Interventional procedure overview of maximal effort cytoreductive surgery for advanced ovarian cancer

Angeles MA, Cabarrou B, Gil-Moreno A et al. (2021) Effect of tumor burden and radical surgery on survival difference between upfront, early interval or delayed cytoreductive surgery in ovarian cancer. Journal of Gynecologic Oncology 32: e78

Cohort study

n=549

The benefit of complete primary debulking surgery compared with neoadjuvant chemotherapy was maximal in patients with a low SCS. In patients with low tumour burden, there was a survival benefit of primary debulking surgery over early interval or delayed debulking surgery. In women with high tumour load, delayed debulking surgery impaired the oncological outcome.

A more recent publication from the same centre is included.

Angeles MA, Rychlik A, Cabarrou B et al. (2020) A multivariate analysis of the prognostic impact of tumor burden, surgical timing and complexity after complete cytoreduction for advanced ovarian cancer. Gynecologic Oncology 158: 614–21

Cohort study

n=549

In multivariable analysis, surgical complexity and cytoreduction to minimal residual disease rather than complete cytoreduction were negatively associated with disease-free survival. Primary debulking surgery offered a survival gain of almost 3 years compared to interval debulking surgery in patients with minimal or no residual disease after surgery. Primary debulking surgery should remain the standard of care for advanced ovarian cancer.

A more recent publication from the same centre is included.

Angioli R, Plotti F, Aloisi A et al. (2013) Does extensive upper abdomen surgery during primary cytoreduction impact on long-term quality of life? International Journal of Gynecological Cancer 23: 442-447

Prospective non-randomised comparative study (standard surgery versus extensive upper abdomen surgery)

n=80

Follow up not stated

There were no statistical differences in terms of major surgical complication rates (15% versus 10%). Both groups had same times of beginning of chemotherapy (median, 19 versus 21 days) and no severe related toxicities. Quality-of-life scores of both questionnaires were comparable between groups, except for Global Health Status in QLC-30.

Small non-randomised study

Bacalbasa N, Dima S, Balescu I et al. (2015) Results of primary cytoreductive surgery in advanced-stage epithelial ovarian cancer: a single-center experience. Anticancer Research 35: 4099–104

Cohort study

n=338

A more extensive surgical approach is justified and associated with improved survival in patients with advanced-stage epithelial ovarian cancer. However, careful patient selection is needed because the general preoperative status can impact survival.

Larger or more recent studies are included.

Baldewpersad Tewarie NMS, van Driel WJ, van Ham M et al. (2021) Postoperative outcomes of primary and interval cytoreductive surgery for advanced ovarian cancer registered in the Dutch Gynecological Oncology Audit (DGOA). Gynecologic oncology 162: 331–8

Cohort study

n=2,382

A higher complete cytoreduction rate was achieved in primary compared to interval debulking surgery. This is associated with a higher complication with reintervention rate in the primary debulking surgery group. The higher rate of complication with reintervention is subsequently correlated with a delay in starting adjuvant chemotherapy. Maintaining a balance in aggressiveness of surgery and outcome of the surgical procedure with respect to severe complications is important.

The main aim was to compare outcomes after primary debulking surgery and interval debulking surgery.

Barlin JN, Long KC, Tanner EJ et al. (2013) Optimal (≤1cm) but visible residual disease: is extensive debulking warranted? Gynecologic Oncology 130: 284–8

Cohort study

n=219

Patients cytoreduced to 1 cm or less but visible residual disease who needed upper abdominal surgery did not have a worse overall survival than those who did not need upper abdominal surgery. Overall survival was similar if residual disease involved the small bowel or not. For ovarian cancer patients with disease not amenable to complete gross resection, extensive surgery should still be considered to achieve 1 cm or less but visible residual disease status, including cases where the residual disease involves the small bowel.

Larger or more recent studies are included.

Baum J, Braicu EI, Hunsicker O et al. (2021) Impact of clinical factors and surgical outcome on long-term survival in high-grade serous ovarian cancer: A multicenter analysis. International Journal of Gynecological Cancer 31: 647–55

Non-randomised comparative study (propensity score matched)

n=276

After propensity score matching and multivariable adjustment, platinum sensitivity (p=0.002) was an independent favourable prognostic factor whereas recurrence (p<0.001) and ascites (p=0.021) were independent detrimental predictors for long-term survival. More long-term survivors tested positive for mutation in the BRCA1 gene than the BRCA2 gene (p=0.016). Intraoperatively, these patients had less tumour involvement of the upper abdomen at initial surgery (p=0.024). Complexity of surgery and surgical techniques were similar in both cohorts.

Larger studies are included.

Bernard L, Boucher J, Helpman L (2020) Bowel resection or repair at the time of cytoreductive surgery for ovarian malignancy is associated with increased complication rate: An ACS-NSQIP study. Gynecologic oncology 158: 597–602

Cohort study

n=4,965

Patients who had bowel resection or repair at the time of cytoreductive surgery are at increased risk of surgical site infections, without increased risk of 30-day mortality.

Studies with more outcomes have been included.

Berretta R, Capozzi VA, Sozzi G et al. (2018) Prognostic role of mesenteric lymph nodes involvement in patients undergoing posterior pelvic exenteration during radical or supra-radical surgery for advanced ovarian cancer. Archives of Gynecology and Obstetrics 297: 997–1004

Cohort study

n=83

The absence of residual disease after surgery is an independent prognostic factor; to achieve this result should be recommended a radical bowel resection during debulking surgery for advanced ovarian cancer with bowel involvement.

Small retrospective study.

