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Assessment of factors associated with PSA level in prostate cancer cases and controls from three geographical regions.

ABSTRACT: It is being debated whether prostate-specific antigen (PSA)-based screening effectively reduces prostate cancer mortality. Some of the uncertainty could be related to deficiencies in the age-based PSA cut-off thresholds used in screening. Current study considered 2779 men with prostate cancer and 1606 men without a cancer diagnosis, recruited for various studies in New Zealand, US, and Taiwan. Association of PSA with demographic, lifestyle, clinical characteristics (for cases), and the aldo-keto reductase 1C3 (AKR1C3) rs12529 genetic polymorphisms were analysed using multiple linear regression and univariate modelling. Pooled multivariable analysis of cases showed that PSA was significantly associated with demographic, lifestyle, and clinical data with an interaction between ethnicity and age further modifying the association. Pooled multivariable analysis of controls data also showed that demographic and lifestyle are significantly associated with PSA level. Independent case and control analyses indicated that factors associated with PSA were specific for each cohort. Univariate analyses showed a significant age and PSA correlation among all cases and controls except for the US-European cases while genetic stratification in cases showed variability of correlation. Data suggests that unique PSA cut-off thresholds factorized with demographics, lifestyle and genetics may be more appropriate for prostate cancer screening.

SUBMITTER: Karunasinghe N

PROVIDER: S-EPMC8742081 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Association of serum prostate-specific antigen (PSA) level and circulating tumor cell-based PSA mRNA in prostate cancer.

Project description:BackgroundProstate-specific antigen (PSA) is used for diagnosing prostate cancer, but does not reflect the characteristics of prostate cancer cells to allow assessment of cancer progression. PSA mRNA and circulating tumor cells (CTCs) could be potential biomarkers. However, the relationship between serum PSA levels and PSA mRNA in CTCs is unclear, and this study aimed to investigate this relationship.MethodsHealthy donors (HD, n = 9), and patients with local non-metastatic stage prostate cancer (n = 30), metastatic hormone-sensitive prostate cancer (mHSPC, n = 10), and metastatic castration-resistant prostate cancer (mCRPC, n = 75), were included. The expression of PSA mRNA in CTCs was measured by droplet digital PCR. Serum PSA (ng/mL) levels and PSA mRNA (copies/μL) in CTCs were then compared using Spearman correlation coefficients.ResultsPSA mRNA expression in CTCs was observed in 30% (9/30) of patients with localized cancer, 60.0% (6/10) among patients with mHSPC, 65.3% (49/75) among patients with mCRPC, and 0% among patients with HD, indicating that the detection rate of PSA mRNA increased with cancer stage. PSA mRNA expression in CTCs also increased from localized to metastatic stages. PSA mRNA levels rapidly increased in the mHSPC and mCRPC stages. Interestingly, PSA mRNA expression in CTCs was not correlated with serum PSA levels at the localized stage (R = 0.064, P = 0.512). However, there were significant correlations between serum PSA levels and PSA mRNA expression in mHSPC (R = 0.532, P = 0.041) and mCRPC (R = 0.566, P = 0.025). The number of CTCs isolated from mHSPC and mCRPC was not proportional to serum PSA and PSA mRNA levels.ConclusionCTC PSA mRNA has the potential to be used as a biomarker to complement serum PSA protein analysis or replace serum PSA in metastatic stages of prostate cancer.

| S-EPMC8844604 | biostudies-literature

Characteristics of α2,3-sialyl N-glycosylated PSA as a biomarker for clinically significant prostate cancer in men with elevated PSA level.

Project description:BackgroundThe presence of glycosylated isoforms of prostate-specific antigen (PSA) in prostate cancer (PC) cells is a potential marker of their aggressiveness. We characterized the origin of α2,3-sialylated prostate-specific antigen (S23PSA) by tissue-based sialylation-related gene expression and studied the performance of S23PSA density (S23PSAD) alone and in combination with multiparametric magnetic resonance imaging (MRI) for the detection of clinically significant prostate cancer in men with elevated PSA.MethodsTissue-based quantification of S23PSA and sialyltransferase and sialidase gene expression was evaluated in 71 radical prostatectomy specimens. The diagnostic performance of S23PSAD was studied in 1099 men retrospectively enrolled in a multicenter systematic biopsy (SBx) cohort. We correlated the S23PSAD with Prostate Imaging Reporting and Data System (PI-RADS) scores in 98 men prospectively enrolled in a single-center MRI-targeted biopsy (MRI-TBx) cohort. The primary outcome was the PC-diagnostic performance of the S23PSAD, the secondary outcome was the avoidable biopsy rate of S23PSAD combined with DRE and total PSA (tPSA), and with or without PI-RADS.ResultsS23PSA was significantly higher in Gleason pattern 4 and 5 compared with benign prostate tissue. In the retrospective cohort, the performance of S23PSAD for detecting PC was superior to tPSA or PSA density (PSAD) (AUC: 0.7758 vs. 0.6360 and 0.7509, respectively). In the prospective cohort, S23PSAD was superior to tPSA, PSAD, and PI-RADS (AUC: 0.7725 vs. 0.5901, 0.7439 and 0.7305, respectively), and S23PSAD + PI-RADS + DRE + tPSA was superior to DRE + tPSA+PI-RADS with avoidance rate of MRI-TBx (13% vs. 1%) at 30% risk threshold.ConclusionsThe diagnostic performance of S23PSAD was superior to conventional strategies but comparable to mpMRI.

