Long-term safety of fertility sparing surgery in early stage ovarian cancer: Comparison to standard radical surgical procedures

doi:10.1016/j.ygyno.2015.05.004

Gynecologic Oncology

Volume 138, Issue 1, July 2015, Pages 78-82

https://doi.org/10.1016/j.ygyno.2015.05.004 Get rights and content

Highlights

•
Conservative treatment of early stage ovarian cancer does not impact on survival outcomes.
•
High-risk ovarian cancer patients undergoing conservative surgery experience similar outcomes than those undergoing non-conservative approach.

Abstract

Objective

Fertility-sparing surgery (FSS) is a strategy often considered in young patients with low-grade (G1–2) early-stage epithelial ovarian cancer (eEOC), while is still controversial in high-risk patients. We investigated the role of FSS in low and high-risk eEOC patients undergoing comprehensive surgical staging.

Methods

We analyzed data from patients operated for an eEOC from 1975 to 2011, focusing on patients submitted to FSS. Seventy patients out of 307 with eEOC were identified. Patients underwent FSS were compared with 237 patients underwent radical-comprehensive-staging (RCS) in the same period. Disease free (DFS) and overall (OS) survivals were evaluated using Kaplan–Meier and Cox models.

Results

Overall, 307 patients had surgery for eEOC: 70 (22.8%) and 237 (77.2%) women had FSS and RCS, respectively. At univariate analysis, the execution of FSS not influenced DFS (HR:1.06 (95%CI: 0.56,2.02); p = 0.84) and OS (HR:1.94 (95%CI: 0.75,4.98); p = 0.16). Stage of disease was the only factor correlating with DFS (HR:4.73; 95%CI: 2.01,11.11; p < 0.001). Independently, increased age (HR per 1-unit of age:1.06 (95%CI: 1.03,1.11); p < 0.001) and high risk disease (HR:3.26; 95%CI: 1.23,8.62; p = 0.01) remained associated with worse OS. Focusing on the high risk group (stage IAG3 or more) we observed that type of surgery (FSS v. RCS) did not influence DFS (p = 0.77, log-rank test) and OS (p = 0.08, log-rank test).

Conclusions

FSS upholds oncologic effectiveness of RCS, preserving reproductive and endocrine functions. FSS does not increase risk of recurrence among high risk eEOC patients. Further prospective studies on this issue are warranted to improve patients' care.

Introduction

Ovarian cancer represents the primary cause of death among gynecological malignancies and it is projected that more than 14,000 American women will die due to ovarian cancer in 2014 [1]. Traditionally, standard treatments of ovarian cancer lead to permanent sterility, since the extirpation of the uterus and the adnexal structures is considered mandatory.

Although the majority of cases occur in post-menopausal women, it is estimated that about 3–14% of invasive ovarian cancer is diagnosed in women aged less than 40 years old [2], [3]. These patients are in some cases identified at early stage of disease and could potentially receive a conservative surgical treatment, with the preservation of the uterus and the contra-lateral ovary. Fertility and hormonal preservation is considered as one of the most important quality of life (QoL) indicators among pre-menopausal ovarian cancer patients [4]. However, generally, surgeons are reluctant to perform a conservative treatment because of the risk of leaving a microscopic tumor at the site of the preserved ovary.

Albeit no mature evidence is available, accumulating data suggest the safety of fertility-sparing surgery (FSS) in young patients with early stage ovarian cancer (eEOC) [3], [5], [6], [7]. However, consensus concerning the selection criteria for FSS is still lacking. Wide ranges of restrictive criteria are reported across different studies available in medical literature. In fact, although the majority of these studies agree in concept the safety of FSS in patients affected by well-differentiated, ovarian-confined tumors, only few investigations evaluated the effectiveness of this approach in patients affected by poorly differentiated eEOC [6], [7], [8].

