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

Cohort study (SOCQER-2)

UK, India and Australia

2015 to 2016

n=247 (113 low surgical complexity score [SCS], 70 intermediate SCS and 64 high SCS)

Patients with late-stage ovarian cancer

mean not reported; 104 (42%) patients were older than 65

Patients with suspected or confirmed epithelial ovarian cancer with radiological spread beyond the pelvis and if primary or delayed debulking surgery was planned. Patients having neoadjuvant chemotherapy could be recruited before chemotherapy or immediately before delayed debulking surgery. Patients who did not have FIGO stage‑3 or 4 epithelial ovarian cancer on histology following surgery, or who did not have debulking surgery as planned, were subsequently excluded.

Primary or delayed debulking surgery. The complexity of surgery varied across centres. Low-, intermediate-and high-SCS procedures were done in 46% (113), 28% (70) and 26% (64) of patients, respectively. Surgical complexity was defined using the validated Aletti SCS: low (score 1 to 3), intermediate (score 4 to 7) or high (score 8+). Pancreatic tail resection, cholecystectomy, resection from lesser sac and porta hepatis disease were not included in the original score and were allocated a score of 5.

2 years

SOCQER2 study in the UK was commissioned and funded by the National Institute for Health and Care excellence. The funder had no role in interpretation of results from the study. The SOCQERoOZ study received a research grant from Australian Society of Gynaecologic Oncologists Inc. The SOCQER2 India study was part funded by the Department of Science Technology, India -UKIERI grant and Jiv Daya Foundation, US.

Authors have received honoraria, grants or fees outside the submitted work from the following companies or organisations: Astra Zeneca, MSD, GSK, Ethicon, Tesaro, Clovis, Roche, Barts Charity, The Eve Appeal. One author reported royalty from Newcastle University (Clovis Oncology) related to the work of development of rucaparib. This is unrelated to the submitted work.

Mean

SD

Mean

SD

Low

3.4

1.8 (n=88)

4.3

2.1 (n=51)

Intermediate

4.0

2.1 (n=55)

5.1

2.2 (n=41)

High

4.3

2.1 (n=51)

5.1

2.2 (n=35)

p

0.048

0.133

Non-randomised comparative study (Surgery in Ovarian Cancer Quality of life Evaluation Research study [SOCQER 1])

UK

2011 to 2014

n=88 (32 benign, 32 cancer standard surgery, 24 cancer extensive surgery)

Patients having primary surgery for suspected ovarian cancer or delayed debulking surgery for biopsy-confirmed diagnosis of ovarian, primary peritoneal, or fallopian tube cancer

median 62 years

All patients referred to a single Gynaecological Cancer Centre having primary surgery for suspected ovarian cancer or delayed debulking surgery for biopsy-confirmed diagnosis of ovarian, primary peritoneal, or fallopian tube cancer were eligible. Patients who had a planned surgical procedure but at laparotomy were deemed unresectable were not included in the analysis.

All patients had surgery with an intention to achieve complete cytoreduction.

Neoadjuvant chemotherapy (NACT) was used as a standard approach in patients with significant ascites and low albumin level to facilitate surgery and to enhance postoperative recovery and in patients with stage 4 disease.

Overall, 20 patients had primary debulking surgery, and 36 patients had platinum-based NACT followed by delayed debulking surgery. Most (88%) of the 56 patients with malignant disease completed 6 cycles of chemotherapy irrespective of aggressiveness of surgical procedure.

Standard surgery was done in patients with less disease burden, ranging from FIGO stages 1 to 4 disease, whereas extensive surgery was only done for advanced-stage ovarian cancer (stage 3 and 4 disease).

Median 8.5 months

None

Global health score

Benign

55.38 (30.01)

73.89 (15.06)

77.63 (15.73)

75.69 (23.15)

70.83 (26.5)

0.26

Cancer standard

58.33 (21.62)

58.33 (20.59)

55.63 (18.7)

60.91 (18.75)

65.1 (20)

Cancer extensive

63.1 (25.63)

63.64 (16.36)

53.89 (14.73)

60.42 (17.96)

63.46 (26.25)

Functional score

Benign

71.04 (23.31)

80.89 (15.01)

86.13 (13.22)

85.72 (26.44)

79.73 (24.57)

0.13

Cancer standard

64.71 (28.5)

68.43 (26.67)

67.63 (23.62)

73.16 (26.05)

73.89 (23.14)

Cancer extensive

67.94 (24.95)

48.24 (20.29)

58.93 (20.56)

62.73 (18.48)

68.49 (23.21)

Symptom score

Benign

25.97 (16.84)

17.53 (11.71)