| S-EPMC9293073 | biostudies-literature

Correlation Between Trough Level of Abiraterone and Prostate-Specific Antigen (PSA) Response in Metastatic Hormone-Sensitive Prostate Cancer.

Project description:BACKGROUND Prostate cancer growth is primarily driven by testosterone and 5a-dihydrotestosterone. Abiraterone is an irreversible inhibitor of CYP17, and CYP17 inhibition is a required step in testosterone biosynthesis. Previous studies have shown that abiraterone trough levels are predictive of prostate-specific antigen (PSA) response in metastatic castrate-resistant prostate cancer (mCRPC). It has not been demonstrated if this association exists for patients with metastatic hormone-sensitive prostate cancer (mHSPC). In this study, we aimed to explore the correlation and association between abiraterone trough levels and PSA levels in patients with mHSPC. MATERIAL AND METHODS This was a single-center, prospective, observational study of patients with mHSPC being treated with abiraterone acetate (AA) 1000 mg once daily. Abiraterone trough levels (22-26 h after drug administration) were drawn at 1, 3, and 7 months after treatment initiation. RESULTS Thirteen patients with mHSPC were enrolled, and complete pharmacokinetic data were available for 8 patients. The mean trough levels at 1 month, 3 months, and 7 months were 34.49 ng/mL (3.36-240.46), 13.82 ng/mL (2.91-29.96), and 15.7 ng/mL (3.58-26.86), respectively. The correlation between the 1-month abiraterone trough level and 1-month PSA level was 0.29 (P=0.38), between 3-month abiraterone trough and 3-month PSA was -0.61 (P=0.08), and between 7-month abiraterone trough and 7-month PSA was -0.31 (P=0.54). CONCLUSIONS This study demonstrated a trend toward a negative correlation between 3-month abiraterone trough levels and PSA levels, but the correlation was not statistically significant. A study with a larger prospective sample size is needed to validate these findings.

| S-EPMC9578325 | biostudies-literature

Association of Polymorphisms in the Prostate-Specific Antigen (PSA) Gene Promoter with Serum PSA Level and PSA Changes after Dutasteride Treatment in Korean Men with Benign Prostatic Hypertrophy.

Project description:PurposeStudies of genetic variation in the prostate-specific antigen (PSA) gene have improved the diagnostic accuracy of PSA for diagnosing prostate diseases in Caucasians. However, the reference ranges and pharmacokinetics of PSA differ significantly according to race. Therefore, we evaluated the association between genetic variations in the PSA promoter area and benign prostatic hyperplasia (BPH) phenotypes in Korean BPH patients.Materials and methodsOne hundred twenty-one men were enrolled. The initial serum PSA level, prostate size, and PSA changes at 3 months after treatment with dutasteride were determined. We amplified the promoter region of the PSA gene (nucleotide positions -158 to -356 and -5217 to -5429) and sequenced the products.ResultsThree relatively well characterized single-nucleotide polymorphisms (SNPs; rs3760722, rs266867, and rs266868), six uncharacterized SNPs (rs17554958, rs266882, rs4802754, rs2739448, rs2569733, and rs17526278), and one novel SNP (nucleotide position -5402) were found. There were no statistically significant correlations between any of the SNPs of the PSA promoter area and age-adjusted prostate sizes, initial PSA levels, or PSA variations after 3 months of dutasteride treatment.ConclusionsSNPs in the PSA promoter area were not associated with BPH phenotypes. We could not predict serum PSA changes after dutasteride treatment on the basis of PSA promoter genotype in Korean patients with BPH.

| S-EPMC3016427 | biostudies-literature

Risk of Prostate Cancer-related Death Following a Low PSA Level in the PLCO Trial.

