Borderline Ovarian Tumors in Women of Childbearing Age: Balancing Cancer Care and Fertility

Table of Contents

• Key Points
• Background: What Are Borderline Ovarian Tumors?
• Study Methods: How This Review Was Conducted
• Understanding the Two Main Tumor Types
• The Surgical Approach: Staging, Frozen Section, and Laparoscopy
• Adnexal Surgery: Which Operation Is Best?
• Disease Recurrence: What Are the Real Numbers?
• Fertility Outcomes After Fertility-Sparing Surgery
• Borderline Ovarian Tumors During Pregnancy
• Conclusion: What This Means for Patients
• Limitations: What This Review Could Not Prove
• Recommendations for Patients
• Frequently Asked Questions
• Source Information

Key Points

• Borderline ovarian tumors have excellent survival: about 95% at 5 years for stages I–III, and over one-third occur in women under 40.
• Fertility-sparing surgery preserves the uterus and ovary tissue and does not appear to affect overall survival, but it does increase relapse risk.
• Recurrence rates are higher after cystectomy (30.3%) than after removing one ovary (11%) or both ovaries (1.7%) in a French study.
• Most serous tumor recurrences are borderline again and can be treated with repeat conservative surgery; mucinous recurrences are more often invasive.
• Follow-up in the first two years is important because most recurrences happen then, but relapses can occur up to 15 years later.

Background: What Are Borderline Ovarian Tumors?

Borderline ovarian tumors (BOTs) are a group of growths that sit somewhere between benign cysts and full ovarian cancer. Doctors also call them tumors of "low malignant potential." They are defined by abnormal cell growth (epithelial proliferation) and cell irregularity (nuclear atypia), but they lack the destructive tissue invasion seen in true cancers. In plain terms: they can spread and come back, but they behave far less aggressively than ovarian carcinoma.

These tumors account for approximately 15% of all epithelial ovarian cancers. The good news is that in nearly 80% of cases, the diagnosis is made at stage I, meaning the tumor is still confined to the ovary. Fewer than 1% of women are diagnosed at stage IV, the most advanced stage.

Because more than a third of BOTs occur in women younger than 40 who wish to preserve their childbearing potential, the question of conservative surgical management — treatment that saves the uterus and at least some ovarian tissue — has become critically important.

Survival Statistics: The Outlook Is Favorable

Survival rates for BOTs are very encouraging. For women with FIGO stage I–III disease, overall survival is 95% at 5 years and 90% at 10 years. Even at stage IV, survival is nearly 77%.

Peritoneal spread (tumor cells reaching the lining of the abdomen) is present in about 10% of BOTs. These implants are divided into two categories:

• Non-invasive implants (nearly 85% of cases): mortality rate of 4.7%
• Invasive implants (the remaining 15%): mortality rate of 34%

These numbers show why the distinction between invasive and non-invasive spread matters so much for treatment planning and prognosis.

Study Methods: How This Review Was Conducted

The authors performed an electronic database search of PubMed, Medline, and Embase up to April 2022. They developed a search algorithm incorporating the following medical terms: "borderline ovarian tumors," "low malignant potential," "conservative surgery," "fertility-sparing surgery," "laparoscopy," "invasive implants," "micropapillary patterns," and "recurrence."

All pertinent articles evaluating diagnostic and therapeutic approaches centered on fertility-sparing treatment were included. The researchers considered all original studies, meta-analyses, systematic reviews, and case reports published in English. They also systematically reviewed reference lists to identify additional studies for this narrative review.

Understanding the Two Main Tumor Types

The vast majority of BOTs have either serous or mucinous histotypes (cell types seen under the microscope). Knowing which type a patient has is essential for choosing the right surgical strategy. Other rare types (less than 5%) include clear cell, endometrioid, and Brenner tumors.

Serous Borderline Ovarian Tumors (sBOTs)

Serous tumors make up about two-thirds of all BOTs. They are bilateral (affect both ovaries) in 15%–25% of cases, and non-invasive peritoneal spread is present in 15%–40% of cases. The risk of invasive peritoneal spread in early-stage serous tumors is very low. Only in a small percentage of cases do the implants infiltrate the underlying tissue; according to the 2014 WHO classification, these are considered low-grade serous carcinoma.

