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Biological targetvolumesView Articles

Volume 8, Supplement 1Review Articles

Fused Radioimmunoscintigraphy for Treatment Planning

Prostate Cancer Imaging

Rodney J EllisDeborah A Kaminsky

Advances in imaging technologies, including computerized tomography (CT) and single-photon emission tomography (SPECT), are improving the role of imaging in prostate cancer diagnosis and treatment. Hybrid (SPECT/CT) imaging, in particular, shows an increased sensitivity for identification of prostate cancer. Published studies have also recently proposed a new paradigm in the administration of radiation therapy for prostate cancer, favoring doseescalation strategies to improve tumor control for localized disease. Conventional dose-escalation protocols have previously relied primarily on margin extension to the entire prostate gland to achieve dose-escalation; extending increased risk to radiosensitive normal structures. A newer strategy proposes use of advanced imaging to confine dose-escalation to biological target volumes identified on capromab pendetide SPECT/CT-fused image sets or imageguided radiation therapy (IGRT). This strategy defines a shift in radiation dosimetry and planning from uniform glandular prescription dosing with doseescalation applied generically to the peripheral regions and margin extension; to dose-escalation confinement to discrete regions of known disease as defined by focal uptake on radioimmunoscintigraphy fusion with anatomic image sets, with minimal margin extension. The introduction of advanced imaging for IGRT in prostate cancer has also introduced an improved capability for the early-identification of patients at risk for metastatic disease, where more aggressive therapeutic interventions may prove beneficial. [Rev Urol. 2006;8(suppl 1):S11-S19]

Prostate cancerRadiotherapyBrachytherapyProstaScintSPECT/CTBiological targetvolumesSurvival

BiomarkerView Articles

Volume 16, Number 4Review Articles

A Guide for Clinicians in the Evaluation of Emerging Molecular Diagnostics for Newly Diagnosed Prostate Cancer

Diagnosis Update

Michael J KemeterPhillip G FebboSteven E CanfieldAdam S KibelH Jeffrey LawrenceJudd W Moul

Prostate-specific antigen (PSA) screening is associated with a decline in prostate cancerrelated mortality. However, screening has also led to overdiagnosis and overtreatment of clinically insignificant tumors. Recently, certain national guidelines (eg, US Preventive Services Task Force) have recommended against PSA screening, which may lead to a reverse-stage migration. Although many prostate tumors are indolent at presentation, others are aggressive and are appropriate targets for treatment interventions. Utilization of molecular markers may improve our ability to measure tumor biology and allow better discrimination of indolent and aggressive tumors at diagnosis. Many emerging commercial molecular diagnostic assays have been designed to provide more accurate risk stratification for newly diagnosed prostate cancer. Unfamiliarity with molecular diagnostics may make it challenging for some clinicians to navigate and interpret the medical literature to ascertain whether particular assays are appropriately developed and validated for clinical use. Herein, the authors provide a framework for practitioners to use when assessing new tissue-based molecular assays. This review outlines aspects of assay development, clinical and analytic validation and clinical utility studies, and regulatory issues, which collectively determine whether tests (1) are actionable for specific clinical indications, (2) measurably influence treatment decisions, and (3) are sufficiently validated to warrant incorporation into clinical practice. [Rev Urol. 2014;16(4):172-180 doi: 10.3909/riu0644] © 2014 MedReviews®, LLC

Prostate cancerBiomarkerClinical utilityGenomic prostate scoreAdverse pathologyClinical validationMolecular diagnostics

Biopsy rateView Articles

Volume 17, Number 4Original Research

The 4Kscore® Test Reduces Prostate Biopsy Rates in Community and Academic Urology Practices

Jason HafronStephen M ZappalaDipen J ParekhDanielle OsterhoutJeffrey SchockRandy M ChudlerGregory M OldfordKenneth M KernenBadrinath R Konety

