A woman who selects FSS receives the benefits of preserving the possibility of having a child in the future, regardless of the risk of unexpected recurrence. When we consider whether FSS should be selected for a woman with early-stage EOC at reproductive age, we subconsciously fear the risk of a future recurrence or subsequent death from disease. Here, we encounter the fundamental question of how much the preservation of the contralateral ovary and uterus is associated with the recurrence. On considering clinical information on the extent that recurrence is increased or how different long-term survival is between patients with FSS and those receiving radical surgery, it is beneficial for the patient and physician to share risk-and-benefit data before selecting this surgery. The randomized controlled trial (RCT) is a solution to this problem, but it is actually very difficult to perform for ethical reasons. In our earlier study, we preliminarily reported that the 5-year overall survival rates in the three groups of patients with stage I EOC were 90.8% (FSS at reproductive age), 88.3% (non-FSS at reproductive age), and 90.6% (non-FSS in the elderly), concluding that there was no significant difference on three-group comparison [
15]. Since then, several retrospective studies have demonstrated similar results, suggesting the non-inferiority of the long-term outcome in patients who underwent FSS, compared with those received conventional surgery [
7,
8]. Nevertheless, these investigations had a critical limitation associated with any retrospective study, involving the possibility of selection bias and treatment heterogeneity. Even if showing a non-significant difference in oncologic outcomes, a number of clinicopathological profiles were inconsistent between the two cohorts. At least, considering major clinical backgrounds of patients with stage I EOC, the three categories of “substage”, “degree of differentiation”, and “histological type” overlap with one another and are complicated. For example, we can easily expect that patients with favorable clinicopathological factors, including an encapsulated, well-differentiated, chemosensitive histological type will tend to undergo FSS. Thus, considering this underlying bias, the results showing no difference in the oncologic outcome may erroneously suggest that FSS has a negative effect on survival. An RCT is actually very difficult to perform because of ethical problems. PS-matching is an efficient methodology to reduce bias by balancing many measured confounders between treatment and control groups. Recently, abundant evidence revealed the usefulness of a PS-matching technique mimicking some aspects of an RCT [
14,
16‐
19]. In the present study, to assess the appropriateness of FSS, we compared the survival between larger groups of patients who had undergone FSS and those who had received non-FSS radical surgery using the original and PS-matching cohorts. Consequently, the comparison between the two surgical groups revealed no difference in recurrence-free or overall survival rates. Thus, the current PS-matching study provides evidence that the implementation of FSS does not necessarily lead to lower progression-free and overall survival than conventional non-FSS surgery. Furthermore, we showed the therapeutic efficacy of FSS in the treatment of early-stage EOC at reproductive age. Taken together, FSS is worthy of consideration for young patients diagnosed with early-stage EOC.
Our current work still includes several limitations. Initially, because the present study was essentially a retrospective study, many factors relevant to the treatment decision were not as strictly controlled as they would be in an RCT. Particularly, our PS-matching model was still not balanced for the age and receipt of adjuvant chemotherapy. Subsequently, the composition of the study subjects may have been influenced by referral bias owing to its multicentric design for a long-term study period. Lastly, several critical data, such as socioeconomic profiles, were not provided, which may affect the reliability of the estimated PS. In contrast, the strengths of our study: firstly, the performance of central pathological review by expert pathologists for gynecologic malignancy; secondly, the relatively high patient number; and thirdly, the same chemotherapeutic criteria and protocol as for the identical study group (TOTSG group).