Abstract

Simple SummaryIn this review, we discuss the different treatment strategies in recurrent endometrial cancer. The incidence of endometrial cancer is rising. The available treatment options increase with the development of novel radiotherapy techniques and new systemic therapies. Dependent on the site of recurrence and previous therapy, the treatment of recurrent endometrial cancer can be curative or palliative. Newly emerging medical treatments, such as immunotherapy, might be of benefit in selected patients. Moreover, combinations of different treatments can lead to a better outcome. Recent insights on oligometastatic disease lead us to expect that ablative or radical local treatment for distant metastasis will be of benefit in selected patients. Due to the complexity of the cases, it is recommended to discuss individual cases in a multidisciplinary tumor board. Shared decision-making principles are recommended to maximize treatment personalization.The treatment of recurrent endometrial cancer is a challenge. Because of earlier treatments and the site of locoregional recurrence, in the vaginal vault or pelvis, morbidity can be high. A total of about 4 to 20% of the patients with endometrial cancer develop a locoregional recurrence, mostly among patients with locally advanced disease. The treatment options are dependent on previous treatments and the site of recurrence. Local and locoregional recurrences can be treated curatively with surgery or (chemo)radiotherapy with acceptable toxicity and control rates. Distant recurrences can be treated with palliative systemic therapy, i.e., first-line chemotherapy or hormonal therapy. Based on the tumor characteristics and molecular profile, there can be a role for immunotherapy. The evidence on targeted therapy is limited, with no approved treatment in the current guidelines. In selected cases, there might be an indication for local treatment in oligometastatic disease. Because of the novel techniques in radiotherapy, disease control can often be achieved at limited toxicity. Further studies are warranted to analyze the survival outcome and toxicity of newer treatment strategies. Patient selection is very important in deciding which treatment is of most benefit, and better prediction models based on the patient- and tumor characteristics are necessary.

Highlights

  • Endometrial cancer (EC) is the most common gynecological cancer in the Western world

  • Cancers 2021, 13, 6275 with low-risk tumors can be treated with surgery alone, whereas patients with high-risk tumors are eligible for adjuvant chemotherapy and/or radiotherapy

  • The treatment of a vaginal recurrence usually requires a combination of external beam radiotherapy (EBRT) with elective nodal irradiation and brachytherapy boost

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Summary

Introduction

Endometrial cancer (EC) is the most common gynecological cancer in the Western world. The classification according to the molecular profile is upcoming with tumor types such as POLE, MSI, and P53, where the first two predominantly have a favorable prognosis and the latter is considered to be an aggressive subtype [7,8]. Cancers 2021, 13, 6275 with low-risk tumors can be treated with surgery alone, whereas patients with high-risk tumors are eligible for adjuvant chemotherapy and/or radiotherapy. Despite optimal surgical and adjuvant treatment, 7–15% of early stage (I-II) patients present with recurrent disease [12–14]. This can be locoregional recurrence, distant metastasis, or both. Patients with advanced-stage disease at diagnosis or with a more aggressive subtype have a higher probability of both locoregional and distant recurrence [17]. We will give an overview of the local and systemic treatment options for patients with recurrent endometrial cancer and intend to provide insight regarding the different treatment strategies for patients with an increasingly personalized approach in the future

Vaginal Vault Recurrence
Locoregional and Abdominal Recurrence
Solitary Distant Metastasis
Pelvic Recurrence
Oligometastases
MR Linac (MRL)
Chemotherapy
Immunotherapy
Targeted Therapy
Hormonal Treatment
Findings
Conclusions and Future Perspectives

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