At present, RP is the treatment of chioce for most clinical localized PCa patients[3]. The prognosis of patients is affected by pathological conditions such as postoperative ISUP, surgical margin, extracapsular extension and Seminal vesicle invasion. So far, the exact mechanism between obesity and PCa aggressiveness is unclear. Previous studies have reported different associations between obesity and PCa, with the Amercian study sugessting that postoperative pathology in obese PCa patients was more aggressive than that of normal weight patients[12]. The studies in European countries have also reported obesity and adverse pathology characteristics after RP, such as higher Gleason score, positive surgical margins[14, 15]. However, most of these figures come from western rather than Asian countries, especially China. Asians are thinner and have a lower BMI than Westerners, suggesting that the effects of BMI may differ between Asian and Western race. Obesity rate is rising in China as lifestyles become more westernized, and may have a secondary impact on PCa. In order to minimize the differences with Western race, the BMI grouping of this study is based on the “Chinese Adult Overweight and Obesity”.
The effect of BMI on pathological features in our study was different from that reported in other studies. Our results showed among Chinese PCa patients undergoing LRP, higher BMI was statistically significant with seminal vesicle invasion, but other adverse pathological features such as PSMs, higher ISUP group, and extracapsular extension were not statiscally significant in different BMI subgroups. Similarly, Vidal et al[12].analyzed data of 5929 American men treated by RP, and found that both white and black men with higher BMI were more likely to have PSMs and seminal vesicle invasion in PCa patients. Multivariate analysis found that obesity was associated with increased risk of PSMs. In contrast, Isbarn et al[11].analyzed 1538 European PCa and Narita et al[10].analyzed 1257 Japanese PCa who received RP and demonstrated multivariate analysis that BMI was not associated with adverse pathological outcomes. A study of 880 PCa patients in south Korea, also from East Asia, reached the opposite conclusion. The result showed that normal weight Korean PCa patients have a higher Gleason score compared to overweight and obese patients[13]. Differences of pathological characteristics in the above studies ,on the one hand ༌may be due to the fact that some studies relied on historical data and used various main treatment methods, cases mixes and environmental risk factors, on the other hand may be caused by differences in ethic background. After all, the average BMI of Asians is much lower than that of Westerners. Even with the same BMI, Asian men have a higher body fat rate than Western men[16]. However, the reason for the difference in results between the studied Chinese patients and the Japanese and South Korean patients may be due to the biopsy driven by PSA screening. Compared with Japan and South Korea, China currently has a lower PSA screening rate[17].
The serum PSA level of obese men is lower than that of normal weight men of the same age[18]. The relationship between the two has been emphasized, but the underlying mechanism is still unclear. The most commonly accepted explanations are the effect of blood dilution and low serum testosterone[19, 20]. On the one hand, obese men have greater blood volume, which dilutes the tumor markers in the serum, such as PSA. On the other hand, the prostate is an androgen-dependent organ. Patients with higher BMI produce less testosterone[20], and the Chinese diet contains higher levels of estrogen. Elevated levels of estrogen cause PCa to be more dependent on androgens and more aggressive, simultaneously, lower testosterone levels may cause decreased prostate PSA secretion[21]. A recent study showed that the two effects may lead to a 81% and 19% reduction in serum PSA concentration in obese men[19]. At present, serum PSA testing is still the most important way to screen for PCa. As the PSA screening test is not popular in China, obese men have a reduced chance on undergoing biopsy compared to normal weight men. Therefore, PCa in Chinese patients usually has a higher pathological stage at the time of diagnosis[22]. This is also consistent with our study. In the higher BMI subgroup, the median PSA level decreased, while the final pathological stage increased. This may also indicate that the increased risk of postoperative seminal vesicle invasion in PCa patients with higher BMI is due to the disease itself rather than surgical skills, because the difference in positive margins in all BMI subgroups is not statistically significant.
It is worth noting that some studies have found that the fat around the prostate is biologically active, and can secrete factors that promote the growth of PCa, and may be related to more aggressive diseases[23, 24]. However, in this study, we did not find a link between obesity and extracapsular extension, which is inconsistent with the paracrine fat around the prostate that promotes the growth of PCa, and further research may be needed.
If the prognosis of obese PCa patients is poor, this indicates that weight control may be able to effectively reduce morbidity and mortality. However, several large cohort studies did not find the association between physical activity and locally advanced, high-risk PCa or treatment failure[25, 26]. Overweight or obesity is associated with an increased risk of some chronic diseases, such as diabetes and cardiovascular disease. In this regard, physical activity may improve the prognosis of PCa patients. After all, the ultimate cause of death in some PCa patients is not the tumor itself[27].
The current research has several limitations. First, retrospective analysis of RP patients may have led to selection bias. Only those patients who are suitable for surgical treatment were included in the study cohort, so these results may not be applicable to patients undergoing other treatments. In addition, these patients are from the same hospital and may not be representative of the entire Chinese population. We did not investigate tumor volume, lymph node metastasis, or preoperative hormone levels. These results, especially changes in multiple hormones, may also affect the aggressiveness of the disease. Since the patient has not been followed up for a long time, the impact of BMI on the long-term prognosis cannot be clarified. In the future, multi-center, prospective, and well-controlled studies may be needed to further illustrate the relationship between obesity and PCa.