Optimal Management for Stage IVB Endometrial Cancer: A Systematic Review

SIMPLE SUMMARY: Stage IVB endometrial cancer, as defined in the 2009 edition of the FIGO staging system, encompasses a diverse group of patients with a wide-ranging distribution of disease, including intra- and extra-abdominal metastasis. The presence of peritoneal carcinomatosis and/or distant or parenchymal metastasis complicates the establishment of definitive recommendations regarding the optimal primary treatment and adjuvant therapy. Current guidelines advocate for primary cytoreductive surgery when feasible, while there are no stringent indications for adjuvant treatment. Meanwhile, neo-adjuvant chemotherapy is increasingly employed, primarily due to the growing reassuring evidence in ovarian cancer. However, evidence in the context of advanced-stage endometrial cancer mainly derives from retrospective case series. A systematic review of the current literature may assist in identifying which factors should be considered when determining the optimal management for stage IVB endometrial cancer patients. ABSTRACT: (1) Background: Endometrial cancer (EC) is a common gynecological malignancy, often diagnosed at an early stage with a high overall survival rate. Surgical treatment is the primary approach, guided by pathological and molecular characteristics. Stage IVB EC, characterized by intra and/or extra-abdominal metastasis, presents a significant challenge with no clear consensus on optimal management. (2) Methods: A systematic literature review was conducted from January to May 2023, covering studies from 2000 to 2023. Eligible studies included retrospective case series, prospective trials, and randomized clinical trials. (3) Results: Of 116 studies identified, 21 were deemed relevant: 7 on primary surgery, 10 on neoadjuvant chemotherapy (NACT), and 4 on adjuvant treatment. Notably, the impact of residual tumor after primary surgery was a critical factor affecting survival. The use of NACT followed by interval debulking surgery showed promise, particularly in cases deemed unresectable. Adjuvant treatment, combining radiotherapy and chemotherapy, demonstrated improved survival but lacked consensus regarding its role. (4) Conclusions: Stage IVB EC poses a complex challenge with limited evidence to guide management. Optimal cytoreduction remains crucial, and NACT should be considered for unresectable cases. Multimodality adjuvant therapy may benefit patients, even with disease spread beyond the pelvis. Future advances in molecular classification and targeted therapies are expected to enhance treatment strategies.