Deborah Neesham

Quality of life after total laparoscopic hysterectomy versus total abdominal hysterectomy for stage I endometrial cancer (LACE): a randomised trial

BACKGROUND This two-stage randomised controlled trial, comparing total laparoscopic hysterectomy (TLH) with total abdominal hysterectomy (TAH) for stage I endometrial cancer (LACE), began in 2005. The primary objective of stage 1 was to assess whether TLH results in equivalent or improved quality of life (QoL) up to 6 months after surgery compared with TAH. The primary objective of stage 2 was to test the hypothesis that disease-free survival at 4.5 years is equivalent for TLH and TAH. Here, we present the results of stage 1. METHODS Between Oct 7, 2005, and April 16, 2008, 361 participants were enrolled in the QoL substudy at 19 centres across Australia, New Zealand, and Hong Kong; 332 completed the QoL analysis. Randomisation was done centrally and independently from other study procedures via a computer-generated, web-based system (providing concealment of the next assigned treatment), using stratified permuted blocks of three and six patients. Patients with histologically confirmed stage I endometrioid adenocarcinoma and Eastern Cooperative Oncology Group performance status less than 2 were randomly assigned to TLH (n=190) or TAH (n=142), stratified by histological grade and study centre. Patients and study personnel were not masked to treatment assignment. QoL was measured at baseline, 1 and 4 weeks (early), and 3 and 6 months (late) after surgery, using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. The primary endpoint was the difference between groups in QoL change from baseline at early and late timepoints (a 5% difference was considered clinically significant). Analysis was done according to the intention-to-treat principle. Patients for both stages of the trial have now been recruited and are being followed up for disease-specific outcomes. The LACE trial is registered with ClinicalTrials.gov, number NCT00096408. FINDINGS Eight of 332 patients (2.4%) had treatment conversion-seven from TLH to TAH and one from TAH to TLH (patient preference). In the early phase of recovery, patients who had TLH reported significantly greater improvement in QoL from baseline compared with those who had TAH, in all subscales apart from emotional and social wellbeing. Improvements in QoL up to 6 months after surgery continued to favour TLH, except in the emotional and social wellbeing measures of FACT and the visual analogue scale of the EuroQoL five dimensions (EuroQoL-VAS). Operating time was significantly longer in the TLH group (138 min [SD 43]) than in the TAH group (109 min [34]; p=0.001). Although the proportion of intraoperative adverse events was similar between groups (TAH eight of 142 [5.6%] vs TLH 14 of 190 [7.4%]; p=0.53); postoperatively, twice as many patients in the TAH group experienced adverse events of grade 3 or higher (33 of 142 [23.2%] vs 22 of 190 [11.6%] in the TLH group; p=0.004). Postoperative serious adverse events occurred more in the TAH group (27 of 142 [19.0%]) than in the TLH group (16 of 190 [7.9%]; p=0.002). INTERPRETATION QoL improvements from baseline during early and later phases of recovery, and the adverse event profile, favour TLH compared with TAH for treatment of stage I endometrial cancer. FUNDING Cancer Council Queensland, Cancer Council New South Wales, Cancer Council Victoria, Cancer Council Western Australia; NHMRC project grant 456110; Cancer Australia project grant 631523; The Women and Infants Research Foundation, Western Australia; Royal Brisbane and Womens Hospital Foundation; Wesley Research Institute; Gallipoli Research Foundation; Gynetech; TYCO Healthcare, Australia; Johnson and Johnson Medical, Australia; Hunter New England Centre for Gynaecological Cancer; Genesis Oncology Trust; and Smart Health Research Grant QLD Health.

Improved surgical safety after laparoscopic compared to open surgery for apparent early stage endometrial cancer: Results from a randomised controlled trial

AIM To compare Total Laparoscopic Hysterectomy (TLH) and Total Abdominal Hysterectomy (TAH) with regard to surgical safety. METHODS Between October 2005 and June 2010, 760 patients with apparent early stage endometrial cancer were enroled in a multicentre, randomised clinical trial (LACE) comparing outcomes following TLH or TAH. The main study end points for this analysis were surgical adverse events (AE), hospital length of stay, conversion from laparoscopy to laparotomy, including 753 patients who completed at least 6 weeks of follow-up. Postoperative AEs were graded according to Common Toxicity Criteria (V3), and those immediately life-threatening, requiring inpatient hospitalisation or prolonged hospitalisation, or resulting in persistent or significant disability/incapacity were regarded as serious AEs. RESULTS The incidence of intra-operative AEs was comparable in either group. The incidence of post-operative AE CTC grade 3+ (18.6% in TAH, 12.9% in TLH, p 0.03) and serious AE (14.3% in TAH, 8.2% in TLH, p 0.007) was significantly higher in the TAH group compared to the TLH group. Mean operating time was 132 and 107 min, and median length of hospital stay was 2 and 5 days in the TLH and TAH group, respectively (p<0.0001). The decline of haemoglobin from baseline to day 1 postoperatively was 2g/L less in the TLH group (p 0.006). CONCLUSIONS Compared to TAH, TLH is associated with a significantly decreased risk of major surgical AEs. A laparoscopic surgical approach to early stage endometrial cancer is safe.

