Cytoreductive surgery plus chemotherapy versus chemotherapy alone for recurrent epithelial ovarian cancer.

OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the benefits and harms of secondary CRS and chemotherapy in comparison to chemotherapy alone for women with platinum-sensitive recurrent epithelial ovarian cancer.

Abnormal preoperative haematological parameters in Endometrial cancer; reflecting tumour aggressiveness or reduced response to radiotherapy?

BACKGROUND: In endometrial cancer (EC), preoperative anaemia, thrombocytosis and leucocytosis appear to be associated with worse prognosis. It remains unclear whether these parameters solely reflect tumour aggressiveness, or also impact response to adjuvant treatment. Therefore, our primary aim is to evaluate the prognostic relevance of anaemia, thrombocytosis and leucocytosis on survival in EC. Secondary, to explore their predictive relevance in response to radiotherapy in EC. METHODS: A retrospective multicentre cohort study was performed within 10 hospitals. Preoperative haematological parameters were defined as: Anaemia - haemoglobin <7.45 mmol/L (<12 g/Dl), thrombocytosis - platelets >400 × 109 platelets/L, leucocytosis - leukocytes >10 × 109/L. The relationship of haematological parameters with clinicopathological characteristics, ESGO/ESTRO/ESP risk groups and survival were evaluated. Furthermore, the predictive value of haematological parameters was determined on the overall response to adjuvant radiotherapy and for the ESGO/ESTRO/ESP intermediate-risk group solely receiving radiotherapy. RESULTS: A total of 894 patients were included with a median follow-up of 4.5 years. Anaemia was present in 103 (11.5%), thrombocytosis in 79 (8.8%) and leucocytosis in 114 (12.7%) patients. The presence of anaemia or thrombocytosis was significantly associated with ESGO/ESTRO/ESP high-risk (respectively, P = 0.002 and P = 0.041). In the entire cohort, anaemia remained independently associated with decreased disease-specific survival (HR 2.31, 95% CI (1.19-4.50), P = 0.013) after adjusting for age, the abnormal haematological parameters and ESGO/ESTRO/ESP risk groups. In patients that were treated with adjuvant radiotherapy (n = 239), anaemia was associated with significant reduced 5-year disease-specific and recurrence-free survival (P = 0.005 and P = 0.025, respectively). In ESGO/ESTRO/ESP intermediate risk patients that received solely vaginal brachytherapy (n = 74), anaemia was associated with reduced disease-specific survival (P = 0.041). CONCLUSIONS: Current data demonstrate the importance of preoperative anaemia as independent prognostic factor in patients with EC. Moreover, anaemia seems to be associated with reduced response to radiotherapy. Prospective validation in a larger study cohort is needed to verify anaemia as predictive biomarker for radiotherapy.What is already known on this subject? In endometrial cancer, preoperative abnormal haematological parameters like, anaemia, thrombocytosis and leucocytosis appears to be associated with FIGO advanced-stage and unfavourable outcome.What do the results of this study add? It remains unclear whether anaemia, thrombocytosis or leucocytosis solely reflecting worse prognosis by advanced tumour stage, or also impact response to adjuvant treatment. Current data demonstrate that anaemia is independent associated with decreased disease-specific survival and anaemia seems related with reduced response to radiotherapy and in specific to vaginal brachytherapy in ESGO/ESTRO/ESP intermediate risk patients.What are the implications of these findings for clinical practice and/or further research? Specific applied adjuvant treatment is needed if patients with anaemia have a reduced response to radiotherapy in EC. Prospective validation in a larger study cohort is required to verify anaemia as predictive biomarker for radiotherapy and to further evaluate the prognostic/predictive impact of anaemia in addition to the molecular subgroups.

In this study we focused on three specific blood values before surgery to predict survival outcomes in endometrial cancer patients: low haemoglobin (anaemia), high platelet count (thrombocytosis) and high white blood cell count (leucocytosis). We studied 894 patients with endometrial cancer over about 4.5 years, in which 11.5% had anaemia, 8.8% thrombocytosis and 12.7% leucocytosis. Anaemia was linked to a lower chance of surviving endometrial cancer, even after we considering patients' age, thrombocytosis, leucocytosis and the endometrial cancer risk classification groups. In patients who received radiotherapy after surgery (293 patients), anaemia was linked to a lower change of surviving and cancer coming back within 5 years. In patients within the intermediate endometrial cancer risk classification group who only received specific radiotherapy (74 patients), anaemia was even linked with lower chance of survival. In conclusion, anaemia is an important factor in predicting endometrial cancer outcomes, and it might also make radiotherapy less effective for some patients.

Evaluation of treatment, prognostic factors, and survival in 198 vulvar melanoma patients: Implications for clinical practice.

OBJECTIVE: To identify clinicopathological characteristics, treatment patterns, clinical outcomes and prognostic factors in patients with vulvar melanoma (VM). MATERIALS & METHODS: This retrospective multicentre cohort study included 198 women with VM treated in eight cancer centres in the Netherlands and UK between 1990 and 2017. Clinicopathological features, treatment, recurrence, and survival data were collected. Overall and recurrence-free survival was estimated with the Kaplan-Meier method. Prognostic parameters were identified with multivariable Cox regression analysis. RESULTS: The majority of patients (75.8%) had localized disease at diagnosis. VM was significantly associated with high-risk clinicopathological features, including age, tumour thickness, ulceration, positive resection margins and involved lymph nodes. Overall survival was 48% (95% CI 40-56%) and 31% (95% CI 23-39%) after 2 and 5 years respectively and did not improve in patients diagnosed after 2010 compared to patients diagnosed between 1990 and 2009. Recurrence occurred in 66.7% of patients, of which two-third was non-local. In multivariable analysis, age and tumour size were independent prognostic factors for worse survival. Prognostic factors for recurrence were tumour size and tumour type. Only the minority of patients were treated with immuno- or targeted therapy. CONCLUSION: Our results show that even clinically early-stage VM is an aggressive disease associated with poor clinical outcome due to distant metastases. Further investigation into the genomic landscape and the immune microenvironment in VM may pave the way to novel therapies to improve clinical outcomes in these aggressive tumours. Clinical trials with immunotherapy or targeted therapy in patients with high-risk, advanced or metastatic disease are highly needed.

