The Stockholm-3 Model for Prostate Cancer Detection: Algorithm Update, Biomarker Contribution, and Reflex Test Potential

Abstract

BACKGROUND: It has been shown that the Stockholm-3 model (S3M) outperforms prostate-specific antigen (PSA) as a screening tool for prostate cancer. OBJECTIVE: To update the S3M, to give a detailed account of the value of each predictor in the S3M, and to evaluate the S3M as a reflex test for men with PSA ≥3ng/ml. DESIGN, SETTING, AND PARTICIPANTS: During 2012-2015, the Stockholm-3 study evaluated the S3M relative to PSA as tests for Gleason score ≥7 prostate cancers among men aged 50-69 yr. The participants (n=59 159) underwent both tests, and biopsy was recommended if at least one was positive. A total of 5073 men had a biopsy because of elevated PSA (≥3ng/ml). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic regression was used to update the S3M: intact PSA was removed, HOXB13 was included, and the model was fitted to data from the Stockholm-3 training and validation cohorts. To compare S3M with PSA, we fixed the sensitivity for detection of high-grade cancer and evaluated the performance as the number of biopsies needed to achieve that sensitivity for each test. RESULTS AND LIMITATIONS: The updated S3M slightly improved the area under the receiver operating characteristic curve compared to previously published results (0.75 vs 0.74). When used as a reflex test for men with PSA ≥3ng/ml, S3M reduced the number of biopsies needed by 34% compared to the use of PSA alone, with equal sensitivity. A limitation is the ethnically homogeneous population. CONCLUSIONS: A major problem with PSA screening-too many unnecessary biopsies-can be mitigated if S3M is used as a reflex test. PATIENT SUMMARY: To find aggressive prostate cancer with the minimum number of negative biopsies and detection of clinically insignificant cancers, we evaluated the use of a personalized diagnostic prediction model as a second test for men with a positive prostate-specific antigen (PSA) test. We found that this two-step approach could reduce prostate biopsies by a third compared to using PSA alone.