17.22 (10.73)

16.9 (18.87)

18.67 (15.05)

0.19

Cancer standard

27.74 (20.17)

26.18 (16.46)

28.39 (20.62)

24.96 (17.67)

24.57 (15.89)

Cancer extensive

30.35 (21.61)

31.86 (11.89)

33.06 (15.57)

35.03 (17.02)

26.85 (15.12)

Estimated blood loss, ml

<500

24 (75%)

4 (17%)

500 to 999

5 (16%)

11 (46%)

1,000 to 1,500

3 (9%)

9 (38%)

0.0001

>1,500

0 (0%)

0 (0%)

Intraoperative blood transfusion

0 (0%)

0 (0%)

Postoperative blood transfusion

2 (6%)

5 (21%)

0.048

Major complications (> grade 2 according to the Memorial Sloan Kettering Cancer Center grading system)

Splenic tear

2 (6%)

0 (0%)

Hepatic tear

0 (0%)

2 (8%)

Bladder injury

0 (0%)

1 (4%)

Infectious

3 (9%)

5 (21%)

0.6

Gastrointestinal

0 (0%)

1 (4%)

Cardiopulmonary

0 (0%)

4 (17%)

Thromboembolic

0 (0%)

0 (0%)

Median length of stay (range), days

6 (2 to 22)

9 (6 to 17)

Cohort study

UK

2015 to 2016

n=1,471

Patients with ovarian cancer stage 3, 4 or unknown

110 (8%) age 0 to 49, 620 (42%) age 50 to 69, 463 (32%) age 70 to 79, 278 (19%) age 80 and over

Female patients with ovarian cancer stage 3, 4 or unknown were included.

Tumours with borderline or sex stromal or germ cell morphologies were excluded.

Centres were classified into 3 groups based on their SCS; those practicing mainly low complexity, (5/11 centres with more than 70% low SCS procedures, 759 patients), mainly intermediate (3/11, 35 to 50% low SCS, 356 patients), or mainly high complexity surgery (3/11, more than 35% high SCS, 356 patients). Rates of patients who had surgery were 43% in the mainly low SCS group, 58% in the intermediate group and 61% in the mainly high SCS group (p<0.001).

Treatment of ovarian cancer was defined as the delivery of systemic anti-cancer therapy ('chemotherapy') or major surgical resection ('surgery') during the primary (first) course of treatment, defined as the 9 months following diagnosis.

24 months

The study received funding from NICE.

The authors declared no conflict of interest.

Chemotherapy only

214 (28.2)

54 (15.2)

83 (23.3)

Surgical resection only

25 (3.3)

20 (5.6)

41 (11.5)

Surgical resection and chemotherapy

303 (39.9)

188 (52.8)

139 (39.0)

Total

759

356

356

% in each surgical centre grouping

51.6%

24.2%

24.2%

Cohort study

Sweden

2008 to 2016

n=3,728 (1,746 before and 1,982 after national guidelines were published)

Women with primary stage 3C or 4 cancer of the ovary, fallopian tube, peritoneum or undesignated primary site

Mean 67.4 years (range 20 to 100)

The study included all women aged 18 or over, registered in the Swedish Quality Registry for Gynecologic Cancer 2008 to 2011 or 2013 to 2016 for primary stage 3C or 4 cancer of the ovary, fallopian tube, peritoneum or undesignated primary site. The year 2012 was excluded because the speed of implementation of the national guidelines varied across the country.

Patients who did not have surgery were also included.

Patients had primary (n=1,803) or interval (n=723) debulking surgery.

The guidelines recommended primary debulking surgery (to R0 if achievable) followed by standard chemotherapy. Recommended standard chemotherapy consisted of combination therapy, carboplatin and paclitaxel every 3 weeks for 6 cycles. Recommendations for neoadjuvant chemotherapy included standard chemotherapy for 2 to 3 cycles before interval debulking surgery, followed by an additional 3 to 4 cycles. In June 2015 bevacizumab was recommended to high risk groups. More complex surgical procedures were done after the implementation of the guidelines.