There is also a variant called the micropapillary/cribriform pattern. Compared with typical serous tumors, this variant carries a higher rate of bilateral ovarian involvement, recurrence, and invasive peritoneal implants.

Mucinous Borderline Ovarian Tumors (mBOTs)

Mucinous tumors are the second most common subtype, accounting for 30%–50% of all BOTs. They are nearly always unilateral (one ovary only) and tend to be larger than serous tumors, with an average diameter of 20 centimeters (about the size of a grapefruit or larger).

Patients with mucinous tumors relapse less frequently than those with serous disease. However, when an extraovarian relapse does occur, the risk of invasive recurrence and possible death is higher. Because of this, unilateral salpingo-oophorectomy (removing one ovary and its tube) is often the recommended surgery for mucinous tumors.

Quick Comparison Table: Serous vs. Mucinous BOTs

• Prevalence: Serous — about two-thirds of all BOTs; Mucinous — more than one-third
• Overall survival rate: Serous — around 97%; Mucinous — around 94%
• Location: Serous — often bilateral; Mucinous — nearly always unilateral
• Peritoneal spread: Serous — 30% of cases; Mucinous — less frequent
• Average diameter: Serous — 10 cm; Mucinous — 20 cm
• Relapse: Serous — more frequent; Mucinous — less frequent
• Type of recurrence: Serous — generally non-invasive (except micropapillary patterns); Mucinous — more often invasive
• Reliability of frozen section: Serous — higher; Mucinous — lower

The Surgical Approach: Staging, Frozen Section, and Laparoscopy

Fertility-sparing surgery (FSS) is defined as the preservation of the uterus and ovarian tissue in one or both adnexa (the ovaries and fallopian tubes). More than a third of BOTs affect women of reproductive age who wish to preserve fertility. In early-stage disease, FSS is the mainstay of treatment, an alternative to radical surgery that removes all reproductive organs.

For advanced stages, the oncological safety of conservative treatment is less clear. As a general rule, patients with advanced-stage BOT should not be offered conservative surgery if they have invasive implants, or if they have non-invasive implants that cannot be completely removed.

Uterine Preservation and Fertility Options

Recent attention has focused on preserving the uterus even when saving healthy ovarian tissue is not feasible. Several options can help a woman build her family later:

• Ovarian tissue cryopreservation (freezing ovarian tissue) at the time of surgery
• Oocyte freezing (egg freezing)
• Oocyte donation
• Transfer of frozen embryos obtained before surgery

Notably, FSS does not appear to affect overall survival. However, conservative treatment does increase the relapse rate. Patients must receive full, honest information about this risk before deciding.

The Role of Frozen Section (Intraoperative Pathology)

The frozen section (FS) is a technique where a tissue sample is rapidly frozen and examined under a microscope during the operation, helping the surgeon decide how much to remove in real time. While FS has a high diagnostic accuracy for benign and malignant ovarian tumors, it is notably less accurate for BOTs:

• Frozen samples under-diagnose BOT as benign tumors in 25%–30% of cases
• Frozen samples improperly identify BOT as carcinoma in 20%–30% of cases

Extra caution is needed with bulky (large) tumors, where the intraoperative histology can miss features like microinvasion, papillary variants, or intraepithelial carcinoma.

Complete Surgical Staging

Although formal surgical staging does not significantly change survival rates, an initial complete staging appears to significantly reduce recurrence among BOT patients. A complete staging procedure includes:

1. A complete exploration of the abdominal-pelvic peritoneal cavity
2. Peritoneal washing (flushing the abdomen and collecting the fluid for testing)
3. Multiple peritoneal biopsies
4. Infracolic omentectomy (removal of part of the omentum, a fatty apron in the abdomen)
5. Complete resection of all visible implants

The complete removal of all peritoneal implants is a primary task, for both staging and treatment. Wide resection of surrounding tissue is needed so the pathologist can tell whether implants are invasive or non-invasive.

Surgical restaging should be considered in patients with higher risk of malignancy (mucinous type, micropapillary variant) who had an incomplete visual exploration of the abdominal-pelvic peritoneum at their first surgery. Lymph node involvement carries low prognostic value, and removing lymph nodes (lymphadenectomy) has not been shown to improve survival. It is usually suggested only when lymph nodes are visibly enlarged or when invasive tumors are found on frozen examination.

