The optimal adjuvant therapy for intermediate risk group (FIGO stage IA G2, IB and IC G1) and high-risk group (FIGO stage IAG3, IB G2-G3, IC G2-G3 and clear cell) had not yet been established until 2003 when solid scientific proof of the clinical effectiveness of adjuvant chemotherapy was provided. In 2003, in fact, two large prospective randomized trial (ICON 1 and ACTION) and two meta-analyses including five trials [41] on 1,234 patients addressing the positive role of adjuvant chemotherapy (AC) in reducing the risk of progression and death in eEOC were published. Until that no studies in eEOC had shown the effect, if any, of adjuvant treatment (using either radiotherapy or chemotherapy) but all the trials have insufficient power to detect any difference between treatments because too few patients were randomly assigned and insufficient surgical staging was performed [42–44].

ICON1 [45] was a pragmatic trial in which 477 women with FIGO stage I–II ovarian cancer for which clinicians had some uncertainty of the need of adjuvant chemotherapy (AC) were randomized to receive adjuvant platinum-based chemotherapy or observation. Recommended surgical staging was less stringent than in the ACTION trial [5], with the minimum requirement being the removal of all visible disease. The majority of women in the treatment group (87 %) received carboplatin AUC 5 for six cycles. The authors reported a significant benefit for chemotherapy in terms of both OS (Hazard Ratio, HR 0.66) and PFS (HR 0.65). Update results after 9.2 years follow up confirmed survival advantage for chemotherapy treated patients (72 % vs 64 %; HR 0.74) [46]. The trial also reported the results of a sub group analysis on the effect of AC by level of risk: among the high- risk women (IA G3, IB or IC G2 or G3, clear cell), those who received AC had significantly better OS and RFS than those who did not receive chemotherapy (HR 0.48 and HR 0.52 respectively), whereas among low/medium- risk women (IA G1 and G2, IB or IC G1) there was no significant difference in survival outcomes between treatment arms (HR 0.96 and HR 0.96 respectively). Given that the analysis were not pre-planned and the number of patients in each sub group not provided, these results must be evaluated with caution and need to be confirmed.

ACTION [5] was a RCT run by the European Organization for Research and Treatment of Cancer (EORTC) which recruited 448 FIGO stage IA and IB G2-G3, all stage IC and stage IIA women. Surgical staging procedures were specified and recommended, nevertheless only 34 % of patients received optimal surgical staging. Patients were randomized to receive platinum based chemotherapy (47 % had cisplatin in combination with cyclophosphamide and 33 % had single-agent carboplatin) for at least four cycles versus no further treatment. The authors reported a significant benefit of chemotherapy in terms of RFS (HR 0.63) and a non significant benefit in terms of OS (HR 0.69). In a preplanned sub group analysis the effect of AC with respect to surgical staging adequacy was evaluated: among the 295 sub-optimally staged women, those who received adjuvant chemotherapy had significantly better OS and RFS than those who did not, whereas among the 151 optimally staged women, there was no significant difference in survival outcomes. A similar phenomenon was seen for RFS. Moreover in the suboptimally staged patients, the salvage rates at the time of recurrence in the observation arm and the AC arm were super imposable, whereas in the optimally staged patients, salvage chemotherapy treatment at the time of recurrence did well in the observation arm than in the AC arm. Although the number of patients involved in this sub group analysis was small, it is of interest that the same difference in the effectiveness of salvage chemotherapy treatment in optimally staged patients not receiving AC was found in the Bolis trial [43]. However we should consider that ACTION trial was not designed to compare different surgical staging procedures, nor were women prospectively stratified by these categories; in addition, the number of participants in the ‘optimally staged’ subgroup was small and the number of events even lesser (18 events) so that some benefit of AC in optimally staged disease cannot be excluded. For this reason, almost all the authors support the practice of offering adjuvant chemotherapy to optimally staged women, who have other risk factors coming from histology [47]. Moreover, given that even inside a randomized controlled clinical trial with recommended staging procedures only one third of patients received optimal staging, it appears reasonable to consider that suboptimally staged patients represent the “real word” and the results of these two trial may be applied to all eEOC patients.

Since the two largest ICON 1 and ACTION trial were conducted in parallel and spanned the same 10 years period, their results were matched. The analysis of the combined trials [48], on 925 patients, showed better OS for patients in the AC arm than for patients in the observation arm (82 % versus 74 %, respectively). RFS was also better for patients in the AC arm (76 % versus 65 %, respectively). A systematic review of 5 RCTs, enrolling 1,277 women, was published and subsequently updated [41, 47]: meta-analysis of three trials, assessing 1,008 women, indicated that women who received adjuvant platinum-based chemotherapy had better OS than those who did not (HR 0.71); meta-analysis of four trials, on 1,170 women, indicated that women who received AC had better PFS than those who did not (HR 0.67). This review would seem the definitive proof of the benefit of platinum based AC for all patient with intermediate and high risk eEOC, but unfortunately many questions need to be answered.

Comprehensive surgical staging with para-aortic and pelvic lymph node dissection is mandatory in eEOC. A group of patients with eEOC and no other risk factors will not benefit from further treatment if fully staged, while those with undetected metastases risk to be undertreated if not surgically evaluated. However, a tailored approach should always be kept in mind; based on literature data, omitting a systematic lymphadenectomy can be considered in mucinous tumors regardless of grade.

The Literature data demonstrate the feasibility of FSS in eEOC. FSS in eEOC underwent comprehensive surgical staging is safe with oncological results comparable to radical surgery group. The opportunity to extent the indication to conservative surgery to women with more advanced disease is highly controversial and needs further investigations. Clearer data are warranted by prospective controlled studies.

In spite of the generally favorable outcome of early stage disease there is considerable 20–50 % risk of recurrence.

Platinum-based adjuvant chemotherapy has reported to increase progression-free and overall survival in intermediate risk and high-risk ovarian cancer patients.

A high priority for upcoming studies will be to use molecular markers, gene expression and microarray profiles, to further separate poor from good prognosis early stage patients who do not require additional therapy.