Prostate-Specific Antigen Variation as a Predictor of Prostate Cancer in Patients With Prostate-Specific Antigen ≤20 ng/mL Who Underwent Magnetic Resonance Imaging-Targeted Prostate Biopsy

Prostate Specific Antigen and Human Glandular Kallikrein 2 in Early Detection of Prostate Cancer

Study Type--Prognostic (cohort). Level of Evidence 2b. What's known on the subject? And what does the study add? Previous studies have attempted to characterize the normal biological variability in PSA among men without prostate cancer. These reports suggest that PSA variability is unrelated to age, but there are conflicting data on its association with the baseline PSA level. There are limited published data regarding the effects of prostate volume on PSA variability. A prior study assessing whether prostate volume changes would confound the use of PSA velocity in clinical practice reported that prostate volume changes were not significantly related to PSA changes. This study did not directly address the effect of baseline prostate volume on serial PSA variability. The objective of the current study was to further examine the relationship between prostate volume and PSA variability. Our hypothesis was that larger baseline prostate volume would be associated with increased PSA variability in men without known prostate cancer and in those with suspected small-volume disease. The results of the study suggest that baseline PSA, not prostate volume, is the primary driver of PSA variability in these populations. • To clarify the relationship between serial prostate-specific antigen (PSA) variability and prostate volume in both cancer-free participants from the Baltimore Longitudinal Study of Aging (BLSA) and patients with low-risk prostate cancer from the Johns Hopkins Active Surveillance Program (AS). • In all, 287 men from the BLSA and 131 patients from the AS were included in the analysis, all with at least two PSA measurements and concurrent prostate volume measurements. • PSA variability was calculated in ng/mL per year, and a linear mixed-effects model was used to determine the relative effects of prostate volume, baseline PSA and age on PSA change over time. • In a model with prostate volume, age and baseline PSA, there was no significant relationship between prostate volume and PSA variability (BLSA, P= 0.57; AS, P= 0.49). • Only baseline PSA showed a significant relationship to PSA yearly variability (PSAYV) (P < 0.001). Specifically, a one unit higher baseline PSA (ng/mL) corresponded on average to 0.09 and 0.06 ng/mL per year higher PSAYV in the BLSA and AS populations, respectively. • The results of the present study suggest that the primary driver of PSA variability is the baseline PSA level, rather than prostate volume. • Clinicians might consider the baseline PSA level to help predict the expected variability in serial PSA measurements.

THE INCIDENCE OF PROSTATE CANCER IN A SCREENING POPULATION WITH A SERUM PROSTATE SPECIFIC ANTIGEN BETWEEN 2.5 AND 4.0 NG./ML.: RELATION TO BIOPSY STRATEGY

OPTIMAL PREDICTORS OF PROSTATE CANCER ON REPEAT PROSTATE BIOPSY: A PROSPECTIVE STUDY OF 1,051 MEN

Kinetics of postbiopsy levels of serum free prostate-specific antigen and percent free prostate-specific antigen

Magnetic Resonance Imaging/Ultrasound Fusion Guided Prostate Biopsy Improves Cancer Detection Following Transrectal Ultrasound Biopsy and Correlates With Multiparametric Magnetic Resonance Imaging

Biological Variation of Prostate Specific Antigen Levels In Serum: An Evaluation of Day-to-Day Physiological Fluctuations in a Well-Defined Cohort of 24 Patients

A number of different prostate-specific antigen (PSA) assays are in common use. There has been little consideration of the possible clinical implications of interassay variation. The availability of two assays in the same laboratory provided an opportunity to audit the clinical implications of the interassay variation in PSA levels. The same serum samples from patients with prostate cancer on follow-up were analyzed for PSA by the Abbott AxSYM assay and by the Abbott ARCHITECT assays. To assess within-patient reproducibility of the interassay variation, repeat analysis of PSA by both assays was conducted in a second sample obtained at least 1 month after the first. Samples from 156 cases were analyzed. The mean ratio of serum PSA values by the two assays (AxSYM assay/ARCHITECT assay) was 0.89 (range 0.5-2.27). The interassay coefficient of variation was 20%. In a subgroup of 50 cases with repeat samples available, the correlation coefficient, r, of the interassay variation in PSA between the first and second samples was 0.441. Interassay variation in serum PSA is clinically significant, both between patients and on repeated measurement within the same patient. Clinicians should be aware that simple correction factors may not accurately control for variation between PSA assays. Ideally, patients on follow-up for prostate cancer should be monitored using a single PSA assay.