Taking a biopsy from a normal-appearing opposite ovary is not helpful for reducing recurrence risk. Instead, an accurate preoperative ultrasound and careful inspection during surgery are considered sufficient.

Laparoscopy vs. Open Surgery

Minimally invasive (laparoscopic) surgery has increased dramatically in recent years due to fewer complications, less blood loss, shorter recovery, and better cosmetic results. However, the choice of approach depends on tumor features, patient factors, and the surgeon's skill.

One key risk is tumor rupture during removal. Published data show that rupture happens more often during laparoscopic cystectomies, with tumor size as the main predictor:

• In a retrospective study of 105 patients, tumor rupture was significantly more frequent during laparoscopy than during open surgery: 29.5% vs. 13.1% (p = 0.038).
• Another retrospective analysis found that an adnexal mass larger than 10 cm in maximum diameter carried a 4-fold higher risk of surgical spillage with the laparoscopic approach: 54.5% vs. 12.1% compared with open surgery.

Rupture of an intact tumor during removal can change the FIGO stage and affect recurrence risk, regardless of surgical method. Despite this, laparoscopy has not shown a negative impact on recurrence rate, survival, or surgical feasibility when performed carefully. The conversion rate from laparoscopy to open surgery is reported at approximately 30% for BOT patients. If surgery without risk of rupture is possible, the laparoscopic approach is considered feasible, safe, and recommended over laparotomy.

Robotic surgery is another feasible alternative, but haptic feedback (the sense of touch that helps the surgeon measure tissue tension and avoid cyst rupture) is only present in some robotic platforms. Prospective randomized studies are still needed to define its role. Ultra-minimally invasive "mini-laparoscopy" using 2.4 mm needleoscopic instruments has also been described as a beneficial tool in borderline disease, though data remain limited to case reports.

Adnexal Surgery: Which Operation Is Best?

There are no clear international guidelines on the optimal fertility-sparing procedure. For stage I disease, surgical options include:

• Unilateral or bilateral cystectomy (removing only the cyst, leaving the ovary)
• Unilateral salpingo-oophorectomy (USO, removing one ovary and one fallopian tube)
• USO plus contralateral cystectomy (removing one full side and only the cyst on the other side)

The histological subtype and the presence of poor-prognosis factors (microinvasion, micropapillary pattern, peritoneal implants) strongly influence which operation makes sense.

What the Data Show for Different Operations

A large French multicenter study of 313 patients with stage I BOTs found these recurrence rates by surgery type:

• After cystectomy: 30.3% recurrence
• After unilateral salpingo-oophorectomy: 11% recurrence
• After bilateral salpingo-oophorectomy: 1.7% recurrence

A recent systematic review confirmed these results: the recurrence rate correlates with the type of conservative surgery, with the highest rate after cystectomy.

However, not all studies agree. Palomba and colleagues reported that bilateral cystectomy (compared with USO plus contralateral cystectomy in patients with bilateral disease, mainly serous subtype) increases the fertility rate without increasing the recurrence rate. A meta-analysis by Vasconcelos and colleagues confirmed this: in bilateral serous BOT, USO plus contralateral cystectomy had no advantage over bilateral cystectomy in terms of recurrence: 26.1% vs. 25.6%.

The authors' practical conclusion: whenever cystectomy is chosen, the patient should receive careful counseling about a possibly higher risk of local and peritoneal recurrence compared with salpingo-oophorectomy.

Which Operation for Which Tumor?

Because most mucinous BOTs carry a higher risk of invasive recurrence, and because they can coexist with invasive cancer areas, unilateral salpingo-oophorectomy is the preferred treatment for these tumors. Cystectomy is acceptable only for bilateral mucinous disease, or when a contralateral cystectomy is the only way to preserve fertility in a patient who previously had a salpingo-oophorectomy on the other side.

For serous BOTs, which are often bilateral and behave relatively benignly compared with mucinous tumors, the reproductive advantage of cystectomy over USO is still debated. The reproductive outcome appears similar between the two operations, but concerns about higher recurrence after cystectomy remain.

For bilateral serous BOT, cystectomy or unilateral salpingo-oophorectomy plus contralateral cystectomy is the only fertility-sparing option. The same applies to the rare patient who has already had a salpingo-oophorectomy on one side.

