Updated ASTRO Recommendations for Adjuvant Treatment of Endometrial Cancer

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In a new set of guidelines from the American Society for Radiation Oncology for the treatment of adjuvant endometrial cancer, experts noted that molecular characterization data should be considered when making recommendations.

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

The working group that wrote the recommendations was made up of multidisciplinary experts in the field of oncology, including radiation oncologists, medical oncologists and gynecologist-oncologists, as well as a radiation oncology resident and a representative patients. The guidelines have been reviewed by a total of 16 official peer reviewers.

The guidelines were shaped by a systemic search of the Ovid MEDLINE database focusing on English-language publications ranging from January 2000 and January 2015 to August 2021. To be included, the publication had to present adult patients 18 years of age and older who have been diagnosed with stage I non-metastatic IVA endometrial carcinoma. Retrospective studies had to be more recent to present modern treatment techniques. Literature reviews had 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 the 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 a low risk of disease recurrence. For this reason, guidelines do not recommend the use of radiation therapy in the absence of uterine risk factors in people with FIGO stage IA, grade 1/2 endometrioid carcinoma. As VBT is considered well tolerated with low risks 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 for recurrence.

Although rare, FIGO stage IA, substantial lymphovascular space involvement (LVSI) grade 1/2, EBRT can be considered as an option to reduce the risk of locoregional recurrence, especially when surgical lymph node staging is not possible. is not performed. Additionally, people with grade 3 endometrioid carcinoma minus myoinvasion or residual disease in the hysterectomy biopsy specimen may receive treatment with or without VBT.

Histologies and radiotherapy of high-risk endometrial cancer

High-risk histologies, although featured in a handful of trials, have not been included in randomized controlled trials evaluating the role of radiotherapy; in particular, studies have not focused on high-risk histologies at an early stage. When high-risk histologies were included, studies were often underpowered to draw specific conclusions. After reviewing this lack of clinical research, experts have stated that VBT more or less is conditionally recommended for FIGO stage IA myoinvasive high-risk histological endometrial carcinoma. However, an alternative treatment strategy includes EBRT, which is especially recommended when significant LVSI is detected without surgical nodal assessment.

In patients with high-risk FIGO stage IB or II disease, experts conditionally recommend the use of EBRT plus chemotherapy. Additionally, individuals with high-risk histology with disease confined to a polyp or without myometrial invasion were not included or underrepresented in clinical research, leading the authors to recommend individualized strategies using TLV more or less chemotherapy.

Recommended dosage for adjuvant pelvic EBRT

Investigators stated that adjuvant EBRT should be administered at a total dose of 4500 cGY to 5040 cGY to 180 cGY to 200 cGY per fraction. An additional dose can be used at selected sites of residual nodal disease via an integrated sequential or simultaneous booster. In particular, an equivalent dose of 200 cGY ranging from 5,500 cGY to 6,500 cGY should be used on raw lymph nodes depending on size, location and dose per fraction, taking into account nearby organs that may be at risk. Despite this, evidence on specific nodal booster dosing was limited.

There are also limited data to support specific dose constraints or planning goals for pelvic adjuvant intensity-modulated radiation therapy in people diagnosed with endometrial cancer. For this reason, the authors noted that normal tissue planning goals are reasonable to follow. Although a literature search was conducted to draft evidence-based recommendations for planning goals, there was insufficient evidence to make recommendations.

Optimal dosage of vaginal brachytherapy

The delivery of VBT has changed with its widespread use in early-stage endometrial cancer that lacks risk factors. Notable variation in split dosing regimens, duration of vaginal treatment, and specific depth of dose for monotherapy and booster therapies has been observed in the United States. Historical dose fractionation regimens for adjuvant TPV have been between 6000 cGy and 6500 cGY vaginal surface equivalent, although more contemporary lower dosage regimens have been shown to be effective in reducing the risk of recurrence.

Among patients who might be at higher risk for local recurrence due to LVIG or high-risk histology, it may be worth considering longer vaginal treatment. Limited data support the use of VBT boost after EBRT despite its common use in practice. The VBT boost is most conditionally recommended for close or positive vaginal margins after surgery or in people with cervical stromal involvement. If narrow or positive parametric margins or other margins inaccessible to VBT are observed, EBRT or enhanced interstitial brachytherapy might also be a viable option.

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

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