Endometrial cancer (EC) is one of the most prevalent malignant tumors of the female reproductive system worldwide, with an increasing incidence, particularly in developed countries (1). Most patients with endometrial cancer present at early stages, typically due to abnormal vaginal bleeding (2). Following surgical resection of the tumor, along with comprehensive surgical staging and the addition of radiotherapy or chemotherapy, the overall recurrence rate of EC is approximately 15-20% (3–5). Given the large patient population, those who experience recurrence represent a significant group that cannot be overlooked.

Research indicates that the timing of recurrence is an independent prognostic factor for survival in patients with recurrent EC (6, 7). A shorter time to recurrence generally suggests higher malignancy, increased treatment difficulty, and an elevated risk of mortality (8). Early recurrence within one year after surgery is associated with decreased survival rates in EC patients (9, 10). Recurrence shortly after the completion of intensive treatment is understandably distressing for both patients and their families. Early recurrence not only adversely affects survival rates but also complicates treatment, often necessitating more invasive and aggressive adjuvant therapies, such as repeat surgeries, additional radiotherapy, and chemotherapy. Therefore, it is crucial for clinicians to understand and identify the high-risk factors for recurrence in this population.

Currently, studies on the factors influencing recurrence in EC predominantly focus on recurrences occurring 3-5 years post-treatment, with limited exploration of early recurrences, particularly those occurring within one year of treatment completion (11, 12). Furthermore, previous studies primarily utilized the 2009 International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer, which has undergone significant revisions with the release of the updated 2023 FIGO staging system (13). Thus, this study aims to investigate the risk factors for early recurrence in endometrial cancer patients based on the 2023 FIGO staging system, with the goal of improving postoperative management and enhancing the quality of life for these patients.

Our findings indicate that patients with early recurrence exhibit distinct recurrence patterns and have significantly worse prognoses compared to those with late recurrence or no recurrence. Patients with a higher FIGO stage, presence of LVSI, ER negativity, and abnormal P53 expression are at an increased risk of early recurrence. Previous studies have reported that earlier recurrence of endometrial cancer is associated with a higher risk of mortality (7). Although a risk stratification system for EC has been established, there remains no consensus on the specific risk factors for early recurrence, particularly within the first year following treatment. Identifying these risk factors is crucial for clinicians in formulating individualized treatment plans, selecting appropriate adjuvant therapies, and developing postoperative follow-up strategies. For high-risk patients—especially those with FIGO stage III, LVSI positivity, ER negativity, and abnormal P53 expression, who are more likely to experience early treatment failure—more aggressive postoperative adjuvant therapies should be considered, such as extended cycles of radiotherapy and chemotherapy, as well as additional targeted or hormone therapies. Furthermore, more intensive postoperative follow-up is essential for reducing recurrence rates and improving survival outcomes.

This study identified differences in the recurrence patterns between early and late recurrence groups. Patients with early recurrence had a higher proportion of distant metastasis, whereas those with late recurrence exhibited a greater incidence of local recurrence. These findings suggest that patients with early recurrence may benefit from systemic therapy and close monitoring for distant metastasis, while patients with late recurrence may require prolonged local surveillance. One study reported that for advanced endometrial cancer, particular attention should be given to the primary site of the disease, as the risk of recurrence at this site is elevated (18). Future research should focus on elucidating the molecular drivers of different recurrence patterns to develop targeted interventions and optimize follow-up strategies.

As the FIGO stage increases, the risk of early recurrence significantly rises, which is consistent with the natural course and progression of endometrial cancer. Higher FIGO stages are associated with increased tumor aggressiveness and an increased likelihood of tumor cells spreading to lymph nodes or distant organs, thereby elevating the risk of recurrence (19). Patients in stage I have a lower risk of recurrence, while those in stage III—where the tumor may have already invaded surrounding tissues or lymph nodes—show a significantly higher recurrence rate. This underscores the importance for clinicians to pay particular attention to the recurrence risks in stage III patients when developing postoperative treatment plans and considering more aggressive adjuvant therapies.

