Conservative and radical treatment of borderline ovarian tumors: the experience of the Oncology Institute of the Republic of Moldova (2010–2024)

Introduction

Borderline ovarian tumors (BOTs) represent a distinct subgroup of epithelial ovarian neoplasms, characterized by biological and clinical features that are intermediate between benign and malignant tumors. Histopathologically, they are defined by atypical epithelial proliferation without stromal invasion and are frequently associated with a more favorable prognosis compared to invasive ovarian carcinomas [1-4].

According to epidemiological data, BOTs account for approximately 10–20% of all epithelial ovarian tumors and are more frequently diagnosed in young women of reproductive age [5]. This biological characteristic has generated, over the past decades, an intense debate regarding the optimal therapeutic strategy – balancing the need for complete oncologic treatment with the desire to preserve reproductive function.

Surgical management remains the cornerstone of therapy. In early-stage BOTs, current guidelines (ESGO, NCCN) allow for conservative approaches, such as cystectomy or unilateral adnexectomy, provided that rigorous surgical staging and adequate postoperative monitoring are ensured [6, 7]. However, the risk of recurrence, particularly in patients treated conservatively, necessitates careful oncological assessment and strict case selection [6, 8].

Conversely, radical treatment – including total hysterectomy with bilateral adnexectomy, omentectomy, and appendectomy – is reserved for patients with tumor extension or those who have completed their reproductive plans. In the absence of firm international consensus regarding the indications for adjuvant treatment (chemotherapy), therapeutic decisions remain variable in clinical practice, influenced by clinical, pathological, and institutional factors [7].

The aim of this study was to evaluate the accumulated experience in the conservative and radical surgical treatment of borderline ovarian tumors (BOTs) at the Oncology Institute of the Republic of Moldova over a 15-year period and to analyze the use of postoperative chemotherapy and its relationship with the clinico-morphological characteristics of the patients.

Material and methods

This retrospective-prospective cohort study included a total of 156 patients diagnosed with BOTs, treated between January 2010 and August 2024 at the Oncology Institute of the Republic of Moldova. The study was conducted within the framework of the Department of Oncology of Nicolae Testemițanu State University of Medicine and Pharmacy and in collaboration with the Departments of Gynecology, Medical Oncology Units 1, 2, and 3, the Department of Pathology, and the Laboratory of Immunology and Molecular Genetics at the Oncology Institute. The study was approved by the Research Ethics Committee of Nicolae Testemițanu State University of Medicine and Pharmacy (approval no. 12, dated 14.11.2016).

The following aspects were analyzed: type of surgical intervention (conservative vs. radical), surgical approach (laparotomy vs. laparoscopy), postoperative chemotherapy regimens, and additional procedures such as peritoneal biopsy and omentectomy. Data were statistically processed using SPSS version 16.0 and Microsoft Excel 2019.

Results

A total of 156 patients diagnosed with borderline ovarian tumors were surgically treated at the Oncology Institute of the Republic of Moldova between January 2010 and August 2024. All patients underwent operative management, either conservative or radical, depending on clinical presentation, tumor characteristics, disease stage, and reproductive intentions. The following section details the surgical approaches employed, including access routes and types of procedures performed. The majority of surgical interventions were performed via laparotomy – 143 cases (91.7%), while laparoscopy was employed in 13 cases (8.3%).

Type of surgical treatment: conservative surgery was performed in 33 patients (21.2%), and radical surgery was performed in 123 patients (78.8%) (Fig. 1).

The conservative surgical interventions included unilateral ovarian cystectomy in 6 cases (3.8%), bilateral cystectomy in 3 cases (1.9%), cystectomy combined with omentectomy in 9 cases (5.8%), cystectomy with omentectomy and appendectomy in 2 cases (1.3%), cystectomy with unilateral adnexectomy and omentectomy in 3 cases (1.9%), unilateral adnexectomy alone in 5 cases (3.2%), unilateral adnexectomy with omentectomy in 3 cases (1.9%), and unilateral adnexectomy combined with omentectomy and appendectomy in 2 cases (1.3%) (Fig. 2).

The radical surgical interventions included total hysterectomy with unilateral adnexectomy and omentectomy in 2 cases (1.3%), total hysterectomy with bilateral adnexectomy in 6 cases (3.8%), total hysterectomy with bilateral adnexectomy and omentectomy in 85 cases (54.5%), and total hysterectomy with bilateral adnexectomy, omentectomy, and appendectomy in 24 cases (15.4%). Among patients with a previous hysterectomy, unilateral adnexectomy with omentectomy was performed in 5 cases (3.2%), and unilateral adnexectomy with omentectomy and appendectomy in 1 case (0.6%) (Fig. 3).

Peritoneal biopsy was performed in 39 patients (25.0%) with the purpose of excluding invasive peritoneal implants and guiding subsequent therapeutic management.

Postoperative chemotherapy was administered to 78 patients (50.0%). Of these, 44 patients (28.2%) received 3 cycles, 19 patients (12.2%) received 4 cycles, 14 patients (9.0%) received 6 cycles, and 1 patient (0.6%) received 8 cycles.