Project description:Longer-than-annual screening intervals have been suggested to improve the balance of benefits and harms in prostate cancer screening. Many researchers, societies, and guideline committees have suggested that screening intervals could depend on the prostate-specific antigen (PSA) result. We analyzed data from men (N = 33,897) ages 55-74 years with a baseline PSA test in the intervention arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial (United States, 1993-2001). We estimated 5- and 10-year risks of aggressive cancer (Gleason ?8 and/or stage III/IV) and 15-year risks of prostate cancer-related mortality for men with baseline PSA ? 0.5 ng/mL (N = 4,862), ?1 ng/mL (N = 15,110), and 1.01-2.5 ng/mL (N = 12,422). A total of 217 men died from prostate cancer through 15 years, although no men with PSA ? 1 ng/mL died from prostate cancer within 5 years [95% confidence interval (CI), 0.00%-0.03%]. The 5-year incidence of aggressive disease was low (0.08%; 95% CI, 0.03%-0.12%) for men with PSA ? 1 ng/mL, and higher for men with baseline PSA 1.01-2.5 ng/mL (0.51%; 95% CI, 0.38%-0.74%). No men aged ?65 years with PSA ? 0.5 ng/mL died from prostate cancer within 15 years (95% CI, 0.00%-0.32%), and their 10-year incidence of aggressive disease was low (0.25%; 95% CI, 0.00%-0.53%). Compared with white men, black men with PSA ? 1 ng/mL had higher 10-year rates of aggressive disease (1.6% vs. 0.4%; P < 0.01). Five-year screening intervals may be appropriate for the 45% of men with PSA ? 1 ng/mL. Men ages ?65 years with PSA ? 0.5 ng/mL could consider stopping screening. Substantial risk disparities suggest appropriate screening intervals could depend on race/ethnicity.

| S-EPMC7339970 | biostudies-literature

Treatment strategy for metastatic prostate cancer with extremely high PSA level: reconsidering the value of vintage therapy.

Project description:The prognostic significance of initial prostate-specific antigen (PSA) level for metastatic prostate cancer remains uncertain. We investigated the differences in prognosis and response to hormonal therapies of metastatic prostate cancer patients according to initial PSA levels. We analyzed 184 patients diagnosed with metastatic prostate cancer and divided them into three PSA level groups as follows: low (<100 ng ml-1), intermediate (100-999 ng ml-1), and high (?1000 ng ml-1). All patients received androgen deprivation therapy (ADT) immediately. We investigated PSA progression-free survival (PFS) for first-line ADT and overall survival (OS) within each of the three groups. Furthermore, we analyzed response to antiandrogen withdrawal (AW) and alternative antiandrogen (AA) therapies after development of castration-resistant prostate cancer (CRPC). No significant differences in OS were observed among the three groups (P = 0.654). Patients with high PSA levels had significantly short PFS for first-line ADT (P = 0.037). Conversely, patients in the high PSA level group had significantly longer PFS when treated with AW than those in the low PSA level group (P = 0.047). Furthermore, patients with high PSA levels had significantly longer PFS when provided with AA therapy (P = 0.049). PSA responders to AW and AA therapies had significantly longer survival after CRPC development than nonresponders (P = 0.011 and P < 0.001, respectively). Thus, extremely high PSA level predicted favorable response to vintage sequential ADT and AW. The current data suggest a novel aspect of extremely high PSA value as a favorable prognostic marker after development of CRPC.

| S-EPMC6116678 | biostudies-literature

Association of KLK3 (PSA) genetic variants with prostate cancer risk and PSA levels.

Project description:Genome-wide association studies have identified genetic markers in kallikrein-related peptidase 3 (KLK3) associated with prostate cancer. However, some of these markers are also associated with prostate-specific antigen (PSA) levels, so it is unclear whether the polymorphisms are causal or if the association with risk is solely due to detection bias through PSA screening. PSA is a biologically active serine protease, cleaving insulin-like growth factor-binding protein. We examined the association of single-nucleotide polymorphisms (SNPs) in KLK3 with prostate cancer risk, disease-specific survival and pre-diagnostic PSA levels in a case-control study nested within the Physicians' Health Study, which began in 1982, with over 27 years of follow-up. We genotyped SNPs spanning the entire KLK3 locus to capture common variation at high resolution. Six polymorphisms were significantly associated with prostate cancer incidence (P < 0.05); the odds ratios per minor allele ranged from 0.88 to 0.73. For four of these, the odds ratios were lower when restricting to cases diagnosed in the pre-PSA screening era (before 1989). The four alleles significantly associated with lower PSA levels were also associated with lower prostate cancer risk. KLK3 variants were not significantly associated with stage at diagnosis, risk of lethal cancer or survival. Our results suggest that detection bias due to the association of KLK3 variants with PSA levels cannot completely explain the association with prostate cancer risk. Understanding the mechanism by which genetic variation in KLK3 affects prostate cancer risk has important implications for study of the biological role of PSA in prostate tumorigenesis.

| S-EPMC3106437 | biostudies-literature

A novel multiplex assay combining autoantibodies plus PSA has potential implications for classification of prostate cancer from non-malignant cases.

