus chemotherapy is conditionally recommended for myoinvasive FIGO stage IA high-risk histology endometrial carcinoma. However, an alternative treatment strategy includes EBRT, which is particularly recommended when substantial LVSI is detected with no surgical nodal assessment.

In patients with FIGO stage IB or II high-risk disease, experts conditionally recommend the use of EBRT plus chemotherapy. Moreover, those with high-risk histology with disease confined to a polyp or no myometrial invasion were not included or underrepresented in clinical research, leading to the authors recommending individualizing strategies using VBT plus or minus chemotherapy.

Recommended Dosing for Adjuvant Pelvic EBRT

Investigators stated that adjuvant EBRT should be delivered at a total dose of 4500 cGY to 5040 cGY at 180 cGY to 200 cGY per fraction. An additional dose may be used at selected sites of residual nodal disease via a sequential or simultaneous integrated boost. Notably, a 200 cGY equivalent dose ranging from 5500 cGY to 6500 cGY should be used on gross nodes depending on size, location, and dose per fraction with consideration for nearby organs that could be at risk. Despite this, evidence on specific nodal boost dosing had been limited.

Ideal dosing for pelvic IMRT from the phase 3 RTOG 1203 study for cervical/endometrial cancer.

There are also limited data to support specific dose constraints or planning aims of adjuvant pelvic intensity-modulated radiotherapy among those diagnosed with endometrial cancer. Due to this, the authors noted that normal tissue planning aims are reasonable to follow. Although a literature search was conducted to draft evidence-based recommendations for planning aims, evidence was insufficient to make recommendations.

Optimal Vaginal Brachytherapy Dosing

VBT delivery has changed with its prevalent use of early-stage endometrial cancer that is lacking risk factors. A notable variation in dose-fractionated regimens, length of vaginal treatment, and dose specific depth for monotherapy and boost therapies have been observed within the United State. The historical dose fractionation regimens for adjuvant VBT has been between 6000 cGy to 6500 cGY equivalent to the vaginal surface, although more contemporary lower dose regimens have demonstrated efficacy in lowering the odds of recurrence.

Among patients who could be at a higher risk of local recurrence because of LVSI or high-risk histology, it may be worth considering a longer length of vaginal treatment. Limited data support the use of VBT boost after EBRT despite its common use in practice. VBT boost is most conditionally recommended for close or positive vaginal margins after surgery or in those with cervical stromal involvement. If close or positive parametrial or other margins inaccessible to VBT are observed, EBRT or interstitial brachytherapy boost could be a viable option, as well.

Reference

Harkenrider MM, Abu-Rustum N. Albuquerque K, et al. Radiation therapy for endometrial cancer: an ASTRO clinical practice guideline. Published online October 21, 2022. doi:10.1016/j.prro.2022.09.002