Recent surgical management of ovarian cancer
Disclosure statement: The authors have no conflict of interest to disclose.
Dr Dennis S. Chi, Memorial Sloan–Kettering Cancer Center, Department of Surgery, Gynecology Service, 1275 York Avenue, New York, NY 10065, USA. Email: email@example.com
Ovarian cancer is the second most common gynecological malignancy in the USA, and the majority of patients with newly diagnosed ovarian cancer present with advanced-stage disease. The standard treatment of these patients involves primary cytoreduction followed by combination chemotherapy. As the evidence has accumulated regarding the benefit of surgical cytoreduction, and as the definition of optimal cytoreduction has evolved, the surgical techniques have expanded in order to achieve this goal. This article discusses the different facets of the surgical management of ovarian cancer, with a special emphasis on the most recent additions to our current knowledge.
Ovarian cancer affects 1 in 70 women, being the second most common gynecological malignancy in the USA. The majority of patients with newly diagnosed ovarian cancer present with advanced-stage disease.1 The standard treatment of these patients involves primary cytoreduction followed by combination chemotherapy.2 As the evidence accumulated regarding the benefit of surgical cytoreduction, and as the definition of optimal cytoreduction evolved, the surgical techniques expanded in order to achieve this goal.
Regardless of the debate on whether it is the biology of the tumor rather than the surgical effort that allows optimal cytoreduction,3,4 and regardless of whether the patient has already received a course of neoadjuvant chemotherapy,5 once the decision to proceed with surgery is taken, its goal should be to achieve maximal cytoreduction.
This article will review the different facets of the surgical management of ovarian cancer, with a special emphasis on the most recent additions to our current knowledge. The data reviewed pertain mainly to high-grade serous carcinoma. Discussing the role of primary versus interval debulking is beyond the scope of this article and will not be reviewed here.
Cytoreduction for Primary Disease
Ovarian cancer is one of the few solid tumors where surgical cytoreduction is indicated in disseminated disease. Since the landmark work by Griffiths in 1975, numerous studies have confirmed the prognostic significance of achieving maximal cytoreduction.6,7 However, the definition of ‘optimal’ surgery in regards to the amount of residual disease has evolved over the last three decades. Griffiths et al., in their cohort of 102 patients, found a progressively worsening survival as the diameter of residual disease increased: of the 102 patients, those with no residual disease had the best survival. As the diameter of residual disease increased, survival worsened. Once the amount of residual disease reached >1.5 cm, debulking surgery no longer had an effect on survival.6 Hoskins et al. in 1994 showed that patients with <2 cm residual disease had a significant survival advantage over those with residual disease > 2 cm. This study also demonstrated that suboptimal debulking, regardless of the diameter of residual disease, offered no survival benefit.8 Chi et al. in 2001 analyzed prognostic factors in patients who had primary surgery for advanced ovarian carcinoma and found no survival benefit to cytoreduction unless <1 cm of residual disease could be attained.9
As the efforts towards achieving optimal cytoreduction continued, the goal of cytoreduction evolved as well, as several groups were consistently reporting an improved survival when complete cytoreduction (i.e. no gross residual disease) was achieved.10–12 Bristow et al. performed a meta-analysis in 2002 that included 6995 patients from 81 studies; all patients were treated in the ‘platinum era’. Based on their data, they developed a theoretical model wherein every 10% increase in maximal or optimal cytoreduction rate was associated with a 5.5% prolongation in median survival.7
Finally, another recently demonstrated critical benefit of minimizing intraperitoneal disease is that it allows the patient to receive intraperitoneal chemotherapy.2
Upper Abdominal Disease
In order to achieve optimal cytoreduction rates > 50%, extensive upper abdominal procedures were incorporated.13–15 These include diaphragm peritonectomy and/or resection, splenectomy, distal pancreatectomy, partial liver resection, cholecystectomy, and resection of tumor from the porta hepatis.14 In the experience of the Memorial Sloan–Kettering Cancer Center, this change in the surgical paradigm allowed optimal (residual disease <1 cm) cytoreduction rates to increase from 46% to 80%.14 Similarly, the percentage of patients left with no gross disease increased from 11% to 27%. In the evaluation of patients with upper abdominal disease, Eisenhauer et al. demonstrated that patients who were optimally cytoreduced using complex upper abdominal procedures had improved survival compared to those who had suboptimal cytoreduction. In addition, the progression-free survival (PFS) and overall survival (OS) of optimally cytoreduced patients were similar between patients who required upper abdominal procedures and patients requiring less extensive surgery.16
As expected, the addition of complex upper abdominal procedures was accompanied by a longer operative time, increased blood loss and blood transfusion requirements, as well as an increase in perioperative morbidity. However, perioperative mortality was not increased, and, most importantly, PFS and OS were significantly improved.14
