Clinical Validation of IsoPSA™, a Single Parameter, Structure Based Assay for Improved Detection of High Grade Prostate Cancer.

PURPOSE: Current prostate specific antigen markers to detect prostate cancer are limited by low specificity for high grade disease. IsoPSA™ is a blood based, structure focused assay which predicts risk by partitioning the isoforms of prostate specific antigen that are linked to cancer in an aqueous 2-phase reagent system. We validated the clinical performance of this assay for identifying high grade disease in a new contemporary biopsy cohort. MATERIALS AND METHODS: We performed a multicenter prospective validation in 271 men scheduled for prostate biopsy at a total of 7 academic and community centers who were enrolled between May 2017 and March 2018. Blood samples were obtained for assay prior to biopsy. The discrimination power of the assay to detect high grade prostate cancer (Gleason 7 or greater) was evaluated by ROC analysis and compared to prior results. Clinical performance was further improved by comparison with multiparametric magnetic resonance imaging-ultrasound vs transrectal ultrasound guided biopsies. RESULTS: The assay AUC was 0.784 for high grade vs low grade cancer/benign histology, which was superior to the AUCs of total prostate specific antigen and percent free prostate specific antigen. If 1,000 patients were biopsied, the assay would have reduced the number of unnecessary biopsies from 705 to 402 (43%) with only 22 missed high grade cancers, of which 7 would have been Gleason sum 4 + 3 or higher. Subset analysis of multiparametric magnetic resonance imaging guided biopsy produced a substantial improvement of the AUC to 0.831. CONCLUSIONS: Validation of the structure based IsoPSA assay demonstrated statistical concordance with previously reported results and verified its superior performance vs concentration based prostate specific antigen and the free-to-total prostate specific antigen ratio. The assay improvement in detecting high grade prostate cancer using multiparametric magnetic resonance imaging-ultrasound guided biopsy may help define a new diagnostic paradigm.

IsoPSA Performance Characteristics are Unaffected by 5-Alpha Reductase Inhibitors or Alpha-Blockers: Results From the IsoPSA Validation Study.

OBJECTIVE: To. determine the impact of 5-α reductase inhibitors or α-blockers on IsoPSA performance for the detection of actionable prostate cancer. MATERIALS AND METHODS: This is a secondary analysis of data from an institutional review board approved, prospective, multicenter(8-sites) study evaluating IsoPSA in men ≥ 50 years of age with a total PSA ≥ 4 ng/mL with planned prostate biopsy who met previously described inclusion and exclusion criteria. Analytic groups included (i)all subjects, (ii-iii)+/- 5-ARI use, (iv-v)+/- α-blocker use. The performance characteristics of IsoPSA in these groups were assessed by ROC curve, sensitivity, and specificity (SP) analysis. RESULTS: A total of 1385 men were recruited with 888 men included in final analysis. Actionable prostate cancer, defined as GG2+, was identified in a total of 316 patients with 40 and 217 patients reporting 5-ARI and α-blocker use respectively. Sensitivity to detect both prostate cancer and actionable cancer was similar between patient subsets (P >.05). SP was similar between patients regardless of 5-ARI(P >.05). Increased SP was noted in patients on α-blockers(GG1+: No-α-blocker: 0.360 vs α-blocker: 0.529, P <.05; GG2+: No-α-blocker: 0.40 vs α-blocker: 0.61, P <.05). ROC analysis demonstrates that IsoPSA performance is unaffected by 5-ARI or α-blocker use for prostate cancer and actionable cancer (GG2+) detection. CONCLUSION: The performance of IsoPSA for detecting any prostate cancer and clinically actionable prostate cancer is unaffected by commonly used medications (5-ARI and α-blockers) for symptoms of benign prostatic hyperplasia.

Elevated IsoPSA Selects for Clinically Significant Prostate Cancer Without a Preference for Any Particular Adverse Histopathologic or Radiographic Feature.