Project description:BackgroundThe lack of sufficient specificity and sensitivity among conventional cancer biomarkers, such as prostate specific antigen (PSA) for prostate cancer has been widely recognized after several decades of clinical implications. Autoantibodies (autoAb) among others are being extensively investigated as potential substitute markers, but remain elusive. One major obstacle is the lack of a sensitive and multiplex approach for quantifying autoAb against a large panel of clinically relevant tumor-associated antigens (TAA).MethodsTo circumvent preparation of phage lysates and purification of recombinant proteins, we identified B cell epitopes from a number of previously defined prostate cancer-associated antigens (PCAA). Peptide epitopes from cancer/testis antigen NY-ESO-1, XAGE-1b, SSX-2,4, as well as prostate cancer overexpressed antigen AMACR, p90 autoantigen, and LEDGF were then conjugated with seroMAP microspheres to allow multiplex measurement of autoAb present in serum samples. Moreover, simultaneous quantification of autoAb plus total PSA was achieved in one reaction, and termed the "A+PSA" assay.ResultsPeptide epitopes from the above 6 PCAA were identified and confirmed that autoAb against these peptide epitopes reacted specifically with the full-length protein. A pilot study was conducted with the A+PSA assay using pre-surgery sera from 131 biopsy-confirmed prostate cancer patients and 121 benign prostatic hyperplasia and/or prostatitis patients. A logistic regression-based A+PSA index was found to enhance sensitivities and specificities over PSA alone in distinguishing prostate cancer from nonmalignant cases. The A+PSA index also reduced false positive rate and improved the area under a receiver operating characteristic curve.ConclusionsThe A+PSA assay represents a novel platform that integrates autoAb signatures with a conventional cancer biomarker, which may aid in the diagnosis and prognosis of prostate cancer and others.

| S-EPMC3102624 | biostudies-literature

Zonal adjusted PSA density improves prostate cancer detection rates compared with PSA in Taiwanese males with PSA < 20 ng/ml

Project description:Background The current study aimed to compare the efficacy of transition zone PSA density (TZPSAD) with traditional PSA and PSA density (PSAD), for the diagnosis of prostate cancer (PCa) in Taiwanese males. Methods Men with PSA between 4.0 and 20.0 ng/ml who underwent a transrectal ultrasound (TRUS) guided prostate biopsy between the studied period were retrospectively identified. The demographic data, PSAD and TZPSAD were calculated in all patients. Receiver operating characteristic (ROC) curves were used to analyze the accuracy of a positive PCa diagnosis. Results The area under the ROC (AUC) was 0.615, 0.748 and 0.746 for PSA, PSAD and TZPSAD, respectively. The best cut-off of value for TZPSAD in predicting PCa in men with a PSA of 4.0–10.0 ng/ml was 0.367 ng/ml/ml with a sensitivity of 50% and a specificity of 77.5%. In men with a PSA of 10.1–20.0 ng/ml, the best cut-off value was 0.454 ng/ml, with a sensitivity of 74.8% and specificity of 70.9%. Conclusion The use of TZPSAD can improve the efficiency and specificity of PSA for the diagnosis of PCa in Taiwanese men with PSA 4.0–20.0 ng/ml. TZPSAD efficiency was similar to PSAD but TZPSAD had better cancer specificity.

| S-EPMC7542736 | biostudies-literature

Genetically adjusted PSA levels for prostate cancer screening.

Project description:Prostate-specific antigen (PSA) screening for prostate cancer remains controversial because it increases overdiagnosis and overtreatment of clinically insignificant tumors. Accounting for genetic determinants of constitutive, non-cancer-related PSA variation has potential to improve screening utility. In this study, we discovered 128 genome-wide significant associations (P < 5 × 10-8) in a multi-ancestry meta-analysis of 95,768 men and developed a PSA polygenic score (PGSPSA) that explains 9.61% of constitutive PSA variation. We found that, in men of European ancestry, using PGS-adjusted PSA would avoid up to 31% of negative prostate biopsies but also result in 12% fewer biopsies in patients with prostate cancer, mostly with Gleason score <7 tumors. Genetically adjusted PSA was more predictive of aggressive prostate cancer (odds ratio (OR) = 3.44, P = 6.2 × 10-14, area under the curve (AUC) = 0.755) than unadjusted PSA (OR = 3.31, P = 1.1 × 10-12, AUC = 0.738) in 106 cases and 23,667 controls. Compared to a prostate cancer PGS alone (AUC = 0.712), including genetically adjusted PSA improved detection of aggressive disease (AUC = 0.786, P = 7.2 × 10-4). Our findings highlight the potential utility of incorporating PGS for personalized biomarkers in prostate cancer screening.

| S-EPMC10287565 | biostudies-literature

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