Upper Abdominal Resections as Part of Tertiary Cytoreduction for Relapsed Ovarian Cancer

Discussion

Patients presenting upper abdominal involvement in the setting of advanced-stage ovarian cancer were considered for a long time as having poor tumor biology and were considered as candidates solely for systemic chemotherapy (2). However, since surgical techniques have improved, extended upper abdominal resections have been associated with good outcomes, demonstrating the effectiveness of these procedures as part of primary debulking surgery. One of the first studies which demonstrated the benefits of these procedures and which destroyed the myth of poor tumor biology was by from Eisenhauer et al. and was published in 2006 (12). The study included 262 patients submitted to surgery between 1998 and 2003 in the Memorial Sloan Kettering Cancer Center, New York, United States of America. According to the time and extent of surgery, the authors classified these patients into three groups: the first group included 57 patients presenting upper abdominal involvement submitted to surgery with curative intent; the second group included 122 patients presenting disease limited to the pelvis and submitted to standard cytoreduction; the remaining 83 cases were included in the third group and were represented by cases presenting upper abdominal involvement in which suboptimal cytoreduction was performed. The authors underlined the fact that cases submitted to suboptimal cytoreduction due to the presence of upper abdominal involvement were submitted to surgery before the year 2000, when extensive upper abdominal resection was added as part of debulking surgery. However, the authors demonstrated that progression-free and overall survival was significantly improved in cases submitted to complete debulking irrespective of the site of involvement. Therefore, patients in the second group presented a median overall survival of 84 months, significantly higher when compared to that reported for the third group (of only 38 months) and similar to that for the first group (which was not reached by 68 months). The most important prognostic factors for the long-term outcomes were the stage of disease, the preoperative level of cancer antigen-125, association with ascites and the presence of residual disease. Moreover, the authors demonstrated similar rates of postoperative complications between the two groups, underlining in this way the safety of the addition of upper abdominal resection (12).

Once the benefits of extending the field of the resection in the upper abdomen were widely demonstrated in patients presenting locally advanced ovarian cancer, attention was focused on determining if such resections were feasible and effective in recurrent disease. Such resections were successfully added in patients presenting disease relapse.

The concept of repetitive cytoreduction was initially introduced by Berek et al., this study group also being the first to demonstrate an inversely proportional relationship between the residual tumoral volume and overall survival after secondary debulking (13).

When it comes to the role of tertiary cytoreduction in relapsed ovarian cancer, the first series was reported by Leitao et al. and was conducted between 1990 and 2002, at the Memorial Sloan-Kettering Cancer Center, New York University, United States of America (14). The study included 26 patients submitted to tertiary cytoreduction after a median time from secondary cytoreduction of 25.6 months and a median treatment-free interval of 13.4 months. The authors reported median disease-specific survival of 36.3 months after tertiary cytoreduction for patients submitted to optimal cytoreduction (defined as a visible tumoral volume lower than 0.5 cm) and of only 15 months than the residual volume was higher (p=0.05). They also demonstrated that cases submitted to complete debulking (defined as no residual disease) had similar long-term outcomes when compared to those submitted to optimal debulking. The univariate analysis demonstrated that other prognostic factors for long-term survival were the time to the first recurrence (>12 months) and the treatment-free interval (>12 months). Regarding the need for extending the resection in the upper abdomen, the authors reported that three cases were submitted to hepatic resection, seven to extended lymph node dissection, one to nephrectomy and another to cholecystectomy. When it comes to postoperative complications, they were reported in 27% of cases and were classified as Clavien–Dindo grade 1, 2 or 3 complications, no reoperation or death being reported (14). Data reported in this study were further completed in the report published by the same study group in 2010. At that time, the authors reported the outcomes of 77 patients submitted to tertiary cytoreductive surgery between 1998 and 2008, the median disease-free survival between secondary and tertiary cytoreduction being of 25.7 months. On univariate analysis, the most significant prognostic factors were residual volume after tertiary cytoreduction and the treatment-free interval; however, on multivariate analysis, only the residual volume after tertiary cytoreduction remained statistically significant (15).

A more recent study which investigated the feasibility and safety of tertiary cytoreduction for relapsed ovarian cancer was a multicenter one and was published in 2017 (16). The study included 103 patients submitted to tertiary cytoreduction at 11 high-volume gynecologic oncology centers between January 2008 and December 2012. The primary endpoints of the study were to study the impact of complete debulking on overall survival and to identify the prognostic factors which might predict the feasibility of complete debulking, while the secondary endpoint was to study the value of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) score on predicting the feasibility of complete cytoreduction. The median overall survival after tertiary cytoreduction was 39.5 months and was significantly influenced by the completeness of cytoreduction, the initial stage at diagnostic, the location of the recurrent tumor and by the interval between the initial diagnosαφ and when tertiary cytoreduction was performed. For the AGO score, the authors demonstrated that a positive score had a negative predictive value for complete cytoreduction of 43.2%. For the extent of the resectional phase in the upper abdomen, the authors reported 39 cases submitted to extended retroperitoneal dissection, nine to diaphragmatic resection, eight to splenectomy, two to cholecystectomy, two to hepatic resection, two to pancreatic tail resection, and one to partial gastrectomy. Moreover, extra-abdominal resections consisting of axillary lymph node dissection, pulmonary lobectomy and resection of brain metastases were performed in one case each. However, the early postoperative morbidity rate was 9.7%, while the postoperative mortality rate was zero, demonstrating once again the safety of tertiary cytoreduction (16).

These data underline once again the fact that the extent of upper abdominal resection, and even extra-abdominal resection, increases over time once the perioperative management of these cases improves.

In order to maximize the efficiency of this procedure and to minimize perioperative complications, certain authors went further and demonstrated the utility of minimally invasive surgery in such cases. In a study conducted by Choi et al. and published in 2014, the authors reported the cases of eight patients submitted to laparoscopic debulking in the setting of secondary cytoreduction and five cases submitted to laparoscopic debulking in the setting of tertiary cytoreduction; among these patients, upper abdominal resection consisted of liver resection in two cases, splenectomy in four, and resection of the mesentery and omentum in one case. The authors reported a single intraoperative complication and no postoperative complications, suggesting the utility of minimally invasive surgery in selected cases (17).