Impact of hormonal biomarkers on response to hormonal therapy in advanced and recurrent endometrial cancer.

BACKGROUND: Approximately 20% of women with endometrial cancer have advanced-stage disease or suffer from a recurrence. For these women, prognosis is poor, and palliative treatment options include hormonal therapy and chemotherapy. Lack of predictive biomarkers and suboptimal use of existing markers for response to hormonal therapy have resulted in overall limited efficacy. OBJECTIVE: This study aimed to improve the efficacy of hormonal therapy by relating immunohistochemical expression of estrogen and progesterone receptors and estrogen receptor pathway activity scores to response to hormonal therapy. STUDY DESIGN: Patients with advanced or recurrent endometrial cancer and available biopsies taken before the start of hormonal therapy were identified in 16 centers within the European Network for Individualized Treatment in Endometrial Cancer and the Dutch Gynecologic Oncology Group. Tumor tissue was analyzed for estrogen and progesterone receptor expressions and estrogen receptor pathway activity using a quantitative polymerase chain reaction-based messenger RNA model to measure the activity of estrogen receptor-related target genes in tumor RNA. The primary endpoint was response rate defined as complete and partial response using the Response Evaluation Criteria in Solid Tumors. The secondary endpoints were clinical benefit rate and progression-free survival. RESULTS: Pretreatment biopsies with sufficient endometrial cancer tissue and complete response evaluation were available in 81 of 105 eligible cases. Here, 22 of 81 patients (27.2%) with a response had estrogen and progesterone receptor expressions of >50%, resulting in a response rate of 32.3% (95% confidence interval, 20.9-43.7) for an estrogen receptor expression of >50% and 50.0% (95% confidence interval, 35.2-64.8) for a progesterone receptor expression of >50%. Clinical benefit rate was 56.9% for an estrogen receptor expression of >50% (95% confidence interval, 44.9-68.9) and 75.0% (95% confidence interval, 62.2-87.8) for a progesterone receptor expression of >50%. The application of the estrogen receptor pathway test to cases with a progesterone receptor expression of >50% resulted in a response rate of 57.6% (95% confidence interval, 42.1-73.1). After 2 years of follow-up, 34.3% of cases (95% confidence interval, 20-48) with a progesterone receptor expression of >50% and 35.8% of cases (95% confidence interval, 20-52) with an estrogen receptor pathway activity score of >15 had not progressed. CONCLUSION: The prediction of response to hormonal treatment in endometrial cancer improves substantially with a 50% cutoff level for progesterone receptor immunohistochemical expression and by applying a sequential test algorithm using progesterone receptor immunohistochemical expression and estrogen receptor pathway activity scores. However, results need to be validated in the prospective Prediction of Response to Hormonal Therapy in Advanced and Recurrent Endometrial Cancer (PROMOTE) study.

Detection of microRNA in urine to identify patients with endometrial cancer: a feasibility study.

OBJECTIVE: To find dysregulated urinary microRNAs associated with endometrial cancer as a first step in finding a non-invasive new diagnostic biomarker. The second objective is to determine the correlation of urinary microRNAs with clinicopathological characteristics. METHODS: A prospective cohort study of patients presenting with abnormal bleeding between March and November 2019 was performed at the Royal Cornwall Hospital Trust Truro. Urine samples were obtained from women diagnosed with endometrial cancer and benign endometrial sampling. MicroRNA was isolated and quantitative real time PCR was used to detect expression levels of microRNAs. RESULTS: A total of 61 women were included in this study: 24 endometrial cancer patients, and 37 controls. Median age was 64 years (range 45-94) and median body mass index was 29 kg/m2 (range 17-54). MiR-223 was significantly up-regulated in urine of endometrial cancers patients (p=0.003). Furthermore, let7-i, miR-34a, and miR-200c were significantly down-regulated and miR-424 was up-regulated in obese women. In addition, miR-148a and miR-222 were significantly down-regulated in elderly women, and miR-16, miR-26b, and miR-200c were significantly deregulated in women with multiple comorbidities. CONCLUSION: MicroRNA expression levels in urine can potentially be used as a non-invasive diagnostic test for endometrial cancer. Furthermore, aberrant microRNA expression in urine is associated with patient characteristics. Further research in larger trials is needed to validate the potential utility of urinary microRNAs.

Postoperative interventions for preventing bladder dysfunction after radical hysterectomy in women with early-stage cervical cancer.

