Thrombospondin 1 and cathepsin D improve prostate cancer diagnosis by avoiding potentially unnecessary prostate biopsies

OBJECTIVES: To investigate and further validate if two novel cancer‐related glycoproteins, discovered by a genetic‐guided proteomics approach, can distinguish benign disease from prostate cancer (PCa) in men with enlarged prostates. PATIENTS AND METHODS: A retrospective study was performed that included men with a total prostate‐specific antigen (PSA) concentration of 2.0–10 ng/mL, negative digital rectal examination and enlarged prostate (volume ≥35 mL). Serum samples were collected between 2011 and 2016 at a single centre from 474 men before they underwent prostate biopsy. Serum concentrations of thrombospondin 1 (THBS1) and cathepsin D (CTSD) glycoproteins were combined with the percentage of free PSA to total PSA ratio (%fPSA) to predict any or significant cancer at biopsy. RESULTS: The multivariable logistic regression model including THBS1, CTSD and %fPSA discriminated among biopsy‐positive and biopsy‐negative patients in the validation set with an area under the curve (AUC) of 0.86 (P < 0.001, 95% confidence interval (CI) 0.82–0.91), while %fPSA alone showed an AUC of 0.64 (P < 0.001, 95% CI 0.57–0.71). At 90% sensitivity for PCa, the specificity of the model was 62%, while %fPSA had a specificity of 23%. For high grade (Gleason score ≥ 7 in prostatectomy specimen) PCa, the specificity was 48% at 90% sensitivity, with an AUC of 0.83, (P < 0.001, 95% CI 0.77 to 0.88). Limitations of the study include the retrospective set‐up and single‐centre cohort. CONCLUSIONS: A model combining two cancer‐related glycoproteins (THBS1 and CTSD) and %fPSA can improve PCa diagnosis and may reduce the number of unnecessary prostate biopsies because of its improved specificity for PCa when compared to %fPSA alone.