Boer GMN-D, Hofhuis W, Reesink-Peters N et al. (2022) Adjuvant use of PlasmaJet device during cytoreductive surgery for advanced-stage ovarian cancer: results of the PlaComOv-study, a randomized controlled trial in the Netherlands. Annals of Surgical Oncology; 2022

RCT (use of neutral argon plasma)

n=327

Follow up=6 months

Adjuvant use of PlasmaJet during cytoreductive surgery for advanced-stage ovarian cancer resulted in a significantly higher proportion of complete cytoreductive surgery in patients with resectable disease and higher quality of life at 6 months after surgery.

Study focuses on the effect of using neutral argon plasma during the procedure.

Ceccaroni M, Roviglione G, Bruni F et al. (2018) Laparoscopy for primary cytoreduction with multivisceral resections in advanced ovarian cancer: prospective validation. "The times they are a-changin"? Surgical Endoscopy 32: 2026–37

Non-randomised comparative study

n=66

Follow up=median 51 months

After strict selection, a group of patients with advanced ovarian cancer may have laparoscopic primary cytoreduction with high rates of optimal cytoreduction, satisfactory perioperative morbidity, a short interval to chemotherapy, and encouraging survival outcomes.

Small non-randomised study focusing on laparoscopic surgery.

Chang, SJ, Bristow RE, Chi DS et al. (2015) Role of aggressive surgical cytoreduction in advanced ovarian cancer. Journal of Gynecologic Oncology 26: 336–42

Review

If the patient cannot have near optimal cytoreduction, radical cytoreductive procedures should not be done except for palliation. Multiple factors impact patient survival and complete cytoreduction to no gross residual disease is one of the most powerful determinants in survival. Although published reports supporting the positive prognostic impact of aggressive surgical effort are almost entirely retrospective, the findings of these studies provide potential evidence for the hypothesis that surgical expertise at least partly counteracts the effects of underlying tumour biology. Consequently, aggressive surgical cytoreduction can offer the best opportunity for achieving extended survival in women with advanced ovarian cancer.

Review with no meta-analysis.

Costantini B, Vargiu V, Santullo F et al. (2022) Risk factors for anastomotic leakage in advanced ovarian cancer surgery: a large single-center experience. Annals of Surgical Oncology 2022

Case series

n=515

Anastomotic leakage is confirmed to be an extremely rare but severe postoperative complication of ovarian cancer surgery, being responsible for increased early postoperative mortality. Preoperative nutritional status and surgical characteristics, such as blood supply and anastomosis level, appear to be the most significant risk factors.

Study focuses on a single safety outcome (risk factors for anastomotic leakage).

Datta A, Sebastian A, Chandy RG et al. (2021) Complications and outcomes of diaphragm surgeries in epithelial ovarian malignancies. Indian Journal of Surgical Oncology 12: 822–29

Cohort study

n=616

Of the 616 patients, 13% (81) had diaphragm surgery. Optimal debulking was achieved in 89% of cases. The complexity of surgery was intermediate in 64% of patients and complex in 33% as per Aletti's scoring. Median recurrence-free and overall survival were 22 (95% CI 17 to 27) and 32 months (95% CI 26 to 38) respectively.

Study focuses on a small part of the procedure (diaphragm surgery).

Davidson BA, Broadwater G, Crim A et al. (2019) Surgical complexity score and role of laparoscopy in women with advanced ovarian cancer treated with neoadjuvant chemotherapy. Gynecologic Oncology 152: 554–9

Cohort study

n=282

In women with advanced epithelial ovarian cancer treated with neoadjuvant chemotherapy, older age, SCS 3 or higher, and residual disease more than 1 cm at interval debulking surgery were predictors of worse survival. Minimally invasive surgery appears safe and feasible with acceptable optimal cytoreduction rates.

Study focuses on the role of laparoscopy.

Di Donato V, Di Pinto A, Giannini A et al. (2021) Modified fragility index and surgical complexity score are able to predict postoperative morbidity and mortality after cytoreductive surgery for advanced ovarian cancer. Gynecologic Oncology 161: 4–10

Cohort study

n=263

Patients with a high frailty index score who had intermediate or high-complexity surgery were at higher risk of severe complications.

Studies with more patients or longer follow up are included.

Di Donato V, Bardhi E, Tramontano L et al. (2020) Management of morbidity associated with pancreatic resection during cytoreductive surgery for epithelial ovarian cancer: A systematic review. European Journal of Surgical Oncology 46: 694–702

Systematic review

n=701

(11 studies)

Knowledge of pancreatic surgery and management of possible complications should be present in the oncologic-gynaecologic armamentarium. All patients should be referred to specialised, dedicated, tertiary centres to reduce, promptly recognise and optimally manage complications.

Review focuses on complications related to pancreatic surgical procedures.

Egger EK, Kohls N, Stope MB et al. (2020) Risk factors for severe complications in ovarian cancer surgery. In Vivo 34: 3361–65

Cohort study

n=345

There were no complications in 114 patients, mild complications in 114 patients and severe complications in 117 patients. The risk factor evaluation identified age (p=0.049), smoking (p=0.032) and duration of surgery (p<0.0001) as statistically significant factors for severe postoperative morbidity.

Although duration of surgery was considered as a risk factor, extent of surgery was not described.

Eoh KJ, Lee J-Y, Yoon JW et al. (2017) Role of systematic lymphadenectomy as part of primary debulking surgery for optimally cytoreduced advanced ovarian cancer: Reappraisal in the era of radical surgery. Oncotarget 8: 37807–16

Case series

n=158

Systematic lymph node dissection might have therapeutic value and improve prognosis for patients with optimally cytoreduced advanced ovarian cancer

Study focuses on the role of lymphadenectomy.

