Michael R. Abern, Stephen J. Freedland and Brant A. Inman
Division of Urologic Surgery, Duke University Medical Center, Durham, NC, USA
Obesity is a worldwide epidemic: it is estimated over 300 million adults are obese and over 1 billion are overweight. As obesity is a risk factor for cancers and is modiﬁable, the authors of this report retrospectively analyse the association between body mass index (BMI) and outcomes in a large multinational cohort of bladder cancer patients that underwent radical cystectomy. They found that obese patients were older and more likely to have high-grade tumours. Furthermore, obese patients received inferior lymphadenectomies, had more positive margins, and were less likely to receive adjuvant chemotherapy. The end result is an association between obesity and bladder cancer recurrence, and both cancer-speciﬁc and overall mortality.
Although these data suggest that obesity is associated with poor radical cystectomy outcomes, this contrasts with evidence showing no link between obesity and bladder cancer mortality in population-based trials such as the Cancer Prevention Study II, which prospectively followed over 900 000 participants. Why the discrepancy? One possible explanation is the presence of confounding factors and one possible confounder is the presence of type 2 diabetes. In population-based studies that considered both BMI and diabetes, people with diabetes were noted to have an increased risk of developing bladder cancer independent of BMI, whereas the converse was not true. Additionally, diabetes has been associated with recurrence and progression of non-muscle invasive bladder cancer whereas obesity has not. The impact of diabetes was not adequately addressed in the current study.
Other limitations also probably aﬀect the results. In the current study, overweight patients (BMI 25–30) had signiﬁcantly better cancer-speciﬁc survival (hazard ratio 0.80, P = 0.01) than those of ‘normal’ weight (BMI < 25). However, a threshold BMI ≥ 30 has been shown to have poor sensitivity for obesity in elderly populations, with over 25% of patients with BMI under 30 qualifying as obese based on body fat. This may result in an overstatement of the eﬀect of obesity. Conversely, the inclusion of underweight patients (BMI < 18.5) in the ‘normal’ group may underestimate the eﬀect between obesity and outcome, as cachexia may be associated with poor outcomes. Another factor mentioned by the authors is the inferior lymphadenectomies performed in obese patients, which introduces a detection bias for lymph node positivity, the strongest predictor after advanced stage for all of their tested outcomes on multivariate analysis (hazard ratio 2.01–2.33, P < 0.001).
Although the true eﬀect of obesity may be hard to quantify with these data, all would agree that maintaining a non-obese bodyweight will help many disease states with little apparent harm. Patients undergoing neoadjuvant chemotherapy before radical cystectomy have a 3-month window to lose weight and exercise more. This could improve surgical outcomes, and possibly tolerance of chemotherapy. Furthermore, if we can prove that obesity leads to increased bladder cancer recurrence or progression, a window of opportunity may exist when a low-risk tumour is diagnosed. Otherwise, we are left with the eighteenth century wisdom of Benjamin Franklin: ‘An ounce of prevention is worth a pound of cure.’