IsoPSA® Reduces Provider Recommendations for Biopsy and Magnetic Resonance Imaging in Men with Total Prostate Specific Antigen ≥4 ng/ml: A Real-World Observational Clinical Utility Study.

INTRODUCTION: We assessed the impact of the IsoPSA® test for prostate cancer risk assessment on provider patient management decisions in a real-world clinical setting. METHODS: A total of 38 providers, including advanced practice providers, fellowship trained oncologists and general urologists in the Cleveland Clinic health system including both community-based practices and academic locations, enrolled 900 men being evaluated for prostate cancer; 734 met inclusion criteria (age ≥50 years, total serum prostate specific antigen [PSA] ≥4 and <100 ng/ml and no history of prostate cancer) and IsoPSA indication for use. A standard template was used to document biopsy recommendation prior to and after receiving IsoPSA results. The primary outcome was the number of biopsy and magnetic resonance imaging recommendation changes occurring after IsoPSA testing. RESULTS: IsoPSA testing resulted in a 55% (284 vs 638) net reduction in recommendations for prostate biopsy for men with total PSA ≥4 ng/ml. Additionally, a 9% reduction in recommendations for magnetic resonance imaging was observed. There was strong concordance between IsoPSA results and provider recommendations for prostate biopsy, with 87% of patients with an IsoPSA index above the threshold recommended for biopsy and 92% of patients with an IsoPSA index below the threshold not recommended for biopsy. CONCLUSIONS: In a real-world clinical setting, providers from diverse training backgrounds and practice settings readily adopted IsoPSA with substantial reductions in the rate of recommended prostate biopsies in patients with elevated PSA values (≥4 ng/ml). There was a high concordance between recommendation for or against prostate biopsy and the IsoPSA result.

Decision Analysis Model Comparing Cost of IsoPSA™ vs Repeat Biopsy for Detection of Clinically Significant Prostate Cancer in Men with Previous Negative Findings on Biopsy.

INTRODUCTION: We compared cost of IsoPSA™ vs repeat biopsy in detection of clinically significant prostate cancer in men with previous negative office based prostate biopsy. METHODS: A decision tree model compared cost of biopsy for all men with previous negative biopsy and rising prostate specific antigen (standard arm) vs initial IsoPSA with biopsies performed only in cases of abnormal IsoPSA. Study endpoints were cost, number of biopsies and cancers detected. Cost was based on Medicare reimbursement and peer reviewed literature. Cost of sepsis, complications and loss of work were incorporated into the analysis. Sensitivity analyses were performed varying model assumptions. A separate analysis incorporated cost of treatment for patients with cancer. RESULTS: Using the baseline model with 20.5% prostate cancer incidence yielded an overall cost for 100 men of $197,700 and $165,300 for the standard and IsoPSA arms, respectively, including the cost of the IsoPSA assay, herein assumed to be $350. The IsoPSA arm detected 0.8 fewer Gleason 7-10 prostate cancers (12.6 vs 13.4) but generated 34% fewer biopsies. The IsoPSA arm was less expensive if overall biopsy cost is more than $1,027, if IsoPSA cost is less than $674 or cancer rate was less than 70%. In the model incorporating treatment of men with a cancer diagnosis the IsoPSA arm was also less expensive, generating savings of $53,300 per 100 men. CONCLUSIONS: The use of IsoPSA to select patients for repeat biopsy reduced the number of biopsies needed by 34% and generated significant cost savings.

Carrier screening by next-generation sequencing: health benefits and cost effectiveness.

BACKGROUND: Compared with conventional genotyping, which typically tests for a limited number of mutations, next-generation DNA sequencing (NGS) provides increased accuracy for carrier screening. The objective of this study was to evaluate the cost effectiveness of carrier screening using NGS versus genotyping for 14 of the recessive disorders for which medical society guidelines recommend screening. METHODS: Data from published literature, population surveys, and expert opinion were used to develop a decision tree model capturing decisions and outcomes related to carrier screening and reproductive health. RESULTS: Modeling a population of 1,000,000 couples that was representative of the United States population and that contained 83,421 carriers of pathogenic mutations, carrier screening using NGS averted 21 additional affected births as compared with genotyping, and reduced costs by approximately $13 million. As compared with no screening, NGS carrier screening averted 223 additional affected births. The results are sensitive to assumptions regarding mutation detection rates and carrier frequencies in multiethnic populations. CONCLUSION: This study demonstrated that NGS-based carrier screening offers the greater benefit in clinical outcomes and lower total healthcare cost as compared with genotyping.

Colorectal cancer screening using stool DNA analysis in clinical practice: early clinical experience with respect to patient acceptance and colonoscopic follow-up of abnormal tests.

BACKGROUND: Stool-based DNA screening for colorectal cancer (CRC) was recently made available for use in daily clinical practice (PreGen-Plus). The main objectives of this study were to examine patients' screening experiences with stool DNA testing in routine clinical practice and the results of diagnostic colonoscopy in patients with an antecedent abnormal stool DNA test. PATIENTS AND METHODS: Patients undergoing stool-based DNA testing were asked to complete and return via mail an anonymous 10-item questionnaire inquiring about their test-related experiences. Colonoscopy findings for all abnormal stool-based DNA tests were ascertained via a telephone survey of the ordering primary care clinicians' offices. RESULTS: Patient survey responses were collected between August 2003 and July 2005 and reflect an 18% (1211 of 6730) response rate. The majority reported that the specimen collection process was very easy/easy to perform (87%), that they were very likely/likely to use the test again (91%), and that they had never been screened for CRC previously by any method (52%). Tests were ordered predominantly by the patient's primary care clinician (90%), including obstetrician/gynecologist providers. Colonoscopy findings from 69 of 159 patients with an antecedent abnormal stool DNA test screened with PreGen-Plus between August 2003 and July 2004 were available for review. An abnormal stool DNA test correlated with a colonoscopically demonstrable abnormality in 49% of cases (34 of 69). Abnormal findings, including CRC in 3 patients (4%; 1 with Dukes A and 2 with Dukes B disease), single or multiple adenomatous polyps in 23 patients (33%), hyperplastic polyps in 3 patients (4%), and colitis in 5 patients (7%). Colonoscopy was reported as negative in 51% of patients (35 of 69), including 2 cases (3%) with an altered BAT-26 microsatellite caused by a normal polymorphism. CONCLUSION: Stool DNA testing provides an acceptable noninvasive alternative for CRC screening that can identify early-stage CRCs and adenomatous polyps in routine clinical practice. Ongoing and broader surveys are indicated to support these early findings.