Fagotti A, Ferrandina MG, Vizzielli G et al. (2020) Randomized trial of primary debulking surgery versus neoadjuvant chemotherapy for advanced epithelial ovarian cancer (SCORPION-NCT01461850). International Journal of Gynecological Cancer 30:1657–64

RCT

n=171

Neoadjuvant chemotherapy and primary debulking surgery have the same efficacy when used at their maximal possibilities, but the toxicity profile is different.

Study aimed to compare neoadjuvant chemotherapy followed by interval debulking surgery with primary debulking surgery.

Feldheiser A, Braicu E-I, Bonomo T et al. (2014) Impact of ascites on the perioperative course of patients with advanced ovarian cancer undergoing extensive cytoreduction: results of a study on 119 patients. International Journal of Gynecological Cancer 24: 478–87

Case series

n=119

The presence of a high amount of ascites at cytoreductive surgery is associated with higher amounts of blood transfusions. The length of hospital stay and the postoperative intensive care unit treatment are statistically significantly prolonged compared with those of patients without ascites.

Small case series, which focuses on the impact of ascites on the outcome of surgery.

Fotopoulou C, Jones BP, Savvatis K et al. (2016) Maximal effort cytoreductive surgery for disseminated ovarian cancer in a UK setting: challenges and possibilities. Archives of Gynecology and Obstetrics 294: 607–14

Cohort study

n=118

Maximal effort cytoreductive surgery for ovarian cancer is feasible within a UK setting with acceptable morbidity, low intestinal stoma rates and without clinically relevant delays to postoperative chemotherapy. Careful patient selection, and coordinated multidisciplinary effort appear to be the key for good outcome. Future evaluations should include quality of life analyses.

Larger or more recent studies are included.

Ghirardi V, Moruzzi MC, Bizzarri N et al. (2020) Minimal residual disease at primary debulking surgery versus complete tumor resection at interval debulking surgery in advanced epithelial ovarian cancer: A survival analysis. Gynecologic Oncology 157: 209–13

Non-randomised comparative study

n=207

Follow up=median 56 months

Median progression-free survival was 16 months and 19 months for primary debulking surgery and interval debulking surgery, respectively (p=0.111). Median overall survival was 41 months and 52 months for primary and interval surgery group, respectively (p=0.022).

Study focuses on comparison of primary and interval debulking surgery.

Gockley AA, Fiascone S, Hicks Courant K et al. (2019) Clinical characteristics and outcomes after bowel surgery and ostomy formation at the time of debulking surgery for advanced-stage epithelial ovarian carcinoma. International Journal of Gynecological Cancer 29: 585–92

Cohort study

n=554

Patients who had primary surgery were more likely to have bowel resection, compared with those who had interval surgery (37% versus 14%, p<0.001). Of the 139 (25%) patients who had bowel surgery, 25 (18%) had ostomy formation. Rates of ostomy formation were similar between the groups (6% primary versus 3% interval, p=0.10). Multivariate analysis showed that a high SCS was associated with ostomy formation.

Study focuses on a single aspect of the procedure (ostomy formation).

Greggi S, Falcone F, Carputo R et al. (2016) Primary surgical cytoreduction in advanced ovarian cancer: An outcome analysis within the MITO (Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies) Group. Gynecologic Oncology 140: 425–9

Non-randomised comparative study

n=205

Complete surgical cytoreduction was associated with oncological referral centres (60% compared with 25% in non-oncological referral centres, p<0.001). The proportion of patients who had additional surgical procedures was different (at least 1 additional procedure was done in 81% in oncological referral centres compared to 51% in the others, p<0.001). Despite the more aggressive surgery done in oncological referral centres, the perioperative outcome measures were not statistically significantly different in the 2 groups.

The main focus of the study was to assess surgical management of advanced ovarian cancer and compare outcomes for different types of treatment centres.

Hall M, Savvatis K, Nixon K, et al. (2019) Maximal-effort cytoreductive surgery for ovarian cancer patients with a high tumor burden: variations in practice and impact on outcome. Annals of Surgical Oncology 26: 2943–51

Non-randomised comparative study

n=249

Follow up: mean 24 months

Incorporating surgery into the initial management of epithelial ovarian cancer, even for those patients with a greater tumour burden and more disseminated disease, may need more complex procedures and more resources in terms of theatre time and hospital stay, but seems to be associated with a significant prolongation of overall survival compared with chemotherapy alone.

Studies with more patients or longer follow up are included.

Harter P, Sehouli J, Vergote I et al. (2021) Randomized trial of cytoreductive surgery for relapsed ovarian cancer. The New England Journal of Medicine 385: 2123-2131

RCT

n=407

A complete resection was achieved in 76% of the patients in the surgery group who had the procedure. The median overall survival was 53.7 months in the surgery group and 46.0 months in the no-surgery group (hazard ratio for death, 0.75; 95% CI 0.59 to 0.96; p=0.02). Patients with a complete resection had the most favourable outcome, with a median overall survival of 61.9 months.

Study focuses on patients with recurrence of ovarian cancer.

Harter P, Sehouli J, Lorusso D et al. (2019) Randomized trial of lymphadenectomy in patients with advanced ovarian neoplasms. New England Journal of Medicine 380: 822– 32

RCT

n=647

Systematic pelvic and paraaortic lymphadenectomy in patients with advanced ovarian cancer who had undergone intraabdominal macroscopically complete resection and had normal lymph nodes both before and during surgery was not associated with longer overall or progression-free survival than no lymphadenectomy and was associated with a higher incidence of postoperative complications.

Study focuses on a single aspect of the procedure (lymphadenectomy).

