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.