Fertility-Sparing Surgery Outcomes Comparable With Radical Surgery in Stage I Epithelial Ovarian Cancer

There were no significant differences in disease-free survival (DFS), overall survival (OS), or recurrence rates among patients with stage I epithelial ovarian cancer (EOC) who received fertility-sparing surgery (FSS) vs those who received radical surgery (RS), according to a study published in the World Journal of Surgical Oncology.¹

The researchers explained that OC is the fifth leading cause of cancer-related mortality in women, with EOC being the most common histological type of ovarian tumor.^2,3 They noted that the standard surgical treatment for early-stage EOC is RS.¹ Of patients with early-stage EOC who receive RS, about 92% do not experience recurrence for at least 5 years after treatment.⁴ Conversely, RS leads to a loss of reproductive potential in nulliparous patients, resulting in a worse quality of life.¹

FSS, which involves the conservation of the uterus and at least part of one ovary, was introduced to preserve patients’ reproductive function. However, it remains unclear whether FSS has the same impact on patients’ survival and disease recurrence as RS.

Consequently, the researchers extracted findings from previous studies that compared patients with stage I EOC who underwent FFS with those who underwent RS; they conducted a meta-analysis of the risk ratios (RRs) for DFS, OS, and recurrence rate.

Researchers found no significant differences in disease-free survival (DFS), overall survival (OS), and recurrence rates between fertility-sparing surgery (FSS) and radical surgery (RS) for patients with stage I epithelial ovarian cancer (EOC). | Image Credit: Dr_Microbe - stock.adobe.com

They searched for relevant studies in electronic databases, like PubMed, Web of Science, and Embase, between their inception and November 29, 2023. Afterward, they manually reviewed the reference lists of relevant articles and general reviews. Conversely, they excluded studies not relevant to EOC, that did not include both RS and FFS, or that involved pregnant patients during treatment; they also excluded any case reports, reviews, commentaries, study protocols, letters, and abstracts.

During the search, 2 independent reviewers screened the titles and abstracts. Then, they obtained and assessed potentially eligible articles using the full text; disagreements were resolved by consensus. From eligible studies, the researchers extracted various data, including the study design, sample size, and oncological outcomes, namely DFS, OS, and recurrence rates.

Meta-analyses were performed using Review Manager, Version 5.4. The researchers calculated the RRs and corresponding 95% CIs using the Mantel Haenszel method and a fixed effects model. Also, sensitivity analyses were performed by removing studies item by item and repeating a meta-analysis to evaluate the stability of the results.

Initially, the researchers identified 5529 potential articles, but, after analyzing them further, they included 12 articles in the final meta-analysis. Of the included studies, 11 were retrospective and 1 was prospective. They examined patients with stage I EOC from China (n = 5), Sweden (n = 1), Italy (n = 2), Denmark (n = 1), South Korea (n = 1), Japan (n = 1), and the US (n = 1).

Among the 12 studies, the number of patients who underwent FFS ranged from 11 to 384, and the number of patients who underwent RS ranged from 11 to 1396; the ages of those who underwent FFS were significantly younger than those of patients who underwent RS.

DFS was reported in 7 studies, which included 192 patients in the FSS group and 405 patients in the RS group. During follow-up, death occurred in 14 patients (7.3%) in the FSS group and 44 patients (10.9%) in the RS group. Therefore, the researchers found no significant DFS differences between the FFS and RS groups (RR, 0.90; 95% CI, 0.51-1.58).

Additionally, 10 studies reported OS, which involved 699 patients in the FFS group and 1949 patients in the RS group. During follow-up, death occurred in 41 patients (5.9%) in the FFS group and 149 patients (7.6%) in the RS group. These results demonstrated no significant OS differences between the 2 treatment groups (RR, 0.74; 95% CI, 0.53-1.03; P = .07).

Also, the researchers obtained recurrence rates from 6 studies, which included 262 patients undergoing FSS and 274 patients undergoing RS. They found that 31 patients (11.8%) in the FSS group and 29 (10.6%) in the RS group experienced recurrence. Therefore, no significant difference was observed in the recurrence rate between the 2 groups (RR, 1.10; 95% CI, 0.69-1.76; P = .68).

Lastly, through sensitivity analyses, the researchers observed a significant difference between FSS and RS for OS when excluding one particular study (before exclusion: RR, 0.74; 95% CI, 0.53-1.03; P = .07; after exclusion: RR, 0.70; 95% CI, 0.50-0.99; P =.04).⁵ More specifically, in this sensitivity analysis, the FFS group had decreased OS compared with the RS group.¹

The researchers acknowledged their limitations, one being that their analysis was based on evidence from trials that were not randomized and/or controlled, which provided a lower evidence level than randomized controlled trials. Also, some studies did not differentiate between the use and nonuse of chemotherapy, which may have influenced their findings. Despite these limitations, the researchers expressed confidence in their findings and hypothesized about their future implications.

“FSS was associated with a similar DFS and risk of recurrence as RS,” the authors concluded. “Decreased OS in the FSS group could not be attributed to distant metastases from EOC. We believe that this could have guiding significance in clinical work.”

References

1. Guan Z, Zhang C, Lin X, Zhang J, Li T, Li J. Oncological outcomes of fertility-sparing surgery versus radical surgery in stage - epithelial ovarian cancer: a systematic review and meta-analysis. World J Surg Oncol. 2024;22(1):170. doi:10.1186/s12957-024-03440-3
2. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12-49. doi:10.3322/caac.21820
3. Nishida T, Nishida N. Reinstatement of "germinal epithelium" of the ovary. Reprod Biol Endocrinol. 2006;4:42. doi:10.1186/1477-7827-4-42
4. Reid BM, Permuth JB, Sellers TA. Epidemiology of ovarian cancer: a review. Cancer Biol Med. 2017;14(1):9-32. doi:10.20892/j.issn.2095-3941.2016.0084
5. Chen J, Wang FF, Zhang Y, et al. Oncological and reproductive outcomes of fertility-sparing surgery in women with early-stage epithelial ovarian carcinoma: a multicenter retrospective study. Curr Med Sci. 2020;40(4):745-752. doi:10.1007/s11596-020-2239-4