BACKGROUND: Bladder dysfunction is a common complication following radical hysterectomy, caused by the damage to pelvic autonomic nerves that innervate the muscles of the bladder, urethral sphincter, and pelvic floor fasciae. Bladder dysfunction increases the rates of urinary tract infection, hospital visits or admission, and patient dissatisfaction. In addition, bladder dysfunction can also negatively impact patient quality of life (QoL). Several postoperative interventions have been proposed to prevent bladder dysfunction following radical hysterectomy. To our knowledge, there has been no systematic review evaluating the effectiveness and safety of these interventions for preventing bladder dysfunction following radical hysterectomy in women with cervical cancer. OBJECTIVES: To evaluate the effectiveness and safety of postoperative interventions for preventing bladder dysfunction following radical hysterectomy in women with early-stage cervical cancer (stage IA2 to IIA2). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 4) in the Cochrane Library, MEDLINE via Ovid (1946 to April week 2, 2020), and Embase via Ovid (1980 to 2020, week 16). We also checked registers of clinical trials, grey literature, conference reports, and citation lists of included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) evaluating the effectiveness and safety of any type of postoperative interventions for preventing bladder dysfunction following a radical hysterectomy in women with stage IA2 to IIA2 cervical cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently selected potentially relevant RCTs, extracted data, assessed risk of bias, compared results, and made judgments on the quality and certainty of the evidence. We resolved any disagreements through discussion or consultation with a third review author. Outcomes of interest consisted of spontaneous voiding recovery one week after the operation, quality of life (QoL), adverse events, post-void residual urine volume one month after the operation, urinary tract infection over the one month following the operation, and subjective urinary symptoms. MAIN RESULTS: We identified 1464 records as a result of the search (excluding duplicates). Of the 20 records that potentially met the review criteria, we included five reports of four studies. Most of the studies had unclear risks of selection and reporting biases. Of the four studies, one compared bethanechol versus placebo and three studies compared suprapubic catheterisation with intermittent self-catheterisation. We identified two ongoing studies. Bethanechol versus placebo The study reported no information on the rate of spontaneous voiding recovery at one week following the operation, QoL, adverse events, urinary tract infection in the first month after surgery, and subjective urinary symptoms for this comparison. The volume of post-void residual urine, assessed at one month after surgery, among women receiving bethanechol was lower than those in the placebo group (mean difference (MD) -37.4 mL, 95% confidence interval (CI) -60.35 to -14.45; one study, 39 participants; very-low certainty evidence). Suprapubic catheterisation versus intermittent self-catheterisation The studies reported no information on the rate of spontaneous voiding recovery at one week and post-void residual urine volume at one month following the operation for this comparison. There was no difference in risks of acute complication (risk ratio (RR) 0.77, 95% CI 0.24 to 2.49; one study, 71 participants; very low certainty evidence) and urinary tract infections during the first month after surgery (RR 0.77, 95% CI 0.53 to 1.13; two studies, 95 participants; very- low certainty evidence) between participants who underwent suprapubic catheterisation and those who underwent intermittent self-catheterisation. Available data were insufficient to calculate the relative measures of the effect of interventions on QoL and subjective urinary symptoms. AUTHORS' CONCLUSIONS: None of the included studies reported rate of spontaneous voiding recovery one week after surgery, time to a post-void residual volume of urine of 50 mL or less, or post-void residual urine volume at 6 and 12 months after surgery, all of which are important outcomes for assessing postoperative bladder dysfunction. Limited evidence suggested that bethanechol may minimise the risk of bladder dysfunction after radical hysterectomy by lowering post-void residual urine volume. The certainty of this evidence, however, was very low. The effectiveness of different types of postoperative urinary catheterisation (suprapubic and intermittent self-catheterisation) remain unproven.

Usefulness of microRNA detection in the diagnostics of endometrial cancer.

INTRODUCTION: MicroRNAs (miRNAs) are noncoding RNAs that regulate gene expression and contribute to the development of cancer. They have been shown to be stable in tissue samples and may be promising diagnostic biomarkers for endometrial cancer. MATERIAL AND METHODS: A retrospective cohort study of women diagnosed with endometrial cancer between January 2017 and December 2017 was performed at the Royal Cornwall Hospital. Archived formalin-fixed paraffin-embedded samples were obtained from patients with endometrial cancer and healthy women. MicroRNA was isolated and quantitative real-time polymerase chain reaction was used to detect expression levels of miRNAs. RESULTS: A total of 76 women were included: 36 endometrial cancer patients, 40 healthy controls. A distinct panel of miR-200a, miR-200b, miR-200c, miR-205, and miR-182 showed an area under the curve of 0.958, sensitivity 92%, specificity 89%, positive predictive value of 89% (95% CI 82%-94%) and negative predictive value of 91% (95% CI 85%-96%) in diagnosing endometrial cancer. High miR-182 expression levels were significantly related to high-grade endometrioid tumors compared with low-grade tumors. CONCLUSIONS: We demonstrated high diagnostic accuracy of miRNA for detecting endometrial cancer. In addition, miRNA contributed to an improvement in distinguishing between high-grade and low-grade endometrioid tumors.

The impact of socioeconomic deprivation on mortality in cervical cancer patients in Cornwall (England).

OBJECTIVES: To assess the association between risk factors, including socioeconomic deprivation, and mortality, recurrence and chemo- or radiation toxicity in cervical cancer patients. METHODS: Retrospective study of cervical cancer patients diagnosed between January 2007 and July 2018. Patient characteristics and mortality data, including recurrence, were assessed, together with socioeconomic deprivation measures evaluated using the English Indices of Multiple Deprivation. Markov multi-state models were used to model mortality and recurrence, and logistic regression models were used to model chemo- or radiation toxicity. RESULTS: Included were 243 women with a median age of 49 years. A total of 57 patients died (23%), of which 41 due to cervical cancer, and 21 (9%) had recurrent disease. Hazard ratios (HR) showed no evidence of association between socioeconomic deprivation and cancer-specific hazard of mortality from diagnosis or recurrence, hazard of mortality due to other causes or hazard of cancer recurrence. Furthermore, there was no evidence of association between socioeconomic deprivation and chemo- or radiation toxicity (bowel, bladder or vaginal stenosis). CONCLUSIONS: No associations were found between socioeconomic deprivation and cancer mortality or recurrence in cervical cancer patients in the population of Cornwall. In addition, no association was found between socioeconomic deprivation and chemo- or radiation toxicity.

