Guideline 75: Epithelial ovarian cancer

Epithelial ovarian cancer
Section 4: Surgical management

4.1 Preparation for surgery

4.1.1 BOWEL PREPARATION

Only a minority of ovarian cancer patients require bowel resection at the time of either primary surgery or surgery for recurrent disease. One retrospective review showed incidences of colonic surgery in ovarian cancer patients of 14% and 34% for primary and secondary surgery respectively.⁵⁶ A second retrospective cohort study confirmed the significantly lower incidence of infectious complications in those patients receiving preoperative bowel preparation.⁵⁷ Preoperative bowel preparation for patients undergoing colorectal surgery is described in the SIGN Guideline for Colorectal Cancer.⁵⁸ Evidence level 2+

Preoperative bowel preparation in ovarian cancer patients should be undertaken where clinical findings and imaging reveal that advanced disease with bowel involvement is present.

4.1.2 STOMA COUNSELLING AND MARKING

A poorly sited stoma due to missing or inadequate preoperative marking can lead to an awkwardly fitting appliance, with subsequent leakage, painful excoriated skin and failure of the appliance to remain secure. This contributes to poor physical and psychological rehabilitation in the postoperative period. Preoperative patient counselling and potential stoma site marking by a trained stoma nurse reduce the incidence of postoperative stoma complications.^{58,
59, 60} Evidence level 2++

Patients for whom preoperative bowel preparation is indicated should see a trained stoma nurse for counselling and potential stoma site marking.

4.1.3 VENOUS THROMBOEMBOLIC PROPHYLAXIS (VTE)

Ovarian cancer patients are at significant risk of developing VTE.⁶¹ Perioperative VTE prophylaxis reduces this risk.⁶¹ Unfractionated heparin (UFH)⁶² or low molecular weight heparins (LMWH)⁶³ can be used. VTE prophylaxis is described in a previous SIGN Guideline.⁶¹ Evidence level 1+,4

4.1.4 CA125 ESTIMATION

Preoperative serum CA125 levels can be used to predict disease bulk, and may be of benefit in identifying patients in whom optimal cytoreductive surgery is feasible.^{64,
65} CA125 levels are higher in serous rather than mucinous tumours, as well as in postmenopausal compared to premenopausal patients.⁶⁶ The sensitivity and specificity of CA125 in predicting the possibility of cytoreductive surgery range from 62 to 78% and 73 to 83% respectively.^{64,
65} It is not possible to determine if a particular preoperative CA125 level can be used to predict whether optimal cytoreduction is possible. CA125 may be elevated in women who have had a recent laparotomy (see section 3.1.2). Evidence level 3,1-

Serum CA125 levels are useful in predicting disease bulk and should be assayed preoperatively in women with pelvic masses.

4.1.5 OTHER TUMOUR MARKERS

Carcinoembryonic antigen (CEA) is a tumour marker found in the blood of patients suffering from colorectal cancer. There is no correlation between the CEA level and the FIGO stage of ovarian carcinoma.⁶⁷ Evidence level 3

Measurement of a fetoprotein (AFP) and human chorionic gonadotropin (hCG) in younger women can help exclude non-epithelial ovarian tumours.⁴⁷ Evidence level 4

Routine preoperative CEA estimation should not be performed in patients with ovarian cancer.

4.1.6 ANTIBIOTIC PROPHYLAXIS

The SIGN Guideline on Antibiotic Prophylaxis in Surgery describes the benefits, principles and administration procedures of antibiotic prophylaxis in surgery.⁶⁸

4.2 Pathology

Pathological examination of ovarian and other tissues defines the nature of the tumour and its stage. Staging is performed by examining histological sections of tissue samples and cytological assessment of fluid samples. It is important to adequately sample the ovary using a minimum of a block of tissue for each centimetre of the maximum diameter of the tumour.

4.2.1 INTRAOPERATIVE TECHNIQUES

Epithelial ovarian tumours display a spectrum of pathological changes. Tumours can be benign, borderline (low malignant potential or atypical proliferating lesions), or malignant (see Annex 2). Intraoperative frozen section can be used to confirm the presence of malignant disease but cannot precisely confirm borderline disease.^{69,
70, 71} It is important that surgeons are aware of the limitations of this technique. There is no evidence that intraoperative frozen section can define the grade of the cancer. Evidence level 2+

The clinical situations where the intraoperative, pathological assessment of an ovarian lesion is helpful are:

to confirm malignancy where clinical assessment reveals a complex ovarian cyst with no apparent metastatic disease
to exclude the presence of metastatic disease where suspicious looking extra ovarian lesions are present if fertility conserving surgery is planned for patients with malignant disease confined to an ovary.

To minimise the need for a second operative staging procedure, intraoperative frozen section assessment can be used to diagnose malignancy and to exclude metastatic disease.