In absence of randomized trials on this issue, the evaluation of large retrospective or prospective series is crucial to determinate the long-term effectiveness of FSS. Therefore, we designed the present study to audit our experience in the management of eEOC. The primary goal was to investigate the long-term effectiveness of FSS in young women diagnosed with apparent eEOC. Additionally, as a secondary endpoint, we sought to assess the safety of FSS in low- (well- or moderate-differentiated eEOC) high-risk patients (poorly differentiated or upstaged eEOC).

Section snippets

Materials and methods

After obtaining Institutional Review Board (IRB) approval, we retrospectively searched medical records of all women undergoing FSS for eEOC at National Cancer Institute — Milan (Italy), between February 1975 and January 2011.

Inclusion criteria for FSS were the following: (1) age ≤ 40 years; (2) women interested in preserving their childbearing potential; (3) apparent eEOC (no gross disease in the abdomen) at the time of surgery (4) apparently negative spread to the other ovary (macroscopically or

Results

During the study period, 307 patients undergoing surgical staging for eEOC. Overall, the study group included 70 (22.8%) women who underwent FSS; while 237 (77.2%) patients undergoing RCS represented the control group. Baseline characteristics of the groups are displayed in Table 1. Patients undergoing FSS were younger than patients undergoing RCS. The median age at surgery was 30 (range, 25–35) and 51 (range, 43–58) years for FSS and for RCS, respectively (p < 0.001). Mucinous subtype was the

Discussion

The present study evaluated outcomes of a large series of patients affected by eEOC undergoing FSS and RCS. In our analysis, we observed that stage of disease at presentation is the only factor influencing DFS; while age and high risk disease (FIGO grade 3, stage IA and IB or stage IC or more, regardless on FIGO grade) correlated with a worse OS. FSS is indicated and safe in patients with eEOC FIGO stage IA G1–G2, after accurate comprehensive staging. Patients with high risk disease presented

Conflict of interest statement

No funds have been received. All authors have no financial disclosures.

The authors have no conflict of interest.

References (16)

R. Siegel et al.
Cancer statistics, 2014
CA Cancer J. Clin.
(2014)
J.D. Wright et al.
Fertility preservation in young women with epithelial ovarian cancer
Cancer
(2009)
L.R. Duska et al.
Epithelial ovarian carcinoma in the reproductive age group
Cancer
(1999)
I. Zapardiel et al.
Conservative treatment of early stage ovarian cancer: oncological and fertility outcomes
Eur. J. Surg. Oncol.
(2014)
A. Ditto et al.
Fertility sparing surgery in early stage epithelial ovarian cancer
J. Gynecol. Oncol.
(2014)
R. Fruscio et al.
Conservative management of early-stage epithelial ovarian cancer: results of a large retrospective series
Ann. Oncol.
(2013)
T. Satoh et al.
Outcomes of fertility-sparing surgery for stage I epithelial ovarian cancer: a proposal for patient selection
J. Clin. Oncol.
(2010)
J.Y. Park et al.
Outcomes of fertility-sparing surgery for invasive epithelial ovarian cancer: oncologic safety and reproductive outcomes
Gynecol. Oncol.
(2008)

There are more references available in the full text version of this article.

