open access: Review - Fertility-Sparing Surgery in Early Epithelial Ovarian Cancer: A Viable Option?

Epithelial ovarian cancer (EOC) continues to represent one of the most lethal conditions in women in the western countries. With the shifting of childbearing towards higher age, EOC increasingly affects women with active childbearing wish, resulting in major impacts on treatment management.......

According to the 2007 guidelines of the American College of Obstetrics and Gynecology (ACOG), fertility-sparing surgery for reproductive-age patients with invasive EOC is recommended for highly or moderately differentiated stage IA disease with non-clear-cell histology [14]. In an equivalent manner, the European Society for Medical Oncology (ESMO) referring in 2008 to fertility-sparing techniques in EOC identified patients with unilateral stage I tumor without dense adhesions showing favorable histology (i.e., high or moderate differentiated, non-clear-cell histology) as being the optimal candidates for this procedure [15]. However, the number of published studies concerning fertility-sparing surgery in young EOC patients is rather limited and the evaluated patient’s samples too small to allow unanimous consensus regarding the definition of the selection criteria of the optimal candidate for fertility-sparing surgery in stage I EOC. That leads to a broad variety of national guidelines regarding FSS worldwide, especially in respect to Ic (iatrogenic versus not) and/or poorly differentiated disease and to clear cell histologic subtype [16]. Moreover, under additional consideration of the relatively recently emerging dualistic model theory of EOC pathogenesis, which divides EOC in type I and type II disease [17], patients selection for FSS could theoretically be performed under this perspective and hence indicated for early-stage, type I tumors, even though there is currently no evidence that would support such an approach. Open questions remain if there should be differentiation between iatrogenic Ic disease due to intraoperative tumor rupture versus Ic due to tumor on ovarian surface or malignant cells in peritoneal cytology, whether patients with G3 tumors with no evidence of further metastatic disease in adequate staging are eligible of FSS and whether nonserous or non-endometrioid histologic subtypes should be a priori excluded from any organ-preserving technique.......

Table 1: 
Relevant case series reports in the literature concerning fertility-sparing surgery in epithelial ovarian cancer: oncologic outcome. 

Total patients:  580

Age Ranges:  26–35.9

Cell Type/#'s: 
300 (52%) mucinous
51 (9%) serous
128 (22%) clear cell
65 (11%) endometriod

Mean PFS (mo) or 5 y DFS:  33.3–100% 

5 y OS:  66.7–100%


Death: 18 (3.1%)


Table 2: 
Relevant case series reports in the literature concerning fertility-sparing surgery in epithelial ovarian cancer: reproductive outcome.


Conclusion

After thorough insight of the current literature, FSS in early-stage EOC appears an absolutely viable and safe option for women younger than 40 years who wish to preserve their childbearing potential after careful consideration of histologic subtypes. The optimal indication is referring to stage Ia G1/G2 disease, as well as stage Ic with favorable, that is, non-clear-cell histology. Here there has to be differentiated between iatrogenic—due to intraoperative tumor rupture—versus biologic Ic disease—due to surface involvement or positive Douglas cytology—since the latter is associated with less favorable outcomes after FSS. In case of stage Ic disease and clear cell histology, there is increasing evidence of a poorer relapse-free survival compared to non-clear-cell histology.

For that reason a fertility-sparing approach in this special patients collective should be indicated only after thorough discussion and informed consent of the affected patients with careful balancing of the risks and benefits.

In any case, the treating gynecologic oncologist should be fully aware of his double role in treating the malignant disease as well as in providing oncofertility care to young EOC patients, by considering offering fertility-sparing alternatives when allowed so by tumor stage and histologic differentiation.