4.3 Management of early disease

Early disease refers to disease confined to the ovaries (see Annex 1). There are two clinical scenarios where early disease could be encountered:

the first is where the gynaecologist is alerted to the possibility of malignancy being present prior to the laparotomy
the second is where the gynaecologist had no suspicion of cancer being present prior to surgery.

To minimise the risk of the gynaecologist encountering the second scenario, use should be made of the RMI scoring system if an isolated pelvic mass is discovered on preoperative imaging (see section 3.2.1). In young women the possibility of a non-epithelial ovarian tumour being present should also be considered (see section 4.1.5).

The surgical dilemma in early disease is how comprehensively to stage a case and in particular whether to assess retroperitoneal nodes and take random peritoneal biopsies. The presence of positive retroperitoneal nodes or peritoneal implants upstages the case to stage III (see Annex 1).

Proponents of comprehensive staging argue that it is important to give accurate prognostic information to a patient and that choice of chemotherapy regimen might be influenced by knowledge of the stage of disease (see section 5). Descriptive studies have reported that at least 15% of patients thought to have disease confined to the ovaries are found to have positive lymph nodes.^{72,
73, 74} The opponents of comprehensive staging argue that it cannot be recommended as routine practice due to the lack of RCT data demonstrating any survival benefit conferred to those who undergo full staging including retroperitoneal nodal assessment. Evidence level 3,4

The publication of the ICON 1 and ACTION chemotherapy trials (see section 5) means that it is unlikely that future studies will be designed to answer the role of comprehensive staging in early disease.^{75,
76}

In the ACTION chemotherapy trial (see section 5) one third of patients were optimally staged. Adjuvant chemotherapy in this group of patients was not associated with a statistically significant improvement in overall and disease-free survival. The validity of a subgroup analysis in this study is questionable given the small number of patients involved. When the data from the ACTION trial were combined with that from the ICON 1 trial (in which the majority of patients were not optimally staged) platinum-based adjuvant chemotherapy resulted in an 8% improvement in overall survival and an 11% improvement in disease-free survival.⁷⁷ Evidence level 1+

The guideline development group suggest the following to ensure that cases of suspected stage I disease are thoroughly assessed:

staging should be through a mid-line incision to allow palpation of all peritoneal surfaces
assessment of peritoneal cytology, hysterectomy, removal of ovaries and Fallopian tubes and infracolic omentectomy should be performed
capsular rupture during surgery should be avoided.

Aim to exclude disease involving the liver, spleen, peritoneum, retroperitoneal nodes, appendix and diaphragm by close clinical inspection and palpation.

Cases where only the ovarian cyst was removed should be discussed within the multidisciplinary team. If there is concern that there is a likelihood of metastatic disease restaging is recommended.

4.3.1 FERTILITY CONSERVING SURGERY

In women who wish to conserve their fertility, adequate staging (excluding disease involving the liver, spleen, peritoneum, retroperitoneal nodes, appendix and diaphragm) is required and the risk of recurrent disease developing must be discussed.

No data from RCTs were found. One cohort study reported a 9% risk of recurrence (involvement of contralateral ovary or extraovarian disease) in women treated with fertility sparing surgery.⁷⁸ In this study 56 women aged under 40 years with histologically confirmed ovarian cancer (Grades 1, 2 and 3, see Annex 2) underwent fertility sparing surgery which involved adequate staging (unilateral salpingo-oophorectomy, omentectomy, appendectomy, biopsies from peritoneal cavity and retroperitoneal lymph node sampling).⁷⁸ The mean age of the women was 29 years and 32 had FIGO 1A disease, two had FIGO 1B disease and 22 FIGO 1C disease (see Annex 1). Five women developed recurrence (9%) and in two of these women recurrence involved the residual ovary (3.6%). Metastatic endometrial cancer was found at a second look operation in one woman. Evidence level 2+

In another publication the risk of endometrial cancer being present (metastatic involvement or synchronous tumour) has been reported to be as high as 14%, particularly when the ovarian tumour is of endometriod or clear cell subtypes.⁷⁹ Evidence level 4

In women who wish to conserve their fertility a unilateral salpingo-oophorectomy may be performed if the contralateral ovary appears normal.

4.4 Optimal surgery for advanced disease

Advanced disease refers to cases where the disease has spread beyond the ovaries (FIGO stage Ic and above, see Annex 1). Treatment for these cases involves surgery and chemotherapy. This section addresses the issue of surgery before the initiation of chemotherapy. Imaging with ultrasound prior to surgery can identify advanced disease. It is unclear whether additional imaging with computerised tomography is necessary with every case of advanced disease (see section 3.2.2).

There are two surgical scenarios:

aggressive surgical cytoreduction with the aim of leaving no residual disease
optimal cytoreduction where residual tumour deposits are no more than 2 cm in diameter.