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To describe strategy and results of fertility preservation (FP) in patients with malignant and borderline ovarian tumors.
Consecutive cohort study of 43 women with malignant or borderline ovarian tumors who underwent FP between February 2013 and July 2019.
The study was conducted in national expert center in Tenon University Hospital, Sorbonne University: French ESGO-certified ovarian cancer center and pregnancy-associated cancer network (CALG). Main outcome measure was FP technique proposed by multidisciplinary committee, FP technique used, time after surgery, number of fragments, histology and follicle density (if ovarian tissue freezing), number of expected, retrieved and frozen oocytes (if ovarian stimulation).
Pathological diagnosis was malignant epithelial ovarian tumor in five women (11.6%), rare malignant ovarian tumor in 14 (32.6%), borderline in 24 (55.8%), and mostly unilateral (79.1%) and stage I (76.7%). Mean age at diagnosis was 26.8 ± 6.9 years and mean tumor size 109.7 ± 61 mm. Before FP, mean AFC was 11.0 ± 6.1 and AMH levels were 2.7 ± 4.6 ng/mL. Six ovarian tissue-freezing procedures were performed (offered to 13). Twenty-four procedures of ovarian stimulation and oocyte freezing were performed after surgical treatment for 19 women (offered to 28) with a median interval of 188 days. The mean number of mature oocytes retrieved per stimulation was 12.4 ± 12.8. At least 10 mature oocytes were frozen for 52.6% of the women. No FP was offered to five women.
Oocyte and ovarian tissue cryopreservation should be offered to patients with malignant and borderline ovarian tumors. More data are needed to confirm ovarian stimulation and ovarian tissue grafting safety.
Fertility-sparing Surgery for Patients with Cervical, Endometrial, and Ovarian Cancers
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Citation Excerpt :
For more aggressive early-stage disease, platinum-based adjuvant chemotherapy is recommended—this includes stage IC disease (low-grade serous, grade 1 endometrioid, or mucinous) as well as stage IA disease (high-grade serous, grade 2/3 endometrioid, or possibly clear cell) [89]. The recurrence rate after fertility-sparing surgery in stage IA EOC is between 5% and 29%, but the overall survival rate is approximately 94% [93,94]. Prognosis is similar for patients with recurrence after fertility-sparing surgery and after standard treatment, but higher grade and stage increase the risk of recurrence [95].
Nearly 10% of the 1.3 million women living with a gynecologic cancer are aged <50 years. For these women, although their cancer treatment can be lifesaving, it's also life-altering because traditional surgical procedures can cause infertility and, in many cases, induce surgical menopause. For appropriately selected patients, fertility-sparing options can reduce the reproductive impact of lifesaving cancer treatments. This review will highlight existing recommendations as well as innovative research for fertility-sparing treatment in the 3 major gynecologic cancers.
For early-stage cervical cancers, fertility-sparing surgeries include cold knife conization, simple hysterectomy with ovarian preservation, or radical trachelectomy with placement of a permanent cerclage. In locally advanced cervical cancer, ovarian transposition before radiation therapy can help preserve ovarian function. For endometrial cancers, fertility-sparing treatment includes progestin therapy with endometrial sampling every 3 to 6 months. After cancer regression, progestin therapy can be halted to allow attempts to conceive. Hysterectomy with ovarian preservation can also be considered, allowing for fertility using assisted reproductive technology and a gestational carrier. For ovarian cancers, fertility-sparing surgery includes unilateral salpingo-oophorectomy or bilateral salpingo-oophorectomy (with lymphadenectomy and staging depending on tumor histology). With higher-risk histology or higher early-stage disease, adjuvant chemotherapy is recommended—however, this carries a 3% to 10% risk of ovarian failure. Use of oocyte or embryo cryopreservation in patients with early-stage ovarian malignancy remains an area of ongoing research.
Overall, fertility-sparing management of gynecologic cancers is associated with acceptable rates of progression-free survival and overall survival and is less life-altering than more radical surgical approaches.
Outcomes after Fertility-sparing Surgery for Women with Ovarian Cancer: A Systematic Review of the Literature
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A recent multi-institution study used propensity-score matching to adjust for age, stage, histology, and receipt of chemotherapy, and demonstrated that 5-year overall survival (OS) rates were similar between patients who underwent FSS (87.5%) and those who had conventional surgery (91.8%) [55]. Other cohort studies also found that the type of surgery did not influence progression-free survival or OS [46,48]. Studies using population-level data have also demonstrated that FSS is safe [41,52,54,56].
