Clarifying the Trade-Offs of Risk-Stratified Screening for Prostate Cancer: A Cost-Effectiveness Study.

Cancer risk prediction is necessary for precision early detection, which matches screening intensity to risk. However, practical steps for translating risk predictions to risk-stratified screening policies are not well established. We used a validated population prostate-cancer model to simulate the outcomes of strategies that increase intensity for men at high risk and reduce intensity for men at low risk. We defined risk by the Prompt Prostate Genetic Score (PGS) (Stratify Genomics, San Diego, California), a germline genetic test. We first recalibrated the model to reflect the disease incidence observed within risk strata using data from a large prevention trial where some participants were tested with Prompt PGS. We then simulated risk-stratified strategies in a population with the same risk distribution as the trial and evaluated the cost-effectiveness of risk-stratified screening versus universal (risk-agnostic) screening. Prompt PGS risk-adapted screening was more cost-effective when universal screening was conservative. Risk-stratified strategies improved outcomes at a cost of less than $100,000 per quality-adjusted life year compared with biennial screening starting at age 55 years, but risk stratification was not cost-effective compared with biennial screening starting at age 45. Heterogeneity of risk and fraction of the population within each stratum were also important determinants of cost-effectiveness.

Impact of prostate-specific antigen on a baseline prostate cancer risk assessment including genetic risk.

OBJECTIVE: To determine to what extent prostate cancer (PCa) risk prediction is improved by adding prostate-specific antigen (PSA) to a baseline model including genetic risk. METHODS: Peripheral blood deoxyribonucleic acid was obtained from Caucasian men undergoing prostate biopsy at the University of Toronto (September 1, 2008 to January 31, 2010). Thirty-three PCa risk-associated single nucleotide polymorphisms were genotyped to generate the prostate cancer genetic score 33 (PGS-33). Primary outcome is PCa on study prostate biopsy. Logistic regression, area under the receiver-operating characteristic curves (AUC), and net reclassification improvement were used to compare models. RESULTS: Among 670 patients, 323 (48.2%) were diagnosed with PCa. The PGS-33 was highly associated with biopsy-detectable PCa (odds ratio, 1.66; P = 5.86E-05; AUC, 0.59) compared with PSA (odds ratio, 1.33; P = .01; AUC, 0.55). PSA did not improve risk prediction when added to a baseline model (age, family history, digital rectal examination, and PGS-33) for overall risk (AUC, 0.66 vs 0.66; P = .86) or Gleason score ≥7 PCa (AUC, 0.71 vs 0.73; P = .15). Net reclassification improvement analyses demonstrated no appropriate reclassifications with the addition of PSA to the baseline model for overall PCa but did show some benefit for reclassification of men thought to be at higher baseline risk in the high-grade PCa analysis. CONCLUSION: In a baseline model of PCa risk including the PGS-33, PSA does not add to risk prediction for overall PCa for men presenting for "for-cause" biopsy. These findings suggest that PSA screening may be minimized in men at low baseline risk.

Prospective trial to identify optimal bladder cancer surveillance protocol: reducing costs while maximizing sensitivity.

OBJECTIVE: • To assess the cost-effectiveness of using cytological evaluation, NMP22 BladderChek®, and fluorescence in situ hybridization (FISH) UroVysion® in addition to cystoscopy in patients with a history of bladder cancer undergoing surveillance for recurrence. PATIENTS AND METHODS: • In all, 200 consecutive patients with a history of bladder cancer not invading the muscle were prospectively enrolled at The University of Texas MD Anderson Cancer Center. • Five surveillance strategies were compared: (i) cystoscopy alone; (ii) cystoscopy and NMP22; (iii) cystoscopy and FISH; (iv) cystoscopy and cytology; and (v) cystoscopy and positive NMP22 confirmed by positive FISH. • The cost per cancer detected was calculated. • For patients with an initial positive test and negative cystoscopy, tumour detected at first follow-up was assumed to be too small to be visualized at the initial assessment and the biomarker was credited with early detection. RESULTS: • Cancer was detected in 13 patients at study entry. • Detection rates for the five surveillance strategies were: (i) 52%, (ii) 56%, (iii) 72%, (iv) 60%, and (v) 56%. • The costs per tumour detected (at the time of initial marker analysis) were (i) $7692; (ii) $12,000; (iii) $26,462; (iv) $11,846; and (v) $10,292. • When early detection of biomarkers was factored in, the CPTD became: (i) $7692; (ii) $11,143; (iii) $19,111; (iv) $10,267; and (v) $9557. • There were 12 new cancers detected at first follow-up (median time, 4.1 months). None of the tumours detected by biomarkers but not by cystoscopy were invasive. CONCLUSIONS: • Cystoscopy alone remains the most cost-effective strategy to detect recurrence of bladder cancer not invading the muscle. • The addition of urinary markers adds to cost, without improved detection of invasive disease.