Survival analysis of borderline ovarian tumors: a 23-year retrospective study in a Middle Eastern cohort

Borderline ovarian tumors (BOTs), also known as low malignant potential tumors, are a histologically heterogeneous subset of epithelial ovarian neoplasms characterized by atypical epithelial proliferation without stromal invasion [1]. BOTs constitute less than 20% of all ovarian tumors and are predominantly serous or mucinous in histology. Unlike invasive epithelial ovarian cancers, BOTs exhibit a relatively indolent clinical course and a more favorable prognosis [2]. Because these tumors are often diagnosed in women of reproductive age, clinical management requires careful consideration of both oncologic safety and fertility preservation [2, 3].

Borderline ovarian tumors are most frequently identified at an early stage, with epidemiological evidence showing that nearly 70% of cases present at FIGO stage I, followed by 10% at stage II, 19% at stage III, and only 1% at stage IV [4]. The clinical outcome of affected patients is influenced by several key factors, including the stage of disease at diagnosis, histopathological subtype, reproductive characteristics (such as parity and menopausal status), and the extent and type of surgical management performed [5]. BOTs are generally associated with favorable long-term outcomes. Among women diagnosed at FIGO stages I–III, the five-year survival rate is approximately 95%, and the ten-year survival rate remains close to 90%, underscoring the excellent prognosis observed in early to intermediate stages of the disease. In contrast, patients presenting with FIGO stage IV BOTs exhibit a markedly reduced survival rate of about 77%, reflecting the adverse impact of advanced disease and metastatic dissemination. These findings underscore the prognostic relevance of disease stage at diagnosis and highlight the critical importance of early detection and appropriate clinical management in optimizing patient outcomes [6].

The extant literature on borderline ovarian tumors (BOTs) has predominantly concentrated on isolated prognostic determinants. Although some studies have delved into surgical approaches and survival outcomes [7], others have centered on non-invasive peritoneal implants [8], histopathological subtypes [9, 10], or reproductive covariates, including parity and fertility aspirations [11]. However, few studies have provided a comprehensive survival analysis that integrates demographic, reproductive, and treatment-related variables. The present retrospective investigation seeks to redress this shortfall by proffering a multifaceted appraisal of prognostic determinants for short-term (1- and 3-year) and long-term (5- and 10-year) survival among women diagnosed with borderline ovarian tumors (BOTs) between 2000 and 2023.

Borderline ovarian tumors (BOTs) are a heterogeneous group of ovarian lesions characterized by atypical epithelial proliferation without stromal invasion [1]. Their prognosis primarily depends on the stage at diagnosis and histopathological features, with most studies reporting favorable outcomes [7]. BOTs are frequently diagnosed at early stages, contributing to high survival rates. However, like invasive ovarian carcinomas, BOTs can spread to the peritoneum and lymph nodes, necessitating the identification of risk factors for aggressive recurrence or disease-related mortality [8, 12].

This retrospective cohort study evaluated survival rates and their associated determinants in a cohort of 135 patients diagnosed with borderline ovarian tumors (BOTs)، and referred to the Gynecologic Oncology Department at Urmia University of Medical Sciences between January 2000 and December 2023. Participants were prospectively monitored for a follow-up period ranging from 15 to 237 months (mean 99.05 ± 54.2 months). One of the principal methodological strengths of this investigation lies in its multivariate analysis of survival outcomes, stratified by demographic, reproductive, and therapeutic covariates, underpinned by an extended observational period that affords a comprehensive evaluation of long-term clinical trajectories. Furthermore, within the Middle Eastern region, retrospective studies encompassing an approximate 23-year follow-up duration and a cohort of 135 patients remain exceedingly scarce.

Our findings indicate that most BOTs were serous (57.8%), followed by mucinous (41.5%), with the majority being unilateral and diagnosed at FIGO stage I. These results align with studies identifying serous BOTs as the most common subtype [9, 11]. In contrast, a large cohort study by Karlsen et al. reported nearly equal prevalence of serous and mucinous BOTs [13]. while other studies noted a higher prevalence of mucinous BOTs [14], These variations may be attributed to geopolitical and demographic factors, including ethnicity, environmental exposures, and lifestyle differences. Notably, serous BOTs appear to be more prevalent in Middle Eastern populations, whereas mucinous BOTs are more commonly observed in East Asian populations [15]. The near-total absence of the endometrioid subtype of borderline ovarian tumors (endometrioid BOTs) observed in the present cohort may underscore region-specific epidemiological idiosyncrasies. This observation aligns with corroborative evidence from select investigations. It merits emphasis that, notwithstanding their infrequency, the discernment of endometrioid BOTs assumes paramount clinical significance, given their propensity to evolve into low-grade endometrioid carcinoma [16].