Mean 33 months (range 0 to 135 months)

None

Peritoneal Diaphragmal resection

38 (3.9%)

242 (29.0%)

<0.001

10 (3.0%)

58 (14.9%)

<0.001

Intestinal resections

56 (5.8%)

272 (32.6%)

<0.001

18 (5.4%)

71 (18.3%)

<0.001

Splenectomy

15 (1.5%)

117 (14.0%)

<0.001

6 (1.8%)

37 (9.5%)

<0.001

Pelvic Lymph Node Dissection

21 (2.2%)

93 (11.1%)

<0.001

4 (1.2%)

9 (2.3%)

0.40

Paraaortal Lymph Node Dissection

22 (2.3%)

89 (10.7%)

<0.001

6 (1.8%)

7 (1.8%)

1.0

Postoperative residual tumour

<0.001

<0.001

0 mm

224 (28.9%)

430 (53.3%)

105 (36.8%)

177 (50.1%)

1 mm to 10 mm

216 (27.9%)

149 (18.5%)

61 (21.4%)

74 (21.0%)

>10 mm

296 (38.2%)

207 (25.7%)

86 (30.2%)

90 (25.5%)

Not evaluable

38 (4.9%)

21 (2.6%)

33 (11.6%)

12 (3.4%)

Missing

194

28

49

36

Cohort study

Sweden

2009 to 2011 (cohort 1) and 2014 to 2016 (cohort 2)

n=752 (364 in cohort 1 and 388 in cohort 2 [after paradigm shift to upfront and aggressive ultra-radical surgery])

Women with advanced epithelial ovarian cancer

mean not reported

Patients with FIGO stages 3 and 4 epithelial ovarian/fallopian tube/peritoneal cancer and cancer in the abdomen of unknown origin (epithelial ovarian cancer without a biopsy specifically from the adnexa).

Exclusion criteria in cohort 2: Eastern Cooperative Oncology Group above 2, aged over 80, involvement of tumour in the root of the mesentery (with risk of resection of the superior mesenteric artery and/or vein), involvement of tumour in the pancreas, in more than just the pancreatic tail, tumour involvement of the superior mesenteric artery, coeliac trunk, portal vein, duodenum and the hepatoduodenal ligament (superficial carcinomatosis excluded), involvement of tumour in the lesser omentum with need of resection of left gastric artery (leading to gastrectomy if also splenectomy is performed), disseminated carcinomatosis in the small bowel with need of resection leading to short bowel syndrome, multiple lung metastases bigger than 1 cm, multiple liver metastasis or metastases in both liver lobes, non-resectable extra-abdominal lymph nodes, patient does not accept blood transfusion, patient does not accept stoma formation, massive comorbidity where the surgeon decides the patient inoperable or the anaesthetist decides the patient not eligible for general anaesthesia, serum albumin less than 20 g/l.

In the first cohort, surgery was done by gynaecologic oncologists, gynaecologists without training in surgical gynaecologic oncology and, in selected cases, by colorectal surgeons. There was no structured surgical management, no uniform preoperative work-up or structured postoperative management. In the second cohort, the aim was that all surgery was done independently by surgical gynaecologic oncologists. If achieving residual disease of less than 1 cm was deemed impossible at time of surgery in FIGO stage 3, surgery was discontinued except for histological verification of disease including ovarian biopsy. For FIGO stage 4, surgery was discontinued if complete resection was deemed impossible.

The median SCS increased in cohort 2 from 3 to 7 (p=0.001), and the proportion of ultra-radical procedures increased.

Median 29 months (cohort 1) and 27 months (cohort 2)

None

Cohort study (retrospective analysis of chemotherapy trials)

US

Not reported

n=2,655 (low surgical complexity score=456, moderate=1,770 and high=429)

Patients with advanced epithelial ovarian cancer or primary peritoneal cancer who had primary cytoreductive surgery to achieve complete surgical resection or less than 1 cm of residual disease

Mean or median not reported

Inclusion criteria: patients with FIGO stage 3 or 4 histologically confirmed epithelial ovarian cancer or primary peritoneal cancer who were enrolled onto the Gynecologic Oncology Group 182 study.

All patients had primary cytoreductive surgery before being randomly assigned to 1 of 5 platinum and paclitaxel–based chemotherapy regimens. Surgical complexity was based on a complexity score, calculated using a published scoring system. Each procedure was assigned a weighted score ranging from 1 to 3, and the composite surgical complement was calculated by summing the weights for each patient. Patients were classified into 3 groups: SCS low (score 1 to 3), SCS moderate (score 4 to 7), or SCS high (score 8 or above).

Not reported

None

Cohort study

US

2001 to 2013

n=978 (Group 1: 2001 to 2005, n=315; group 2: 2006 to 2009, n=320; group 3: 2010 to 2013, n=343)

Patients with advanced ovarian cancer who had primary debulking surgery

Median 61 years (range 19 to 95 years)

All patients with FIGO 2009 stage 3b to 4 ovarian, fallopian tube or primary peritoneal carcinoma, who had primary debulking surgery at a single centre with the intent of maximal cytoreduction between 1/1/2001 and 31/12/2013. Patients who had exploratory laparotomy for anticipated debulking but who were ultimately declared unresectable due to extensive disease burden, were still included in the analysis. The study was restricted to high-grade epithelial histologies. Those who had neoadjuvant chemotherapy or presented for management of recurrent disease were excluded.

