Accommodating heterogeneous missing data patterns for prostate cancer risk prediction
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Objective: We compared six commonly used logistic regression methods for accommodating missing risk factor data from multiple heterogeneous cohorts, in which some cohorts do not collect some risk factors at all, and developed an online risk prediction tool that accommodates missing risk factors from the end-user. Study Design and Setting: Ten North American and European cohorts from the Prostate Biopsy Collaborative Group (PBCG) were used for fitting a risk prediction tool for clinically significant prostate cancer, defined as Gleason grade group greater or equal 2 on standard TRUS prostate biopsy. One large European PBCG cohort was withheld for external validation, where calibration-in-the-large (CIL), calibration curves, and area-underneath-the-receiver-operating characteristic curve (AUC) were evaluated. Ten-fold leave-one-cohort-internal validation further validated the optimal missing data approach. Results: Among 12,703 biopsies from 10 training cohorts, 3,597 (28 1,757 of 5,540 (32 the available cases method that pooled individual patient data containing all risk factors input by an end-user had best CIL, under-predicting risks as percentages by 2.9 the worst CIL (-13.3 optimal in internal cross-validation and thus used for development of an online risk tool. For end-users of the risk tool, two risk factors were mandatory: serum prostate-specific antigen (PSA) and age, and ten were optional: digital rectal exam, prostate volume, prior negative biopsy, 5-alpha-reductase-inhibitor use, prior PSA screen, African ancestry, Hispanic ethnicity, first-degree prostate-, breast-, and second-degree prostate-cancer family history.
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