Laparoscopy versus laparotomy for the management of endometrial cancer
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To compare the overall survival and disease free survival for laparoscopic surgery versus laparotomy in women with endometrial cancer.
Background
Endometrial carcinoma (cancer of the lining of the womb) is the most common gynaecological malignancy in developed countries (Jemal 2002). The incidence of endometrial cancer is steadily rising and risk factors include an aging population, obesity, diabetes mellitus, nulliparity, late menopause, unopposed oestrogen intake or oestrogen producing tumours, a history of breast cancer and the use of Tamoxifen (Hacker 2000).
The majority of patients (75%) present at stage 1 with abnormal vaginal bleeding. The overall survival in stage 1 disease is high with more than 90% of women being disease‐free five years after surgery (Creasman 2001). The prognosis depends on various factors, which include histological grading, depth of invasion into the myometrium, lymph node involvement, stage of disease and treatment. For patients with endometrial cancer, removal of the uterus (hysterectomy) and removal of both fallopian tubes and ovaries is considered current standard treatment. Other treatments include adjuvant radiotherapy and chemotherapy. Traditionally, surgery for endometrial cancer is performed through a laparotomy (Marana 1999). However, reports addressing the selective use of laparoscopic techniques in the management of gynaecological malignancies have been published with increasing frequency (Chi 1999; Dottino 1999; Eltabbakh 2001; Vinatier 1996).
Some studies suggest that the laparoscopic approach results in a reduction in operative morbidity in overweight and elderly women (eg wound infection and intestinal obstruction (ileus)) (Eltabbakh 2000; Obermair 2005; Scribner 2001). Laparoscopy is generally associated with less immediate postoperative morbidity and some studies suggest that the overall survival (OS) and disease free survival (DFS) is comparable to laparotomy (Eltabbakh 2002; Obermair 2004; Tozzi 2005). There have been a few reports of port site recurrence and vaginal recurrence after laparoscopy for endometrial cancer (Muntz 1999; Sanjuan 2005). The risk of port site metastases may be reduced by closure of the port site in layers (Tjalma 2003) and the risk of vaginal recurrence reduced by avoiding uterine manipulation during laparoscopy. It is not yet established whether laparoscopy is as good as or better than the conventional laparotomy for the treatment of endometrial cancer.
The International Federation of Gynaecology and Obstetrics (FIGO) staging in endometrial cancer is surgical and hysterectomy is required to determine the depth of myometrial invasion and cervical involvement (Shepherd 1989). The presence of cancer cells in the peritoneal washing is equal to stage 3A and controversy remains about the role of lymphadenopathy.
The laparoscopic approach described is either laparoscopic assisted vaginal hysterectomy (LAVH) or total laparoscopic hysterectomy (TLH). LAVH is where part of the hysterectomy is performed by laparoscopic surgery and part vaginally, but the laparoscopic component of the operation does not necessarily involve division of the uterine vessels. The final removal of the uterus is completed through the vagina. Currently this is the most common type of laparoscopic hysterectomy performed. TLH is where the entire operation (including suturing of the vaginal vault) is performed laparoscopically and there is no vaginal component.
Both procedures have been shown to be feasible, safe and associated with less tissue trauma, blood loss, pain and shorter hospital stays than the open laparotomy (Lumsden 2000).
Objectives
To compare the overall survival and disease free survival for laparoscopic surgery versus laparotomy in women with endometrial cancer.
Methods
Criteria for considering studies for this review
Types of studies
Randomised controlled trials (RCTs) and quasi RCTs (such as alternation, date of birth or case record number).
