Utility of noninvasive biomarker testing and MRI to predict a prostate cancer diagnosis.

PURPOSE: To assess the diagnostic performance and utility of the ExoDx IntelliScore and an OPKO4K score to predict prostate cancer in men presenting with elevated PSA-both as independent predictors and in combination with clinical/MRI characteristics. METHODS: Patients with elevated PSA were retrospectively reviewed. Abnormal tests were defined as an OPKO4K score ≥ 7.5% and an ExoDx IntelliScore ≥ 15.6. Four regression models and ROC curves were generated based on: (1) age, PSA, and DRE, (2) model 1 + OPKO4K 4Kscore ≥ 7.5%, (3) model 2 + ExoDx IntelliScore ≥ 15.6, and (4) model 3 + MRI PIRADS 4-5. RESULTS: 359 men received an OPKO4K test, 307 had MRI and 113 had ExoDx tests. 163 men proceeded to prostate biopsy and 196 (55%) were saved from biopsy. Mean age was 65.0 ± 8.7 years and mean PSA was 7.1 ± 6.1 ng/mL. Positive biopsies were found in 84 (51.5%) men. The sensitivity and negative predictive value of an OPKO4K score were 86.7% and 72.3%; values for an ExoDx test were 76.5% and 77.1%, respectively. On regression analysis, clinical markers (Age, PSA, DRE) generated an AUC of 0.559. The addition of an OPKO4K score raised the AUC to 0.653. The stepwise addition of an ExoDx score raised the AUC to 0.766. The combined use of both biomarkers, patient characteristics, and MRI yielded an AUC of 0.825. CONCLUSION: This analysis demonstrates the high negative predictive value of both the OPKO4K score and ExoDX IntelliScore independently while demonstrating that the combination of an OPKO4K score, an ExoDX IntelliScore, and MRI increases predictive capability for biopsy confirmed prostate cancer.

Biomarkers for Prostate Cancer: From Diagnosis to Treatment.

Prostate cancer (PCa) is a widespread malignancy with global significance, which substantially affects cancer-related mortality. Its spectrum varies widely, from slow-progressing cases to aggressive or even lethal forms. Effective patient stratification into risk groups is crucial to therapeutic decisions and clinical trials. This review examines a wide range of diagnostic and prognostic biomarkers, several of which are integrated into clinical guidelines, such as the PHI, the 4K score, PCA3, Decipher, and Prolaris. It also explores the emergence of novel biomarkers supported by robust preclinical evidence, including urinary miRNAs and isoprostanes. Genetic alterations frequently identified in PCa, including BRCA1/BRCA2, ETS gene fusions, and AR changes, are also discussed, offering insights into risk assessment and precision treatment strategies. By evaluating the latest developments and applications of PCa biomarkers, this review contributes to an enhanced understanding of their role in disease management.

A multi-institutional study of 1,111 men with 4K score, multiparametric magnetic resonance imaging, and prostate biopsy.

OBJECTIVE: Prostate magnetic resonance imaging (MRI) and biomarkers are often used in conjunction to enhance the selection process for prostate biopsy. However, the optimal sequence of ordering these tests has not been established. A comprehensive evaluation was conducted on a large multi-institutional cohort of patients who underwent MRI, 4K score, and biopsy of the prostate to examine the impact of utilizing both tests vs. either test alone and to determine if the order in which these tests are administered affects the ability to detect clinically significant prostate cancer (csCaP). METHODS AND MATERIALS: We evaluated men from 8 different institutions who were referred for prostate cancer evaluation and underwent MRI, 4K score test, and prostate biopsy. The primary outcome was the presence of csCaP, defined as grade group 2 or higher cancer on a biopsy of the prostate. We used logistic regression, calibration plots, and decision curve analysis to evaluate using a 4K score or MRI alone vs. both tests together for detecting csCaP. In addition, we evaluated several strategies using one or both tests for selecting men for biopsy and compared them based on the proportion of biopsies avoided and the csCaP's missed. RESULTS: Among the 1,111 men who formed the final cohort, 553 (49.8%) had prostate cancer, and 353 (31.8%) had csCaP. We found that using MRI and 4K score together had better discrimination, calibration, and a higher clinical utility on decision curve analysis compared to using either test individually. Using both tests together resulted in fewer biopsies avoided and missed cancers compared to using either test alone. Strategies that sequence MRI and 4K score tests resulted in the largest biopsy reduction, with no appreciable difference between starting with an MRI vs. a biomarker. CONCLUSIONS: We found that using both an MRI and 4K score together was superior to using either test alone but found no appreciable difference between starting with an MRI vs. starting with a 4K score. Prospective studies are needed to identify the best strategy to sequence MRI and biomarkers in the evaluation of csCaP.

A 4K score/MRI-based nomogram for predicting prostate cancer, clinically significant prostate cancer, and unfavorable prostate cancer.