The chemotherapy regimens used included CP (Cisplatin + Cyclophosphamide) in 43 cases (55.1%), CAP (Cisplatin + Cyclophosphamide + Adriamycin) in 25 cases (32.1%), Carboplatin + Paclitaxel in 8 cases (10.3%), and CMF (Cisplatin + Methotrexate + Cyclophosphamide) in 2 cases (2.6%) (Fig. 4).

Discussion

The results of this study confirm that the treatment of borderline ovarian tumors (BOTs) remains a balance between oncologic safety and the preservation of reproductive function, particularly in young women. In our cohort, radical surgical treatment was applied in 78.8% of cases, whereas only 21.2% of patients underwent conservative procedures. This relatively low rate of conservative management reflects a cautious clinical approach in the absence of universally accepted criteria for patient selection [9, 10].

According to ESGO guidelines and multicenter studies (Tropé et al., 2012; Uzan et al., 2010), conservative treatment (e.g., cystectomy, unilateral adnexectomy) is recommended for stage IA and IB BOTs in women under the age of 40 who wish to preserve fertility, provided that rigorous postoperative surveillance is ensured [2, 6, 7, 11]. In our study, simple cystectomy or cystectomy combined with omentectomy was the most frequently performed conservative procedure, accounting for 13 cases (8.3%). This is consistent with international data, which report an increasing use of such procedures in carefully selected patients [9, 10].

Regarding radical treatment, the majority of patients in our study underwent total hysterectomy with bilateral adnexectomy and omentectomy (54.5%), in accordance with classical oncological principles. More extensive procedures, including appendectomy, were performed in cases with suspected mucinous BOTs or peritoneal involvement, in line with current recommendations (Seidman et al., 2000) [1, 3, 4].

Another important aspect is the use of adjuvant chemotherapy, administered in 50% of patients, despite the lack of firm international consensus on its efficacy in BOTs. Tropé and collaborators have shown that the benefit of chemotherapy in BOTs with invasive features remains controversial and is usually reserved for advanced-stage cases or those with peritoneal implants [2]. In our study, the most frequently used regimens were CP and CAP – classical protocols, albeit with considerable toxicity. The relatively limited use of the modern Carboplatin + Paclitaxel regimen (only 10.3% of cases) may reflect restricted availability during the study period or a therapeutic preference for well-established regimens.

Furthermore, the low rate of peritoneal biopsies (25%) suggests variable practice in achieving complete surgical staging – an issue also noted in other clinical series [9]. Incomplete staging may lead to undertreatment or undetected early recurrences.

Compared to international literature, studies reported a conservative treatment rate of 25–35% in specialized centers [7-9]. ESGO studies indicate that the recurrence rate is higher among patients treated conservatively; however, this does not appear to significantly affect overall survival [7]. In our study, the conservative treatment rate was 21.2%, slightly lower than European figures, which may be explained by the clinical and social context, as well as the advanced disease stage at the time of diagnosis in many patients [7, 9, 10].

Conclusions

This 15-year single-center experience highlights substantial variability in the management of borderline ovarian tumors, particularly in fertility-sparing surgery, surgical staging, and postoperative systemic treatment. The findings support the development of a standardized institutional algorithm integrating disease extent, clinico-morphological features, and reproductive goals to improve treatment consistency while preserving oncologic safety and fertility when appropriate.

Competing interests

None declared.

Authors’ contributions

MV was responsible for conceptualization, data collection, statistical analysis, and drafting of the manuscript. TR contributed to methodology, supervision, and critical revision of the content. DS performed the histopathological data analysis and figure preparation. LR provided clinical validation and reviewed the oncological strategy. VS contributed to surgical data interpretation and patient follow-up. All authors read and approved the final version of the manuscript.

Acknowledgements and funding

The authors wish to thank the staff of the Department of Oncology, Department of Molecular Biology and Genetics of Nicolae Testemițanu State University of Medicine and Pharmacy, and the Gynecology Department of the Oncology Institute of the Republic of Moldova for their support in conducting this study. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Ethics approval

The study was approved by the Research Ethics Committee of Nicolae Testemițanu State University of Medicine and Pharmacy (approval no. 12, dated 14.11.2016). All patients signed informed consent forms prior to data collection and analysis, in accordance with the ethical principles outlined in the Declaration of Helsinki.

Provenance and peer review

Not commissioned, externally peer-reviewed.

Authors’ ORCID IDs

Mariana Vîrlan, MD, PhD, https://orcid.org/0000-0002-1661-5160
Tudor Rotaru, MD, PhD, https://orcid.org/0000-0001-9393-1549
Ludmila Rotaru, MD, PhD, https://orcid.org/0000-0002-8044-479X
Sofroni Dumitru, MD, PhD, https://orcid.org/0009-0005-8095-748X
Vasile Simcov, MD, PhD, https://orcid.org/0009-0006-7804-0290

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