Body mass index and sexual function in women with gynaecological cancer.

OBJECTIVES: To investigate the association between body mass index (BMI) and sexual functioning in gynaecologic cancer patients. To determine the association between socio-economic deprivation and sexual functioning. METHODS: This is a prospective cohort study on women undergoing surgery for suspected or proven gynaecological cancer between September 2014 and February 2016 in the Royal Cornwall Hospital Trust. Patients were invited to participate by completing the Female Sexual Function Index (FSFI) at three time points: preoperative, 3 months postoperative, and 1 year postoperative. A semiparametric model of the FSFI score was used to establish the association between BMI and sexual functioning. RESULTS: A total of 257 patients were approached of which 166 patients were included. Fifty-two patients (33.8%) were overweight (BMI, 25-29.9 kg/m2 ), 44 (28.6%) were obese (BMI, 30-39.9 kg/m2 ), and a further 20 (13.0%) morbidly obese (BMI ≥ 40 kg/m2 ). Overweight and obese women reported improved sexual functioning compared with normal-weight women in endometrial, ovarian, and vulvar cancers. Among cervical cancer, worse sexual functioning was seen in women with an increased BMI; however, this was not significant. Younger age was associated with improved sexual function, and sexual functioning was better postoperatively for all patients compared with preoperatively. There was no evidence of relationship between deprivation and sexual functioning in gynaecological cancer patients. CONCLUSION: Higher BMI is associated with improved sexual functioning in endometrial, ovarian, and vulvar cancer; however, this was not seen in cervical cancer patients. There is no evidence of correlation between deprivation and sexual functioning.

Nerve-sparing radical hysterectomy compared to standard radical hysterectomy for women with early stage cervical cancer (stage Ia2 to IIa).

BACKGROUND: Radical hysterectomy is one of the standard treatments for stage Ia2 to IIa cervical cancer. Bladder dysfunction caused by disruption of the pelvic autonomic nerves is a common complication following standard radical hysterectomy and can affect quality of life significantly. Nerve-sparing radical hysterectomy is a modified radical hysterectomy, developed to permit resection of oncologically relevant tissues surrounding the cervical lesion, while preserving the pelvic autonomic nerves. OBJECTIVES: To evaluate the benefits and harms of nerve-sparing radical hysterectomy in women with stage Ia2 to IIa cervical cancer. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 4), MEDLINE via Ovid (1946 to May week 2, 2018), and Embase via Ovid (1980 to 2018, week 21). We also checked registers of clinical trials, grey literature, reports of conferences, citation lists of included studies, and key textbooks for potentially relevant studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) evaluating the efficacy and safety of nerve-sparing radical hysterectomy compared to standard radical hysterectomy for women with early stage cervical cancer (stage Ia2 to IIa). DATA COLLECTION AND ANALYSIS: We applied standard Cochrane methodology for data collection and analysis. Two review authors independently selected potentially relevant RCTs, extracted data, evaluated risk of bias of the included studies, compared results and resolved disagreements by discussion or consultation with a third review author, and assessed the certainty of evidence. MAIN RESULTS: We identified 1332 records as a result of the search (excluding duplicates). Of the 26 studies that potentially met the review criteria, we included four studies involving 205 women; most of the trials had unclear risks of bias. We identified one ongoing trial.The analysis of overall survival was not feasible, as there were no deaths reported among women allocated to standard radical hysterectomy. However, there were two deaths in among women allocated to the nerve-sparing technique. None of the included studies reported rates of intermittent self-catheterisation over one month following surgery. We could not analyse the relative effect of the two surgical techniques on quality of life due to inconsistent data reported. Nerve-sparing radical hysterectomy reduced postoperative bladder dysfunctions in terms of a shorter time to postvoid residual volume of urine ≤ 50 mL (mean difference (MD) -13.21 days; 95% confidence interval (CI) -24.02 to -2.41; 111 women; 2 studies; low-certainty evidence) and lower volume of postvoid residual urine measured one month following operation (MD -9.59 days; 95% CI -16.28 to -2.90; 58 women; 2 study; low-certainty evidence). There were no clear differences in terms of perioperative complications (RR 0.55; 95% CI 0.24 to 1.26; 180 women; 3 studies; low-certainty evidence) and disease-free survival (HR 0.63; 95% CI 0.00 to 106.95; 86 women; one study; very low-certainty evidence) between the comparison groups. AUTHORS' CONCLUSIONS: Nerve-sparing radical hysterectomy may lessen the risk of postoperative bladder dysfunction compared to the standard technique, but the certainty of this evidence is low. The very low-certainty evidence for disease-free survival and lack of information for overall survival indicate that the oncological safety of nerve-sparing radical hysterectomy for women with early stage cervical cancer remains unclear. Further large, high-quality RCTs are required to determine, if clinically meaningful differences of survival exist between these two surgical treatments.

Laparoscopy versus laparotomy for the management of early stage endometrial cancer.