In 2001, extensive upper abdominal procedures started to be incorporated into the debulking armamentarium. In 2006, the goal for primary debulking surgery evolved from residual disease 10 mm or less to either complete gross resection or as minimal residual tumour as possible. During 2010 to 2013, 3 additional changes were gradually adopted: routine performance of cardiophrenic lymph node resection, use of specific selection criteria for neoadjuvant chemotherapy, and implementation of earlier operative start times.

Almost all patients had postoperative primary platinum/taxane-based chemotherapy (n=949, 99%). Intraperitoneal chemotherapy was administered in 34% (n=322) of patients.

Median 77.7 months (range 1.3 to 198 months)

Outside the submitted work, 1 author is on the Medical Advisory Boards of Bovie Medical Co. and Verthermia Inc. The other authors have no conflict of interest.

Complete gross resection

26.5 (24 to 29.1)

25.3% (21 to 29.7%)

1

<0.001

Minimal residual

16.5 (14.9 to 18.2)

12.9% (9.7 to 16.5%)

1.66 (1.42 to 1.94)

Suboptimal

12.6 (11.2 to 14.2)

7.3% (4.2 to 11.5%)

2.61 (2.17 to 3.14)

Complete gross resection

79.1 (68.7 to 87.1)

59.3% (54.1 to 64%)

1

<0.001

Minimal residual

52.5 (48.8 to 58.4)

42.8% (37.6% to 47.8%)

1.68 (1.41 to 2)

Suboptimal

36.6 (32.1 to 40.2)

27.4% (21.2% to 33.9%)

2.58 (2.11 to 3.17)

Cohort study

France and Spain

2008 to 2015

n=549

Patients who had primary, interval or closure debulking surgery with either complete cytoreduction or cytoreduction to minimal residual disease for Stage 3c to 4 epithelial ovarian, fallopian, or primary peritoneal cancer

Median 61 years (range 21 to 88 years)

Exclusion criteria: patients with unresectable disease, with residual disease 2.5 mm or more and patients with non-epithelial subtype histology or borderline tumours.

All surgical procedures were done or supervised by experienced oncological surgeons. The surgical goal was to achieve absence of residual disease, evaluated with the completeness of cytoreduction score. Hysterectomy and bilateral salpingooophorectomy, infragastric omentectomy and pelvic plus paraaortic lymphadenectomy were systematically done during debulking surgery.

Median 65 months

None

Age at diagnosis

≤60 years

1.00

>60 years

1.07

0.89 to 1.29

0.445

Surgical timing

Primary

1.00

1.00

Early interval

1.51

1.21 to 1.89

<0.001

1.53

1.22 to 1.92

<0.001

Delayed

1.43

1.12 to 1.83

1.65

1.27 to 2.15

<0.001

FIGO stage

3c

1.00

1.00

4

1.27

1.01 to 1.60

0.044

1.18

0.93 to 1.50

0.185

PCI

≤10

1.00

1.00

>10

1.52

1.26 to 1.83

<0.001

1.40

1.11 to 1.75

0.004

Aletti score

<8

1.00

1.00

≥8

1.35

1.12 to 1.62

0.002

1.23

0.98 to 1.53

0.071

Completeness of cytoreduction

0 (no residual tumour)

1.00

1.00

1 (residual <2.5 mm)

1.56

1.19 to 2.04

0.001

1.49

1.13 to 1.95

0.004

Postoperative complications

Less than Grade 3

1.00

1.00

Grade 3 or higher

1.32

1.06 to 1.64

0.012

1.35

1.07 to 1.69

0.010

HR

95% CI

p value

HR

95% CI

p value

Age at diagnosis

≤60 years

1.00

>60 years

1.20

0.95 to 1.51

0.125

Surgical timing

Primary

1.00

1.00

Early interval

1.60

1.19 to 2.14

<0.001

1.65

1.23 to 2.23

0.001

Delayed

1.73

1.27 to 2.35

2.04

1.47 to 2.81

<0.001

FIGO stage

3c

1.00

4

1.01

0.75 to 1.37

0.953

PCI

≤10

1.00

1.00

>10

1.43

1.13 to 1.80

0.002

1.34

1.02 to 1.77

0.038

Aletti score

<8

1.00

1.00

≥8

1.33

1.05 to 1.67

0.017

1.25

0.96 to 1.63

0.103

Completeness of cytoreduction

0 (no residual tumour)

1.00

1.00

1 (residual <2.5 mm)