Following fertility assessment after conservative surgical intervention, four patients achieved successful pregnancies, with one patient experiencing three such outcomes. It merits emphasis that the study was conducted in a demographic context characterized by early marital unions and childbearing among women. Considering that the majority of participants were approximately 35 years of age, the reported number of pregnancies is relatively low.

We found that patients with serous borderline ovarian tumors had higher survival rates than those with mucinous BOTs, though this difference was not statistically significant(P = 0.069). These findings align with some studies [17, 18], while others report a significant difference [16], possibly due to variations in disease stage across study populations. Additionally, certain studies suggest that mucinous BOTs have a greater potential for malignant transformation and progression to invasive carcinoma [19, 20].Our study results demonstrate that BOTs are distinct from invasive ovarian cancers. The lack of significant survival differences based on clinic pathological factors, such as tumor size(P = 0.752) or bilaterality (P = 0.969), suggests that molecular and genetic features may be more reliable predictors of recurrence or survival [21].

Our study results showed that traditional clinic pathological factors have limited predictive value for survival in borderline ovarian tumors (BOTs). Instead, molecular profiles provide a more accurate assessment of biological behavior. Recent studies have identified frequent mutations in the KRAS, BRAF, and ERBB2 genes in serous and mucinous BOTs. These mutations affect the MAPK signaling pathway and influence tumor pathogenesis and clinical outcomes [22, 23].

Overall survival among patients with BOTs at FIGO stages I to III showed no statistically significant differences (P = 0.746). This contrasts with studies reporting lower 5-year survival rates with advancing disease stage, typically due to increased mortality risk at higher stages [13, 24]. A possible explanation for the lack of a significant association in our study is that the majority of patients were diagnosed at stage I, while the number of cases identified at stage III was too small to yield reliable comparisons. This limited representation of advanced-stage cases is considered one of the main limitations of our study.

In the present study, the mean patient age was approximately 40 years, with the majority of participants aged between 30 and 50 years; nonetheless, a wide age distribution was evident. This finding is consistent with reports from select prior investigations [11, 24]. Conversely, certain studies have documented a higher mean age at diagnosis relative to the current cohort [13, 25], whereas others have indicated a lower mean age [14]. These inconsistencies may be attributable to differences in participant recruitment strategies and sociocultural variations in healthcare utilization patterns, particularly those influencing the timing of ovarian tumor detection. Notably, no substantial disparities in survival outcomes were identified across age strata in this analysis(P = 0.44). Such results diverge from those of other studies [3, 17], which may be explained by the age-related propensity for malignant progression in recurrent borderline ovarian tumors.

No significant disparity in median survival rates was observed between patients undergoing total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH + BSO) and those receiving conservative surgical management(P = 0.199). This observation aligns with results from select prior investigations [9, 26]. For instance, Mencher et al. examined 225 patients with borderline ovarian tumors, including 147 with FIGO stages II–III who underwent hysterectomy, and similarly reported no substantial difference in overall survival [26]. These results challenge the imperative role of hysterectomy in treating advanced-stage borderline ovarian tumors, positioning conservative surgery as a viable alternative for women desiring fertility preservation [27].

The findings of this study underscore that patients with borderline ovarian tumors, especially those identified at early stages and managed via conservative surgery, manifest exceptionally favorable survival outcomes. The lack of substantial disparities in survival across variables such as age, tumor size, bilaterality, or FIGO stage suggests that conventional histopathological parameters may hold limited prognostic value in this population. Furthermore, the comparable survival rates observed between patients receiving total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH + BSO) and those undergoing conservative procedures affirm the viability and safety of fertility-preserving interventions, particularly among younger women. Survival outcomes underscore the need to avoid unnecessary surgical procedures, thereby optimizing patient-centered care.