BACKGROUND: This is an update of a previous Cochrane Review published in 2012, Issue 9.Surgery for endometrial cancer (hysterectomy with removal of both fallopian tubes and ovaries) is performed through laparotomy. It has been suggested that the laparoscopic approach is associated with a reduction in operative morbidity. Over the last two decades there has been a steady increase of the use of laparoscopy for endometrial cancer. This review investigated the evidence of benefits and harms of laparoscopic surgery compared with laparotomy for presumed early stage endometrial cancer. OBJECTIVES: To compare overall survival (OS) and disease free survival (DFS) for laparoscopic surgery versus laparotomy in women with presumed early stage endometrial cancer. SEARCH METHODS: For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 5) in the Cochrane Library, MEDLINE via Ovid (April 2012 to June 2018) and Embase via Ovid (April 2012 to June 2018). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. The trial registers included NHMRC Clinical Trials Register, UKCCCR Register of Cancer Trials, Meta-Register and Physician Data Query Protocol. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing laparoscopy and laparotomy for early stage endometrial cancer. DATA COLLECTION AND ANALYSIS: We independently abstracted data and assessed risk of bias. We used hazard ratios (HRs) for OS and recurrence free survival (RFS), risk ratios (RR) for severe adverse events and mean differences (MD) for continuous outcomes in women who received laparoscopy or laparotomy with 9% confidence intervals (CI). These were pooled in random-effects meta-analyses. MAIN RESULTS: We identified one new study in this update of the review. The review contains nine RCTs comparing laparoscopy with laparotomy for the surgical management of early stage endometrial cancer.All nine studies met the inclusion criteria and assessed 4389 women at the end of the studies. Six studies assessing 3993 participants with early stage endometrial cancer found no significant difference in the risk of death between women who underwent laparoscopy and women who underwent laparotomy (HR 1.04, 95% 0.86 to 1.25; moderate-certainty evidence) and five studies assessing 3710 participants found no significant difference in the risk of recurrence between the laparoscopy and laparotomy groups (HR 1.14, 95% CI 0.90 to 1.43; moderate-certainty evidence). There was no significant difference in the rate of perioperative death; women requiring a blood transfusion; and bladder, ureteric, bowel and vascular injury. However, one meta-analysis of three studies found that women in the laparoscopy group lost significantly less blood than women in the laparotomy group (MD -106.82 mL, 95% CI -141.59 to -72.06; low-certainty evidence). A further meta-analysis of two studies, which assessed 3344 women and included one very large trial of over 2500 participants, found that there was no clinical difference in the risk of severe postoperative complications in women in the laparoscopy and laparotomy groups (RR 0.78, 95% CI 0.44 to 1.38). Most studies were at moderate risk of bias. All nine studies reported hospital stay and results showed that on average, laparoscopy was associated with a significantly shorter hospital stay. AUTHORS' CONCLUSIONS: This review found low to moderate-certainty evidence to support the role of laparoscopy for the management of early endometrial cancer. For presumed early stage primary endometrioid adenocarcinoma of the endometrium, laparoscopy is associated with similar OS and DFS. Furthermore, laparoscopy is associated with reduced operative morbidity and hospital stay. There is no significant difference in severe postoperative morbidity between the two modalities.The certainty of evidence for OS and RFS was moderate and was downgraded for unclear risk of bias profiles and imprecision in effect estimates. However, most studies used adequate methods of sequence generation and concealment of allocation so studies were not prone to selection bias. Adverse event outcomes were downgraded for the same reasons and additionally for low event rates and low power thus these outcomes provided low-certainty evidence.

Locally advanced vulva cancer: A single centre review of anovulvectomy and a systematic review of surgical, chemotherapy and radiotherapy alternatives. Is an international collaborative RCT destined for the "too difficult to do" box?

INTRODUCTION: Treatment of locally advanced vulva cancer (LAVC) remains challenging. Due to the lack of randomised trials many questions regarding the indications for different treatment options and their efficacy remain unanswered. METHODS: In this retrospective study we provide the largest published series of LAVC patients treated with anovulvectomy, reporting oncological outcomes and morbidity. Additionally, a systematic literature review was performed for all treatment options 1946-2015. RESULTS: In our case series, 57/70 (81%) patients were treated in the primary setting with anovulvectomy and 13 patients underwent anovulvectomy for recurrent disease. The median overall survival (OS) was 69months (1-336) with disease specific survival of 159months (1-336). Following anovulvectomy for primary disease, time to progression and OS were significantly higher in node negative disease (10 vs. 96months; 19 vs. 121months, p<0.0001). Post-surgical complications were observed in 36 (51.4%), the majority of which were Grade I/II infections. There was one peri-operative death. Review of the literature showed that chemotherapy, radiotherapy or combination treatments are alternatives to surgery. Evidence relating to all of these consisted mostly of small retrospective series, which varied considerably in terms of patient characteristics and treatment schedules. Significant patient and treatment heterogeneity prevented meta-analysis with significant biases in these studies. It was unclear if survival or morbidity was better in any one group with a lack of data reporting complications, quality of life, and long term follow-up. However, results for chemoradiation are encouraging enough to warrant further investigation. CONCLUSIONS: There remains inadequate evidence to identify an optimal treatment for LAVC. However, there is sufficient evidence to support a trial of anovulvectomy versus chemoradiation. Discussions and consensus would be needed to determine trial criteria including the primary outcome measure. Neoadjuvant chemotherapy or radiotherapy alone may be best reserved for the palliative setting or metastatic disease.