There is significant concern regarding prostate cancer screening because of the potential for overdiagnosis and overtreatment of men who are discovered to have abnormal prostate specific antigen (PSA) levels and/or digital rectal examination (DRE) results. The 4Kscore® Test (OPKO Diagnostics, LLC) is a blood test that utilizes four kallikrein levels plus clinical information in an algorithm to calculate an individual’s percentage risk (< 1% to > 95%) for aggressive prostate cancer (Gleason score ≥ 7) on prostate biopsy. The 4Kscore Test, as a follow-up test after abnormal PSA and/or DRE test results, has been shown to improve the specificity for predicting the risk of aggressive prostate cancer and reduce unnecessary prostate biopsies. A clinical utility study was conducted to assess the influence of the 4Kscore Test on the decision to perform prostate biopsies in men referred to urologists for abnormal PSA and/or DRE results. The study population included 611 patients seen by 35 academic and community urologists in the United States. Urologists ordered the 4Kscore Test as part of their assessment of men referred for abnormal PSA and/or DRE test results. Results for the patients were stratified into low risk (< 7.5%), intermediate risk (7.5%-19.9%), and high risk (≥ 20%) for aggressive prostate cancer. The 4Kscore Test results influenced biopsy decisions in 88.7% of the men. Performing the 4Kscore Test resulted in a 64.6% reduction in prostate biopsies in patients; the actual percentage of cases not proceeding to biopsy were 94.0%, 52.9%, and 19.0% for men who had low-, intermediate-, and high-risk 4Kscore Test results, respectively. A higher 4Kscore Test was associated with greater likelihood of having a prostate biopsy (P < 0.001). Among the 171 patients who had a biopsy, the 4Kscore risk category is strongly associated with biopsy pathology. The 4Kscore Test, as a follow-up test for an abnormal PSA and/or DRE results, significantly influenced the physician and patient shared decision in clinical practice, which led to a reduction in prostate biopsies while increasing the probability of detecting aggressive cancer. [Rev Urol. 2015;17(4):231-240 doi: 10.3909/riu0699] © 2016 MedReviews®, LLC

Prostate cancerProstate-specific antigen4KscoreGleason scoreDigital rectal examinationBiopsy rateProstate cancer prognosis

Black menView Articles

Volume 22, Number 3Review Articles

A Trend Toward Aggressive Prostate Cancer

Original Research

Navin ShahVladimir Ioffe

To compare prostate biopsy (Pbx) characteristics before and after the 2012 United States Preventive Services Task Force (USPSTF) prostate cancer (PCa) screening guidelines, we completed a retrospective comparative analysis of 1703 sequential patients that had a Pbx in 2010 to 2012 (3 years) with 383 patients biopsied in 2018 and 310 patients biopsied in 2019. Data was collected on patient age, race, serum prostate specific antigen (PSA) level, digital rectal examination (DRE) results, total number of biopsies performed, and Gleason sum score (GSS). Data were analyzed to determine whether the 2012 USPSTF screening recommendations against PCa screening may have affected PCa characteristics. Three study groups were defined as Group A, Group B, and Group C. Group A represents Pbx prior to the 2012 USPSTF screening guidelines (2010-2012), Group B represents Pbx in 2018, and Group C represents Pbx in 2019. The patient population consisted of 73% Black men, 16% White men, and 11% men of other races. The number of patients that had a biopsy in Groups A through C, respectively, were 567 patients/year, 383 patients/year, and 310 patients/year. The annual positive Pbx rate for Group A through C was 134/year, 175/year, and 201/year, respectively. High-grade PCa (GSS 7-10) in Groups A through C was 51.5%, 60.5%, and 60.0%. The proportion of patients with a serum PSA level 10 ng/mL or greater in Groups A through C was 25.4%, 29.3%, and 33%. For patients age 70 to 80 years, there was an increasing trend for serum PSA levels 10 ng/mL and higher: 31%, 38%, and 39%, respectively. In this age group, high-grade tumors (GSS 7-10) occurred in 61%, 65%, and 68%, respectively. In 2019, Grade Group 3, 4, and 5 was present in 37.7% of 70- to 80-year-old men and 34.6% of Black men. More than 50% positive biopsy cores were present in 46.3% of 70- to 80-year-old men and 36.6% of Black men. Our data through 2019 continued to show that after the 2012 USPSTF recommendations against PCa screening, PCa screening has decreased. We found decreased Pbx, increased PCa diagnosis, and increased high-grade PCa (GSS 7-10). As our patient population consisted of 73% Black patients and 33% of men age 70 to 80 years, our results support aggressive PCa screening for high-risk patients, which include Black men, men with a family history of PCa, and healthy men age 70 to 80 years. [Rev Urol. 2020;22(3):102-109] © 2020 MedReviews®, LLC

Prostate cancerElderly menUnited States Preventive Services Task ForceProstate-specific antigen screeningBlack men