Adjuvant chemotherapy vs radiotherapy in high-risk endometrial carcinoma: results of a randomised trial

Patients with high-risk endometrial carcinoma (stage IcG3, IIG3 with myometrial invasion >50%, and III) receive adjuvant therapy after surgery but it is not clear whether radiotherapy (RT) or chemotherapy (CT) is better. We randomly assigned 345 patients with high-risk endometrial carcinoma to adjuvant CT (cisplatin (50 mg m−2), doxorubicin (45 mg m−2), cyclophosphamide (600 mg m−2) every 28 days for five cycles, or external RT (45–50 Gy on a 5 days week−1 schedule). The primary end points were overall and progression-free survival. After a median follow-up of 95.5 months women in the CT group as compared with the RT group, had a no significant hazard ratio (HR) for death of 0.95 (95% confidence interval (CI), 0.66–1.36; P=0.77) and a nonsignificant HR for event of 0.88 (95% CI, 0.63–1.23; P=0.45). The 3, 5 and 7-year overall survivals were 78, 69 and 62% in the RT group and 76, 66 and 62% in the CT group. The 3, 5 and 7-year progression-free survivals were, respectively, 69, 63 and 56 and 68, 63 and 60%. Radiotherapy delayed local relapses and CT delayed metastases but these trends did not achieve statistical significance. Overall, both treatments were well tolerated. This trial failed to show any improvement in survival of patients treated with CT or the standard adjuvant radiation therapy. Randomised trials of pelvic RT combined with adjuvant cytotoxic therapy compared with RT alone are eagerly awaited

A tool to balance benefit and harm when deciding about adjuvant therapy

Adjuvant therapy aims to prevent outgrowth of residual disease but can induce serious side effects. Weighing conflicting treatment effects and communicating this information with patients is not elementary. This study presents a scheme balancing benefit and harm of adjuvant therapy vs no adjuvant therapy. It is illustrated by the available evidence on adjuvant pelvic external beam radiotherapy (RT) for intermediate-risk stage I endometrial carcinoma patients. The scheme comprises five outcome possibilities of adjuvant therapy: patients who benefit from adjuvant therapy (some at the cost of complications) vs those who neither benefit nor contract complications, those who do not benefit but contract severe complications, or those who die. Using absolute risk differences, a fictive cohort of 1000 patients receiving adjuvant RT is categorised. Three large randomised clinical trials were included. Recurrences will be prevented by adjuvant RT in 60 patients, a majority of 908 patients will neither benefit nor suffer severe radiation-induced harm but 28 patients will suffer severe complications due to adjuvant RT and an expected four patients will die. This scheme readily summarises the different possible treatment outcomes and can be of practical value for clinicians and patients in decision making about adjuvant therapies

Staging quality is related to the survival of women with endometrial cancer: a Scottish population based study.Deficient surgical staging and omission of adjuvant radiotherapy is associated with poorer survival of women diagnosed with endometrial cancer in Scotland during 1996 and 1997

The association between treatment variation and survival of women with endometrial cancer was investigated. A retrospective cohort based upon the complete Scottish population registered on in-patient and day-case hospital discharge data (Scottish Morbidity Record-1) and cancer registration (Scottish Morbidity Record-6) coded C54 and C55 in ICD10, between 1st January 1996 to 31st December 1997 were analysed. Seven hundred and three patients who underwent surgical treatment out of 781 patients that were diagnosed with endometrial cancer in Scotland during 1996 and 1997. The overall quality of surgical staging was poor. The quality of staging was related to both the year that the surgeon passed the Member of the Royal College of Obstetricians and Gynaecologists examination and also to ‘specialist’ status but was not related to surgeon caseload. Two clinically important prognostic factors were found to be associated with survival; whether the International Federation of Obstetrics and Gynaecology stage was documented, RHR=2.0 (95% CI=1.3 to 3.1) and also to the use of adjuvant radiotherapy, RHR=2.2 (95% CI=1.5 to 3.5). The associations with survival were strongest in patients with advanced disease, International Federation of Obstetrics and Gynaecology stages 1C through to stage 3. Deficiencies in staging and variations in the use of adjuvant radiotherapy represent a possible source of avoidable mortality in patients with endometrial cancer. Consequently, there should be a greater emphasis on improving the overall quality of surgical staging in endometrial cancer

Psychometric validation of the European Organisation for Research and Treatment of Cancer–Quality of Life Questionnaire Sexual Health (EORTC QLQ-SH22)

BACKGROUND: The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group developed a questionnaire to assess sexual health in patients with cancer and cancer survivors. This study evaluates the psychometric properties of the questionnaire. METHODS: The 22-item EORTC sexual health questionnaire (EORTC QLQ-SH22) was administered with the EORTC QLQ-C30 to 444 patients with cancer. The hypothesised scale structure, reliability and validity were evaluated through standardised psychometric procedures. RESULTS: The cross-cultural field study showed that the majority of patients (94.7%) were able to complete the QLQ-SH22 in less than 20 min; 89% of the study participants did not need any help to fill in the questionnaire. Multi-item multi-trait scaling analysis confirmed the hypothesised scale structure with two multi-item scales (sexual satisfaction, sexual pain) and 11 single items (including five conditional items and four gender-specific items). The internal consistency yielded acceptable Cronbach's alpha coefficients (.90 for the sexual satisfaction scale, .80 for the sexual pain scale). The test-retest correlations (Pearson's r) ranged from .70 to .93 except for the scale communication with professionals (.67) and male body image (.69). The QLQ-SH22 discriminates well between subgroups of patients differing in terms of their performance and treatment status. CONCLUSION: The study supports the reliability, the content and construct validity of the QLQ-SH22. The newly developed questionnaire is clinically applicable to assess sexual health of patients with cancer at different treatment stages and during survivorship for clinical trials and for clinical practice

ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma

A European consensus conference on endometrial carcinoma was held in 2014 to produce multidisciplinary evidence-based guidelines on selected questions. Given the large body of literature on the management of endometrial carcinoma published since 2014, the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy & Oncology (ESTRO) and the European Society of Pathology (ESP) jointly decided to update these evidence-based guidelines and to cover new topics in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide. ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (27 experts across Europe). To ensure that the guidelines are evidence-based, the literature published since 2014, identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 191 independent international practitioners in cancer care delivery and patient representatives. The guidelines comprehensively cover endometrial carcinoma staging, definition of prognostic risk groups integrating molecular markers, pre- and intra-operative work-up, fertility preservation, management for early, advanced, metastatic, and recurrent disease and palliative treatment. Principles of radiotherapy and pathological evaluation are also defined

ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma

A European consensus conference on endometrial carcinoma was held in 2014 to produce multi-disciplinary evidence-based guidelines on selected questions. Given the large body of literature on the management of endometrial carcinoma published since 2014, the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly decided to update these evidence-based guidelines and to cover new topics in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide

Vulvar cancer subclassification by HPV and p53 status results in three clinically distinct subtypes

Objective. There is great need for better risk stratification in vulvar squamous cell carcinoma (VSCC). Our aim was to define the prognostic significance of stratifying VSCC based on p16 and p53 immunohistochemistry (IHC) as surrogate markers for HPV and TP53 mutations. Methods. A large retrospective cohort of surgically treated women with primary VSCC was used. VSCC were classified into three subtypes: HPV-positive (HPVpos), HPV-negative/p53 mutant (HPVneg/p53mut), and HPVnegative/p53 wildtype (HPVneg/p53wt). Overall survival (OS), relative survival (RS), and recurrence-free period (RFP) were depicted using the Kaplan-Meier method and survival curves for relative survival; associations were studied using univariable and multivariable Cox proportional hazard models. Results. Of the 413 VSCCs, 75 (18%) were HPVpos, 63 (15%) HPVneg/p53wt, and 275 (66%) HPVneg/p53mut VSCC. Patients with HPVneg/p53mut VSCC had worse OS and RS (HR 3.43, 95%CI 1.80–6.53, and relative excess risk (RER) of 4.02; 95%CI 1.48–10.90, respectively, and worse RFP (HR 3.76, 95%CI 2.02–7.00). HPVpos VSCC patients showed most favorable outcomes. In univariate analysis, the molecular subtype of VSCC was a prognostic marker for OS, RS and RFP (p = 0.003, p = 0.009, p < 0.001, respectively) and remained prognostic for RFP even after adjusting for known risk factors (p = 0.0002). Conclusions. Stratification of VSCC by p16- and p53-IHC has potential to be used routinely in diagnostic pathology. It results in the identification of three clinically distinct subtypes and may be used to guide treatment and follow-up, and in stratifying patients in future clinical trials

Total laparoscopic hysterectomy versus total abdominal hysterectomy with bilateral salpingo-oophorectomy for endometrial carcinoma: a randomised controlled trial with 5-year follow-up

This report is on recovery and long-term outcomes in a small-scale randomised controlled trial (RCT) after total laparoscopic hysterectomy versus total abdominal hysterectomy in (potential) endometrial carcinoma patients. An RCT was performed among women with atypical endometrial hyperplasia and endometrial carcinoma scheduled for hysterectomy in a teaching hospital in The Netherlands. Women were randomised to total laparoscopic hysterectomy versus total abdominal hysterectomy both with bilateral salpingo-oophorectomy and were followed until 5 years after the intervention. Patients completed the RAND 36-Item Short Form Health Survey (RAND-36), Quality of Recovery-40 (QoR-40) and Recovery Index-10 (RI-10) until 12 weeks after surgery. Main outcome measure was quality of life and recovery in the first 12 weeks after surgery. A linear mixed model was used for statistical analysis while accounting for baseline values where applicable. Seventeen women were included, of whom 11 allocated to the laparoscopic arm and 6 to the abdominal arm. Laparoscopic hysterectomy performed better on all scales and subscales used in the study. A statistically significant treatment effect, favouring laparoscopic hysterectomy, was found in the total RAND-36 (difference between groups 142 units, 95% confidence interval 46; 236). Clinical follow-up was completed after median 60 months, but this study was too small for conclusions regarding the safety and survival. Laparoscopic hysterectomy results in better postoperative quality of life in the first 12 weeks after surgery when compared with abdominal hysterectomy