Disease Recurrence: What Are the Real Numbers?

Conservative management has a significant impact on recurrence compared with radical surgery. The numbers are:

• Recurrence after conservative surgery: 5%–34%
• Recurrence after radical surgery: 3.2%–7%
• Overall risk of recurrence: 2%–24%
• Risk of invasive recurrence: 0.5%–3.8%

Recurrences can appear in the remaining ovary after cystectomy, in the contralateral ovary, or as extraovarian peritoneal and omental implants.

When Do Recurrences Happen?

Recurrence rates are time-dependent. About 25% of recurrences are diagnosed after 5 years, and relapses can occur as late as 15 years after surgery. Recurrences are most frequent during the first two postoperative years, making close follow-up critical during this period. Follow-up typically includes systematic clinical examination, transvaginal ultrasound, and serum markers.

Unfortunately, only about 40% of women with stage I BOTs have elevated levels of the CA125 blood marker, so many patients cannot rely on this test alone for early detection of relapse.

Recurrence by Tumor Type

Most serous BOT recurrences are, in large part, borderline tumors again — not full cancers. These can often be treated safely with repeated conservative surgery in patients who still want children. Mucinous tumors relapse less often, but when they do, the recurrence is more likely to be invasive.

High-Risk Features: Microinvasion and Micropapillary Patterns

Several factors identify patients at higher risk of invasive recurrence, although not all experts agree on every factor:

• Early stage by FIGO classification is a known independent risk factor for recurrence (and may seem counterintuitive — the authors note higher rates of extraovarian recurrence in stage IC3 and grade 3 tumors, which should be recognized as limits of conservative management for oncological safety).
• Micropapillary pattern in serous tumors is associated with advanced stage, bilateral ovarian involvement, and invasive recurrence. Notably, serous BOTs with a micropapillary pattern but no invasive implants (stage I) or with only non-invasive implants (stages II and III) may have the same good prognosis as typical serous BOTs.
• Stromal microinvasion (tumor cells invading the supportive tissue to a depth of 5 mm or less) is a predictor of relapse.

The Numbers Behind Microinvasion

One case series followed 171 borderline mucinous tumors and found that the microinvasive pattern carried a significantly higher recurrence rate (p = 0.013):

• Without microinvasion: 1.7% recurrence (2 of 116 cases)
• With microinvasion: 14.3% recurrence (4 of 28 cases)

A retrospective study of 902 BOT patients confirmed this finding. Patients with microinvasive BOT had a significantly higher recurrence rate than those without: 17.4% vs. 7.8% (odds ratio 3.55, 95% CI 1.091–11.59, p = 0.03). Stromal microinvasion was also a prognostic factor for significantly shorter disease-free survival: 26.7 months vs. 11.9 months (p = 0.031).

Data from 209 patients showed that microinvasive BOTs recurred earlier than non-invasive BOTs, with a median time to recurrence of 10.5 months for microinvasive tumors versus 17 months for non-invasive ones. Unilateral salpingo-oophorectomy rather than cystectomy did not seem to prevent relapses in microinvasive disease — recurrences were recorded in 27% of patients even after this more extensive surgery. Encouragingly, overall survival did not differ significantly from BOTs without microinvasion.

Microinvasion frequently coexists with the micropapillary variant in serous tumors, which complicates efforts to determine each factor's exact role in recurrence. For young patients with these high-risk features, fertility-sparing surgery may still be a reasonable option, but only if an accurate, strict follow-up is possible.

Fertility Outcomes After Fertility-Sparing Surgery

Studies give mixed results on how fertility-sparing treatments affect ovarian function, and it remains unclear whether pregnancy outcomes depend on the specific procedure chosen (unilateral salpingo-oophorectomy versus ovarian cystectomy). What is clear is that ovarian surgery — especially a second operation — can reduce healthy ovarian tissue, increasing the risk of infertility. Postoperative adhesions (scar tissue) can also interfere with fallopian tube function.

That said, the news is largely positive: after fertility-sparing surgery, pregnancy outcomes are encouraging, and most pregnancies are achieved spontaneously as early as 3 months after surgery.