OBJECTIVE: To explore if elevated IsoPSA selects for particular adverse radiographic or histopathologic features among men destined to undergo radical prostatectomy (RP) because of clinically significant prostate cancer identified at biopsy. MATERIALS AND METHODS: Single center, retrospective review of patients who had undergone IsoPSA testing, prostate biopsy and RP at our institution from 2019-2021. A consecutive cohort of patients whom had undergone RP within the same period without pre-operative IsoPSA served as controls. Pre-operative prostate Magnetic Resonance Imaging (MRI) was included in our analysis. Adverse histopathologic and MRI features were compared between both groups. Concordance, downstaging, and upstaging grade group rates (GG) was evaluated. Pearson Chi-Square test was used to compare categorical variables, Wilcoxon-Rank sum test for quantitative variables, and binary logistic regression to identify predictors of upstaging at RP. RESULTS: Eighty-three patients underwent IsoPSA and RP while 44 patients were controls. The IsoPSA group had significantly higher pre-operative PSA (IsoPSA group: 7.8 ng/mL vs Control group: 5.2 ng/mL, P<.001 ). Elevated IsoPSA index (>6.0) did not select for any specific adverse histopathologic features at RP. Excluding PSA density, elevated IsoPSA was not selective for adverse MRI features. There were no differences in concordance, downstaging, and upstaging GG rates from biopsy to RP. IsoPSA testing was not a predictor of GG upstaging (Odds Ratio: 0.63, P .58). CONCLUSION: Elevated IsoPSA is a diagnostic tool that can detect clinically significant prostate at the time of biopsy. In doing so, it does not select for any particular adverse prostate MRI or pathologic feature at RP.

Clinical validation of IsoPSA, a single parameter, structure-focused assay for improved detection of prostate cancer: A prospective, multicenter study.

BACKGROUND: IsoPSA is a blood-based test that assesses prostate cancer (CaP) risk by partitioning and detecting cancer-specific structural isoforms of prostate specific antigen (PSA) with an aqueous 2- phase system. OBJECTIVE: To validate the diagnostic performance of IsoPSA for High-Grade CaP and Any CaP risk on biopsy in men age ≥ 50 with total PSA ≥ 4 ng/ml. DESIGN, SETTING, AND PARTICIPANTS: Prospective, multicenter study of 888 men scheduled for prostate biopsy at 8 academic and community sites between August 2015 and August 2020. INTERVENTION: IsoPSA test. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Receiver operating characteristic and likelihood ratio analysis used to validate diagnostic performance for previously established IsoPSA Index cutoffs for High-Grade CaP (Gleason Score ≥ 7) and Any CaP (Gleason Score ≥ 6), compare IsoPSA to total PSA and % free PSA, and evaluate subgroups (total PSA 4-10 ng/ml, total PSA > 10 ng/ml, biopsy naïve, prior negative biopsy). RESULTS AND LIMITATIONS: The disease prevalence was 35.6% (High-Grade CaP) and 58.9% (Any CaP). The area under the receiver operating characteristic curve was 0.783 (High-Grade CaP) and 0.770 (Any CaP). IsoPSA outperformed total PSA and % free PSA on area under the receiver operating characteristic curve, specificity, positive and negative predictive value at similar sensitivity. Using selected IsoPSA Index cutoffs, an estimated 46% (High-Grade CaP) and 42% (Any CaP) of biopsies could be avoided in low-risk patients. IsoPSA displayed statistically informative likelihood ratio-based predictive characteristics. IsoPSA maintained accuracy in clinically relevant subgroups. CONCLUSIONS: IsoPSA diagnostic performance and predictive value is validated for High-Grade CaP and Any CaP in men age ≥ 50 with total PSA ≥ 4 ng/ml undergoing diagnostic biopsy. IsoPSA outperforms total and % free PSA in discriminating the risk of prostate cancer on biopsy. PATIENT SUMMARY: IsoPSA has the potential to reduce unnecessary biopsies and improve the risk-benefit ratio for CaP early detection.

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.

Heterogenous Dose-escalated Prostate Stereotactic Body Radiation Therapy for All Risk Prostate Cancer: Quality of Life and Clinical Outcomes of an Institutional Pilot Study.