We determine whether the different molecular forms of prostate-specific antigen (PSA) and other PSA variables can predict prostate cancer in men undergoing repeat prostate needle biopsy. Between 1997 and 2001, repeat biopsy was performed in 97 patients who had undergone prior negative prostate biopsy. The ability of total PSA (tPSA), complexed PSA (cPSA), free PSA (fPSA), free-to-total PSA (fPSA/tPSA), free-to-complexed PSA (fPSA/cPSA), complexed-to-total PSA (cPSA/tPSA), tPSA density (tPSAD), cPSA density (cPSAD), transition zone tPSA density (tPSATZ) and transition zone cPSA density (cPSATZ) was assessed by univariate and multivariate analyzes as well as receiver operating characteristics (ROC) curves. Prostate cancer on repeat biopsy was detected in 24% of subjects (23 of 97) who had a negative initial biopsy. The PSA parameters cut-off to ensure a 96% sensitivity of cancer detection, were 29% using fPSA/tPSA, 32% using fPSA/cPSA, 0.18 ng/mL/cc using tPSATZ and 0.16 ng/mL/cc using cPSATZ. The fPSA/tPSA would have prevented 32% of negative biopsies, the fPSA/cPSA 28%, the tPSATZ 23% and the cPSATZ 30%. ROC curve analysis fPSA/tPSA, fPSA/cPSA ratios, tPSATZ and cPSATZ were significantly better predictors of repeat biopsy results than tPSA or cPSA, but there was no significant difference in the ROC curves among these four PSA parameters. In the multivariate logistic regression analysis these four PSA parameters were significant predictors for cancer detection in the repeat biopsy group (P < 0.001). fPSA/tPSA ratio, fPSA/cPSA ratio, tPSATZ and cPSATZ enhance the specificity of PSA testing compared to tPSA or cPSA when determining which patients should undergo repeat biopsy.

To assess the association between prostate-specific antigen (PSA) density (PSAD) and prostate cancer mortality after a benign result on systematic transrectal ultrasonography (TRUS)-guided prostate biopsy. This retrospective study used data from the Finnish Randomised Study of Screening for Prostate Cancer (FinRSPC) collected between 1996 and 2020. We identified men aged 55-71 years randomised to the screening arm with PSA ≥4.0 ng/mL and a benign systematic TRUS-guided biopsy result. The cumulative prostate cancer mortality of men stratified by a PSAD cutoff of 0.15 ng/mL/cm3 was modelled with competing risk functions. The ability of PSAD, PSA, and base variables (age at biopsy, DRE result, socioeconomic status, 5α-reductase inhibitor usage, family history, and Charlson Comorbidity Index (CCI)) to predict prostate cancer death was compared using c-statistics and a likelihood ratio test. After excluding 10 men without PSA data within 2 years of the biopsy and 65 without prostate volume data, 2276 men were eligible for inclusion in the study. A total of 50 men died from prostate cancer and 1028 from other causes during a median (interquartile range) follow-up of 17.4 (13.2-20.9) years. The cumulative prostate cancer mortality of men with PSAD <0.15 ng/mL/cm3 was significantly lower than that of men with PSAD ≥0.15 ng/mL/cm3: 0.5% (95% confidence interval [CI] 0.2%-1.1%) vs 2.0% (95% CI 1.2%-3.1%) at 15 years (Grey's test, P = 0.001). The model consisting of PSAD, PSA and the base variables predicted prostate cancer mortality (c-statistic 0.781) significantly better than either the base variables alone (c-statistic 0.737; likelihood-ratio test, P = 0.003) or the base variables and PSA (c-statistic 0.765; likelihood-ratio test, P = 0.039). Prostate cancer mortality after a benign systematic TRUS-guided biopsy is low. In these patients, PSAD predicts prostate cancer mortality and provides additional value to other clinical variables. PSAD-based stratification can be used to guide follow-up strategy.

