The clinical manifestation of PCa is a spectrum that can range from a non-aggressive, slow-growing disease to a fast-growing, highly aggressive disease . Recent guidelines and protocols focus on how to maximize the early detection of PCa that requires treatment and to minimize the overdiagnosis of unnecessary indolent diseases . Serum PSA has been the most widely used marker for PCa screening and detection since its initial publication in 1987 . However, the sensitivity and efficacy of PSA has been questioned. PSA screening may reduce PCa mortality but it is also associated with possible false-positive biopsy results that are accompanied by unnecessary biopsy-related complications , and the overdiagnosis of early stage disease . Therefore, to avoid causing unnecessary harm, various methods have been introduced to try and increase the sensitivity of cancer detection, while maintaining good specificity, thus eliminating unnecessary biopsies.
Several PSA derivatives have been proven to be superior to PSA in predicting PCa. Benson et al.  first studied PSAD in 1992, which is serum PSA divided by prostate volume ratio, and showed that it was superior to PSA for identifying PCa. Kalish et al.  proposed the use of TZPSAD as an improved parameter for PCa instead of PSAD, for the traditional PSA “grey zone” (PSA levels between 4.1 ng/mL and 10.0 ng/ml.). They hypothesized that since BPH mainly arose from the transition zone , PSA changes due to BPH should also result from the hypertrophied glands of the transition zone. Therefore, PSA formed by the outer zones (peripheral zone and central zone) should be relatively constant and less influenced in BPH patients. So, adjusting the PSA level with TZV and neglecting PSA changes from the outer glands should increase the ability of PSA to discriminate BPH from PCa. Several studies have shown that TZPSAD is a superior parameter compared with PSA alone [8, 10, 11, 17, 18].
PSA level and the prevalence of PCa differ among races and the efficacy of different PCa detection strategies may also vary for different races . Tang et al. hypothesized that the true grey zone for PSA in Asian males should be higher than the traditional grey zone (4.1 ng/mL and 10.0 ng/ml.). They demonstrated that using TZPSAD can improve the efficiency of PSA in PCa diagnosis and avoid unnecessary prostatic biopsies in men with a PSA of both 4.0–10.0 and 10.1–20.0 ng/ml. The current study showed similar results to Tang et al. However, it is still unclear whether TZPSAD performed better than PSAD in predicting PCa. Despite some studies showing that TZPSAD outperformed PSAD in distinguishing PCa from BPH [8, 10, 19, 20], other investigators have claimed a different conclusion, saying that TZPSAD was not obviously superior to PSAD [21-23]. In the current study, similar AUCs and diagnostic efficiencies of TZPSAD and PSAD were found in all groups and there were not statistically significant differences. The two parameters showed equal efficacy and were both superior to PSA alone. However, the specificity of TZPSAD was better than PSAD, both overall and after PSA stratification, indicating that using TZPSAD as a method for PCa detection could improve the efficacy compared with traditional PSA and increase specificity, which may potentially avoid unnecessary biopsies when compared with PSAD.
There were several limitations to the current study that need to be addressed. (1) its retrospective nature; (2) the accuracy of ultrasound measurements is operator dependent. Therefore, measurements by different sonographers may differ and influence the outcomes of TZPSAD. In the present study, all of the prostate volumes were measured by 3 very experienced staff to minimize this bias. (3) All the data and patients were collected from a single medical center. The strategies used for PCa diagnosis, including TRUS measurement and TRUS biopsy, may differ from other institutions, which may cause an inherent bias. Therefore, further studies should be conducted with a larger number of patients who are prospectively randomized, to minimize the bias.