Weight-loss interventions in endometrial cancer survivors

Background
Endometrial or womb cancer is a common cancer in women and the number of cases is rising. This is due, in part, to increasing levels of obesity, which is a major risk factor for the disease. Whilst survival following endometrial cancer is generally excellent if diagnosed early, affected women are more likely to die early due to an increased risk of heart attacks and strokes and to have poorer quality of life. This review assessed the evidence for weight-loss interventions in overweight and obese endometrial cancer survivors to determine whether they were of benefit compared with usual care.

Study characteristics
We included three randomised controlled trials in which women were allocated at random to receive one of several interventions (treatments) and which involved 161 obese participants. The trials were conducted in the USA and the UK. All compared lifestyle advice (diet and exercise) plus self-help techniques (to encourage adherence to the advice) with usual care. The evidence is current to January 2018.

Key results
We found no benefit for endometrial cancer survivors from receiving lifestyle advice in terms of survival, cardiovascular events or quality of life, though such interventions were not associated with significant or serious harms to participants. They did, however, report higher rates of musculoskeletal symptoms, presumably due to increases in physical activity. Whilst some women lost weight with these interventions, others did not, meaning that overall there was little or no benefit.

Quality of the evidence
The quality of included studies was, however, low or very low and all were small in terms of the number of participants and not designed to specifically look at the effect of their intervention on survival. Additional high-quality studies are required in this field and currently there are five ongoing trials.

Authors' conclusions: 

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 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, although musculoskeletal problems were increased, presumably due to increased activity levels. Our conclusion is based on low- and very low-quality evidence from a small number of trials and very few patients. We therefore have very little confidence in the evidence: the true effect of weight-loss interventions in obese women with endometrial cancer is currently not known.

Further methodologically-rigorous, adequately-powered RCTs are required with follow-up of 5 to 10 years duration. These should focus on the effects of varying dietary modification regimens, pharmacological treatments associated with weight loss and bariatric surgery on survival, quality of life, weight loss and adverse events.

Read the full abstract...
Background: 

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, a frequent cause of death in endometrial cancer survivors.

Objectives: 

To determine the impact of weight-loss interventions, in addition to standard management of endometrial cancer, on overall survival and the frequency of adverse events.

Secondary objectives include an assessment of weight-loss interventions on endometrial cancer-specific survival, weight loss achieved, cardiovascular event frequency and quality of life both overall and stratified according to patient body mass index (BMI), where possible.

Search strategy: 

This review searched Cochrane Central Register of Controlled Trials, MEDLINE, Embase and reference lists of articles, trial registries, and international gynaecological oncology conference abstracts from inception to January 2018.

Selection criteria: 

Randomised controlled trials (RCTs) of interventions to facilitate weight loss in overweight or obese women undergoing treatment for, or previously treated for, endometrial cancer were selected.

Data collection and analysis: 

Two review authors independently selected studies, assessed trial quality, and extracted data with disagreements resolved by a third review author. Study authors were contacted to obtain missing data, including details of any adverse events.

Main results: 

We included three RCTs in the review, randomising a total of 161 overweight and obese women with endometrial cancer. All studies compared combined behavioural and lifestyle interventions to facilitate weight loss through dietary modification and increased physical activity. The 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 (attrition rate up to 29%).

Combined behaviour and lifestyle interventions were not associated with improved overall survival (risk ratio (RR mortality), 0.23 95% confidence interval (CI) 0.01 to 4.55, P = 0.34, one RCT, 37 participants; very low-certainty evidence) compared with usual care at 24 months. There was no evidence that such interventions were associated with improvements in cancer-specific survival or cardiovascular event frequency as no cancer-related deaths, myocardial infarctions or strokes were reported in the included studies. None of the included RCTs reported data for the outcome of recurrence-free survival. Combined behaviour and lifestyle interventions were not associated with significant weight loss at either six months (mean difference (MD) -1.88 kg, 95% CI -5.98 to 2.21 kg, P = 0.37, three RCTs, 131 participants, I2= 0%; low-certainty evidence)or 12 months (MD -8.98 kg, 95% CI -19.88 to 1.92 kg, P = 0.11, two RCTs, 91 participants, I2= 0%; very low-certainty evidence) when compared with usual care. Combined behaviour and lifestyle interventions were not associated with increased quality of life, when measured using either the SF-12 Physical Health questionnaire or FACT-G at six months (FACT-G MD 2.51, 95% CI -5.61 to 10.64, P = 0.54, two RCTs, 95 participants, I2= 83%; very low-certainty evidence), or by FACT-G alone at 12 months (MD 2.77, 95% CI -0.65 to 6.20, P = 0.11, two RCTs, 89 participants, I2= 0%; very low-certainty evidence) when compared with usual care. No serious adverse events, for example hospitalisation or deaths, were reported in included trials. Lifestyle and behavioural interventions were associated with a higher risk of musculoskeletal symptoms (RR 19.03, 95% CI 1.17, 310.52, P = 0.04, two RCTs, 91 participants; low-certainty evidence).

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