While complete surgical resection combined with systemic platinum-based chemotherapy remains the principle of advanced ovarian cancer treatment, the extent and timing of surgical debulking continues to be a matter of debate. However, over the past three decades, one factor has remained unchanged: the volume of residual disease after debulking surgery is a strong prognostic factor in ovarian cancer, reinforcing the importance and relevance of surgical effort in the care of these patients (1–3). Based on this and the fact that the majority of the patients are diagnosed at a late stage of the disease, there is a shift towards advanced extra-pelvic procedures also known as ultra-radical surgery. International bodies in gynaecological oncology have acknowledged the importance of ultra-radical surgery for advanced ovarian cancer with the recommendation that upper abdominal procedures should be included as part of the training curriculum for gynaecology oncology trainees. As a result, the National Institute for Health and Care Excellence (NICE) recommends that ultra-radical surgery should be practiced in tertiary centers with relevant expertise and be audited regularly (4).
In our tertiary referral center, ultra-radical surgery has been performed since 2012, with the numbers increasing every year. Between 2012 and 2020, 39 patients who were treated surgically for advanced ovarian cancer met the criteria of having ultra-radical surgery as defined by NICE. It is worth mentioning that during 2020-2021, the number of patients who had radical surgery significantly decreased due to the impact of the COVID-19 pandemic. Every patient referred to our tertiary center is reviewed in the weekly multidisciplinary meeting. Following careful selection of the patients with advanced ovarian cancer who require ultra-radical surgery, they are booked in combined theatre lists with the hepatobiliary/upper gastrointestinal surgeons. The input of upper gastrointestinal surgeons is crucial for cases that require extensive upper abdominal surgery such as liver resection, gastrectomy and splenectomy and this might have contributed to the good intra and postoperative outcomes of this study. Recently, the british gynaecological cancer society (BGCS) and the association of upper surgery of Great Britain (AUGIS) have published a document that highlights the importance of having a multidisciplinary approach with the support of the colorectal, upper gastrointestinal and general surgeons when performing this extensive type of procedures (5).
In our study, primary debulking surgery was found to be significantly associated with 59% lower probability of recurrence, compared to interval debulking surgery, with no statistical difference in the survival rate. Two randomized phase three trials (EORTC55971 and CHORUS) provide evidence that interval debulking following neoadjuvant chemotherapy is an equal approach to advanced ovarian cancer, although both studies were criticized owing to limitations (6,7). One of the most recent studies worth mentioning is the SCORPION study, a phase 3 randomized clinical trial, which showed that neoadjuvant chemotherapy and primary debulking surgery have the same efficacy when used at their maximal possibilities but the toxicity profile is different (8). The Trial on Radical Upfront Surgery in Advanced Ovarian Cancer (TRUST) will hopefully enlighten the management of patients with advanced ovarian cancer, establish predictive and prognostic biomarkers of operability and survival and prove the superiority of primary surgery over the neoadjuvant chemotherapy plus interval debulking (9).
Regarding survival, the median survival time was 5 years with 51.4% probability of surviving at 5 years. Comparing this to the Office National Statistics of UK, the survival rates for stage III and IV ovarian cancer are 25% and 15%, respectively (10). The survival reported in this study is above the national rate which is also highlighted in the Ovarian Cancer Audit Feasibility Pilot in 2020. This pilot demonstrated that Humber, Coast and Vale Cancer Alliances performed well in the survival rates for ovarian cancer between 2013 and 2017 reaching 36.2% net survival of 5 years which is higher compared to the national standards of 34.7% in England (11). The two prognostic factors significantly associated with survival were the age and the complete resection of the tumour. The mean age of our sample was 61.9 years old. Complete resection of tumour was achieved in 61.5% which is higher compared to the 54.1% of the Norfolk and Norwich Hospital study (12). Similar studies have found that complete resection is significantly associated with increased survival and it is one of the main reasons why the ultra-radical approach has been utilized more and more in recent years (13-17). Incorporating surgery, even for those patients with a greater tumour burden and more disseminated disease who may require more complex procedures and more resources in terms of theater time and hospital stay, seems to be associated with a significant prolongation of the patients’ overall survival compared with chemotherapy alone (18).
Despite the above, skeptics highlight the increased morbidity rate for these patients following surgical intervention. Our data demonstrated that the major complications were limited, affecting only 7 patients of the sample (17.9%). 4 of them required surgical intervention and they returned to the theater; 3 patients had wound dehiscence and 1 an exploratory laparotomy and washout. 2 patients had intra-abdominal collection drainage by the Interventional Radiology and 1 patient required chest drain insertion and intubation due to pneumothorax. There was no perioperative death. It is important to mention that these extensive surgeries were performed under the joint care of the gynaecology oncology and upper gastrointestinal surgeon consultants. This is probably the contributing factor that resulted in an acceptable morbidity rate. In ultra-radical procedures with extensive disease, involvement of other specialties might limit the surgical time and reduce the morbidity while achieving the best care for the patients.
As a result of the above mentioned morbidity rate, 87.2% of the patients commenced adjuvant chemotherapy without delay. Moreover, the median duration of hospitalization was only 8 days. The study from Yakup Yalcin et al demonstrated that 22.4% of the patients with advanced ovarian cancer who underwent extensive upper abdominal surgeries had major complications within 30 days after surgery (19). Furthermore, receipt of chemotherapy was similar among women with and without postoperative complications in the retrospective review by Zhaomin Xu et al (20). However, in the dutch gynaecological oncology audit (DGOA), it was apparent that the higher percentage of complications resulted in a prolonged time to start adjuvant chemotherapy (21). In contrast to this study, the retrospective population-based study in the United States by Joseph A. Dottino et.al, showed that in matched primary and interval cytoreductive surgery cohorts, ultra-radical surgery was associated with the increased likelihood of post-operative complications and use of acute care services. Also, in both primary and interval cytoreductive surgery patients, those who had bowel and upper abdominal procedures had multiple 30-day postoperative complications and higher rates of readmission (22).