OBJECTIVES: Previous prostate stereotactic body radiation therapy studies delivered uniform doses of 35 to 40 Gy/5 fx. Attempts at uniform dose escalation to 50 Gy caused high rates of gastrointestinal (GI) toxicity. We hypothesize that heterogeneous dose escalation to regions nonadjacent to sensitive structures (urethra, rectum, and bladder) is safe and efficacious. MATERIALS AND METHODS: Patients were enrolled on a prospective pilot study. The primary endpoint was treatment-related GI and genitourinary (GU) toxicity. The secondary endpoints included quality of life (QOL) assessed by the EPIC-26 questionnaire and biochemical control. The target volume received 36.25 Gy/5 fx. The target >3 mm from sensitive was dose escalated to 50 Gy/5 fx. RESULTS: Thirty-five patients were enrolled. Three patients had low, 14 intermediate, and 18 high-risk disease. The mean initial prostate specific antigen was 15.1 ng/mL. Androgen deprivation therapy was given to 19 patients. Median follow-up was 46 months. Urinary irritation/obstructive and urinary bother scores declined by minimal clinically important difference threshold from baseline at 6 weeks, but subsequently recovered by 4 months. No differences in QOL scores were observed for urinary incontinence, bowel domain, bloody stools, or sexual domain. One patient developed acute grade 4 GU toxicity and acute grade 4 GI toxicity. The incidence of late high grade toxicity was 1/35 for GU toxicity and 2/35 for GI toxicity. Freedom from biochemical failure at 3 years was 88.0%. CONCLUSIONS: Heterogeneous dose-escalated prostate stereotactic body radiation therapy is feasible with low rates of acute and late toxicities and favorable QOL outcomes in patients with predominantly intermediate-risk and high-risk prostate cancer.

Charlson comorbidity index and success of extracorporeal shock wave lithotripsy.

INTRODUCTION/OBJECTIVE: We examined the potential correlation between Charlson comorbidity index (CCI) and stone free rate after extracorporeal shock wave lithotripsy (ESWL). MATERIALS AND METHODS: Two hundred twenty-six adult patients were treated with 241 ESWL procedures for a renal or ureteral stone(s) over a 3 year period. Age, race, comorbidities, CCI, stone size and location, number of shocks and power level were determined. Treatment efficacies were evaluated at a mean of 56.1 days after each ESWL with computed tomography, abdominal x-ray, intravenous pyleography and/or renal ultrasound. Multivariate logistic regression analysis was performed. RESULTS: There was no correlation between CCI and any of the following: stone burden, number of shocks, or power level. There was no difference in stone burden, number of shocks or power level between those who were and were not stone free. Stone free rates for patients with CCI of zero, one, and two or greater were 44.7% (71/159), 27% (13/48) and 41.2% (14/34) respectively. Patients with an index of one were 2.1 times more likely to have a residual stone burden than patients with an index of zero (95% CI 0.99-4.42, p = 0.05). Patients with one comorbidity were 2.4 times more likely to have a residual stone burden than patients with none (95% CI 1.04-5.72, p = 0.04). Patients with upper ureteral stones were less likely to have a residual stone burden than patients with renal stones (RR = 0.52, 95% CI 0.27-0.98, p = 0.04). Those with lower ureteral stones were less likely to have a residual stone burden than those with renal stones (RR = 0.20, 95% CI 0.09-0.43, p <0.0001). The only significant predictors of the stone free rate were stone location and number of comorbidities. CONCLUSIONS: Stone location and number of comorbidities were significant predictors of ESWL outcome. The CCI may underestimate the magnitude of comorbidities and their effect on stone treatment efficacy.

Medical therapy versus surgery and minimally invasive surgical therapies for lower urinary tract symptoms and benign prostatic hyperplasia: what makes better economic sense?

From a clinical standpoint, the emergence of selective pharmacologic therapies and minimally invasive procedural treatments has changed clinical management paradigms for benign prostatic hyperplasia (BPH). Choosing from among the available treatment options can be complex for both patient and physician as factors including clinical outcomes, cost, and reimbursement are weighed and evaluated. Pharmacologic therapies produce modest improvements in objective outcomes measures and subject patients to long-term costs and risks including disease progression and the potential need for subsequent procedural treatment. Procedural interventions for obstructive BPH have changed dramatically in the past several decades as minimally invasive therapies have been developed to produce substantial improvement in outcomes measures and limit the potential morbidity associated with traditional surgical therapies. This paper reviews the current literature to provide a framework for understanding the relationship between clinical outcomes and costs with respect to commonly used medical and procedural therapies for the management of symptomatic BPH and associated lower urinary tract symptoms. The objective is to provide the clinician with an assessment of peer-reviewed evidence-based data to facilitate informed decision making on patient treatment for obstructive BPH.