Intraoperative frozen section analysis for the diagnosis of early stage ovarian cancer in suspicious pelvic masses.

BACKGROUND: Women with suspected early-stage ovarian cancer need surgical staging which involves taking samples from areas within the abdominal cavity and retroperitoneal lymph nodes in order to inform further treatment. One potential strategy is to surgically stage all women with suspicious ovarian masses, without any histological information during surgery. This avoids incomplete staging, but puts more women at risk of potential surgical over-treatment.A second strategy is to perform a two-stage procedure to remove the pelvic mass and subject it to paraffin sectioning, which involves formal tissue fixing with formalin and paraffin embedding, prior to ultrathin sectioning and multiple site sampling of the tumour. Surgeons may then base further surgical staging on this histology, reducing the rate of over-treatment, but conferring additional surgical and anaesthetic morbidity.A third strategy is to perform a rapid histological analysis on the ovarian mass during surgery, known as 'frozen section'. Tissues are snap frozen to allow fine tissue sections to be cut and basic histochemical staining to be performed. Surgeons can perform or avoid the full surgical staging procedure depending on the results. However, this is a relatively crude test compared to paraffin sections, which take many hours to perform. With frozen section there is therefore a risk of misdiagnosing malignancy and understaging women subsequently found to have a presumed early-stage malignancy (false negative), or overstaging women without a malignancy (false positive). Therefore it is important to evaluate the accuracy and usefulness of adding frozen section to the clinical decision-making process. OBJECTIVES: To assess the diagnostic test accuracy of frozen section (index test) to diagnose histopathological ovarian cancer in women with suspicious pelvic masses as verified by paraffin section (reference standard). SEARCH METHODS: We searched MEDLINE (January 1946 to January 2015), EMBASE (January 1980 to January 2015) and relevant Cochrane registers. SELECTION CRITERIA: Studies that used frozen section for intraoperative diagnosis of ovarian masses suspicious of malignancy, provided there was sufficient data to construct 2 x 2 tables. We excluded articles without an available English translation. DATA COLLECTION AND ANALYSIS: Authors independently assessed the methodological quality of included studies using the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2) domains: patient selection, index test, reference standard, flow and timing. Data extraction converted 3 x 3 tables of per patient results presented in articles into 2 x 2 tables, for two index test thresholds. MAIN RESULTS: All studies were retrospective, and the majority reported consecutive sampling of cases. Sensitivity and specificity results were available from 38 studies involving 11,181 participants (3200 with invasive cancer, 1055 with borderline tumours and 6926 with benign tumours, determined by paraffin section as the reference standard). The median prevalence of malignancy was 29% (interquartile range (IQR) 23% to 36%, range 11% to 63%). We assessed test performance using two thresholds for the frozen section test. Firstly, we used a test threshold for frozen sections, defining positive test results as invasive cancer and negative test results as borderline and benign tumours. The average sensitivity was 90.0% (95% confidence interval (CI) 87.6% to 92.0%; with most studies typically reporting range of 71% to 100%), and average specificity was 99.5% (95% CI 99.2% to 99.7%; range 96% to 100%).Similarly, we analysed sensitivity and specificity using a second threshold for frozen section, where both invasive cancer and borderline tumours were considered test positive and benign cases were classified as negative. Average sensitivity was 96.5% (95% CI 95.5% to 97.3%; typical range 83% to 100%), and average specificity was 89.5% (95% CI 86.6% to 91.9%; typical range 58% to 99%).Results were available from the same 38 studies, including the subset of 3953 participants with a frozen section result of either borderline or invasive cancer, based on final diagnosis of malignancy. Studies with small numbers of disease-negative cases (borderline cases) had more variation in estimates of specificity. Average sensitivity was 94.0% (95% CI 92.0% to 95.5%; range 73% to 100%), and average specificity was 95.8% (95% CI 92.4% to 97.8%; typical range 81% to 100%).Our additional analyses showed that, if the frozen section showed a benign or invasive cancer, the final diagnosis would remain the same in, on average, 94% and 99% of cases, respectively.In cases where the frozen section diagnosis was a borderline tumour, on average 21% of the final diagnoses would turn out to be invasive cancer.In three studies, the same pathologist interpreted the index and reference standard tests, potentially causing bias. No studies reported blinding pathologists to index test results when reporting paraffin sections.In heterogeneity analyses, there were no statistically significant differences between studies with pathologists of different levels of expertise. AUTHORS' CONCLUSIONS: In a hypothetical population of 1000 patients (290 with cancer and 80 with a borderline tumour), if a frozen section positive test result for invasive cancer alone was used to diagnose cancer, on average 261 women would have a correct diagnosis of a cancer, and 706 women would be correctly diagnosed without a cancer. However, 4 women would be incorrectly diagnosed with a cancer (false positive), and 29 with a cancer would be missed (false negative).If a frozen section result of either an invasive cancer or a borderline tumour was used as a positive test to diagnose cancer, on average 280 women would be correctly diagnosed with a cancer and 635 would be correctly diagnosed without. However, 75 women would be incorrectly diagnosed with a cancer and 10 women with a cancer would be missed.The largest discordance is within the reporting of frozen section borderline tumours. Investigation into factors leading to discordance within centres and standardisation of criteria for reporting borderline tumours may help improve accuracy. Some centres may choose to perform surgical staging in women with frozen section diagnosis of a borderline ovarian tumour to reduce the number of false positives. In their interpretation of this review, readers should evaluate results from studies most typical of their population of patients.

