James L. Nicklin

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.

Accuracy of frozen section for the operative management of endometrial cancer

Objective To assess the accuracy of intra‐operative frozen section reports at identifying the features of high risk uterine disease compared with final histopathology.

Impact of Hemoglobin Levels Before and During Concurrent Chemoradiotherapy on the Response of Treatment in Patients with Cervical Carcinoma Preliminary Results

In patients undergoing radiation for cervical carcinoma, there is evidence that anemia is associated with an impaired outcome. For patients undergoing chemoradiation, there are no data available. The objective of this retrospective study was to examine the impact of anemia before and during chemoradiation in patients with cervical carcinoma.

Prognostic Importance of Preoperative CA-125 in International Federation of Gynecology and Obstetrics Stage I Epithelial Ovarian Cancer: An Australian Multicenter Study

PURPOSE To evaluate the prognostic significance of preoperative CA-125 levels on overall survival of patients with International Federation of Gynecology and Obstetrics (FIGO) stage I epithelial ovarian cancer (EOC). PATIENTS AND METHODS Data from 518 patients with FIGO stage I EOC treated in seven gynecologic oncology centers throughout Australia between 1990 and 2002 were analyzed. Patients with borderline tumors and nonepithelial ovarian carcinomas were excluded, as were women in whom CA-125 had not been determined preoperatively. Preoperative CA-125 levels were studied in surgically staged and incompletely staged patients and compared with prognostic factors, such as substage, grade, and histologic type. Multivariate Cox models were calculated. RESULTS CA-125 levels more than 30 U/mL were associated with higher grade, substage 1B and 1C, nonmucinous histologic type, and older age. In univariate analysis, higher histologic grade, the absence of surgical staging, and preoperative CA-125 levels more than 30 U/mL were associated with impaired survival. Multivariate analysis identified histologic grade, preoperative CA-125, and surgical staging as independent predictors for survival. In the subgroup of completely surgically staged patients, the 5-year overall survival rate was 82% (95% CI, 76% to 88%) for patients with CA-125 levels more than 30 U/mL and 95% (95% CI, 90% to 99%) for patients with CA-125 levels of 30 U/mL or less (P = .028). In the group of incompletely staged patients, the 5-year survival rates were similar for patients with elevated and normal serum CA-125 levels. CONCLUSION Complete surgical staging, histologic grade, and preoperative serum CA-125 levels are independent prognostic factors and should be included in the decision making for chemotherapy.

Peritoneal cytology: impact on disease-free survival in clinical stage I endometrioid adenocarcinoma of the uterus

The prognostic significance of positive peritoneal cytology in endometrial carcinoma has led to the incorporation of peritoneal cytology into the current FIGO staging system. While cytology was shown to be prognostically relevant in patients with stage II and III disease, conflicting data exists about its significance in patients who would have been stage I but were classified as stage III solely and exclusively on the basis of positive peritoneal cytology (clinical stage I). Analysis was based on the data of 369 consecutive patients with clinical stage I endometrioid adenocarcinoma of the endometrium. Standard treatment consisted of an abdominal total hysterectomy, bilateral salpingo-oophorectomy with or without pelvic lymph node dissection. Peritoneal cytology was obtained at laparotomy by peritoneal washing of the pouch of Douglas and was considered positive if malignant cells could be detected regardless of the number of malignant cells present. Disease-free survival (DFS) was considered the primary statistical endpoint. In 13/369 (3.5%) patients, positive peritoneal cytology was found. The median follow-up was 29 months and 15 recurrences occurred. Peritoneal cytology was independent of the depth of myometrial invasion and the grade of tumour differentiation. Patients with negative washings had a DFS of 96% at 36 months compared with 67% for patients with positive washings (log-rank P<0.001). The presence of positive peritoneal cytology in patients with clinically stage I endometrioid adenocarcinoma of the endometrium is considered an adverse prognostic factor.

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.

Endometrial adenocarcinoma ‐ presenting pathology is a poor guide to surgical management

Summary: We aimed to evaluate the correlation between the histological grade of endometrial cancer diagnosed on endometrial biopsy or curettage, with the definitive grade and stage of lesion as determined by surgery and histopathological examination and to make recommendations about the suitability of conservative surgery based on preoperative determination of the grade of endometrial adenocarcinoma.