1.49

1.08 to 2.04

0.013

1.34

0.97 to 1.86

0.078

Postoperative complications

Less than Grade 3

1.00

1.00

Grade 3 or higher

1.25

0.95 to 1.64

0.112

1.31

0.99 to 1.74

0.056

Surgical timing, n (%)

0.007

Primary

175 (31.9)

125 (29.3)

50 (40.7)

Early interval

224 (40.8)

172 (40.4)

52 (42.3)

Delayed

150 (27.3)

129 (30.3)

21 (17.1)

PCI, n (%)

0.003

10 or lower

287 (52.9)

237 (56.3)

50 (41.0)

Above 10

256 (47.1)

184 (43.7)

72 (59.0)

Surgical procedure, n (%)

Hysterectomy

491 (89.4)

378 (88.7)

113 (91.9)

0.319

Salpingoophorectomy

502 (91.4)

385 (90.4)

117 (95.1)

0.098

Pelvic lymphadenectomy

495 (90.2)

383 (89.9)

112 (91.1)

0.706

Aortic lymphadenectomy

488 (88.9)

380 (89.2)

108 (87.8)

0.664

Infragastric omentectomy

540 (98.4)

419 (98.4)

121 (98.4)

1.000

Small bowel resection

44 (8.0)

28 (6.6)

16 (13.0)

0.021

Large bowel resection

225 (41.0)

157 (36.9)

68 (55.3)

<0.001

If large bowel resection, rectosigmoid resection (n=225)

204 (90.7)

139 (88.5)

65 (95.6)

0.095

Multiple bowel resection

48 (8.7)

29 (6.8)

19 (15.4)

0.003

Diaphragmatic stripping

330 (60.1)

246 (57.7)

84 (68.3)

0.035

Right diaphragmatic stripping

327 (59.6)

243 (57.0)

84 (68.3)

0.025

Left diaphragmatic stripping

163 (29.7)

112 (26.3)

51 (41.5)

0.001

If diaphragm stripping, diaphragm resection (n=330)

72 (21.8)

53 (21.5)

19 (22.6)

0.837

Atypical hepatic resection

15 (2.7)

11 (2.6)

4 (3.3)

0.753

Cholecystectomy

45 (8.2)

27 (6.3)

18 (14.6)

0.003

Celiac lymph node resection

65 (11.8)

48 (11.3)

17 (13.8)

0.440

Splenectomy

127 (23.1)

80 (18.8)

47 (38.2)

<0.001

Distal pancreatectomy

31 (5.6)

18 (4.2)

13 (10.6)

0.007

Partial gastrectomy

11 (2.0)

9 (2.1)

2 (1.6)

1.000

Extensive peritonectomy

256 (46.6)

177 (41.5)

79 (64.2)

<0.001

Glissonectomy

46 (9.8)

30 (8.4)

16 (14.3)

0.069

Mesentery or bowel vaporisation

125 (22.8)

91 (21.4)

34 (27.6)

0.143

Partial abdominal wall resection

100 (18.2)

79 (18.5)

21 (17.1)

0.710

Partial cystectomy/ureteral resection

8 (1.5)

7 (1.6)

1 (0.8)

0.691

Cardiophrenic lymph node resection

10 (1.8)

9 (2.1)

1 (0.8)

0.470

Inguinal lymph node resection

13 (2.4)

6 (1.4)

7 (5.7)

0.012

Axillary lymph node resection

2 (0.4)

2 (0.5)

0 (0)

1.000

Completeness of cytoreduction score

0.701

0 (no residual tumour)

481 (87.6)

372 (87.3)

109 (88.6)

1 (residual disease less than 2.5 mm)

68 (12.4)

54 (12.7)

14 (11.4)

Aletti score (SCS), n (%)

<0.001

Lower than 8

300 (54.6)

252 (59.2)

48 (39.0)

8 or above

249 (45.4)

174 (40.8)

75 (61.0)

Surgical timing

0.434

Primary

1.00

Early interval

0.82

0.51 to 1.34

Delayed

0.46

0.25 to 0.84

0.011

PCI 10 or lower

1.00

PCI above 10

0.77

0.43 to 1.38

0.380

Aletti score

Lower than 8

1.00

8 or above

0.93

0.42 to 2.07

0.863

Small bowel resection

No

1.00

Yes

1.44

0.60 to 3.47

0.415

Large bowel resection

No

1.00

Yes

1.57

0.78 to 3.18

0.205

Multiple bowel resection

No

1.00

Yes

1.15

0.48 to 2.77

0.754

Diaphragmatic stripping

No

1.00

Yes

0.52

0.25 to 1.06

0.072

Cholecystectomy

No

1.00

Yes

1.21

0.58 to 2.51

0.614

Splenectomy

No

1.00

Yes

1.80

0.98 to 3.28

0.057

Distal pancreatectomy

No

1.00

Yes

1.66

0.70 to 3.96

0.251

Extensive peritonectomy

No

1.00

Yes

2.98

1.45 to 6.15

0.003

Cohort study

UK

2007 to 2017

n=608 (453 [74.5%] standard surgery and 155 [25.5%] ultra-radical surgery according to the NICE classification described below.