Progestogen treatment options for early endometrial cancer

Please cite this paper as: Cade T, Quinn M, Rome R, Neesham D. Progestogen treatment options for early endometrial cancer. BJOG 2010;117:879–884.

Effect of total laparoscopic hysterectomy vs total abdominal hysterectomy on disease-free survival among women with stage I endometrial cancer. A randomized clinical trial

Importance Standard treatment for endometrial cancer involves removal of the uterus, tubes, ovaries, and lymph nodes. Few randomized trials have compared disease-free survival outcomes for surgical approaches. Objective To investigate whether total laparoscopic hysterectomy (TLH) is equivalent to total abdominal hysterectomy (TAH) in women with treatment-naive endometrial cancer. Design, Setting, and Participants The Laparoscopic Approach to Cancer of the Endometrium (LACE) trial was a multinational, randomized equivalence trial conducted between October 7, 2005, and June 30, 2010, in which 27 surgeons from 20 tertiary gynecological cancer centers in Australia, New Zealand, and Hong Kong randomized 760 women with stage I endometrioid endometrial cancer to either TLH or TAH. Follow-up ended on March 3, 2016. Interventions Patients were randomly assigned to undergo TAH (n = 353) or TLH (n = 407). Main Outcomes and Measures The primary outcome was disease-free survival, which was measured as the interval between surgery and the date of first recurrence, including disease progression or the development of a new primary cancer or death assessed at 4.5 years after randomization. The prespecified equivalence margin was 7% or less. Secondary outcomes included recurrence of endometrial cancer and overall survival. Results Patients were followed up for a median of 4.5 years. Of 760 patients who were randomized (mean age, 63 years), 679 (89%) completed the trial. At 4.5 years of follow-up, disease-free survival was 81.3% in the TAH group and 81.6% in the TLH group. The disease-free survival rate difference was 0.3% (favoring TLH; 95% CI, −5.5% to 6.1%; P = .007), meeting criteria for equivalence. There was no statistically significant between-group difference in recurrence of endometrial cancer (28/353 in TAH group [7.9%] vs 33/407 in TLH group [8.1%]; risk difference, 0.2% [95% CI, −3.7% to 4.0%]; P = .93) or in overall survival (24/353 in TAH group [6.8%] vs 30/407 in TLH group [7.4%]; risk difference, 0.6% [95% CI, −3.0% to 4.2%]; P = .76). Conclusions and Relevance Among women with stage I endometrial cancer, the use of total abdominal hysterectomy compared with total laparoscopic hysterectomy resulted in equivalent disease-free survival at 4.5 years and no difference in overall survival. These findings support the use of laparoscopic hysterectomy for women with stage I endometrial cancer. Trial Registration clinicaltrials.gov Identifier: NCT00096408; Australian New Zealand Clinical Trials Registry: CTRN12606000261516

Does experience in colposcopy improve identification of high grade abnormalities

OBJECTIVE This study investigates whether experience in colposcopy improves identification of high grade abnormalities. The sensitivity and positive predictive value (PPV) of colposcopy in identifying high grade intra-epithelial lesions (HSIL) performed by relatively inexperienced as compared to experienced colposcopists are evaluated. STUDY DESIGN Of 18,421 colposcopies performed at the Royal Womens Hospital, Melbourne, Australia, between 1999 and 2004 by 5 senior and 11 junior colposcopists, the colposcopic impression was correlated with the histopathology result of the biopsy taken at 6020 colposcopies, with respect to the experience of the colposcopist. RESULTS Colposcopy had a 60% sensitivity and 60% PPV in identifying HSIL in this study. In case of a high-grade referral smear the sensitivity and PPV in identifying HSIL were, respectively 76% and 73%, compared with 26% and 48% in case of a low-grade referral smear, no difference in overall colposcopic performance between experienced and inexperienced colposcopists was observed. However, the sensitivity of identifying HSIL was significantly higher with inexperienced colposcopists, and the PPV was significantly higher with experienced colposcopists. CONCLUSION In this study experience did not improve colposcopic performance, but differences in colposcopic strategy between the two groups were noted. The rather low overall sensitivity and PPV of colposcopy in identifying HSIL, especially in case of a low-grade referral smear, indicate that the role of colposcopy in the detection and treatment of cervical abnormalities is to assess size, site, and extent of an abnormality, rather than to assess the severity of this abnormality. Histology must remain the gold standard for treatment.