Body mass index and the quality of life of endometrial cancer survivors--a systematic review and meta-analysis.

BACKGROUND: Obesity is a risk factor for developing endometrial cancer and known to negatively affect outcomes and survival. However, the association between obesity and quality of life of endometrial cancer survivors (ECS) remains unclear. OBJECTIVES: To assess the association between body mass index (BMI) and the quality of life of endometrial cancer survivors. In addition we assessed the associations between BMI and anxiety, depression and sexual function of endometrial cancer survivors. METHODS: The review was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, and the Cochrane Handbook for Systematic Reviews of Interventions. We performed a search of Medline (1946-2014), Embase (1980-2014), Cinahl (1981-2014), and PsycInfo (1806-2014) to identify studies that reported on the association between BMI and quality of life outcomes in endometrial cancer survivors. RESULTS: Seven studies fulfilled the inclusion criteria, of which four studies could be included in the analysis. The four studies which included 1362 patients, showed that obese survivors had a significantly poorer physical functioning (P=0.001, MD: -11.61, 95% CI: -18.66 to -4.55), social functioning (P=0.01, MD: -4.37, 95% CI: -7.75 to -1.00) and role functioning (P=0.002, MD: -5.44 95% CI: -8.90 to -1.98) when compared to non-obese women. Emotional functioning and cognitive functioning did not show significant differences (P=0.18, P=0.21). AUTHORS' CONCLUSIONS: Obesity is associated with poorer quality of life outcomes in endometrial cancer survivors, including poorer physical, role and social functioning. Future research should be directed at lifestyle interventions aiming to enhance the quality of life of this group of survivors.

The effect of lifestyle interventions on the quality of life of gynaecological cancer survivors: A systematic review and meta-analysis.

OBJECTIVE: We aimed to evaluate the effectiveness of lifestyle interventions in improving the quality of life (QoL) of endometrial and ovarian cancer survivors. METHODS: The review was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, and the Cochrane Handbook for Systematic Reviews of Interventions. We performed a search of MEDLINE (1946-2015), EMBASE (1980-2015), CINAHL (1981-2015), PsycINFO (1806-2015) and the Cochrane Trial Register to identify studies evaluating the effect of lifestyle interventions on the QoL of endometrial and ovarian cancer survivors. RESULTS: Eight studies fulfilled the inclusion criteria and comprised a total of 413 patients. Three studies were randomised controlled trials (RCTs), which showed that lifestyle interventions may improve physical functioning and significantly reduce fatigue in endometrial cancer survivors. In addition, lifestyle interventions in endometrial cancer survivors resulted in significant weight loss and improved physical activity levels, but did not show improvements in global QoL in the meta-analysis (P=0.75, P=0.49). Non-randomised trials in ovarian cancer survivors support the feasibility of lifestyle interventions and suggest they may result in QoL improvements. CONCLUSIONS: Lifestyle interventions have the potential to improve the QoL of endometrial cancer and ovarian cancer survivors, and may significantly reduce fatigue. However, the current evidence is limited and there is a need for future studies to further evaluate lifestyle interventions and their effect on QoL outcomes.

The impact of BMI on surgical complications and outcomes in endometrial cancer surgery--an institutional study and systematic review of the literature.

OBJECTIVES: We aimed to evaluate the association between body mass index (BMI), perioperative complications and outcomes in endometrial cancer (EC) patients at our institution. In addition, we performed a systematic review to compare our results to the literature. METHODS: This was a retrospective study of surgically managed EC patients between January 2006 and January 2015. Patient characteristics, surgical complications and intra- and postoperative outcomes were evaluated across BMI groups; BMI <30kg/m(2), BMI ≥30kg/m(2) and BMI ≥40kg/m(2). The systematic review was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: In total, we identified 627 women of which 514 were included; 249 women had a BMI of <30kg/m(2), 195 women had a BMI of 30-39.9kg/m(2), and 70 women were morbidly obese (BMI ≥40kg/m(2)). Obese women (BMI ≥30kg/m(2)) had significantly more postoperative surgical complications, including wound complications and antibiotics use, which was confirmed by the systematic review. The increase in complications mainly occurred in open surgery and morbidly obese patients were at highest risk. Obesity did not impact other outcomes including 30-day mortality. CONCLUSION: Obesity is associated with an increased risk of surgical morbidity in EC patients, and is most profound in open surgery and among the morbidly obese. Laparoscopic surgery may well prevent the majority of postoperative complications in this group of patients, and should therefore be the favoured approach.

Body mass index, physical activity and quality of life of ovarian cancer survivors: time to get moving?

OBJECTIVE: To evaluate the association between body mass index (BMI), physical activity (PA) and the quality of life (QoL) of ovarian cancer survivors. METHODS: We performed a two-centre cross-sectional study of women who had been treated for ovarian cancer between January 2007 and December 2014 at the Royal Cornwall Hospital Trust and the Plymouth Hospitals NHS Trust. QoL was assessed using the EORTC QLQ-C30 and QLQ-OV28 questionnaires, and PA using the Godin Leisure Time Exercise questionnaire. RESULTS: In total, 293 ovarian cancer survivors were invited to participate, of which 209 women (71.3%) responded. Thirty-five percent of women were overweight and 18% were obese, whilst only 21% met recommendations for PA. Obesity was associated with significantly poorer global QoL, physical, cognitive and social functioning, a poorer body image and more symptomatology. Sedentary behaviour was associated with poorer QoL scores including global QoL, physical, role, social and sexual functioning. After adjustment, BMI and PA both remained independently associated with QoL scores. CONCLUSION: Obesity and inactivity are associated with poorer QoL among ovarian cancer survivors. Future interventions promoting PA and weight loss should be evaluated as possible means to improve the QoL of this population.