As complete resection of all tumour deposits (aggressive cytoreduction) is usually impossible in advanced disease, surgical treatment for the majority of these patients involves performing optimal cytoreductive surgery.

Three meta-analyses demonstrated a strong correlation between optimal cytoreduction and survival.^{80,
81, 82} None of the meta-analyses determined whether the improved survival and the feasibility of aggressive cytoreduction were related to intrinsic tumour biology. Evidence level 1+

One meta-analysis looked at the independent contribution of both cytoreductive surgery and platinum based chemotherapy on overall survival.⁸⁰ Each 10% increase in maximal cytoreductive surgery was associated with a 4.1% increase in median survival time. Platinum-based chemotherapy produced an estimated 53% rise in median survival time. In this analysis patients were treated with non-platinum based therapy as well as platinum-based therapy hence the magnitude of benefit induced by chemotherapy is likely to be exaggerated. A subsequent meta-analysis has confirmed this.⁸³ Evidence level 1+

The question of specialty of surgeon has been addressed in a retrospective population-based review of 1,866 women treated in Scotland over five non-consecutive years.⁶ The review reports on 1,032 patients operated on by general gynaecologists, 351 by specialist gynaecologists and 216 by general surgeons. The demographics of the three patient groups were different: those cared for by the general gynaecologists had an expected better prognosis after surgery than those operated on by the specialist gynaecologists and the group cared for by the general surgeons were the poorest prognostic group. An attempt was made to correct these differences by adjusting for patient age, histology, tumour differentiation, presence of ascites and socioeconomic status. The results were analysed for each FIGO stage and the endpoint for analysis was death by three years. Of those with stage III disease, those operated on by specialist gynaecologists had a 25% reduction in death compared to those operated on by general gynaecologists (P=0.005). Those operated on by general surgeons had the lowest survival rates. Similar trends were found in the other FIGO stages, but were not significant. These data are supported by a similar retrospective review of 12,316 patients in which patient survival was significantly better in the group operated on by specialist ‘gynaecological oncologists’ compared to ‘obstetrician gynaecologists’ and general surgeons.⁸⁴ Evidence level 2+

Patients with stage IV disease are increasingly being treated with chemotherapy prior to surgery when there is no doubt that the primary tumour is ovarian (see section 5.4). A multidisciplinary team should manage these cases. Evidence level 2+

If aggressive cytoreduction is not possible then optimal cytoreduction is the recommended surgical procedure if performance status allows this to take place.

Patients with stage III disease should be operated on by a gynaecological oncologist rather than a general gynaecologist or general surgeon.

Bowel surgery should only be performed where obstruction is imminent or where it enables optimal cytoreduction or aggressive cytoreduction to be achieved.

4.5 Interval debulking surgery

Interval debulking surgery (IDS) refers to surgery performed in women whose tumour mass has decreased following three courses of chemotherapy and who have previously been suboptimally cytoreduced.

The potential role for IDS has been examined in three RCTs,^{85,
86, 87} with two of these studies demonstrating different results. The first did not demonstrate a statistically significant improvement in survival in the group of women who underwent IDS,⁸⁵ whilst the second reported an increase of six months median survival for those who had IDS.⁸⁶ In the second study 127 women who had IDS were followed up. Following three courses of chemotherapy 83 of the women had tumours greater than 1cm. Of these 83, only 37 had tumours measuring less than 1cm left behind after IDS. It is not possible to identify the characteristics of the small group who responded to chemotherapy and who were left with a decreased tumour load after IDS.⁸⁶ Preliminary results from the third RCT suggest that when the first operation is done by a gynaecological oncologist IDS is not recommended even if optimal cytoreduction was not achieved.⁸⁷ Evidence level 1+

Interval debulking surgery is recommended, if performance status allows, where there is evidence of response to chemotherapy as determined by CA125 and imaging.

4.6 Relapsed disease

There are insufficient data to make recommendations on the surgical management of relapsed disease. Quality of life issues were not considered in the literature identified.⁸⁸

A multidisciplinary team should decide whether there is a role for surgery in the management of relapsed disease where there has been a significant period of disease remission.

4.7 Specialist nursing

One RCT has suggested that the involvement of a nurse specialist has a beneficial effect on patient care (statistical significance was not achieved).⁸⁹ Two studies in breast cancer patients also support the role of specialist nurses.^{90,
91} NHS Quality Improvement Scotland standards state that patients should have access to a specialist nurse in gynaecological cancer.⁹² Evidence level 1-,2-,4

Patients should be given their diagnosis of ovarian cancer after surgery in the presence of a nurse who is a fully integrated member of the clinical team. If a nurse specialist is not available this should be a dedicated named nurse or link nurse.

Patients with ovarian cancer should have access to an appropriately trained nurse, who is an integral member of the gynaecological cancer team, throughout their journey of care.