Discussion
PCa is one of the malignancies with a serum-based biomarker. Since PSA’s discovery in 1979 until clinical application in the late 1980s through 1990s, PSA has evolved into an invaluable tool for detecting, staging, and monitoring prostate cancer in men. For several years, an abnormal DRE, elevated PSA, or both were used to diagnose PCa. Today, most prostate cancers are diagnosed as clinically nonpalpable (stage T1c) disease with PSA levels between 2.5 and 10 ng/mL (11). PSA screening for PCa leads to a small reduction in disease-specific mortality over 10 years but does not affect overall mortality (12). Today, attention has turned from the detection of any PCa to a focus on detecting CSPCa, often interpreted as a Gleason score ≥7 cancer (11). PSAD and f/t PSA are well-known for PCa detection, especially in PSA levels < 10 ng/ml (3,5). The aim of our study is to determine f/t PSA and PSAD’s value in predicting CSPCa.
Recent studies have shown that PSAD is associated with CSPCa. In Omri et al.’s study found that PSAD is correlated with CSPCa (based on radical prostatectomy pathology reports) in small (< 50 cc) and medium (50-75cc) size prostates and level of PSAD is directly associated with the ISUP grade groups (13). In Liu et al.’s study, univariate and multivariate logistic regression analyses demonstrated that PSAD predicted CSPCa (based on prostate biopsy pathology reports) in the PSA level of 4-10 ng/ml (9). Compatible with these studies, we found clinical significance between PSAD and CSPCa (Gleason ≥ 7, ISUP grade group ≥ 2) (p < 0.001). This was not surprising because we found clinical significance between PSA and CSPCa (p < 0,010) and prostate volume and CSPCa (p< 0,030)(Table 2). On the other hand, we also found clinical significance between PSAD and ISUP grade groups, especially for ISUP grade group 4 (Table 3). However, there was no correlation between ISUP grade groups and PSAD. There was no correlation between prostate volume and ISUP grade groups. ISUP grade group 3 had the biggest mean prostate volume in our study, and when we excluded that group, we could see a correlation between PSAD and ISUP grade groups (groups 1, 2, and 4). We thought that there was not a correlation between PSAD and CSPCa for large prostates like Omri et al. said. But we are not sure that size is > 75 cc because all ISUP grade groups mean prostate volume were <75 cc in our study.
Ceylan et al. said that there is a relationship between a higher Gleason score and decreased f/t PSA and f/t PSA can be an indicator for predicting the Gleason score (8). Unlike that, there was no clinical significance between f/t PSA and CSPCa in our study. Unlike PSA values, there was no clinical significance between free PSA and CSPCa. The mean free PSA was not different between the CSPCa and N- CSPCa groups in our study (Table 2). Additionally, there was no correlation between free PSA and ISUP grade groups (Table 3).
PSAD is beneficial, available, cost-effective, and can be used as a tool for predicting CSPCa. In the MRI era for PCa, PSAD can be combined with MRI for superior predictive ability to detect CSPCa (14,15). PSAD can also be used for predicting N-CSPCa. Therefore, PSAD may be used to identify better candidates for active surveillance in the future, as Yun-Sok Ha et al. stated. They found that adopting a lower PSAD threshold of 0.085 decreased the risk of advanced disease to 17.5–21.7% (16). In our study, the PSAD cutoff was 0.130 for predicting CSPCa (sensitivity 75% and specificity 63%).
The first limitation of our study is the limited patient population. The second limitation is that we used prostate biopsy reports for deciding clinically significant PCa, such as Liu J et al.’s and Ceylan et al.’s studies. However, the latest pathology can upgrade in radical prostatectomy specimens. It may be that some of our N-CSPCa patients had CSPCa in reality. In Corcoran et al.’s study, 418 of 1312 patients had an upgrade in Gleason score. Of the 1312 patients, 363 had upgraded Gleason 6 to >6. This study found that PSAD was also a predictor of upgrade of biopsy Gleason 6 (17). We could not use radical prostatectomy pathology reports for deciding CSPCa because some of our patients chose active surveillance or radiation therapy in our center, while others lost follow-up or chose focal therapy alternatives in other centers.