Original article
Obesity is associated with biochemical recurrence after radical prostatectomy: A multi-institutional extended validation study

https://doi.org/10.1016/j.urolonc.2017.01.022Get rights and content

Highlights

  • Overweight and obese status were associated with BCR after radical prostatectomy.

  • Obese status was associated with a higher likelihood of having features of biologically and clinically aggressive PCa (extraprostatic extension and seminal vesicle invasion).

  • Although the addition of BMI did not significantly improve the discriminative ability of the established prognostic factors, its consistent associations with aggressive biology and poor outcomes support further research regarding the underlying mechanism for this biological phenomenon.

Abstract

Background

There are no clear data regarding the association between body mass index (BMI) and outcomes after radical prostatectomy (RP). This study aimed to investigate the association between BMI and biochemical recurrence (BCR) after RP in a large international contemporary cohort of patients with prostate cancer.

Methods

We retrospectively analyzed data from 6,519 patients who underwent RP at 5 institutions. BMI was analyzed as both a continuous and categorical variable (<25 kg/m2, 25–29.9 kg/m2 [overweight], and≥30 kg/m2 [obese]). The associations of continuous and categorical BMI with BCR were evaluated using univariable and multivariable Cox models, and prognostic accuracy was assessed using Harrell׳s C-index.

Results

The median BMI was 28 kg/m2 (interquartile range: 24–32 kg/m2); 2,155 patients (33.1%) had a BMI = 25 to 29.9 kg/m2 and 2,462 patients (37.7%) had a BMI≥30 kg/m². Overweight and obese status were associated with extracapsular extension (P = 0.001) and seminal vesicle invasion (P = 0.005). The median follow-up was 28 months, and the estimated 5-year BCR-free survival rates for patients with a BMI<25 kg/m2, 25 to 29.9 kg/m2, and≥30 kg/m² were 92%, 86%, and 79%, respectively (P<0.001). Multivariable analyses (adjusted for preoperative prostate-specific antigen levels, biopsy Gleason score, and clinical stage) revealed that obesity was associated with the risk of extracapsular extension (P<0.001), seminal vesicle invasion (P<0.001), and BCR (hazard ratio: 1.37, P<0.001). BMI and obesity remained associated with BCR after adjusting for postoperative characteristics. Addition of BMI slightly increased the discrimination of the multivariable clinical prognostic model (from 79.9%–80.9%).

Conclusions

Overweight and obese status was associated with adverse pathological features and BCR after RP. However, the addition of BMI did not significantly improve the prognostic accuracy of a model that was based on established predictors.

Introduction

Prostate cancer (PCa) is the most common malignancy in men and the second leading cause of cancer-related mortality among European men [1]. Radical prostatectomy (RP) and radiation therapy are the standard of care for clinically localized PCa, although up to 40% of patients subsequently experience biochemical recurrence (BCR) [2]. Nomograms can predict BCR before and after RP, although their accuracy remains suboptimal [3].

Body fat is typically measured using body mass index (BMI) that is calculated using body weight and height. According to the World Health Organization definitions, overweight and obese status are defined using BMI values of≥25 and≥30 kg/m², respectively. It has been hypothesized that both overweight and obese status can affect the carcinogenic, endocrine, and biochemical microenvironments, which subsequently lead to tumor development and progression [4]. Several studies have evaluated the effects of overweight and obese status on PCa incidence, pathological features, and BCR after RP. Those studies revealed that increasing BMI values were associated with a higher incidence of PCa, as well as adverse pathological features at the diagnosis [5]. Furthermore, a recent meta-analysis of 36,927 patients revealed that a 5-kg/m² increase in BMI was associated with a 16% increase in the risk of BCR after RP and radiation therapy [5]. However, that study was limited by the nonlinear relationship between BMI and BCR, which could not be addressed using conventional meta-analytical techniques. Moreover, other studies failed to identify a significant association between BMI and outcomes after RP [6], [7]. Therefore, this study aimed to assess the association between BMI and BCR in a large international contemporary cohort of patients who underwent RP for PCa.

Section snippets

Patient selection and data collection

This study was performed using institutional data from the participating institutions. The appropriate ethical review boards approved this study׳s design, and all participating institutions signed data-sharing agreements before the study׳s initiation. Data from 7,402 patients with clinically localized PCa who underwent RP at 5 centers between 2000 and 2011 were reviewed and entered into a computerized database. However, we excluded patients with a clinical suspicion of lymph node metastasis,

Patient characteristics

The patients׳ baseline characteristics are shown in Table 1. The median BMI was 28 kg/m2 (interquartile range: 24–32 kg/m2); 2,155 patients (33.1%) were overweight (BMI: 25–29.9 kg/m2) and 2,462 patients (37.7%) were obese (BMI≥30 kg/m2). Overweight and obese patients were significantly more likely to have a biopsy Gleason score of 6 (vs. patients with a normal BMI; P<0.001), although no significant difference was observed after the RP (P = 0.71). Overweight or obese patients were also

Discussion

Obesity is a major health issue in industrialized countries, and two-thirds of American adults are considered either overweight or obese based on their BMI. Obesity is also associated with an increased risk of death that is related to cardiovascular disease or diabetes or both. Furthermore, solid evidence now suggests that obesity is associated with a higher incidence of cancer and poor outcomes. Therefore, this study aimed to assess the prognostic value of overweight or obese status among a

Conclusion

Being overweight or obese was associated with a higher likelihood of having more locally advanced PCa and of experiencing BCR after supposedly successful RP. Although the addition of BMI did not significantly improve the discriminative ability of the established prognostic factors, its consistent associations with aggressive biology and poor outcomes support further research regarding the underlying mechanism for this biological phenomenon.

Ethical standards

This study was approved by the appropriate ethics committees.

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