Initial Incomplete Surgery Modifies Prognosis in Advanced Ovarian Cancer Regardless of Subsequent Management

Results

Overall, 99 patients with a mean age of 54.58 years (range=19-77 years) were eligible for this study. All patients had been previously submitted to biopsy or incomplete cytoreduction and were presumed to have residual disease at the time of enrolment into our study. Twenty-eight patients underwent direct re-operation after biopsy, while 71 of them underwent neoadjuvant chemotherapy. The mean time between biopsy and re-operation was 73 days (range=7-158 days) for patients who did not undergo chemotherapy and 186 days (range=49-368 days) for those who underwent neoadjuvant chemotherapy. The mean number of chemotherapy cycles was 6 (range=3-12 cycles), the most frequent chemotherapeutic protocol consisted of taxane–platinum salt association. Sixty-four out of 71 patients were re-operated on immediately after ending the chemotherapeutical protocol, while seven cases initially formerly refused surgery; they self-referred to our Institution when symptoms reappeared, at a mean interval of 12 months (rang=8-24 months) after ending neoadjuvant chemotherapy. At the time of the initial surgery at other institutions, 67 patients underwent biopsies by laparotomy only, while 32 underwent incomplete cytoreduction.

The most often encountered stage at re-operation was IIIC (82 patients), while 9 patients were diagnosed with stage IV ovarian cancer; in 8 cases no residual disease was found during re-operation. The main characteristics are shown in Table I.

The associated resections at the time of re-operation are shown in Table II. In 60 out of the 71 cases who underwent chemotherapy after biopsy, complete resection was achieved at re-operation. Residual disease less than 1 cm (R1 resection) was encountered in one case, while in three cases, the remnant tumor measured more than 1 cm (R2 resection). Surgery was limited to being palliative in seven cases. In cases who were submitted to direct re-operation, R0 resection was achieved in 23 cases; in one case an R1 resection was performed, while two other cases presented residual disease of more than 1 cm (R2 resection); palliative surgery was performed in two cases presenting visceral peritoneal carcinomatosis with retraction of the mesentery (Table III). In 38 cases, hyperthermic intraperitoneal chemotherapy (HIPEC) was associated to the debulking procedure.

The postoperative mortality was 7.1% in cases who underwent direct re-operation and 5.6% in cases who underwent interval debulking surgery (IDS). The main postoperative complications are shown in Table IV. Classification of postoperative morbidity according to the Clavien–Dindo scale is presented in Table V.

Disease-free survival was 27 months in cases with immediate re-operation and 29 months in cases submitted to neoadjuvant chemotherapy. The median overall survival was 43 months in cases submitted to neoadjuvant chemotherapy and only 33 months in cases with immediate re-operation, while the mean overall survival was 54 months in patients with neoadjuvant chemotherapy and only 31 months for those with direct re-operation (p=0.048) (Figure 1).

When studying the influence of age at diagnosis on overall survival in both studied groups, elderly patients had a better prognosis although statistical significance was not obtained. In the group pre-treated with chemotherapy, patients aged over 60 years had a mean survival of 51 months, while in the younger patient group, the mean survival was 48 months (p=0.56) (Figure 2). When studying the same parameter (age cut-off of 60 years) in the group who underwent direct re-operation, the mean survival for elderly patients was 34 months, while younger patients had an overall survival of 28 months. However, this fact did not have statistical significance (p=0.823) (Figure 3).

The two groups (represented by patients with IIIC epithelial ovarian cancer who underwent direct re-operation and those who underwent neoadjuvant chemotherapy and IDS, respectively, in whom R0 resection was acheived) were retrospectively compared with a group of 197 patients with IIIC ovarian cancer who benefitted from per-primam complete cytoreduction. (Figure 4). The median survival time in this last category was 51 months, while the mean overall survival was 72 months. Comparison of the overall survival of cases who underwent per-primam complete cytoreduction and those who underwent direct re-operation after biopsy was statistically significantly different: the mean overall survival was 72 months in the first group and only 31 months in the latter (p=0.001) (Figure 5). When comparing the other two groups, i.e. patients who underwent complete cytoreduction at initial surgery and those who underwent chemotherapy after biopsy and IDS, differences were also obtained (mean overall survival of 72 months for the former and only 54 months for the latter) but with no statistical significance (p=0.437).