Because of concerns about pregnancies complicated by recurrent disease, many physicians recommend delaying pregnancy until a sufficient follow-up period has passed after initial treatment. Little is known about how often BOTs occur or are managed during pregnancy itself, though expectant management appears safe if a recurrence is found during pregnancy.

There is no specific data on infertility treatment after conservative surgery for BOTs, and it is unclear whether fertility drugs affect recurrence rates. More research is needed, particularly because ovulation induction and in vitro fertilization (IVF) may be required to help these patients conceive.

Borderline Ovarian Tumors During Pregnancy

BOTs diagnosed during pregnancy appear to have more concerning features than those found in non-pregnant patients. Reports describe a higher incidence of advanced stage at presentation, a higher percentage of mucinous BOTs with intraepithelial carcinoma and microinvasion, and more serous BOTs with micropapillary components.

Management data during pregnancy are limited, based mostly on case reports. Standardized treatment strategies are therefore difficult to create, and current practice follows the gold-standard treatment for non-pregnant women. The authors advise:

• Close surveillance to exclude signs of malignant transformation, such as rapid tumor enlargement, abnormal vascularization, or the presence of solid tissue within the tumor.
• Delivery in a tertiary center specialized in gynecologic oncology.

Because performing complete staging at the initial surgery is technically difficult in pregnancy, some patients may need a postpartum completion of staging, a debulking procedure, or possibly adjuvant chemotherapy.

Conclusion: What This Means for Patients

Fertility-sparing surgery is a well-established strategy for patients with BOTs who want to preserve fertility. The procedure offers an excellent reproductive outcome and long-term survival in the vast majority of cases.

Invasive recurrences remain one of the main concerns with conservative management, which is why the choice of surgical procedure must be individualized. The balance between accurate staging and optimal fertility outcomes requires honest counseling about the risks and benefits of each option.

The bottom line: a woman diagnosed with a borderline ovarian tumor has an excellent chance of long-term survival and, in many cases, of having a child. The key is working with a specialized gynecologic oncology team to choose the approach that fits her specific tumor type, stage, and fertility goals.

Limitations: What This Review Could Not Prove

This article is a narrative review of existing literature, not a new clinical trial. The authors note several specific gaps in the evidence:

• Prospective randomized studies are still needed to determine the relevance of robotic surgery in this context.
• The oncological safety of conservative treatment in advanced stages of BOTs has still to be clarified.
• Findings are inconclusive about the impact of fertility-sparing treatments on ovarian function.
• It is unknown whether pregnancy outcomes are determined by the type of conservative approach used.
• There is no specific data on the management of infertility after conservative treatment, and the impact of fertility drugs on recurrence remains unclear.
• Data on BOTs during pregnancy are based mostly on case reports, making standardized recommendations difficult.
• The frequency and types of exams to perform during follow-up surveillance are not firmly established.

Recommendations for Patients

Based on the evidence reviewed, here is what patients should discuss with their care team:

1. Know your tumor type. Ask whether your tumor is serous or mucinous, and whether any high-risk features (microinvasion, micropapillary pattern) were found. This strongly influences which surgery is safest.
2. Understand the recurrence trade-off. Cystectomy offers the best fertility preservation but carries a higher recurrence risk (up to 30.3% in one large study) compared with salpingo-oophorectomy (11%) or bilateral salpingo-oophorectomy (1.7%). Most recurrences are still borderline tumors, not invasive cancers, and can often be treated with repeat conservative surgery.
3. Expect close follow-up, especially in the first two years. Recurrences are most frequent then, but can appear up to 15 years later. Follow-up usually combines clinical exams, transvaginal ultrasound, and CA125 blood tests — though remember CA125 is only elevated in about 40% of stage I patients.
4. Ask about fertility options before surgery. Egg freezing, embryo freezing, or ovarian tissue cryopreservation may be available, especially if removal of both ovaries is being considered.
5. Pregnancy plans can be realistic. Most pregnancies after fertility-sparing surgery occur spontaneously, often within months of surgery. Many doctors recommend a follow-up period before trying to conceive.
6. If you are pregnant with a BOT, seek a tertiary center with gynecologic oncology expertise for delivery and ongoing management.
7. Get a second opinion if your tumor was large or your first surgery was incomplete. Surgical restaging may be recommended for mucinous tumors or micropapillary variants when the first operation did not include full abdominal exploration.