Hernandez-Lopez LA, Elizalde-Mendez A (2020) How far should we go in optimal cytoreductive surgery for ovarian cancer? Chin Clin Oncol 9:70. doi: 10.21037/cco-20-40

Review

An important factor playing a role in survival and in the probability of surgical cytoreductive success is tumour biology; there has been described a clear difference between serous and mucinous tumours, but some groups advocate that maximal surgical effort in mucinous tumours may compensate morbidity with an increase in survival. The extension of resection in cytoreduction is still controversial; some authors have confirmed that the most important factor is the residual disease and that radical surgery is superior to non-radical surgery in terms of overall survival. An important factor is for procedures to be done in specialised centres.

Review without meta-analysis.

Horner W, Peng K, Pleasant V et al. (2019) Trends in surgical complexity and treatment modalities utilized in the management of ovarian cancer in an era of neoadjuvant chemotherapy. Gynecologic Oncology 154: 283–89

Cohort study

n=68,889

The use of neoadjuvant chemotherapy increased from 8% in 2004 to 28% in 2015 (p-trend<0.001). The proportion of moderate complexity surgeries increased from 29% to 34% and high complexity surgeries from 26% to 30% (p-trend<0.001, for both). Trends in increasing surgical complexity were seen in both neoadjuvant chemotherapy and primary surgery cohorts. The increase in surgical complexity was seen most profoundly at high-volume centres. Overall 30-day mortality decreased from 3% in 2004 to 1% in 2015; and 90-day mortality decreased from 8% to 4%. During the same time, 5‑year survival increased from 40% to 49%.

Study focuses on trends in surgical complexity.

Javellana M, Hoppenot C, Lengyel E et al. (2019) The road to long-term survival: Surgical approach and longitudinal treatments of long-term survivors of advanced-stage serous ovarian cancer. Gynecologic Oncology 152: 228–34

Case control study

n=123

Aggressive surgical treatment intended to achieve microscopic disease, primary debulking surgery, preservation of sensitivity to chemotherapy, and recurrence amenable to secondary debulking are associated with long-term survival.

Larger studies are included.

Kengsakul M, Nieuwenhuyzen-de Boer GM, Bijleveld AHJ et al. (2021) Survival in advanced-stage epithelial ovarian cancer patients with cardiophrenic lymphadenopathy who underwent cytoreductive surgery: a systematic review and meta-analysis. Cancers 7: 5017

Systematic review

n=727

15 studies

Enlarged cardiophrenic lymph nodes in preoperative imaging is highly associated with metastatic involvement. Patients with cardiophrenic lymph nodes adenopathy had a lower survival rate, compared with patients without it. Further randomised controlled trials should be conducted to definitively demonstrate whether cardiophrenic lymph node resection at the time of cytoreductive surgery is beneficial.

Review focuses on effect of enlarged cardiophrenic lymph nodes on outcomes.

Kumar S, Long J, Kehoe S et al. (2019) Quality of life outcomes following surgery for advanced ovarian cancer: a systematic review and meta-analysis. International Journal of Gynecological Cancer 29: 1285–91

Systematic review

n=1,064

5 studies

Studies on patient reported outcomes after ovarian cancer surgery are limited and potentially confounded. Quality of life after primary surgery or surgery after chemotherapy is not different. There is insufficient evidence for quality of life after extensive surgery for advanced ovarian cancer.

Review only included 2 studies comparing standard with extensive surgery, both of which were observational (Angioli et al., 2013 and Soo Hoo et al., 2015). These were not included in the meta-analysis.

Kumar A, Janco JM, Mariani A et al. (2016) Risk-prediction model of severe postoperative complications after primary debulking surgery for advanced ovarian cancer. Gynecologic Oncology 140: 15–21

Cohort study

n=620

Follow up=90 days

138 (22%) of patients who had primary surgery had a grade ≥3 complication. Age (OR 1.21 per 10 years increase in age), BMI (OR 1.35 for BMI<25 kg/m² versus reference, OR 2.83 for BMI≥40 kg/m² versus reference), ASA score≥3 (OR 1.49), stage (OR 1.69 stage 4) and surgical complexity (OR 2.32 high complexity versus intermediate) were predictive of an accordion grade≥3 complication. Within 90 days of surgery, 55 (9%) patients died. A multivariable model included age (OR 1.76 per 10 year increase in age), ASA score≥3 (OR 3.28), preoperative albumin<3.5 (OR 4.31), and BMI (OR 2.04 for BMI<25 kg/m² versus reference, OR 3.64 for BMI≥40 kg/m² versus reference) was predictive of 90-day mortality.

Study includes all patients who had primary debulking surgery, only a proportion of whom had high complexity surgery.

La Russa M, Liakou CG, Akrivos N et al. (2020) Learning curve for gynecological oncologists in performing upper abdominal surgery. Minerva Ginecologica 72: 325–31

Case series

n=126

Surgical skills in the upper abdomen evolved, demonstrated by an increase in the percentage of patients who had primary surgery, with the surgical team doing more complex procedures, less involvement of other specialties and simultaneously achieving higher rates of complete cytoreduction.

Small study, focusing on the learning curve.

Leandersson P, Granasen G, Borgfeldt C (2017) Ovarian cancer surgery - a population-based registry study. Anticancer Research 37: 1837–45

Cohort study

n=458 (with advanced disease)

Tertiary centres do more extensive surgery compared to regional hospitals without increased frequency of major complications. Tertiary centres show differences among patient selection for primary debulking surgery, as well as achieving no residual tumour.

The main aim was to compare tertiary centres with regional hospitals.