The Single-parameter, Structure-based IsoPSA Assay Demonstrates Improved Diagnostic Accuracy for Detection of Any Prostate Cancer and High-grade Prostate Cancer Compared to a Concentration-based Assay of Total Prostate-specific Antigen: A Preliminary Report.

BACKGROUND: IsoPSA is a serum-based assay that predicts prostate cancer (PCa) risk by partitioning isoforms of prostate-specific antigen (PSA) with an aqueous two-phase reagent. OBJECTIVES: To determine the diagnostic accuracy of IsoPSA in identifying the presence or absence of PCa and the presence of high-grade disease in a contemporary biopsy cohort. DESIGN, SETTING, AND PARTICIPANTS: Multicenter prospective study of 261 men scheduled for prostate biopsy at five academic and community centers in the USA enrolled between August 2015 and December 2016. INTERVENTION: Performance of the IsoPSA assay. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Discrimination power was evaluated using receiver operating characteristic (ROC) analysis. The outcome of the IsoPSA assay was transformed into risk probability using logistic regression. Decision curve analysis (DCA) was used to compare the net benefit of IsoPSA against other clinical protocols. RESULTS AND LIMITATIONS: The overall prevalence was 53% for any PCa and 34% for high-grade PCa. The area under the ROC curve was 0.79 for any cancer versus none and 0.81 for high-grade PCa versus low-grade PCa/benign histology. In this preliminary study, DCA revealed a superior net benefit of IsoPSA against no biopsy, all biopsy, and the modified Prostate Cancer Prevention Trial Risk Calculator 2.0. At a cutoff selected to recommend biopsy, IsoPSA demonstrated a 48% reduction in false-positive biopsies; at a cutoff selected to identity men at low risk of high-grade disease, there was a 45% reduction in the false-positive rate. CONCLUSION: The structure-based IsoPSA assay outperformed concentration-based PSA measurement, and provided a net benefit against other protocols. Once validated, clinical use of IsoPSA could significantly reduce unnecessary biopsies while identifying patients needing treatment. PATIENT SUMMARY: The IsoPSA assay outperformed prostate-specific antigen in predicting the overall risk of prostate cancer and the risk of clinically significant cancer in a preliminary study. The IsoPSA assay could assist in determining the need for prostate biopsy for patients.

Dose-Escalated Stereotactic Body Radiation Therapy for Patients With Intermediate- and High-Risk Prostate Cancer: Initial Dosimetry Analysis and Patient Outcomes.

PURPOSE: To report the short-term clinical outcomes and acute and late treatment-related genitourinary (GU) and gastrointestinal (GI) toxicities in patients with intermediate- and high-risk prostate cancer treated with dose-escalated stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Between 2011 and 2014, 24 patients with prostate cancer were treated with SBRT to the prostate gland and proximal seminal vesicles. A high-dose avoidance zone (HDAZ) was created by a 3-mm expansion around the rectum, urethra, and bladder. Patients were treated to a minimum dose of 36.25 Gy in 5 fractions, with a simultaneous dose escalation to a dose of 50 Gy to the target volume away from the HDAZ. Acute and late GU and GI toxicity outcomes were measured according to the National Cancer Institute Common Terminology Criteria for Adverse Events toxicity scale, version 4. RESULTS: The median follow-up was 25 months (range, 18-45 months). Nine patients (38%) experienced an acute grade 2 GU toxicity, which was medically managed, and no patients experienced an acute grade 2 GI toxicity. Two patients (8%) experienced late grade 2 GU toxicity, and 2 patients (8%) experienced late grade 2 GI toxicity. No acute or late grade ≥3 GU or GI toxicities were observed. The 24-month prostate-specific antigen relapse-free survival outcome for all patients was 95.8% (95% confidence interval 75.6%-99.4%), and both biochemical failures occurred in patients with high-risk disease. All patients are currently alive at the time of this analysis and continue to be followed. CONCLUSIONS: A heterogeneous prostate SBRT planning technique with differential treatment volumes (low dose: 36.25 Gy; and high dose: 50 Gy) with an HDAZ provides a safe method of dose escalation. Favorable rates of biochemical control and acceptably low rates of acute and long-term GU and GI toxicity can be achieved in patients with intermediate- and high-risk prostate cancer treated with SBRT.

