To the best of our knowledge, this is the first retrospective study to evaluate the prevalence and trend of biopsy use for PCa after the increasing use of PSA screening in a Chinese population. We also evaluated the predictive performance of variables for PCa and high-grade PCa.
Most studies conducted in western countries had positive detection rates <35%, much lower than the rates (47%) we observed in our study. However, some of the previous studies had large populations and were based on randomized screening trials 
. In addition, most of those studies used tPSA levels of 1.25 ng/mL–2.5 ng/mL as their cutoff values to perform prostate biopsy, compared with the cutoff value of tPSA>4 ng/mL used in our study. Therefore, the detection rates reported in those studies are not comparable to our study. One the other hand, there are a few studies that used single institute cohorts including New York Presbyterian Hospital (Weill Medical College of Cornell University, New York, NY), Cleveland Clinic (Cleveland Clinic, Cleveland, OH, USA) and Durham VA (Durham VA Medical Center, Durham, NC, USA). The detection rates from those studies were 31%, 39% and 47% respectively, which were more comparable to ours 
. The positive rate of prostate biopsy has decreased over the years at our institute. Zhu et al. (2009) observed similar findings in a Chinese population 
. This may be due to the fact that PSA testing was not popular in China during earlier years and patients were more likely to be biopsied because they were experiencing other symptoms (e.g. hematuria, dysuria). Therefore, they observed higher detection rates of PCa and dropped thereafter due to widespread use of PSA test.
According to results from studies conducted in western countries, the risk for developing PCa varies from 15% (Goteborg cohort) to 40% (SABOR cohort) when a tPSA threshold of 4 ng/mL is used 
. Our study showed that only 4.7% of men with a tPSA level of 4 ng/mL were diagnosed with PCa, much lower than rates in western countries. Even men with a tPSA level of 10 ng/mL had lower risk (14.8%) than men that participated in western studies. In addition, according to our data, although the sensitivity for tPSA
10 ng/mL was 92.4%, lower (P<0.05) than that for 4 ng/mL (99.7%), the specificity for tPSA
10 ng/mL (37.3%) was much higher (P<0.05) than that for tPSA
4 ng/mL (4.4%). Using a cutoff value of 4 ng/mL for prostate biopsy will cause a large number of men to undergo unnecessary prostate biopsies. Thus, we believe that using a cutoff value of tPSA>4 ng/mL for prostate biopsy in China is not appropriate. We suggest that when using tPSA>4 ng/mL as cutoff value for prostate biopsy, fPSA/tPSA, PSAD or other clinical information should be comprehensively considered before a new cutoff value is set up based on further prospective and larger population studies.
The tPSA levels at diagnosis for Chinese men were much higher than levels for men in western countries. Our tPSA level at diagnosis fluctuated from 28.6 ng/mL to 50.9 ng/mL (median), while in western trials the median ranged from 11.8 ng/mL to 6.3 ng/L 
. We also found that the percentage of patients with Gleason scores >8 was 43.58%, much higher than those of studies from western countries, which ranged from 2% (Goteborg cohort) to 21% (Tyrol cohort ) 
. Overall, the downward trend of high-grade PCa percentages shows that there are benefits to PSA screening.
The SEER database documented a decline in age at diagnosis from 72 to 69.4 yr from 1990 to 1994 due to the increasing use of PSA testing and increased ability of early detection of serum PSA 
. However, our data showed a different result with a slight increase of age at diagnosis from 2003 to 2011 (). This may be due to the fact that, with the increasing use of PSA testing, clinicians were more likely to monitor or use active surveillance of PSA levels instead of performing prostate biopsies with initial abnormal PSA results.
Studies in the tPSA era have demonstrated a fall in PSA levels at diagnosis 
. The median tPSA level at the time of diagnosis decreased from 11.8 ng/mL in 1990 to 6.3 ng/mL in 1998 
. The levels of tPSA over the years didn't show a significant trend, however, because of the significant decrease of percentage of patients with tPSA>20 ng/mL, we can still conclude that PSA screening had benefits over the years.
We would like to point out that there were two notable changes in the clinical parameters during the study period. First, we obtained 6 cores for prostate biopsy before Oct. 2007 and 10 cores thereafter. Up to a 40% increase in detection rates of PCa were reported in some of the studies when they took extra biopsy cores 
. However, other studies didn't reach this same conclusion 
. In our study, we did not observe a significant difference between detection rates based on 6-core biopsy and 10-core biopsy (Chi-square test, P
0.976). Thus, the number of cores was not included in our multivariate analysis. Second, the International Society of Urological Pathology modified the Gleason scoring system in 2005, thereby introducing some potential bias 
. However, this had limited effects on our study as only 8.7% of our study population were graded using the old Gleason score system before 2005. More importantly, our analysis of high-grade PCa was defined as Gleason score ≥8, and men in this category were least affected by the new scoring system 
Although retrospective, our study presents a good depiction of PCa prevalence and the trends of prostate biopsy in Chinese men. Some of the limitations of this study include the lack of family history and that study participants were recruited from a single institution. Although most tertiary health institutes like Huashan Hospital are located in metropolitan areas of China, patients from all over the country seek their services.