Lepinay K, Szubert S, Lewandowska A et al. (2020) An analysis of long-term outcomes in patients treated by extensive bowel resection due to advanced ovarian cancer relative to the effectiveness of surgery. Gynecologic and Obstetric Investigation 85: 159–66

Cohort study

n=135

Multiple bowel resections seem to improve the overall survival rate of patients when a complete resection of cancerous tissues is achievable. Extensive surgery, including more than 2 segmental bowel resections, should be avoided when complete resection is not feasible.

Small study, focusing on bowel resections.

Liakou CG, Akrivos N, Kumar B et al. (2020) Cholecystectomy as part of cytoreductive surgery for advanced ovarian cancer: perioperative outcomes. Anticancer Research 40: 2331–36

Cohort study

n=144

15% of patients had a cholecystectomy. Patients who had cholecystectomy were more likely to need diaphragmatic peritonectomy, splenectomy, lesser omentectomy, excision of disease from the porta hepatis and liver's capsule (p<0.001). There was no difference in the cytoreductive outcomes (complete or optimal) and the rate of grade 3 to 5 complications between the 2 groups (p=0.10 and p=0.06, respectively). No direct complications related to cholecystectomy were observed.

Small study, focusing on cholecystectomy.

Liberale G, Pop C-F, Polastro L et al. (2020) A radical approach to achieve complete cytoreductive surgery improve survival of patients with advanced ovarian cancer. Journal of Visceral Surgery 157: 79–86

Non-randomised comparative study

n=114

A radical approach in advanced ovarian cancer allows a higher rate of complete cytoreductive surgery impacting overall survival. However, a non-significant trend for increased mild complications rate is observed in this group.

Larger studies are included.

Lim MC, Yoo HJ, Song YJ et al. (2017) Survival outcomes after extensive cytoreductive surgery and selective neoadjuvant chemotherapy according to institutional criteria in bulky stage IIIC and IV epithelial ovarian cancer. Journal of Gynecologic Oncology 28: e48

Case series

n=279

Extensive cytoreductive surgery to minimise residual tumour and selective use of neoadjuvant chemotherapy based on the institutional criteria could result in improved survival outcomes.

Larger studies are included.

Llueca A, Serra A, Climent MT et al. (2021) Postoperative intestinal fistula in primary advanced ovarian cancer surgery. Cancer Management and Research 13: 13–23

Case series

n=107

Gastrointestinal fistula was present in 11% of patients in the study (5 colorectal and 7 small bowel). It was statistically significantly associated with PCI >20, more than 2 visceral resections, and multiple digestive resections. Overall and disease-free survival were also associated with gastrointestinal fistula. Multivariate analysis identified partial bowel obstruction and operative bleeding as independent prognostic factors for survival.

Small study, focusing on a single aspect of the procedure.

Lomnytska M, Karlsson E, Jonsdottir B et al. (2021) Peritoneal cancer index predicts severe complications after ovarian cancer surgery. European Journal of Surgical Oncology 47: 2915–24

Case series

n=256

Peritoneal cancer index of 21 or more was an independent predictor of high-grade complications after ovarian cancer surgery. Increased PCI also impacted overall survival negatively, but high-grade complications did not influence overall survival.

Included patients with any kind of surgery for ovarian cancer.

Mallen A, Todd S, Robertson SE et al. (2021) Impact of age, comorbidity, and treatment characteristics on survival in older women with advanced high grade epithelial ovarian cancer. Gynecologic Oncology 161: 693–99

Case series

n=351

The older cohort had worse Cumulative Illness Rating Scale-Geriatric scores (5.9 versus 4.3, p=0.0001), but no strong associations between comorbidities and treatment characteristics, but less optimal cytoreductive surgery rates (75% versus 87%; p=0.007) with similar surgical complexity and less platinum sensitivity.

Study focused on identifying comorbid conditions and treatment-related factors in older women.

Martinez A, Ngo C, Leblanc E et al. (2016) Surgical complexity impact on survival after complete cytoreductive surgery for advanced ovarian cancer. Annals of Surgical Oncology 23: 2515–21

Case series

n=374

Patients who need complex surgical procedures involving 2 or more visceral resections to achieve successful complete cytoreduction have worse outcome than patients with less extensive procedures. The negative impact of surgical complexity was not significant in patients who had upfront procedures. Tumour volume and extension were associated with decreased disease-free survival in patients who had a primary surgical approach. Even though complete cytoreduction is currently the objective of surgery, tumour load remains an independent poor prognostic factor and probably reflects a more aggressive behaviour.

Larger or more recent studies are included.

Minig L, Patrono MG, Cardenas-Rebollo JM et al. (2016) Use of TachoSil ® to prevent symptomatic lymphocele after an aggressive tumor debulking with lymphadenectomy for advanced stage ovarian cancer. A pilot study. Gynecologic and Obstetric Investigation 81: 497–503

Non-randomised comparative study

n=36

Using TachoSil in women with advanced stage ovarian cancer who had radical debulking with retroperitoneal lymph node dissection was associated with a non-statistically significant reduction in the incidence of symptomatic lymphocele.

Small study, assessing the use of a sponge sealant patch as part of the procedure.

Narasimhulu DM, Bews KA, Hanson KT et al. (2020) Using evidence to direct quality improvement efforts: Defining the highest impact complications after complex cytoreductive surgery for ovarian cancer. Gynecologic Oncology 156: 278–83

Cohort study

n=1,434

Anastomotic leak is the largest contributor to adverse clinical outcomes and increased resource use after complex cytoreductive surgery. Quality improvement efforts to reduce anastomotic leak and its impact should be of highest priority in ovarian cancer surgery.

Study focuses on identifying the complications with most impact.