Types of participants
Inclusion
-
Women diagnosed with endometrial cancer undergoing surgery as primary treatment
-
RCTs on all stages of endometrial cancers
Exclusion
-
Women not treated with primary surgery
-
Women without preoperative diagnosis of endometrial cancer (eg diagnosed with endometrial hyperplasia)
Types of interventions
-
Laparotomy, total abdominal hysterectomy (TAH)
-
Laparoscopy (LAVH or TLH)
Types of outcome measures
Primary outcomes
-
Overall survival
-
Disease free survival
Secondary outcomes
-
Local recurrence (port site, vaginal vault at laparoscopy and abdominal incision at laparotomy)
-
Distant recurrence
-
Post operative and intra operative complications
(a) Surgical complications:
(i) injury (bladder, ureter, vascular, small bowel and colon injuries)
(ii) presence/complication of adhesions
(iii) febrile morbidity
(iv) haematoma
(v) infection
(vi) conversion to laparotomy rate
(b) Systemic complications:
(i) chest infection
(ii) deep venous thrombosis
(iii) pulmonary embolism
(iv) cardiac failure
(v) cardiac ischemias
(vi) cerebrovascular accident
-
Operative time
-
Recovery from surgery: length of hospital day and re‐admission rates
-
Quality of life (QOL) after six months or more post operation
Search methods for identification of studies
Electronic searches
See : Gynaecological Cancer Group search strategy.
Electronic databases : An electronic search was performed using The Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library, Issue 1, 2006), MEDLINE from 1950, EMBASE from 1980, CINAHL from 1982 and CancerLit with the following search strategy (MEDLINE DIALOG web) adapted for the other databases. No language restriction will be applied. The following trial registers will also be searched ‐ NHMRC Clinical Trials Register, UKCCCR Register of Cancer Trials, Meta‐Register and Physician Data Query Protocols.
1 RANDOMIZED CONTROLLED TRIAL.pt.
2 CONTROLLED CLINICAL TRIAL.pt.
3 RANDOMIZED CONTROLLED TRIALS.sh.
4 RANDOM ALLOCATION.sh.
5 DOUBLE BLIND METHOD.sh.
6 SINGLE BLIND METHOD.sh.
7 1 OR 2 OR 3 OR 4 OR 5 OR 6
8 ANIMALS.sh. not HUMANS.sh.
9 7 not 8
10 CLINICAL TRIAL.pt.
11 exp CLINICAL TRIALS/
12 (clin$ adj25 trial$).ti,ab.
13 ((singl$ or doubl$ or trebl$ or tripl$) adj25 (blind$ or mask$)).ti,ab.
14 PLACEBOS.sh.
15 placebo$.ti,ab.
16 random$.ti,ab.
17 RESEARCH DESIGN.sh.
18 10 OR 11 OR 12 OR 13 OR 14 OR 15 OR 16 OR 17
19 18 not 8
20 19 not 9
21 9 or 20
22 exp LAPAROSCOPY/
23 laparoscop$
24 laparoscopically ADJ assisted ADJ vaginal ADJ hysterectomy
25(laparoscop$ ADJ hysterectomy).ti,ab.
26 laparotomy
27 total ADJ laparoscopic ADJ hysterectomy
28 LAVH
29 TLH
30 22 OR 23 OR 24 OR 25 OR 26 OR 27 OR 28 OR 29
31 exp ENDOMETRIAL NEOPLASMS/
32 endometrial ADJ carcinoma
33 uterine ADJ cancer
34 endometr$ ADJ cancer$
35 uterine ADJ malign$
36 endometrial ADJ malignan$
37 31 OR 32 OR 33 OR 34 OR 35 OR 36
38 21 AND 30 AND 37
Reference lists of articles and other reviews on the subject are going to be checked for the purpose of retrieving further information, either published or unpublished, and researchers involved in this area will be contacted.
CENTRAL on the current issue of The Cochrane Library, the National Research Register (NRR) and Clinical Trials Register will also be searched in all fields using the following words: endometrial cancer, laparotomy and laparoscopy.
Searching other resources
The citation list of relevant publications, abstracts of scientific meetings and list of included studies will also be hand searched:
Gynecologic Oncology
International Journal of Gynecological Cancer
British Journal of Cancer
British Cancer Research Meeting
Annual Meeting of the International Gynecologic Cancer Society
Annual Meeting of the American Society of Gynecologic Oncologist
Annual Meeting of The European Society of Medical Oncology (ESMO)
Annual Meeting of the American Society of Clinical Oncology (ASCO)
Finally experts in the field will be contacted to identify further trial reports.
Data collection and analysis
Selection of studies
All titles and abstracts retrieved by electronic searching will be downloaded to a reference database (eg Reference Manager or Endnote), duplicates will be removed and the remaining references will be examined by two authors independently. Those studies which clearly do not meet the inclusion criteria will be excluded and the copies of potentially relevant references will be obtained. Reasons for exclusion will be documented.
