Interventions for weight reduction in obesity to improve survival in women with endometrial cancer.

BACKGROUND: This is an updated version of the original Cochrane Review published in Issue 2, 2018. Diagnoses of endometrial cancer are increasing secondary to the rising prevalence of obesity. Obesity plays an important role in promoting the development of endometrial cancer, by inducing a state of unopposed oestrogen excess, insulin resistance and inflammation. It also affects treatment, increasing the risk of surgical complications and the complexity of radiotherapy planning, and may additionally impact on subsequent survival. Weight-loss interventions have been associated with improvements in breast and colorectal cancer-specific survival, as well as a reduction in the risk of cardiovascular disease, which is a frequent cause of death in endometrial cancer survivors. OBJECTIVES: To evaluate the benefits and harm of weight-loss interventions, in addition to standard management, on overall survival and the frequency of adverse events in women with endometrial cancer who are overweight or obese compared with any other intervention, usual care, or placebo. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was from January 2018 to June 2022 (original review searched from inception to January 2018). SELECTION CRITERIA: We included randomised controlled trials (RCTs) of interventions to facilitate weight loss in women with endometrial cancer who are overweight or obese undergoing treatment for, or previously treated for, endometrial cancer compared with any other intervention, usual care, or placebo.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. overall survival and 2. frequency of adverse events. Our secondary outcomes were 3. recurrence-free survival, 4. cancer-specific survival, 5. weight loss, 6. cardiovascular and metabolic event frequency and 7. quality of Life. We used GRADE to assess certainty of evidence. We contacted study authors to obtain missing data, including details of any adverse events. MAIN RESULTS: We identified nine new RCTs and combined these with the three RCTs identified in the original review. Seven studies are ongoing.  The 12 RCTs randomised 610 women with endometrial cancer who were overweight or obese. All studies compared combined behavioural and lifestyle interventions designed to facilitate weight loss through dietary modification and increased physical activity with usual care. Included RCTs were of low or very low quality, due to high risk of bias by failing to blind participants, personnel and outcome assessors, and significant loss to follow-up (withdrawal rate up to 28% and missing data up to 65%, largely due to the effects of the COVID-19 pandemic). Importantly, the short duration of follow-up limits the directness of the evidence in evaluating the impact of these interventions on any of the survival and other longer-term outcomes.  Combined behaviour and lifestyle interventions were not associated with improved overall survival compared with usual care at 24 months (risk ratio (RR) mortality, 0.23, 95% confidence interval (CI) 0.01 to 4.55, P = 0.34; 1 RCT, 37 participants; very low-certainty evidence). There was no evidence that such interventions were associated with improvements in cancer-specific survival or cardiovascular event frequency as the studies reported no cancer-related deaths, myocardial infarctions or strokes, and there was only one episode of congestive heart failure at six months (RR 3.47, 95% CI 0.15 to 82.21; P = 0.44, 5 RCTs, 211 participants; low-certainty evidence). Only one RCT reported recurrence-free survival; however, there were no events. Combined behaviour and lifestyle interventions were not associated with significant weight loss at either six or 12 months compared with usual care (at six months: mean difference (MD) -1.39 kg, 95% CI -4.04 to 1.26; P = 0.30, I2 = 32%; 5 RCTs, 209 participants; low-certainty evidence). Combined behaviour and lifestyle interventions were not associated with increased quality of life, when measured using 12-item Short Form (SF-12) Physical Health questionnaire, SF-12 Mental Health questionnaire, Cancer-Related Body Image Scale, Patient Health Questionnaire 9-Item Version or Functional Assessment of Cancer Therapy - General (FACT-G) at 12 months when compared with usual care (FACT-G: MD 2.77, 95% CI -0.65 to 6.20; P = 0.11, I2 = 0%; 2 RCTs, 89 participants; very low-certainty evidence). The trials reported no serious adverse events related to weight loss interventions, for example hospitalisation or deaths. It is uncertain whether lifestyle and behavioural interventions were associated with a higher or lower risk of musculoskeletal symptoms (RR 19.03, 95% CI 1.17 to 310.52; P = 0.04; 8 RCTs, 315 participants; very low-certainty evidence; note: 7 studies reported musculoskeletal symptoms but recorded 0 events in both groups. Thus, the RR and CIs were calculated from 1 study rather than 8).  AUTHORS' CONCLUSIONS: The inclusion of new relevant studies has not changed the conclusions of this review. There is currently insufficient high-quality evidence to determine the effect of combined lifestyle and behavioural interventions on survival, quality of life or significant weight loss in women with a history of endometrial cancer who are overweight or obese compared to those receiving usual care. The limited evidence suggests that there is little or no serious or life-threatening adverse effects due to these interventions, and it is uncertain if musculoskeletal problems were increased, as only one out of eight studies reporting this outcome had any events. Our conclusion is based on low- and very low-certainty evidence from a small number of trials and few women. Therefore, we have very little confidence in the evidence: the true effect of weight-loss interventions in women with endometrial cancer and obesity is currently unknown. Further methodologically rigorous, adequately powered RCTs are required with follow-up of five to 10 years of duration. These should focus on the effects of varying dietary modification regimens, and pharmacological treatments associated with weight loss and bariatric surgery on survival, quality of life, weight loss and adverse events.

