Introduction
Prostate cancer (PCa) is the one of the most common malignant tumors among men in developed countries. Thus far, it has been suggested that diet and other environmental factors may affect the incidence of PCa, as this incidence differs between countries and ethnic populations (1). In fact, migration studies showed an increased incidence of PCa in first-generation immigrants to the United States from Japan (2). These observations suggest that diet may play an important role in the incidence of PCa (3). In addition, several articles have reported various endogenous and exogenous factors that may contribute to PCa (4).
Obesity, which is generally measured by body mass index (BMI), is associated with increased mortality for all cancers combined (5). Obesity has also been suggested to be a risk factor in prostate cancer as well as breast and colon cancer (6,7). However, the association of higher BMI with increased PCa incidence remains controversial (8). Previous studies presented evidence that obesity was associated with an increased risk of diagnosis of larger tumors, more aggressive disease and PCa-related mortality (9,10), whereas other studies reported that obesity was not associated with aggressive pathological characteristics (11,12). As regards biochemical recurrence, it has been reported that obese men are at increased risk of biochemical recurrence (13–17). Recently, obesity has become more prevalent among Asian countries, including Japan. Although obesity in Asian countries is less severe compared with that in western countries, certain studies have suggested an association between BMI and PCa, including pathological characteristics (18,19). However, the effect of obesity on PCa-related mortality has been controversial, and it remains unclear whether obesity contributes to the aggressiveness of PCa in Asian patients (20,21). The aim of the present study was to investigate the association between BMI and the clinicopathological characteristics of PCa, and determine whether obesity increases the risk of biochemical recurrence after radical prostatectomy (RP) in Japanese patients.
Discussion
The association between BMI and the clinicopathological characteristics was investigated in 2003 Japanese patients with PCa who underwent RP. First, it was demonstrated that high BMI was associated with adverse pathological findings. These results, supported those of previous studies showing that obese men in the United States who underwent RP had higher-grade and larger tumors (8,10,13–17). In Asian patients, the adverse pathological findings of PCa may be attributable to obesity according to previous reports (18,19).
However, other reports have not demonstrated any association of obesity with the clinicopathological characteristics of PCa (20,21). Such conflicting results may be explained by the different distribution of BMI among countries. As the obese (BMI ≥30 kg/m2) population accounted for only 1–2% of the cases in reports from Asian countries, the cutoff for normal BMI is variably classified as 23.5 or 25.0 kg/m2. In the present study, a significant association of BMI with GS was observed, whereas such an association was not observed for serum PSA level, pT stage, EPE and RM. These results may suggest that a higher BMI was associated with more aggressive phenotypes of PCa.
Although there was no significant association between BMI and serum PSA level (Table I), the overweight group exhibited a greater risk of biochemical recurrence in patients with lower PSA levels (Fig. 1B). Indeed, previous studies reported that BMI is inversely associated with serum PSA levels (23,24), and a higher BMI is associated with higher plasma volume (25). Thus, the reason why obese men have lower serum PSA concentrations may be explained by the hemodilution theory (26,27). Therefore, it is possible that the serum PSA levels may be modified in the overweight group. However, in the multivariate analysis, BMI was not an independent predictor of biochemical recurrence. Recently, PSA mass, which was associated with visceral adipose tissue, was suggested to be a promising indicator for determining an absolute PSA level (28).
Previous studies have also demonstrated an association between obesity and the aggressiveness of PCa through various molecular mechanisms, including oxidative stress, endocrine activities, or other cytokine activities (29). It is known that adipose tissue secretes certain inflammatory cytokines, referred to as adipocytokines (30). In addition, we previously reported a positive correlation between the aggressiveness of PCa and fibroblast growth factor (FGF)-19, including the endocrine FGF subfamily that circulates in the serum and acts in an endocrine-like manner (31). Further investigations are required to elucidate the associations between BMI or obesity and PSA levels.
The present study had certain limitations. First, the median follow-up period for establishing biochemical recurrence after RP was relatively short. Second, this was a retrospective study that involved patients subjected to RP using different procedures by several surgeons, although the oncological outcomes of retropubic, retroperitoneal, laparoscopic and robot-assisted laparoscopic RP were comparable (32,33). Third, we investigated whether obesity affects pathological findings and biological recurrence after RP using only preoperative BMI, as postoperative BMI values were not available. Although it remains unclear whether weight loss may help improve outcomes among patients already diagnosed with PCa, further investigations are required to elucidate the role of BMI post-RP.
In summary, the results of the present study, including 2003 Japanese patients who underwent RP for PCa, provide evidence that a higher BMI may be associated with adverse pathological findings. Although BMI was not an independent predictor for bRFS after RP, BMI may be associated with more aggressive characteristics of PCa.