Quality of life in ovarian cancer survivors: the influence of obesity.

OBJECTIVE: In this study, we evaluated the effect of body mass index (BMI) on the quality of life of ovarian cancer survivors. METHODS: Women diagnosed with ovarian cancer at the Royal Cornwall Hospital Trust between January 2008 and May 2013 were identified. Ovarian cancer survivors were invited to participate by completing the European Organization for Research and Treatment of Cancer QLQ-C30 (quality of life) questionnaire. Univariate and multiple regression analyses were used to determine associations between BMI and quality-of-life outcomes. RESULTS: A total of 176 ovarian cancer survivors were invited to participate, of which 133 were eligible for this study. In total, 81 ovarian cancer survivors (60.4%) completed the questionnaire, of which 26 responders (32.1%) were overweight (BMI, 25-29.9 kg/m²) and 27 (33.3%) were obese (BMI, ≥30 kg/m²). Increasing BMI was significantly associated with poorer quality-of-life outcomes in terms of physical functioning and emotional functioning, and this effect persisted for physical functioning after multiple regression analysis. CONCLUSIONS: Increasing BMI is associated with poorer quality-of-life outcomes in terms of physical and emotional functioning in ovarian cancer survivors. Further research is needed to evaluate the association between BMI and quality of life from diagnosis to survivorship to develop novel interventions.

Follow-up strategies after treatment (large loop excision of the transformation zone (LLETZ)) for cervical intraepithelial neoplasia (CIN): Impact of human papillomavirus (HPV) test.

BACKGROUND: Development of cancer of the cervix is a multi-step process as before cervical cancer develops, cervical cells undergo changes and become abnormal. These abnormalities are called cervical intraepithelial neoplasia (CIN) and are associated with increased risk of subsequent invasive cancer of the cervix. Oncogenic high-risk human papillomavirus (hrHPV), the causative agent of cervical cancer and its precursor lesions, is present in up to one-third of women following large loop excision of the transformation zone (LLETZ) treatment and is associated with increased risk of residual disease and disease recurrence. HPV testing may serve as a surveillance tool for identifying women at higher risk of recurrence. High-risk human papillomavirus testing will enable us to identify women at increased risk of residual or recurrent CIN and therefore will allow us to offer closer surveillance and early treatment, when indicated. OBJECTIVES: • To evaluate the effectiveness and safety of hrHPV testing after large loop excision of the transformation zone (LLETZ) treatment• To determine optimal follow-up management strategies following LLETZ treatment according to hrHPV status SEARCH METHODS: We searched the Cochrane Gynacological Cancer Review Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed and PsycINFO up to August 2013. We searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies, and we contacted experts in the field. SELECTION CRITERIA: We searched for randomised control trials (RCTs) that compared follow-up management strategies following LLETZ treatment for CIN. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. No trials were found; therefore no data were analysed. MAIN RESULTS: The search identified 813 references on MEDLINE, 418 on EMBASE, 22 on CINAHL, 666 on PubMed, 291 on PsycINFO and 145 on CENTRAL. When all references were imported into EndNote and duplications were removed, 1348 references remained. Initial screening of titles and abstracts of these references revealed that 42 references were potentially eligible for this review. After reading the full-text versions, we identified no relevant trials comparing hrHPV and cytology testing versus cytology testing alone for detecting residual or recurrent disease during follow-up to LLETZ treatment of adult women with CIN.We found no evidence on the effects of hrHPV and cytology testing on residual or recurrent CIN2 or higher lesions, anxiety and psychosexual morbidity outcomes in women undergoing colposcopy and treatment for CIN. AUTHORS' CONCLUSIONS: We found no evidence from RCTs to inform decisions about the best surveillance strategy for women following treatment for CIN. A prognostic systematic review is needed to investigate the risk of developing recurrent cervical intraepithelial neoplasia 2+ (CIN2+) in women with a positive hrHPV test after large loop excision of the transformation zone (LLETZ) treatment.

The impact of BMI on quality of life in obese endometrial cancer survivors: does size matter?

BACKGROUND: Survivorship and quality of life issues are becoming increasingly relevant in endometrial cancer as a result of the marked increase in incidence of the disease combined with excellent and improving long term survival. OBJECTIVE: The purpose of this study was to evaluate the effect of obesity on quality of life (QoL) in endometrial cancer survivors. METHODS: Participants were endometrioid endometrial cancer survivors diagnosed between 2008 and 2013. Quality of life was measured through the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ-C30, version 3.0). Associations between BMI and quality of life were determined by means of multivariate analyses. RESULTS: 322 women diagnosed with endometrioid endometrial cancer were invited to participate. Excluded were 15 women with unknown BMI, 40 with non-endometrioid histology and 10 with concurrent cancer. The QLQ-C30 questionnaire was completed by 158 (61.5%) women, of which 63 women (40%) were obese (BMI ≥ 30-39.9), and 30 women (19%) were morbidly obese (BMI ≥ 40). Morbidly obese women reported worse physical, role and social functioning and more somatic complaints. CONCLUSION: Morbid obesity is associated with poorer quality of life in endometrial cancer survivors. Life style interventions such as exercise programs and diet interventions could be viable means to improve the quality of life of obese endometrial cancer survivors. Future research should focus on means to improve quality of life in obese endometrial cancer survivors.