BACKGROUND: The detection of prostate cancer requires histological confirmation in biopsy core. Currently, number of unnecessary prostate biopsies are being performed in the United States. This is due to the absence of appropriate biopsy decision-making protocol. AIM: To develop and validate a 4K score/multiparametric magnetic resonance imaging (mpMRI)-based nomogram to predict prostate cancer (PCa), clinically significant prostate cancer (csPCa), and unfavorable prostate cancer (uPCa). METHODS AND RESULTS: Retrospective, single-center study evaluating a cohort of 574 men with 4K score test >7% or suspicious digital rectal examination (DRE) or Prostate Imaging Reporting and Data System (PI-RADS) scores 3, 4, or 5 on mpMRI that underwent systematic and/or mpMRI/ultrasound fusion-targeted prostate biopsy between 2016 and 2020. External cohort included 622 men. csPCa and uPCa were defined as Gleason score ≥3 + 4 and ≥4 + 3 on biopsy, respectively. Multivariable logistic regression analysis was performed to build nomogram for predicting PCa, csPCa, and uPCa. Validation was performed by plotting the area under the curve (AUC) and comparing nomogram-predicted probabilities with actual rates of PCa, csPCa, and uPCa probabilities in the external cohort. 4K score, a PI-RADS ≥4, prostate volume and prior negative biopsy were significant predictors of PCa, csPCa, and uPCa. AUCs were 0.84, 0.88, and 0.86 for the prediction of PCa, csPCa, and uPCa, respectively. The predicted and actual rates of PCa, csPCa, and uPCa showed agreement across all percentage probability ranges in the validation cohort. Using the prediction model at threshold of 30, 30% of overall biopsies, 41% of benign biopsies, and 19% of diagnosed indolent PCa could be avoided, while missing 9% of csPCa. CONCLUSION: This novel nomogram would reduce unnecessary prostate biopsies and decrease detection of clinically insignificant PCa.

Biomarkers for prostate cancer: prostate-specific antigen and beyond.

In recent years, several new biomarkers supplementing the role of prostate-specific antigen (PSA) have become available for men with prostate cancer. Although widely used in an ad hoc manner, the role of PSA in screening asymptomatic men for prostate cancer is controversial. Several expert panels, however, have recently recommended limited PSA screening following informed consent in average-risk men, aged 55-69 years. As a screening test for prostate cancer however, PSA has limited specificity and leads to overdiagnosis which in turn results in overtreatment. To increase specificity and reduce the number of unnecessary biopsies, biomarkers such as percent free PSA, prostate health index (PHI) or the 4K score may be used, while Progensa PCA3 may be measured to reduce the number of repeat biopsies in men with a previously negative biopsy. In addition to its role in screening, PSA is also widely used in the management of patients with diagnosed prostate cancer such as in surveillance following diagnosis, monitoring response to therapy and in combination with both clinical and histological criteria in risk stratification for recurrence. For determining aggressiveness and predicting outcome, especially in low- or intermediate-risk men, tissue-based multigene tests such as Decipher, Oncotype DX (Prostate), Prolaris and ProMark, may be used. Emerging therapy predictive biomarkers include AR-V7 for predicting lack of response to specific anti-androgens (enzalutamide, abiraterone), BRAC1/2 mutations for predicting benefit from PARP inhibitor and PORTOS for predicting benefit from radiotherapy. With the increased availability of multiple biomarkers, personalised treatment for men with prostate cancer is finally on the horizon.

Are localized prostate cancer biomarkers useful in the clinical practice?

Prostate cancer presents itself in a heterogeneous way with both aggressive and indolent forms. Despite the controversy surrounding its use, prostate-specific antigen screening ultimately leads to a greater number of diagnosed patients. One of the biggest challenges in clinical practice is to select the right patients for biopsy and, among diagnosed patients, to differentiate tumors with an indolent course from those with an unfavorable prognosis, in order to determine the best therapeutic decision for each case, avoiding unnecessary interventions. Currently, several types of biomarkers are available for clinical use in patients with prostate cancer, which include blood-based (prostate-specific antigen, Prostate Health Index®, 4K score®); urine sample-based (PCA3, SelectMDx®, ExoDx Prostate IntelliScore®); and biopsy, transurethral resection, or radical prostatectomy tissue-based (ConfirmMDx®, Oncotype®, Prolaris®, Decipher®). The aim of this review is to provide an overview of the current state of evidence and to highlight recent advances in the evaluation and diagnosis of prostate cancer, with emphasis on biomarkers related to diagnosis and to prognostic evaluation of localized prostate cancer.

Risk stratification of prostate cancer 2016.

Prostate cancer is a common malignancy in men, but its management is fraught with controversy owing to its variable biologic and clinical behavior. Despite evidence that PSA screening reduces prostate cancer specific metastasis and death, it has not gained acceptance by various health authorities. Nevertheless, recent advances in biomarker development potentially address many of the shortcomings of routine PSA testing alone, including improved specificity for the detection of clinically significant cancer, optimized risk stratification to aid clinical management decisions, and discovery of genetic variants that may guide optimized therapy of advanced disease.