Tailoring Radiotherapy for Endometrial Cancer Based on Patient Characteristics & Pathologic Risk

Photo Credit: Dr Microbe

Researchers reviewed NCCN guidelines on adjuvant radiotherapy for endometrial cancer, advising physicians on how to tailor treatment to specific cases.

A research team from the Icahn School of Medicine at Mount Sinai shared relevant clinical and patient considerations for clinicians to optimize radiotherapy for endometrial cancer. The authors published their narrative review in Cancers.

“Unlike many other common cancers, endometrial cancer has been marked by a relative absence of major treatment advances, significant racial disparities in terms of diagnosis and survival, and heterogeneous treatment outcomes likely due to a combination of biologic, socioeconomic, and care-related factors,” wrote the lead author Kristin Hsieh, MD, and colleagues. The researchers added that these factors “highlight the need for personalized treatment according to patient and tumor characteristics.”

Tailoring to Patients’ Risk Profiles

The authors reported that standard care for patients with endometrial cancer includes:

• Total hysterectomy and bilateral salpingo-oophorectomy, plus regional lymph node assessment, for medically operable cases;
• Definitive oncologic resection followed by observation for patients with stage IV disease and no adverse risk factors; and
• Adjuvant therapy to minimize recurrence risk in more advanced cases or patients who have adverse clinical or pathologic features.

In addition, patients who are candidates for fertility-sparing treatment may forgo resection and adjuvant radiotherapy. However, the current guidelines emphasize that clinicians should counsel patients that this option does not align with the standard of care.

The researchers explained that “patients with early-stage endometrial cancer are stratified by adverse clinical and pathologic risk factors including age, pathologic grade, histologic subtype, depth of myometrial invasion, and lymphovascular space invasion (LVSI). In general, a more aggressive approach to adjuvant therapy, such as adjuvant radiotherapy over observation, is considered in patients with numerous risk features.”

Several factors influence the decision to offer patients radiotherapy. Studies have shown older age and pathologic features such as deep myometrial or lymphovascular invasion are unfavorable prognostic factors. As such, Dr. Hsieh and colleagues wrote that adjuvant radiotherapy is recommended over observation for patients with several risk features.

“For patients with more advanced disease, adjuvant radiotherapy (specifically EBRT with or without VBT) is typically warranted, with systemic therapy being considered and sometimes offered depending on the patients’ unique pathologic features and risk for locoregional and metastatic disease,” Dr. Hsieh and colleagues wrote.

The review authors added that clinicians should consider performance status and tolerability when determining the most appropriate treatment course. For instance, definitive radiation or chemoradiotherapy offer alternatives for patients who are not eligible for resection due to their overall health or comorbidities.

“In such cases, radiotherapy is tailored to the patient’s anatomy, with radiation delivered to the uterus, cervix, and upper vagina as per the American Brachytherapy Society consensus statement for medically inoperable endometrial cancer. Though radiation is well tolerated in patients with medical comorbidities, clinicians should evaluate patients for their medical stability and tolerance to undergo radiotherapy, including the simulation and treatment process,” the authors explained.

Selecting Modality & Dosage

The 2009 FIGO staging system recommends adjuvant external beam radiation therapy (EBRT), either alone or combined with vaginal brachytherapy (VBT), for high-grade Stage IB and above. The ASTRO guidelines suggest delivering an EBRT dose of 45–50.4 Gy, with a preference for intensity-modulated radiation therapy (IMRT) to precisely target the area and minimize side effects.

“An internal targeting volume should be used to account for the motion of the parametrium, vaginal cuff, and paravaginal tissues as a result of changes in bladder filling. In addition, daily image guidance is advised to ensure correct bladder filling and adequate targeting,” the authors wrote.

VBT alone is the standard of care for high-grade FIGO Stage IA and low to intermediate-grade FIGO Stage IB disease. Numerous dosing regimens exist, with common prescriptions being 7 Gy in 3 fractions or 6 Gy in 5 fractions. VBT can also be used as a boost after EBRT, aiming to deliver 65–75 Gy to the vaginal surface, depending on the patient’s condition.

Managing Radiation Side Effects

Radiotherapy can cause various toxicities affecting the gastrointestinal, genitourinary, skin, bone, and sexual health of patients, both during and after treatment. Acute toxicities include fatigue, skin irritation, diarrhea, and dysuria, while late toxicities may involve vaginal shortening, pelvic fractures, and adhesions. Pre-existing conditions and radiation modality can influence the severity and duration of these side effects.

In one study, intensity-modulated radiation therapy (IMRT) reduced toxicity incidence and severity compared with conventional 3D conformal radiation therapy. Patients treated with IMRT experienced fewer gastrointestinal and genitourinary symptoms during treatment and up to three years post-treatment. Another study showed that VBT resulted in fewer toxicities than EBRT in patients with high-intermediate risk.

The authors went on to explain that vaginal stenosis and damage to erectile tissues or the pelvic floor muscles may contribute to sexual dysfunction. Vaginal dilation and pelvic floor strengthening exercises can benefit patients who experience these issues.

Per the review, radiation therapy also presents unique challenges for transgender men or transmasculine patients with endometrial cancer, especially those who are considering or have already undergone genital affirmation surgery.

“For example, delivering radiation before genital affirmation surgery may cause surgical complications during and following reconstruction. It is thus important to counsel transgender patients with endometrial cancer who are planning on undergoing gender affirmation surgery on the potential complications that radiation treatment might have on the surgery itself,” the researchers wrote.

Managing Patients After Radiotherapy

The NCCN recommends regular physical exams, including pelvic exams, after patients finish radiotherapy. In addition, physicians may order images when they feel it is clinically appropriate. A previous study showed that increasing the intensity of follow-up did not improve overall survival in patients with endometrial cancer.

“Continued patient education on sexual health, including the use of a vaginal dilator, and counseling on late treatment effects is additionally recommended. Treatment with or without radiotherapy does not impact the post-treatment surveillance recommendation,” Dr. Hsieh and colleagues explained.