Patients with stage 3 or 4 advanced ovarian cancer who had cytoreductive surgery

Median 64.5 years (IQR 56.7 to 72.7)

Patients were included if they were referred from a local primary care provider to the Pan-Birmingham Gynaecological Cancer Centre, had a midline laparotomy, and had a final histological diagnosis of stage 3 or 4 epithelial ovarian, tubal, or peritoneal cancer. Quaternary referrals from outside the region were excluded from this analysis.

Patients either had primary debulking surgery or they had 3 or 4 cycles of carboplatin-based neoadjuvant chemotherapy, with an intention to consider interval debulking surgery or palliation. Typically, surgical procedures included pelvic clearance, omentectomy, and lymphadenectomy. More extensive surgery was introduced in 2008. In appropriately selected patients, gastrointestinal surgery or radical upper abdominal procedures were done if required. Extensive stripping of the para-aortic lymph nodes was not done routinely but enlarged para-aortic lymph nodes were resected.

209 (34%) patients had primary debulking surgery and 399 (66%) had interval debulking surgery. When classified using the SCS, 400 (65.8%) patients had surgery of low complexity, 140 (23.0%) patients had surgery of intermediate complexity, and 68 (11.2%) patients had surgery of high complexity.)

Not reported

There was no funding. 1 author has received fees for lecturing for Astra Zeneca and Roche, and 1 has received personal fees from Astra Zeneca and Roche.

Grade 3 - total

12

13

25

Chest drain insertion with or without bronchoscopy

1

4

5

Return to theatre (haematoma/bleeding)

2

2

4

Return to theatre (collection)

2

2

4

Image-guided drainage (collection)

0

3

3

Return to theatre (no pathology found)

2

1

3

Return to theatre (revision of stoma)

2

0

2

oesophago-gastroduodenoscopy (bleeding)

1

0

1

Return to theatre (closure of laparostomy) and oesophago-gastroduodenoscopy (bleeding)

0

1

1

Return to theatre (removal of packs)

1

0

1

Return to theatre (wound dehiscence)

1

0

1

Grade 4 - total

2

10

12

Return to theatre (anastomotic leak)

2

2

4

Return to theatre (splenectomy, liver failure, renal failure, pancreatitis)

0

1

1

Cardiac pacing after sinus arrest

0

1

1

Intraoperative splenectomy for iatrogenic bleeding

0

1

1

Return to theatre (anastomotic leak) plus sheath dehiscence

0

1

1

Return to theatre (gastric perforation) subsequent enterocutaneous fistula and tracheostomy

0

1

1

Return to theatre spinal surgery for paraspinal infection

0

1

1

Renal failure

0

1

1

Urinary tract fistula

0

1

1

Grade 5 - total

4

2

6

Renal failure

1

0

1

Bowel ischaemia secondary to mesenteric thrombosis

1

0

1

Intra-abdominal sepsis

1

0

1

Pulmonary embolus

0

1

1

Pancreatitis and acute respiratory distress syndrome

0

1

1

Pneumonia, acute respiratory distress syndrome, and renal failure

1

0

1

NICE

Standard

453

18 (4.1)

41.9

1.00

Ultra-radical

155

25 (15.1)

58.1

4.65

2.26 to 8.79

POMEL

Standard

380

8 (2.1)

18.6

0.55

0.24 to 1.25

Radical

61

8 (13.1)

18.6

3.41

1.54 to 7.56

Supra-radical

167

27 (16.2)

62.8

4.20

2.35 to 7.51

Gastrointestinal tract

No gastrointestinal surgery

436

12 (2.8)

27.9

0.72

0.35 to 1.48

Gastrointestinal surgery

172

31 (18.0)

72.1

4.69

2.66 to 8.24

Multiple bowel resections

0 or 1 bowel resections

571

32 (5.6)

74.4

1.46

0.82 to 2.59

2 or more bowel resections

37

11 (29.7)

25.6

7.73

3.92 to 15.26

Diaphragmatic surgery and colorectal anastomosis

No diaphragmatic stripping or gastrointestinal anastomosis

452

16 (3.5)