Prostate-specific antigen/solvent interaction analysis: a preliminary evaluation of a new assay concept for detecting prostate cancer using urinary samples.

OBJECTIVE: To provide preliminary clinical performance evaluation of a novel prostate cancer (CaP) assay, prostate-specific antigen/solvent interaction analysis (PSA/SIA) that focused on changes to the structure of PSA. METHODS: Two-hundred twenty-two men undergoing prostate biopsy for accepted clinical criteria at 3 sites (University Hospitals Case Medical Center in Cleveland, Cleveland Clinic, and Veterans Administration Boston Healthcare System) were enrolled in institutional review board-approved study. Before transrectal ultrasound-guided biopsy, patients received digital rectal examination with systematic prostate massage followed by collection of urine. The PSA/SIA assay determined the relative partitioning of heterogeneous PSA isoform populations in urine between 2 aqueous phases. A structural index, K, whose numerical value is defined as the ratio of the concentration of all PSA isoforms, was determined by total PSA enzyme-linked immunosorbent assay and used to set a diagnostic threshold for CaP. Performance was assessed using receiver operating characteristic (ROC) analysis with biopsy as the gold standard. RESULTS: Biopsies were pathologically classified as case (malignant, n=100) or control (benign, n=122). ROC performance demonstrated area under the curve=0.90 for PSA/SIA and 0.58 for serum total PSA. At a cutoff value of k=1.73, PSA/SIA displayed sensitivity=100%, specificity=80.3%, positive predictive value=80.6%, and negative predictive value=100%. No attempt was made in this preliminary study to further control patient population or selection criteria for biopsy, nor did we analytically investigate the type of structural differences in PSA that led to changes in k value. CONCLUSION: PSA/SIA provides ratiometric information independently of PSA concentration. In this preliminary study, analysis of the overall structurally heterogeneous PSA isoform population using the SIA assay showed promising results to be further evaluated in future studies.

Tubulocystic carcinoma of the kidney: clinicopathologic analysis of 31 cases of a distinctive rare subtype of renal cell carcinoma.

A distinctive tumor described under the terms Bellini duct carcinoma and low-grade collecting duct carcinoma has been referred to by us and others as tubulocystic carcinoma. This renal cell carcinoma subtype is not recognized in the World Health Organization 2004 classification. Herein, we present a detailed study of 31 cases to further characterize this rare subtype of renal cell carcinoma. The tumor occurred in adults (mean age, 54 years) with a strong male predominance (7:1). Grossly, the tumors ranged from 0.7 to 17 cm, and exhibited a spongy or "bubble wrap" appearance reflecting the microscopic presence of variably sized cystically dilated tubules lined by a single layer of epithelium. The lining varied with a cuboidal, flat, and hobnail cell appearance, and the neoplastic cells had abundant eosinophilic cytoplasm and enlarged nuclei with prominent nucleoli. The cysts were closely spaced with an intervening variably fibrotic stroma. Immunohistochemistry and ultrastructural examination showed features of proximal convoluted tubules (Pax 2 immunoreactivity and short microvilli with brush border organization) and distal nephron (kidney-specific cadherin immunoreactivity and cytoplasmic interdigitation). Gene expression profiling showed that tubulocystic carcinoma displayed a unique molecular signature. Twenty-four tumors were stage pT1, 4 stage pT2, and 3 stage pT3. Disease progression (median follow-up of 56 months) occurred in 3 patients; 1 with local recurrence, and 2 with distant metastasis to bone and liver. In light of the distinctive clinicopathologic features and a low but definite metastatic potential, this unique subtype of renal cell carcinoma deserves formal recognition in the contemporary classification of renal neoplasms.

BPH procedural treatment: the case for value-based pay for performance.