Risk factors to predict the incidence of surgical adverse events following open or laparoscopic surgery for apparent early stage endometrial cancer: Results from a randomised controlled trial☆

AIMS To identify risk factors for major adverse events (AEs) and to develop a nomogram to predict the probability of such AEs in patients who have surgery for apparent early stage endometrial cancer. METHODS We used data from 753 patients who were randomised to either total laparoscopic hysterectomy or total abdominal hysterectomy in the LACE trial. Serious adverse events that prolonged hospital stay or postoperative adverse events (using common terminology criteria 3+, CTCAE V3) were considered major AEs. We analysed pre-surgical characteristics that were associated with the risk of developing major AEs by multivariate logistic regression. We identified a parsimonious model by backward stepwise logistic regression. The six most significant or clinically important variables were included in the nomogram to predict the risk of major AEs within 6weeks of surgery and the nomogram was internally validated. RESULTS Overall, 132 (17.5%) patients had at least one major AE. An open surgical approach (laparotomy), higher Charlsons medical co-morbidities score, moderately differentiated tumours on curettings, higher baseline Eastern Cooperative Oncology Group (ECOG) score, higher body mass index and low haemoglobin levels were associated with AE and were used in the nomogram. The bootstrap corrected concordance index of the nomogram was 0.63 and it showed good calibration. CONCLUSIONS Six pre-surgical factors independently predicted the risk of major AEs. This research might form the basis to develop risk reduction strategies to minimise the risk of AEs among patients undergoing surgery for apparent early stage endometrial cancer.

Predictive value of magnetic resonance imaging in assessing myometrial invasion in endometrial cancer: is radiological staging sufficient for planning conservative treatment?

Objectives: There has been an increasing interest in accurately assessing tumors preoperatively to plan appropriate surgery or, in some low-risk patients, conservative treatment. We wish to determine the accuracy of magnetic resonance imaging (MRI) in predicting myometrial invasion in endometrial cancer and whether it is a safe and suitable tool for planning conservative treatment. Materials and Methods: We compared MRI scans and final histopathologic diagnoses of 111 patients with endometrioid adenocarcinoma over a 6-year period at a major tertiary centre. Data were analyzed collectively and according to histological differentiation and types of MRI scans (1.5 vs 3 T). Outcomes were presence versus absence of myometrial invasion and recently revised International Federation of Gynecology and Obstetrics stage IA (up to 50% myometrial invasion) versus deep invasion. Results: Magnetic resonance imaging had a high negative predictive value for the presence of deep invasion (87% overall and 95% for grade 1 disease). However, although the positive predictive value for the presence of any myometrial invasion was high, negative predictive values were poor (35% for all grades and 46% for grade 1). There was no difference between 1.5- and 3-T scanning. Conclusions: Magnetic resonance imaging is a suitable screening tool for the presence of stage IA disease under the newly revised International Federation of Gynecology and Obstetrics staging system. The significance of this finding will depend on whether clinicians are willing to treat all grade 1 stage IA disease (under the revised system) as low risk and to deem selected patients in this group suitable for more conservative treatment.

Pre-diagnosis diet and survival after a diagnosis of ovarian cancer

Background:The relationship between diet and survival after ovarian cancer diagnosis is unclear as a result of a limited number of studies and inconsistent findings.Methods:We examined the association between pre-diagnostic diet and overall survival in a population-based cohort (n=811) of Australian women diagnosed with invasive epithelial ovarian cancer between 2002 and 2005. Diet was measured by validated food frequency questionnaire. Deaths were ascertained up to 31 August 2014 via medical record review and Australian National Death Index linkage. We conducted Cox proportional hazards regression analysis, controlling for diagnosis age, tumour stage, grade and subtype, residual disease, smoking status, body mass index, physical activity, marital status, and energy intake.Results:We observed improved survival with highest compared with lowest quartile of fibre intake (hazard ratio (HR)=0.69, 95% CI: 0.53–0.90, P-trend=0.002). There was a suggestion of better survival for women with highest compared with lowest intake category of green leafy vegetables (HR=0.79, 95% CI: 0.62–0.99), fish (HR=0.74, 95% CI: 0.57–0.95), poly- to mono-unsaturated fat ratio (HR=0.76, 95% CI: 0.59–0.98), and worse survival with higher glycaemic index (HR=1.28, 95% CI: 1.01–1.65, P-trend=0.03).Conclusions:The associations we observed between healthy components of diet pre-diagnosis and ovarian cancer survival raise the possibility that dietary choices after diagnosis may improve survival.

Long‐term outcomes after progestogen treatment for early endometrial cancer

For select women with early endometrial cancer, particularly nulliparous women, nonsurgical options may be considered. There is increasing experience using progestogens, but little is known about the long‐term outcomes and safety of such treatment.

Pseudosinusoidal Fetal Heart Rate Pattern and Fetal Anaemia: Case Report and Review

Summary: The association of a pseudosinusoidal fetal heart rate pattern with fetal anaemia is reported. A system of classifying this cardiotocographic feature as minor, intermediate or major is discussed. The clinical correlates of each of these gradings and the differentiation from a true sinusoidal fetal heart rate pattern are presented.