Nieuwenhuyzen-de Boer GM, van der Kooy J, van Beekhuizen HJ (2019) Effectiveness and safety of the PlasmaJet R Device in advanced stage ovarian carcinoma: a systematic review. Journal of Ovarian Research 12: 71

Systematic review

n=77

(5 studies)

Complete cytoreduction was obtained in 79% of the patients. Apart from 1 pneumothorax after extensive surgery, no harm or additional complications related to the use of the PlasmaJet R Device were reported. Data on disease-free survival or overall survival were not reported. The findings suggest that the device is an efficient and safe innovative surgical device for debulking surgery.

Review only included 5 small studies and was focused on a specific device that has been used for the procedure.

Nieuwenhuyzen-de Boer GM, Gerestein CG, Eijkemans MJC et al. (2016) Nomogram for 30-day morbidity after primary cytoreductive surgery for advanced stage ovarian cancer. European Journal of Gynaecological Oncology 37: 63-8

Case series

n=293

30-day morbidity after primary cytoreductive surgery for advanced stage epithelial ovarian cancer could be predicted by age, haemoglobin, and World Health Organization performance status.

Larger or more recent studies are included.

Nishikimi K, Tate S, Matsuoka A et al. (2020) Aggressive surgery could overcome the extent of initial peritoneal dissemination for advanced ovarian, fallopian tube, and peritoneal carcinoma. Scientific Reports 10: 21307

Case series

n=186

Upper abdominal surgery and bowel resection were done in 149 (80%) and 171 patients (92%), respectively. Residual disease ≤1 cm after surgery was achieved in 164 patients (89%). No residual disease and a high-complexity surgery significantly prolonged progression-free survival (p<0.01 and p=0.02, respectively) and overall survival (p<0.01 and p≤0.01, respectively). The extent of initial peritoneal dissemination did not affect the prognosis when initially disseminated lesions >1 cm were resected.

Larger studies are included.

Nishikimi K, Tate S, Matsuoka A et al. (2020) Learning curve of high-complexity surgery for advanced ovarian cancer. Gynecologic Oncology 156: 54-61

Case series

n=271

Proficiency in performing high-complexity surgery was achieved after approximately 50 cases and this number is greater than the number of cases needed to do moderate-complexity surgery. Acceptable rates of severe perioperative complications were observed even during the initial learning period in cases of high-complexity surgery.

Study focuses on learning curve for high-complexity surgery.

Norell CH, Butler J, Farrell R et al. (2020) Exploring international differences in ovarian cancer treatment: A comparison of clinical practice guidelines and patterns of care. International Journal of Gynecological Cancer 30: 1748–56

Review of guidelines

Findings suggest international variations in ovarian cancer treatment. Characteristics relating to countries with higher stage-specific survival included higher reported rates of primary surgery; willingness to undertake extensive/ultra-radical procedures; greater access to high-cost drugs; and auditing.

Review of clinical practice guidelines.

Norppa N, Staff S, Helminen M et al. (2022) Improved survival after implementation of ultra-radical surgery in advanced epithelial ovarian cancer: Results from a tertiary referral center. Gynecologic Oncology 165: 478–85

Non-randomised comparative study

n=247

Follow up=median 34 months (2013 to 2016) and 27 months 2016 to 2019)

The change of surgical approach towards maximal surgical effort improved both progression free and overall survival. The survival benefit was unquestionable for patients with stage 3 disease but did not reach statistical significance in patients with stage 4 disease.

Overall survival was influenced by residual tumour and Clavien-Dindo complication grade

Studies with more patients or longer follow up are included.

Oseledchyk A, Hunold LE, Mallmann MR et al. (2016) Impact of extended primary surgery on suboptimally operable patients with advanced ovarian cancer. International Journal of Gynecological Cancer 26: 873–83

Cohort study

n=96

Because of the increased morbidity of bowel resections without any evidence for improvement of survival, there should be restraint from further resection of intestines if an optimal debulking seems not feasible after removal of the major tumour bulk.

Small, retrospective study.

Park SJ, Mun J, Lee EJ et al. (2021) Clinical phenotypes of tumors invading the rectosigmoid colon affecting the extent of debulking surgery and survival in advanced ovarian cancer. Frontiers in Oncology 11: 673631

Non-randomised comparative study

n=83

Clinical phenotypes based on tumour separability from the rectosigmoid colon may depend on tumour invasiveness and extensiveness in advanced ovarian cancer. Moreover, these clinical phenotypes may affect surgical outcomes and survival.

Study focuses on effect of clinical phenotypes based on tumour separability from the rectosigmoid colon.

Pinelli C, Morotti M, Casarin J et al. (2020) Interval debulking surgery for advanced ovarian cancer in elderly patients (>=70y): does the age matter? Journal of Investigative Surgery https://doi.org/10.1080/08941939.2020.1733146

Case series

n=153

Older age should not preclude clinicians from offering ultra-radical resection to patients with advanced ovarian cancer after neoadjuvant chemotherapy. In our series, elderly patients had the same treatment with similar outcomes to the younger group.

Small case series, focusing on elderly patients.

Prodromidou A, Pandraklakis A, Iavazzo C (2020) The emerging role of neutral argon plasma (PlasmaJet) in the treatment of advanced stage ovarian cancer: a systematic review. Surgical Innovation 27: 299–306

Systematic review

n=77

(5 studies)

Preliminary data on the use of PlasmaJet for ablation of ovarian cancer implants in the peritoneal cavity showed its safety and presented with promising outcomes in achieving complete cytoreduction.

Review only included 5 small studies and was focused on a specific device that has been used for the procedure.