The concept of "pay for performance" (P4P) applied to the practice of medicine has become a major foundation in current public and private payer reimbursement strategies for both institutional and individual physician providers. "Pay for performance" programs represent a substantial shift from traditional service-based reimbursement to a system of performance-based provider payment using financial incentives to drive improvements in the quality of care. P4P strategies currently embody rudimentary structure and process (as opposed to outcomes) metrics which set relatively low-performance thresholds. P4P strategies that align reimbursement allocation with "free market" type shifts in cognitive and procedural care using evidence-based data and positive reinforcement are more likely to produce large-scale improvements in quality and cost efficiency with respect to clinical urologic care. This paper reviews current paradigms and, using BPH procedural therapy outcomes, cost, and reimbursement data, makes the case for a fundamental change in perspective to value-based pay for performance as a reimbursement system with the potential to align the interests of patients, physicians, and payers and to improve global clinical outcomes while preserving free choice of clinically efficacious treatments.

A clinical outcomes and cost analysis comparing photoselective vaporization of the prostate to alternative minimally invasive therapies and transurethral prostate resection for the treatment of benign prostatic hyperplasia.

PURPOSE: We critically evaluated the clinical outcomes and cost characteristics of alternative procedural treatment options for symptomatic benign prostatic hyperplasia. MATERIALS AND METHODS: An outcomes and cost analysis was performed for benign prostatic hyperplasia treatments, including photoselective vaporization, microwave thermotherapy, transurethral needle ablation, interstitial laser coagulation and transurethral resection. Clinical outcomes were measured by the percent improvement in American Urological Association/International Prostate Symptom Score, the maximum uroflowmetry rate and quality of life score. An economic simulation model was constructed to estimate the expected cost of benign prostatic hyperplasia procedural therapies from a payer perspective. The model included costs of initial treatment, followup care, adverse events and re-treatment. Sensitivity and threshold analyses tested the impact of changing model inputs on base case results. RESULTS: Ablative therapies showed better improvement in symptom score, flow rate and quality of life score compared to thermotherapy procedures. Photoselective vaporization resulted in the largest beneficial changes in American Urological Association/International Prostate Symptom Score, the maximum uroflowmetry rate and the quality of life score at all time points evaluated, followed by transurethral resection and then interstitial laser coagulation. The estimated cost was lower for photoselective vaporization than for any other procedural option at any interval studied. Sensitivity analyses indicated that the results of baseline analyses were robust to reasonable changes in clinical and economic inputs to the model. CONCLUSIONS: Compared to alternative treatment options photoselective vaporization of the prostate is a clinically efficacious and cost-effective treatment for symptomatic benign prostatic hyperplasia.

A novel computer based expert decision making model for prostate cancer disease management.

PURPOSE: We propose a strategic, computer based, prostate cancer decision making model based on the analytic hierarchy process. We developed a model that improves physician-patient joint decision making and enhances the treatment selection process by making this critical decision rational and evidence based. MATERIALS AND METHODS: Two groups (patient and physician-expert) completed a clinical study comparing an initial disease management choice with the highest ranked option generated by the computer model. Participants made pairwise comparisons to derive priorities for the objectives and subobjectives related to the disease management decision. The weighted comparisons were then applied to treatment options to yield prioritized rank lists that reflect the likelihood that a given alternative will achieve the participant treatment goal. Aggregate data were evaluated by inconsistency ratio analysis and sensitivity analysis, which assessed the influence of individual objectives and subobjectives on the final rank list of treatment options. RESULTS: Inconsistency ratios less than 0.05 were reliably generated, indicating that judgments made within the model were mathematically rational. The aggregate prioritized list of treatment options was tabulated for the patient and physician groups with similar outcomes for the 2 groups. Analysis of the major defining objectives in the treatment selection decision demonstrated the same rank order for the patient and physician groups with cure, survival and quality of life being more important than controlling cancer, preventing major complications of treatment, preventing blood transfusion complications and limiting treatment cost. Analysis of subobjectives, including quality of life and sexual dysfunction, produced similar priority rankings for the patient and physician groups. Concordance between initial treatment choice and the highest weighted model option differed between the groups with the patient group having 59% concordance and the physician group having only 42% concordance. CONCLUSIONS: This study successfully validated the usefulness of a computer based prostate cancer management decision making model to produce individualized, rational, clinically appropriate disease management decisions without physician bias.