Frequently Asked Questions

What is a borderline ovarian tumor and how is it different from ovarian cancer?

A borderline ovarian tumor is a growth between a benign cyst and true ovarian cancer. It can spread and return, but lacks destructive tissue invasion. Most cases are diagnosed at stage I, and overall survival at 5 years is about 95% for stages I–III, so the outlook is usually good.

Can I still have children after treatment for a borderline ovarian tumor?

Yes. Fertility-sparing surgery preserves the uterus and ovarian tissue. After such surgery, most pregnancies are achieved spontaneously, often within months. If both ovaries are removed, options like egg or embryo freezing before surgery, or ovarian tissue cryopreservation, may help. Discuss fertility plans with your care team before deciding on surgery.

What are the recurrence risks after cystectomy versus removing the whole ovary?

In a large French study of stage I tumors, recurrence was about 30.3% after cystectomy (removing only the cyst), 11% after unilateral salpingo-oophorectomy (removing one ovary and tube), and 1.7% after bilateral salpingo-oophorectomy. Most recurrences are borderline tumors again, not invasive cancers, and may be treated with repeat surgery.

Which operation is recommended for mucinous borderline ovarian tumors?

For mucinous tumors, the preferred treatment is usually unilateral salpingo-oophorectomy, removing one ovary and its fallopian tube. This is because mucinous tumors can coexist with invasive cancer areas and, if they relapse outside the ovary, the recurrence is more likely to be invasive. Cystectomy is reserved for special situations.

How often does the frozen section test make an incorrect diagnosis?

Frozen section is a rapid test done during surgery. For borderline ovarian tumors, it under-diagnoses them as benign in about 25%–30% of cases and incorrectly identifies them as carcinoma in about 20%–30% of cases. Extra caution is needed with large tumors, where microinvasion or other features might be missed.

If a borderline ovarian tumor is found during pregnancy, what happens next?

Management is based on the same treatment principles as in non-pregnant women. Close surveillance checks for signs of malignancy, and delivery is advised in a specialized gynecologic oncology center. Complete staging may be difficult during pregnancy, so some patients may need postpartum completion of staging or further surgery.

How long after fertility-sparing surgery must I wait before trying to conceive?

Most pregnancies after fertility-sparing surgery occur spontaneously, often as early as 3 months after surgery. However, many physicians recommend delaying pregnancy until a sufficient follow-up period has passed to reduce concerns about recurrent disease. Ask your medical team for advice personalized to your tumor type and treatment.

When should a woman with a borderline ovarian tumor seek a second opinion before choosing fertility-sparing surgery?

A second opinion is worth seeking if your tumor was large, your first surgery did not include full abdominal exploration, or pathology shows a mucinous or micropapillary pattern, since these features affect recurrence risk and whether restaging surgery is recommended. Frozen section analysis can be inaccurate in 25–30% of borderline tumor cases, so expert pathology review may change the diagnosis. Recurrence rates differ by operation: cystectomy up to 30.3%, salpingo-oophorectomy 11%, so confirming your surgical plan is essential. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

Original article title: challenging management of borderline ovarian tumors BOTs in women

Authors: Luigi Della Corte, Antonio Mercorio, Paolo Serafino, Francesco Viciglione, Mario Palumbo, Maria Chiara De Angelis, Maria Borgo, Cira Buonfantino, Marina Tesorone, Giuseppe Bifulco, and Pierluigi Giampaolino

Journal: Frontiers in Surgery, section Obstetrics and Gynecological Surgery

Publication date: Published 23 August 2022 | Accepted 09 August 2022 | Received 19 June 2022

DOI: 10.3389/fsurg.2022.973034

Citation: Della Corte L, Mercorio A, Serafino P, Viciglione F, Palumbo M, De Angelis MC, Borgo M, Buonfantino C, Tesorone M, Bifulco G and Giampaolino P (2022) The challenging management of borderline ovarian tumors (BOTs) in women of childbearing age. Front. Surg. 9:973034. doi: 10.3389/fsurg.2022.973034

This patient-friendly article is based on peer-reviewed research. The original study was an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY), which permits use, distribution, and reproduction provided the original authors and copyright owners are credited. Patients should always discuss their individual situation with their own medical team, as this article is educational and does not replace personalized medical advice.