37.2

0.92

0.47 to 1.80

Diaphragmatic stripping/resection

43

5 (11.6)

11.6

3.02

1.17 to 7.79

Gastrointestinal anastomosis

71

13 (18.3)

30.2

4.76

2.42 to 9.37

Diaphragmatic stripping and gastrointestinal anastomosis

42

9 (21.4)

20.9

5.57

2.65 to 11.72

Aletti

Low surgical complexity

400

12 (3.0)

27.9

0.78

0.38 to 1.61

Intermediate surgical complexity

140

15 (10.7)

34.9

2.79

1.43 to 5.43

High surgical complexity

68

16 (23.5)

37.2

6.12

3.25 to 11.52

Cohort study

Sweden

2013 to 2017

n=384

Women with FIGO stage 3 to 4 ovarian cancer

Median 66 years (range 20 to 89 years)

All women aged 18 years or over registered in the Swedish Quality Register for Gynecological Cancer and diagnosed with ovarian, fallopian tube or primary peritoneal cancer, FIGO stage 3 or 4 who had primary or interval debulking surgery were included in the study.

Exclusion criteria: primary or interval debulking surgery considered to be emergency surgery or surgery intended for diagnosis only when reviewed.

Patients had primary (79%) or interval (21%) debulking surgery. The degree of surgery was categorised according to Aletti and grouped into low (0 to 3; 47%), intermediate (4 to 7; 37%) and high (8 and above; 16%) SCS.

In the total cohort of 384 women, 121 (32%) had an upper abdominal procedure.

Most women in the primary debulking surgery group had adjuvant chemotherapy with carboplatin AUC 5 and paclitaxel 175 mg/m² intravenously every third week for 6 cycles, with the aim to start chemotherapy within 21 days of surgery. The treatment was evaluated at cycles 3 and 6. Women who had neoadjuvant chemotherapy had interval debulking surgery after 3 to 4 cycles of chemotherapy. Treatment was planned according to the Swedish national guidelines. Bevacizumab was implemented in 2013 for women with residual disease and for high-risk patients.

Not reported

None

0

272 (70.8)

1 to 2

70 (18.2)

3a

22 (5.7)

3b

14 (3.6)

4a

3 (0.8)

4b

2 (0.5)

5

1 (0.3)

Clavien-Dindo 3a

22 (5.7)

Pleural fluid, drainage

16 (4.2)

Hydronephrosis, nephrostomy

2 (0.5)

Wound resutured

1 (0.3)

Wound seroma, drainage

1 (0.3)

Wound infection, cleansed

2 (0.5)

Clavien-Dindo 3b

14 (3.6)

Intra-abdominal bleeding, surgical intervention

2 (0.5)

Intra-abdominal abscess, drainage

1 (0.3)

Vaginal vault abscess, drainage

2 (0.5)

Wound hematoma, resutured

1 (0.3)

Wound dehiscence, resutured

2 (0.5)

Intra-abdominal abscess, surgical intervention

1 (0.3)

Stoma necrosis, surgical intervention

1 (0.3)

Urinary tract injury, surgical intervention

1 (0.3)

Intraabdominal abscess and bleeding, surgical intervention

1 (0.3)

Suspected anastomosis leakage, surgical intervention

1 (0.3)

Anastomosis leakage, surgical intervention

1 (0.3)

Clavien-Dindo 4a

3 (0.8)

Bleeding diaphragm, surgical intervention, intensive care

1 (0.3)

Pulmonary failure, intensive care

2 (0.5)

Clavien-Dindo 4b

2 (0.5)

Anastomosis leakage, surgical intervention, intensive care

1 (0.3)

Sepsis, multiple organ failure, intensive care

1 (0.3)

Clavien-Dindo 5

1 (0.3)

Sepsis, multiple organ failure, cardiac arrest

1 (0.3)

Preoperative albumin level (g/L)

Less than 30

1.0

1.0

30 or above

0.93 (0.88 to 0.98)

0.012

0.96 (0.90 to 1.02)

0.180

Primary surgery

Interval debulking surgery

1.0

1.0

Primary debulking surgery

3.78 (1.32 to 15.92)

0.030

4.70 (0.88 to 86.99)

0.143

Complete cytoreduction

No

1.0

1.0

Yes

0.49 (0.24 to 0.94)

0.036

0.47 (0.20 to 1.04)

0.068

SCS

Low (0 to 3)

1.0

1.0

Intermediate (4 to 7)

2.54 (1.19 to 5.67)

0.018

2.62 (1.05 to 7.21)

0.047

High (8 or above)

3.25 (1.32 to 8.02)

0.010

4.11 (1.39 to 12.94)

0.012

Systematic review

Studies were in Europe, US, Asia, and Africa

Search date: May 2015

n=18,579 (46 studies)

Patients who had primary cytoreductive surgery for ovarian cancer

Mean weighted median 65.9 years (range 52 to 74)

Studies with at least 30 patients that reported 30-day mortality after primary cytoreductive surgery for ovarian/tubal/peritoneal cancer were included. Studies that used neoadjuvant chemotherapy were excluded. If a study reported data on neoadjuvant chemotherapy versus primary cytoreductive surgery, only data on primary surgery was considered.