To compare reproductive and oncologic outcomes of patients diagnosed with early-stage epithelial ovarian carcinoma, borderline ovarian tumors, or nonepithelial ovarian carcinoma according to receipt of fertility-sparing surgery or conventional surgery.
PubMed was searched from January 1, 1995, to May 29, 2020.
Studies were included if they (1) enrolled women of childbearing age diagnosed with ovarian cancer between the ages of 18 years and 50 years, (2) reported on oncologic and/or reproductive outcomes after fertility-sparing surgery for ovarian cancer, and (3) included at least 20 patients.
The initial search identified 995 studies. After duplicates were removed, we abstracted 980 unique citations. Of those screened, 167 publications were identified as potentially relevant, and evaluated for inclusion and exclusion criteria. The final review included 44 studies in epithelial ovarian cancer, 42 in borderline ovarian tumors, and 31 in nonepithelial ovarian carcinoma. The narrative synthesis demonstrated that overall survival does not seem to be compromised in patients undergoing fertility-sparing surgery compared with those undergoing conventional surgery, although long-term data are limited. Areas of controversy include safety of fertility-sparing surgery in the setting of high-risk factors (stage IC, grade 3, and clear cell histology), as well as type of surgery (salpingo-oophorectomy vs cystectomy). It seems that although there may be some fertility compromise after surgery, pregnancy and live-birth rates are encouraging.
Fertility-sparing surgery is safe and feasible in women with early-stage low-risk ovarian cancer. Pregnancy outcomes for these patients also seem to be similar to those of the general population.
Fertility preserving surgery for high-grade epithelial ovarian carcinoma confined to the ovary
2020, European Journal of Obstetrics and Gynecology and Reproductive Biology
Citation Excerpt :
Certain providers are hesitant to offer FSS to patients with high-grade EOC given the relative high rates of relapse [6]. Given the rarity of EOC in young women, the majority of the evidence on the oncologic safety of FSS derives from small retrospective case series [2–42]. Given the paucity of evidence, the aim of the present retrospective study was to investigate the oncologic safety of uterine preservation in premenopausal women with early stage high-grade EOC using a large multi-institutional, population-based database.
To investigate the safety of uterine preservation in patients with high-grade epithelial ovarian carcinoma (EOC).
The Surveillance, Epidemiology, and End Results database was accessed (1988–2014) and patients aged < = 45 years, diagnosed with an unilateral high-grade non-clear cell EOC confined to the ovary were selected. Based on surgery codes we determined whether hysterectomy was performed. Overall (OS) and cancer-specific survival (CSS) was estimated calculated following generation of Kaplan-Meier curves and compared using the log-rank test. Cox hazard model was constructed to control for possible confounders.
A total of 1039 patients with a median follow-up of 119 months were identified. Rate of uterine preservation was 31.8 %. Patients who had hysterectomy were older (median 41 vs 32 yrs, p < 0.001). Patients with mucinous tumors were less likely to undergo hysterectomy (58.9 %) compared to those with endometrioid (73.9 %) and serous (75.9 %) carcinoma, p < 0.001. There was no difference in CSS between patients who did and did not have hysterectomy, p = 0.70 (5-yr rates were 93.9 % vs 92.2 %, respectively). After controlling for year of diagnosis, tumor histology (serous vs non-serous), disease stage, performance of lymph node dissection (LND) and tumor grade, uterine preservation was not associated with a worse cancer-specific (HR: 1.08, 95 % CI:0.69,1.71) and overall (HR:0.88, 95 % CI: 0.59, 1.32) mortality.
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View full text

Long-term safety of fertility sparing surgery in early stage ovarian cancer: Comparison to standard radical surgical procedures

Highlights

Abstract

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Materials and methods

Results

Discussion

Conflict of interest statement

Cancer statistics, 2014

CA Cancer J. Clin.

Fertility preservation in young women with epithelial ovarian cancer

Cancer

Epithelial ovarian carcinoma in the reproductive age group

Cancer

Conservative treatment of early stage ovarian cancer: oncological and fertility outcomes

Eur. J. Surg. Oncol.

Fertility sparing surgery in early stage epithelial ovarian cancer

J. Gynecol. Oncol.

Conservative management of early-stage epithelial ovarian cancer: results of a large retrospective series

Ann. Oncol.

Outcomes of fertility-sparing surgery for stage I epithelial ovarian cancer: a proposal for patient selection

J. Clin. Oncol.

Outcomes of fertility-sparing surgery for invasive epithelial ovarian cancer: oncologic safety and reproductive outcomes

Gynecol. Oncol.