Monitoring therapy response in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with novel hormonal therapies, taxanes, and newly approved therapies is crucial for optimizing treatment. [68Ga]Ga-prostate-specific membrane antigen (PSMA)-11 positron emission tomography/computed tomography (PSMA PET/CT) is a promising target for managing treatment in patients with prostate cancer. PSMA is overexpressed in patients with mCRPC; understanding how expression might change in patients undergoing treatment could determine its potential for guiding clinical decisions. We examined PSMA expression in patients with CRPC and compared PET/CT response with prostate-specific antigen (PSA) variation as a prognostic factor for progression-free survival and overall survival (PFS and OS, respectively). Methods: This was a single-center, retrospective observational cohort study in patients with CRPC enrolled in the PSMA-PROSTATA registry study (EudraCT: 2015-004589-27). A first and second (if applicable) PSMA PET/CT were performed to determine PSMA expression (absence or presence). PET/CT response was assessed as responders (patients with stable disease, partial or complete response) versus nonresponders (patients with progressive disease) by comparing the first with the second PET/CT. PSA variation (increase or decrease from baseline) was assessed across the same time period. PFS was defined as the time between second PET/CT and PSA recurrence or evidence of radiologic progression. Results: Overall, 160 patients with CRPC were included in the analysis. At first PET/CT, nearly all (n = 152; 95.0%) patients had PSMA expression (classified as mCRPC), irrespective of prior systemic therapy. SUVmax was positively associated with baseline PSA levels and velocity (both P < 0.001). According to PET/CT response, median SUVmax on first PET/CT was numerically lower in nonresponders than in responders (17.5 vs. 20.4; P = 0.127). Similarly, patients with a PSA increase had significantly lower median SUVmax on first PET/CT (15.8) than did those with a PSA decrease (30.4; P = 0.018). PSA change was, on average, 146% in nonresponders and -57% in responders between first and second PET/CT (P < 0.001). Agreement between PET/CT and PSA response was 79% (k = 0.553, P < 0.001). Among the 63 patients included in PFS/OS analyses, 76.2% had a relapse and 36.5% died before 24-mo follow-up; median PFS and OS were 6.1 and 24 mo, respectively. PET/CT response, independent of PSA variation, was a significant prognostic factor for PFS. OS was not significantly different between PET/CT responders and nonresponders. Conclusion: PSMA PET/CT may be a useful imaging method predictive of treatment response in patients with mCRPC, regardless of ongoing systemic therapy. Data also suggest that response assessed by PET/CT is a potentially more significant prognostic factor than PSA for PFS. Further studies are needed to understand the potential involvement of PSMA expression on survival.

Prostate-specific antigen variability in men without prostate cancer: effect of sampling interval on prostate-specific antigen velocity

To improve the diagnostic efficiency of prostate cancer (PCa) and reduce unnecessary biopsies, we defined and analyzed the diagnostic efficiency of peripheral zone prostate-specific antigen (PSA) density (PZ-PSAD). Patients who underwent systematic 12-core prostate biopsies in Shanghai General Hospital (Shanghai, China) between January 2012 and January 2018 were retrospectively identified (n = 529). Another group of patients with benign prostatic hyperplasia (n = 100) were randomly preselected to obtain the PSA density of the non-PCa cohort (N-PSAD). Prostate volumes and transition zone volumes were measured using multiparameter magnetic resonance imaging (mpMRI) and were combined with PSA and N-PSAD to obtain the PZ-PSAD from a specific algorithm. Receiver operating characteristic (ROC) curve analysis was used to assess the PCa detection efficiency in patients stratified by PSA level, and the area under the ROC curve (AUC) of PZ-PSAD was higher than that of PSA, PSA density (PSAD), and transition zone PSA density (TZ-PSAD). PZ-PSAD could amend the diagnosis for more than half of the patients with inaccurate transrectal ultrasonography (TRUS) and mpMRI results. When TRUS and mpMRI findings were ambiguous to predict PCa (PIRADS score ≤3), PZ-PSAD could increase the positive rate of biopsy from 21.7% to 54.7%, and help 63.8% (150/235) of patients avoid unnecessary prostate biopsy. In patients whose PSA was 4.0–10.0 ng ml−1, 10.1–20.0 ng ml−1, and >20.0 ng ml−1, the ideal PZ-PSAD cut-off value for predicting clinically significant PCa was 0.019 ng ml−2, 0.297 ng ml−2, and 1.180 ng ml−2, respectively (sensitivity >90%). Compared with PSA, PSAD, and TZ-PSAD, the efficiency of PZ-PSAD for predicting PCa is the highest, leading to fewer missed diagnoses and unnecessary biopsies.

INTERVAL AFTER PROSTATE SPECIFIC ANTIGEN TESTING AND SUBSEQUENT RISK OF INCURABLE PROSTATE CANCER

Effect of Digital Rectal Examination and Needle Biopsy on Serum Total and Percentage of Free Prostate Specific Antigen Levels