Characteristics and patterns of care of endometrial cancer before and during COVID-19 pandemic.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer (EC) is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms. Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of EC patients. METHODS: This is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of EC patients before (period 1: March 1, 2019 to February 29, 2020) and during (period 2: April 1, 2020 to March 31, 2021) the COVID-19 outbreak. RESULTS: Medical records of 5,164 EC patients have been retrieved: 2,718 and 2,446 women treated in period 1 and period 2, respectively. Surgery was the mainstay of treatment in both periods (p=0.356). Nodal assessment was omitted in 689 (27.3%) and 484 (21.2%) patients treated in period 1 and 2, respectively (p<0.001). While, the prevalence of patients undergoing sentinel node mapping (with or without backup lymphadenectomy) has increased during the COVID-19 pandemic (46.7% in period 1 vs. 52.8% in period 2; p<0.001). Overall, 1,280 (50.4%) and 1,021 (44.7%) patients had no adjuvant therapy in period 1 and 2, respectively (p<0.001). Adjuvant therapy use has increased during COVID-19 pandemic (p<0.001). CONCLUSION: Our data suggest that the COVID-19 pandemic had a significant impact on the characteristics and patterns of care of EC patients. These findings highlight the need to implement healthcare services during the pandemic.

ESMO management and treatment adapted recommendations in the COVID-19 era: gynaecological malignancies.

The rapid spread of severe acute respiratory syndrome coronavirus 2 infection and its related disease (COVID-19) has required an immediate and coordinate healthcare response to face the worldwide emergency and define strategies to maintain the continuum of care for the non-COVID-19 diseases while protecting patients and healthcare providers. The dimension of the COVID-19 pandemic poses an unprecedented risk especially for the more vulnerable populations. To manage patients with cancer adequately, maintaining the highest quality of care, a definition of value-based priorities is necessary to define which interventions can be safely postponed without affecting patients' outcome. The European Society for Medical Oncology (ESMO) has endorsed a tiered approach across three different levels of priority (high, medium, low) incorporating information on the value-based prioritisation and clinical cogency of the interventions that can be applied for different disease sites. Patients with gynaecological cancer are at particular risk of COVID-19 complications because of their age and prevalence of comorbidities. The definition of priority level should be based on tumour stage and histology, cancer-related symptoms or complications, aim (curative vs palliative) and magnitude of benefit of the oncological intervention, patients' general condition and preferences. The decision-making process always needs to consider the disease-specific national and international guidelines and the local healthcare system and social resources, and a changing situation in relation to COVID-19 infection. These recommendations aim to provide guidance for the definition of deferrable and undeferrable interventions during the COVID-19 pandemic for ovarian, endometrial and cervical cancers within the context of the ESMO Clinical Practice Guidelines.