Additionally, we found that lymphovascular space invasion is another independent risk factor for early recurrence. The presence of LVSI indicates that tumor cells have likely entered the lymphatic or vascular systems, increasing the likelihood of distant metastasis and recurrence (20). Numerous previous studies have supported the significant association between LVSI and recurrence (21, 22). The inclusion of LVSI in the updated FIGO staging system for endometrial cancer underscores its importance in predicting recurrence (13).

Hormone receptor status plays a critical role in the recurrence of endometrial cancer. Our study found that ER-negative patients had a higher risk of recurrence compared to ER-positive patients. The expression of estrogen receptors (ER) is closely linked to the degree of tumor differentiation and aggressiveness (23, 24). ER-positive patients typically respond more favorably to hormone therapy, leading to relatively better prognoses (25, 26). In contrast, ER-negative patients, due to their lack of response to hormone therapy, generally face a higher risk of recurrence (27).

P53 abnormalities were also identified in our study as a risk factor for early recurrence. P53 is a key tumor suppressor gene, and its mutations are often associated with high aggressiveness and poor prognosis (28). Mutations in P53 may allow tumor cells to evade normal cell cycle regulation, increasing their invasiveness and metastatic potential (29). Therefore, P53 status could serve as an important molecular marker for assessing the risk of recurrence in endometrial cancer (30). In recent years, international guidelines have recommended integrating molecular profiling into the risk stratification of EC (31). The molecular subtypes of EC include p53 mutant (p53-mut), POLE-mutated (POLE mut), mismatch repair-deficient (dMMR), and no specific molecular profile (NSMP). However, the high costs and time-consuming nature of genetic testing have limited the application of molecular profiling in certain regions and healthcare institutions. Recent studies have shown that new algorithms combining molecular classification with clinical and pathological features can help guide the assessment of EC recurrence risk, thereby saving resources while still providing valuable guidance for the selection of postoperative adjuvant therapies (32, 33). In the future, P53-targeted therapies may offer more effective treatment options for patients at high risk of recurrence.

It is important to note that while our study suggests that only FIGO stage, LVSI, ER negativity, and P53 status are independent risk factors for early postoperative recurrence in endometrial cancer patients, we do not deny the significance of other factors. For example, lymph node metastasis is a key prognostic factor for EC patients (34). Some studies have found that systematic lymphadenectomy does not necessarily provide survival benefits for early-stage EC patients and may even lead to some adverse treatment reactions (35). In recent years, sentinel lymph node biopsy has gained widespread attention and application. Compared to pelvic lymphadenectomy, it offers higher sensitivity and specificity for detecting lymph node metastasis, while maintaining good safety (36).

To the best of our knowledge, our study may be the first to focus on recurrence within one year after surgery in endometrial cancer patients. However, it is important to note that our study also has some limitations. First, this is a single-center retrospective study, and the relatively small sample size of the included patients may introduce selection bias. Second, proteins such as MMR, L1CAM, and CTNNB1 have recently been reported to be associated with the prognosis of endometrial cancer, and the molecular classification of endometrial cancer proposed by TCGA has also gained wide attention (37). Additionally, certain non-coding RNAs (ncRNAs) play a significant role in the development and progression of EC and may serve as potential predictors of patient prognosis (38). However, due to the retrospective nature of this study, we did not include these factors, and only considered P53 status from the molecular profiling. Large-scale, multicenter prospective studies in the future will help further validate our findings and provide data to support the development of more precise recurrence models. Thirdly, we did not report the treatment for recurrence, which can affect overall survival. Lastly, our study cohort consisted of all pathological types of endometrial cancer patients with FIGO 2023 stages I-III, without further stratification. In fact, patients with endometrioid carcinoma and non-endometrioid carcinoma have different recurrence risks, and early-stage patients (stages I-II) and advanced-stage patients (stage III) also have different recurrence risks. Future research should focus on the early recurrence risk in specific subgroups.

In conclusion, our findings suggest that early recurrence of endometrial cancer after surgery is closely related to FIGO stage, LVSI, ER negativity, and P53 status. Our study contributes to more accurate risk stratification and decision-making in clinical practice. Future research should focus on these risk factors to optimize treatment strategies and prolong patients’ disease-free survival.