Rausei S, Uccella S, D'Alessandro V et al. (2019) Aggressive surgery for advanced ovarian cancer performed by a multidisciplinary team: A retrospective analysis on a large series of patients. Surgery Open Science 1: 43–47

Case series

n=156

5-year cancer-related survival rate was 51%: only histotype and residual tumour had a statistically significant association.

The results highlight the importance of a team of gynaecologists and general surgeons with specific interests and skills to achieve cytoreduction as rapidly as possible, even when it implies very complex manoeuvres.

Larger studies are included.

Ren Y, Jiang R, Yin S et al. (2015) Radical surgery versus standard surgery for primary cytoreduction of bulky stage IIIC and IV ovarian cancer: an observational study. BMC Cancer 15: 583

Non-randomised comparative study

n=353

Follow up=median 25 months

Extensive upper abdominal surgery lengthens the progression-free survival and overall survival of ovarian cancer patients with bulky upper abdominal disease.

Studies with more patients or longer follow up are included.

Rodriguez N, Miller A, Richard SD et al. (2013) Upper abdominal procedures in advanced stage ovarian or primary peritoneal carcinoma patients with minimal or no gross residual disease: an analysis of Gynecologic Oncology Group (GOG) 182. Gynecologic Oncology 130: 487–92

Cohort study

n=2,655

Patients who did not need an upper abdominal procedure likely had a limited disease burden and thus, had improved survival compared to patients who had an upper abdominal procedure. In patients with a high disease burden who have minimal residual disease burden, incorporating an upper abdominal procedure without achieving complete resection had minimal survival impact. In this context, aggressive upper abdominal surgery should be reserved for those patients in whom upper abdominal disease can be completely resected with minimal added morbidity.

Another study using the same data, with similar conclusions, is included (Horowitz et al., 2015).

Said SA, van der Aa MA, Veldmate G et al. (2022) Oncologic outcomes after splenectomy during initial cytoreductive surgery in advanced epithelial ovarian cancer: a nationwide population-based cohort study. Acta Obstetricia et Gynecologica Scandinavica 101: 56-67

Cohort study

n=3,911

Although advanced stage epithelial ovarian cancer patients who have splenectomy during cytoreductive surgery have less favourable perioperative outcomes, no adverse impact of splenectomy was seen on survival. Splenectomy during cytoreductive surgery seems to be justified to achieve complete cytoreduction in patients with advanced stage epithelial ovarian cancer.

Study focuses on a single aspect of the procedure (splenectomy).

Sinno AK, Li X, Thompson RE et al. (2017) Trends and factors associated with radical cytoreductive surgery in the United States: A case for centralized care. Gynecologic Oncology 145: 493–99

Cohort study

n=28,677 admissions

The US rate of radical cytoreductive surgery for advanced ovarian cancer is increasing. At high-volume hospitals, patients receive more radical surgery with fewer complications, supporting further study of a centralised ovarian cancer care model.

Study describes the US national trends and factors associated with cytoreductive surgical radicality.

Son J-H, Kong T-W, Paek J et al. (2019) Perioperative outcomes of extensive bowel resection during cytoreductive surgery in patients with advanced ovarian cancer. Journal of Surgical Oncology 119: 1011–15

Case series

n=172

Multiple bowel resections (up to 2 segments) are feasible and can be safely performed with an acceptable complication rate in patients with advanced ovarian cancer.

Small case series, focusing on a single aspect of the procedure (bowel resection).

Szczesny W, Vistad I, Kaern J et al. (2016) Impact of hospital type and treatment on long-term survival among patients with FIGO Stage IIIC epithelial ovarian cancer: follow-up through two recurrences and three treatment lines in search for predictors for survival. European Journal of Gynaecological Oncology 37: 305–11

Cohort study

n=174

Extensive primary surgery at a teaching hospital, platinol sensitivity, age, and performance status were predictors of survival in this cohort.

More recent studies with more patients are included.

Szubert S, Skowyra A, Wojtowicz A et al. (2021) Total colectomy as a part of ultra-radical surgery for ovarian cancer-short- and long-term outcomes. Current Oncology 28: 4223–33

Case series

n=1,636

Total colectomy as a part of ultra-radical surgery for advanced ovarian cancer results in high rates of optimal debulking. However, survival benefits were observed only in patients with no macroscopic disease.

Study focuses on a single aspect of the procedure (total colectomy).

Tate S, Kato Kazuyoshi, Nishikimi K et al. (2017) Survival and safety associated with aggressive surgery for stage III/IV epithelial ovarian cancer: A single institution observation study. Gynecologic Oncology 147: 73-80

Non-randomised comparative study

n=176

Outcomes improved after implementing aggressive surgery for advanced ovarian cancer, without causing a significant increase in mortality.

Small, non-randomised study with historical controls.

Torres D, Kumar A, Wallace SK et al. (2017) Intraperitoneal disease dissemination patterns are associated with residual disease, extent of surgery, and molecular subtypes in advanced ovarian cancer. Gynecologic Oncology 147: 503–8

Cohort study

n=741

Intraperitoneal disease dissemination patterns are associated with residual disease, surgical complexity, and tumour molecular subtypes. Patients with upper abdominal or miliary dissemination patterns are more likely to have mesenchymal high-grade serous ovarian cancer and in turn achieve lower rates of complete resection.

The main was to investigate the association between intraperitoneal disease dissemination patterns, residual disease, surgical complexity, and molecular subtypes.