Data extraction and management
Trial characteristics
For included studies, data on characteristics of patients and interventions, study quality and endpoints will be abstracted independently by two authors onto a data abstraction form specially developed for the review. This will include:
(a) Type of study design
(b) Study setting
-
single or multicentre
-
location
-
timing and duration
(c) Characteristics of study participants
-
age
-
stage of cancer
-
co‐morbidity
(d) Size of study
-
number of women recruited
-
number of women randomised
-
number of women excluded
-
number of women withdrawn from treatment
-
number of women who did not receive allocated treatment
-
number of women lost to follow‐up
-
number of women analysed
(e) Duration of follow up
Differences between authors will be resolved by discussion or by appeal to a third author if necessary.
Outcome data abstraction
For time to event data (OS and DFS) we will abstract the hazard ratio (HR) and its variance from trial reports. If these are not presented we will attempt to abstract the data required to estimate them using Parmar's methods (Parmar 1998) (eg number of events in each arm and log‐rank p‐value comparing the relevant outcomes in each arm, or relevant data from Kaplan‐Meier survival curves). If it is not possible to estimate the HR we will abstract the number of patients in each treatment arm who experienced the outcome of interest, in order to estimate a relative risk (RR). For continuous outcomes (eg QOL measures) the final value of the outcome of interest in each treatment arm at the end of follow‐up will be abstracted for each study. Where possible all data abstracted will be those relevant to an intention to treat analysis (ITT). All authors of included studies will be contacted for further unpublished details of their studies where necessary.
Assessment of risk of bias in included studies
Quality assessment of randomised clinical trials
The full papers will be assessed for methodological quality by recording a number of items that could either introduce bias or could affect the assessment of the data presented in the study using the Cochrane Collaboration Back Review Group's methodological quality criteria (van Tulder 2003).
Methodological quality of included RCTs will be assessed using the following criteria:
Blinding
We will code the blinding of patients, treatment providers and outcome assessors as:
-
yes
-
no
-
unclear
Randomisation
We will code the randomisation of participants to intervention groups as:
-
adequate (eg a computer generated random sequence ot table of random numbers)
-
inadequate (eg date of birth, clinic id‐ number or surname)
-
unclear (eg not reported)
Allocation of concealment
This will be assessed as described in the Cochrane Reviewer's Handbook (Higgins 2005) as follows:
A ‐ indicates adequate concealment of the allocation, e.g. where the allocation sequence could not be foretold.
B ‐ indicates uncertainty about whether the allocation was adequately concealed
C ‐ indicates that the allocation was definitely not adequately concealed.
Loss to follow up
We will record the number of participants in each intervention arm whose outcomes were not reported at the end of the study; we will not if loss to follow‐up was not reported.
Quality assessment of non‐randomised studies
Methodological quality of non‐randomised studies will be assessed using the Newcastle‐Ottawa Scale for Assessing the Quality of Non randomised Studies in Metanalysis (NOS) (Wells 2007).
Data synthesis
All RCTs and non‐RCTs comparing laparoscopic surgery versus laparotomy on women with invasive endometrial cancer will initially be included. The outcomes will be pooled statistically when no clinical heterogeneity is apparent. Statistical heterogeneity between studies will be assessed by visual inspection of forest plots, by estimation of the percentage heterogeneity between trials which cannot be ascribed to sampling variation (I2) (Higgins 2003) and by a formal statistical test of the significance of the heterogeneity (Deeks 2001). If there is evidence of substantial heterogeneity the possible reasons for this will be investigated and reported.
For time to event data HRs will be pooled using the generic inverse variance facility of RevMan 4.2. For any dichotomous outcomes (eg numbers of patients who relapse or die, if it is not possible to treat these outcomes as time‐to‐event data) the RR will be calculated for each study and statistics from all studies will be pooled. For continuous outcomes (e.g. QOL measures, psychiatric scales) the mean difference between the treatment arms at the end of follow‐up will be calculated for each study. These will be pooled using the mean difference method if all trials have measured the outcome on the same scale, or using the standardised mean difference method otherwise. Random effects models will be used for all meta‐analyses (DerSimonian 1986) .