It is estimated that approximately 10% of patients presenting with advanced-stage ovarian carcinoma will have stage IV disease, and more than a third of those will have pleural effusions.17 When evaluating patients with moderate to large pleural effusions with video-assisted thoracoscopic surgery (VATS), up to 65–69% of patients are found to have macroscopic intrathoracic disease. Of those, the disease encountered is >1 cm in a majority of cases (62–73%).17,18 Even among patients with negative pleural fluid cytology, a significant number of patients (36%) are found to have macroscopic disease.17
At Memorial Sloan–Kettering, a VATS is performed for all patients with suspected ovarian cancer and moderate to large pleural effusions (i.e. effusions occupying more than a third of the pleural cavity). If unresectable disease > 1 cm is encountered, the patient is referred for neoadjuvant chemotherapy and the abdominal cytoreduction is aborted. If intrathoracic disease is not encountered, or is optimally cytoreduced, then abdominal cytoreduction is performed in the same setting, or at a later date, at the surgeon's discretion considering the amount of intrathoracic and intra-abdominal disease present and the overall condition of the patient.17
Although the role of intrathoracic debulking has not been clearly associated with improved survival, it is reasonable not to submit patients with unresectable disease in the chest > 1 cm to extensive abdominal cytoreduction procedures. On the other hand, when feasible, intrathoracic cytoreduction could improve the optimal cytoreduction rates in patients with stage IV ovarian carcinoma. In this regard, it is possible that the mixed results reported in the different studies in regards to primary debulking in stage IV ovarian carcinoma, are due, at least in part, to the presence of undetected macroscopic disease in the chest.
At this time, the role of VATS in triaging patients with moderate to large pleural effusions has proven to be significant: in the most recent analysis on 42 patients from our institution, VATS altered the management in 43% of patients.17 In addition, VATS may better evaluate the extent of full thickness diaphragm disease, and it also constitutes an effective technique for performing pleurodesis.
One of the initial expansions in radical ovarian cancer surgery was the removal of the rectosigmoid colon, either separately or en bloc, in order to clear the pelvis of tumor.19 Disruption of the anastomosis, with a resultant anastomotic leak, is the most feared complication directly related to the colonic resection; it is associated with significantly increased morbidity and mortality.19
In the colorectal literature, prolonged operative time, blood loss and the use of transfusion were correlated with a higher incidence of anastomotic leak. However, when incorporated as part of cytoreductive procedures for ovarian cancer where the above risk factors for anastomotic leak are frequently present, an acceptable low rate of leak (<4%) has been reported in different series, even in the presence of large volume ascites.19–22 The decision to create a protective ileostomy did not affect those rates, and therefore is not mandatory, but can be done at the surgeon's discretion based on other factors (e.g. multiple bowel resections, low anastomosis, previous radiation).19
The rectosigmoid is the most frequently resected segment of colon in ovarian cancer surgery.23 In decreasing order of frequency, the other segments of the colon that can be resected include the ascending colon, the transverse colon, and the descending colon. The least frequently performed colon resections are subtotal colectomies: Silver et al. recently reported on his personal experience of 19 cases that underwent extended left colon resections as part of primary cytoreductive surgery. Good functional outcomes were observed in almost all patients, with the majority of his patients being able to undergo intraperitoneal chemotherapy without delay, despite the creation of a protective ileostomy.24
Cytoreduction for Recurrent Disease
The role of surgical cytoreduction in recurrent disease has been more controversial, as the evidence to support its use is more limited. Nevertheless, secondary cytoreduction should be considered when optimal cytoreduction can be achieved. Similar to what has occurred in primary cytoreduction, the definition of optimal cytoreduction has evolved. In a meta-analysis that included 2019 patients from 40 studies, only complete cytoreduction was independently associated with improved survival.25
Among the variables shown to be associated with survival in different studies, it seems that the disease-free interval, the number of sites of recurrence, and the likelihood of achieving complete cytoreduction are the critical elements in the selection of patients for secondary cytoreduction.26
For recurrences after secondary cytoreduction, the evidence is even more limited, and the evidence to support this practice comes from few studies that included a highly select group of patients.27 As for secondary cytoreduction, patient selection is critical. It is likely that the few patients who may benefit from these interventions are those with relatively longer disease-free intervals with limited site of recurrence; these are patients in whom complete cytoreduction can be achieved.
At this time, complete cytoreduction continues to be, when feasible, the objective to be attempted in the surgical treatment of advanced ovarian cancer. In a significant number of cases, complete cytoreduction involves complex surgical procedures, which require the availability of a dedicated multispecialty surgical team. In order to offer patients the best possible outcome, with the least accompanying morbidity, strong consideration should be given for the referral of such patients to high-volume tertiary care centers.28