Chirurgia Conservativa dei tumori ovarici borderline in età riproduttiva: analisi dei fattori di rischio delle recidive

Introduction: Borderline ovarian tumors (BOTs) are epithelial neoplasms of low malignant potential, defined by the absence of stromal invasion and a favorable prognosis. They comprise different histological subtypes with distinct behaviors and are often diagnosed at an early stage, with near 100% 10-year survival. Prognostic factors such as stage and surgery guide personalized, fertility-sparing management. Reproductive risk factors are recognized, and long-term follow-up is essential due to possible late recurrences. Study objective: This study aimed to evaluate clinical, histopathological, and prognostic factors associated with disease-free survival in patients with BOTs treated with fertility-sparing surgery. Secondary objectives included identifying recurrence risk factors, assessing reproductive outcomes, and evaluating the safety of repeated conservative surgical procedures. Materials and methods: A retrospective cohort study was conducted on patients treated at the European Institute of Oncology (IEO), Milan, between 1997 and 2016. All patients underwent fertility-sparing surgery for BOTs. Cases initially managed elsewhere were centrally reviewed and restaged. Data collected included demographic characteristics, clinical presentation, imaging, surgical details, histopathology, recurrence patterns, and reproductive outcomes. Follow-up consisted of clinical, ultrasound, and serological evaluations every three months for the first two years, every six months for the next three years, and biannually thereafter. The same surveillance protocol was applied after treatment of recurrences. Results: 278 patients were included (FIGO stage I: 62.9%; II: 16.9%; III: 20.1%), with a mean age of 29.8 years. Higher stage was associated with elevated CA125 levels, malignant peritoneal cytology, and ascites. Serous histology was most common (45%), with micropapillary variants more frequent in stage III. Surgical management varied by stage, with conservative laparoscopic procedures more common in stage I and more extensive surgeries in advanced stages. During follow-up, 127 patients experienced recurrence (209 total events). Recurrence-free rates were 74.3% in stage I versus 19-21% in stages II–III. Multiple recurrences occurred mainly in advanced stages, with up to five episodes observed in stage III. Median recurrence-free survival was not reached in stage I, but was 28.3 months in stage II and 23.4 months in stage III (p<0.001 for stage I vs II/III). In multivariable analysis, stage II significantly increased recurrence risk (HR 3.25), while mucinous histology was protective. In recurrent-event models, stage III was associated with increased risk of multiple recurrences (HR 2.41). Progression to invasive carcinoma was rare (15 cases) and more frequent in advanced stages and in patients with multiple recurrences. Overall survival remained excellent (98.2%, with 5 deaths). Regarding reproductive outcomes, 70 patients achieved 133 pregnancies, with an 81.2% live birth rate. Notably, 29 pregnancies occurred despite the presence of disease. Surgical management during pregnancy was generally postponed, with only one laparoscopic intervention performed during the second trimester, resulting in a term delivery. Conclusions: FIGO stage is the primary prognostic factor in BOTs treated with fertility-sparing surgery, with significantly higher recurrence risk in advanced stages. Mucinous histology is associated with better outcomes, whereas serous and micropapillary variants carry increased risk. Despite frequent recurrences, progression to invasive carcinoma is uncommon and overall survival is excellent. Fertility outcomes are favorable, supporting the safety and feasibility of conservative management in selected patients. Prolonged and individualized follow-up remains crucial, particularly in higher-risk groups.