Fertility and Ovarian Function After Conservative Surgery for Germ Cell Tumours of the Ovary

Malignant ovarian germ cell tumours (MOGCT) principally occur in girls and young women and are generally unilateral. Effective combination chemotherapy with conservative surgery has seen a dramatic improvement in survival rates. This increase has shifted the focus to long‐term fertility and reproductive outcome. The present study describes 45 patients with MOGCT treated with conservative surgery to preserve fertility, with or without the addition of chemotherapy. The age range was 10 to 32 years with a mean of 20 years. The majority of the subjects had Stage 1 tumours; 44 underwent unilateral salpingo‐oophorectomy and 1 patient ovarian cystectomy. Adjuvant chemotherapy was administered in 29 patients. Overall mean follow‐up was 58.7 months. There were 4 recurrences and 2 deaths. Survival of those with Stage 1 disease was 97% and for advanced stages 87%. During chemotherapy 50% became amenorrhoeic but 96% resumed normal menstrual function on completion. Seven healthy babies were recorded in the chemotherapy group and no documented birth defects occurred in any of these. There was no case of persistent infertility; 3 patients experienced temporary problems. It is concluded that conservative fertility‐sparing surgery is the treatment of choice in these young women and advanced disease is not necessarily a contraindication. The majority can anticipate normal menstrual function and fertility.

Evaluation of a Maternity Cushion (Ozzlo Pillow) for Backache and Insomnia in Late Pregnancy

EDITORIAL COMMENT: Backache is an important common symptom in pregnancy although usually the topic is listed in textbooks with the other so called ‘Minor Disorders’. This paper evaluates the frequency of backache, its relationship to insomnia and its relief with a locally designed pillow. Unfortunately the ‘minor’ non‐lifethreatening disorders of pregnancy receive scant attention in medical journals, yet not only do they prevent patients enjoying their pregnancy (which should be the ideal), but they can be one reason for patients opting for induction of labour at term, when there is no bonaflde indication for such interference. The same is true of intractable ‘heartburn’ which is another cause of insomnia in late pregnancy. Although the authors provide much detail and many tables they did not tackle the difficult problems of type of backache, radiation of pain, need for analgesia and rest during the day. When backache is severe and incapacitating the patient should be referred for orthopaedic opinion, especially if the pain radiates to the leg along the distribution of one or more of the sciatic nerve roots. A visit to the physiotherapist for education and appropriate exercises is usually of more value than referral to an orthopaedic surgeon. However, the latter must be consulted in the rare patient (less than 1 in 1,000) with intractable pain, or coexistent neurological signs. In most patients backache is relieved by rest, usually in the lateral position, although some women who do not suffer from postural hypotension are more comfortable on their back, on a firm mattress. Backache after pregnancy is also an important problem; if still present at the postnatal visit, the patients symptoms, morale and abdominal shape are often helped by exercises supervised by a physiotherapist.

Nomograms to predict isolated loco-regional or distant recurrence among women with uterine cancer

OBJECTIVE While there is ample literature on prognostic factors for uterine cancer, currently there are nomeans to estimate an individuals risk for recurrence or to differentiate the risk of loco-regional recurrence from distant recurrence. We addressed this gap by developing nomograms to individualize the risk of recurrence. METHODS A total of 2097 consecutive patients who underwent primary surgery between 1997 and 2007 were included. Sixteen covariates were evaluated for their prognostic significance and modeled using multivariable competing risks regression to predict three-year outcomes as part of a nomogram. Each covariate in the nomogram is assigned a value, and a sum of these values form the overall risk score from which three-year incidence probabilities can be predicted for each individual. Predictive accuracy was assessed with concordance index and then corrected for optimism. RESULTS The median follow-up time (inter-quartile range, IQR) was 50.0 (28.3-77.5) months and 221 patients developed a recurrence (127 patients with isolated loco-regional recurrence, 94 patients with distant recurrence). The nomograms included the following covariates: age at diagnosis, FIGO stage (2009), grade, lymphovascular invasion, histological type, depth of myometrial invasion, and peritoneal cytology. Concordance indices for isolated loco-regional and distant recurrences were 0.73 and 0.86, respectively. CONCLUSIONS Our nomograms quantify an individual patients risk of isolated loco-regional and distant recurrence, using factors that are routinely collected. They may assist clinicians to assess an individuals prognosis, individualize treatment and also assist in the risk stratification in prospective randomized clinical trials evaluating the effectiveness of treatments for uterine cancer.