Tozzi R, Ferrari F, Nieuwstad J et al. (2020) Tozzi classification of diaphragmatic surgery in patients with stage IIIC-IV ovarian cancer based on surgical findings and complexity. Journal of Gynecologic Oncology 31: e14

Cohort study

n=170

Diaphragmatic surgery can be classified in 3 types. Type 1 operations are relatively straightforward. They do not add specific morbidity to the debulking surgery and are usually associated with less complex operations. Type 2 operations are the most common. The findings on the diaphragm are extensive, a full thickness resection is often needed, and liver mobilisation is always needed. Type 3 operations are the most complex procedures and are associated with the highest risk of morbidity. Detailed knowledge of the hepatic vascular anatomy is essential.

The aim of the study was to introduce a systematic classification of diaphragmatic surgery in patients with ovarian cancer based on disease spread and surgical complexity.

Turnbull HL, Akrivos N, Wemyss-Holden S et al. (2017) The impact of ultra-radical surgery in the management of patients with stage IIIC and IV epithelial ovarian, fallopian tube, and peritoneal cancer. Archives of Gynecology and Obstetrics 295: 681–7

Case series

n=135

Follow up not reported

Up to 50% of patients needed at least 1 surgical procedure classified as ultra-radical. Cytoreduction to no macroscopic visible disease (complete) and to disease with greater tumour diameter of less than 1 cm (optimal) was achieved in 54% and 34% of the cases, respectively.

The main aim of the study was to estimate the proportion of patients needing ultra-radical surgery.

van de Vrie R, Rutten MJ, Asseler JD et al. (2019) Laparoscopy for diagnosing resectability of disease in women with advanced ovarian cancer. Cochrane Database Syst Rev. 23: 3(3):CD009786. doi: 10.1002/14651858.CD009786.pub3.

Systematic review

n=1,563

18 studies

The studies suggest that laparoscopy can accurately diagnose the extensiveness of disease. When performed after standard diagnostic work‐up fewer women had unsuccessful debulking surgery and therefore resulting in less morbidity. There will still be women having a laparotomy resulting in residual tumour of > 1 cm after surgery.

Review focuses on the use of laparoscopy to diagnose the extensiveness of ovarian cancer.

Wallace S, Kumar A, Mc Gree M et al. (2017) Efforts at maximal cytoreduction improve survival in ovarian cancer patients, even when complete gross resection is not feasible. Gynecologic Oncology 145: 21–26

Cohort study

n=447

Overall survival was statistically significantly better for patients with no residual disease (p≤0.001). Complete resection improved from 33% to 54% (p<0.001), and residual disease >1cm decreased from 20% to 7% (p<0.001) when comparing the 2003 to 2006 (n=202) with 2007 to 2011 (n=245) cohorts. Surgical complexity increased in the latter period (24% versus 41%). 30-day Accordion grade 3 to 4 morbidity remained consistent (19% versus 21%, p=0.60), 30-day mortality decreased (5% to 1%, p=0.035), and median overall survival improved from 36 to 40 months after cytoreduction standardisation.

Larger or more recent studies are included.

Wong DH, Mardock AL, Manrriquez EN et al. (2021) Trends in extent of surgical cytoreduction for patients with ovarian cancer. PloS one 16: e0260255

Case series

n=79,400

From 2013 to 2017, there was a decrease in the proportion of cases with extended procedures (19% to 15%, p<0.001). There were significant decreases in the proportion of cases with small bowel, colon, and rectosigmoid resections (p<0.001). Patients who had extended cytoreduction were more likely treated at a high surgical volume hospital (37% vs 31%, p<0.001) over the study period. For their hospital admission, patients who had extended cytoreduction had increased mortality (1.6% versus 0.5%, p<0.001) and length of stay (10 days versus 5 days, p<0.001).

With the increased use of neoadjuvant chemotherapy from 30% in 2010 to 39% in 2016, it is likely there is a decreased need for extended procedures during cytoreduction.

Study describes trends in surgical treatment for ovarian cancer in the US.

Xu Y, Jia Y, Zhang Q et al. (2021) Incidence and risk factors for postoperative venous thromboembolism in patients with ovarian cancer: Systematic review and meta-analysis. Gynecologic Oncology 160: 610–8

Systematic review

19 studies

Venous thromboembolism, especially subclinical venous thromboembolism, is a prevalent complication in postoperative patients with epithelial ovarian cancer. History of venous thromboembolism, advanced FIGO stages, high complexity of surgery, obesity, older age, ascites, higher ASA score, smoking history and suboptimal debulking are associated with this increased incidence of postoperative venous thromboembolism among patients with epithelial ovarian cancer.

Review focuses on a single aspect of the procedure (postoperative venous thrombo-embolism)

Ye S, Wang Y, Chen L et al. (2022) The surgical outcomes and perioperative complications of bowel resection as part of debulking surgery of advanced ovarian cancer patients. BMC surgery 22: 81

Case series

n=282

Bowel resection as part of debulking surgery in patients with newly diagnosed ovarian cancer resulted in a severe morbidity rate of 9%.

Study focuses on a single aspect of the procedure (bowel resection).

Ye S, He T, Liang S et al. (2017) Diaphragmatic surgery and related complications in primary cytoreduction for advanced ovarian, tubal, and peritoneal carcinoma. BMC Cancer 17, 317 https://doi.org/10.1186/s12885-017-3311-8

Case series

n=150

Diaphragm peritonectomy and diaphragm full-thickness resection as part of an extensive upper abdominal procedure resulted in an acceptable morbidity rate. Pleural effusion, pneumonia and pneumothorax were the most common pulmonary morbidities. The pleural drainage rate was not high enough to justify prophylactic chest tube placement for all patients. However, patients who had diaphragm full-thickness resection merited special consideration for intraoperative prophylactic drainage.

Small study, focusing on a single aspect of the procedure (diaphragmatic surgery).