A quality score was used to assess the studies, based on type of study (prospective=2, retrospective or population=1), total number of patients per study (less than 50=1; 50 to 100=2; more than 100=3), volume of the centre (number of patients per year of study: less than 10=1; 10 to 20=2; more than 20=3). All studies with quality score of less than 4 were excluded.

Primary cytoreductive surgery.

Postoperative period (for most studies, this was 28 or 30 days). Not reported in 10 studies.

None for authors of review.

Infection

35

30.4

Sepsis

26

22.6

Surgical site infection

9

7.8

Hematologic/vascular

31

27

Pulmonary embolus

11

9.6

Deep vein thrombosis

6

5.2

Ictus

3

2.6

Haemorrhage

11

9.6

Organ failure

25

21.7

Respiratory failure

17

14.8

Renal failure

1

0.9

Liver failure

1

0.9

Multiorgan failure

6

5.2

Cardiovascular

10

8.7

Myocardial infarction

6

5.2

Congestive heart failure

4

3.5

Gastrointestinal

3

2.6

Anastomotic leak

2

1.7

Occlusion

1

0.9

Tumour progression

11

9.6

Median age (years)

65.9

65.8 to 66.0

1.109

1.1 to 1.2

0.021

10.9

<0.001

13

American Society of Anesthesiologists >3

48.2

47.8 to 48.6

1.004

1.0 to 1.0

0.018

0.4

0.829

78

FIGO stage 4 ratio

25.7

25.4 to 26.0

1.017

1.0 to 1.0

0.004

1.7

<0.001

6.5

No. of surgical procedures

3.3

3.3 to 3.4

0.832

0.7 to 1.0

0.087

-16.8

0.078

47.8

Surgical complexity

3.8

3.7 to 3.9

0.889

0.7 to 1.0

0.079

-11.1

0.186

47.8

Highest procedure complexity

2.5

2.4 to 2.6

0.847

0.7 to 1.0

0.077

-15.3

0.067

47.8

Overall complication rate

23.8

23.6 to 24.0

1.013

1.0 to 1.0

0.010

1.3

0.190

34.8

Severe complication rate

9.5

9.3 to 9.7

1.057

0.0 to 11.1

0.016

5.7

<0.001

76.0

55

1.2

0.27

0.70 to 1.75

6.8

2.8

1.37 to 12.47

60

1.9

0.32

1.24 to 2.49

10.4

3.8

3.18 to 17.90

65

2.8

0.42

2.02 to 3.66

15.9

5.0

6.18 to 25.93

70

4.3

0.71

2.93 to 5.72

24.3

7.0

10.68 to 38.21

75

6.6

1.39

3.86 to 9.31

37.3

10.5

16.73 to 57.74

Systematic review (Cochrane)

Studies were in: US, France, Republic of Korea

Search date: November 2021

n=924 (3 studies)

Women with stage 3 or 4 epithelial ovarian cancer, who had ultra-radical surgery as part of upfront primary debulking surgery or interval debulking surgery

Median age at diagnosis ranged from 54 to 64 years (ages across studies ranged from 24 to 90 years).

Women diagnosed with stage 3 or 4 epithelial ovarian cancer, having ultra-radical surgery as part of upfront primary debulking surgery or interval debulking surgery (surgery halfway through the course of chemotherapy) were included.

Women with other concurrent malignancies or recurrent disease were excluded.

All 3 studies compared ultra-radical or extensive surgery with standard surgery. The 2 most recent studies also included some elements of extensive surgery in the standard surgery group: segmental small bowel resection, and rectosigmoid resection and appendectomy.

Median follow up ranged from 32 to 49 months

None for authors of systematic review

Case series

US

Not reported

n=4

Patients with diaphragmatic hernia after debulking surgery for advanced ovarian cancer

Mean 46.8 years

Not applicable

All patients had debulking surgery, which included left diaphragm peritonectomy and splenectomy. Of the 4 patients, 2 had primary debulking surgery and 2 had interval debulking surgery.

The hernias were diagnosed at 5, 6, 8 and 18 months after surgery.

None