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Thrombospondin 1 and cathepsin D improve prostate cancer diagnosis by avoiding potentially unnecessary prostate biopsies
Author(s) -
Steuber Thomas,
Tennstedt Pierre,
Macagno Annalisa,
Athanasiou Alcibiade,
Wittig Anja,
Huber Ramy,
Golding Bruno,
Schiess Ralph,
Gillessen Silke
Publication year - 2019
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/bju.14540
Subject(s) - medicine , prostate cancer , prostatectomy , urology , rectal examination , prostate specific antigen , biopsy , prostate , prostate biopsy , retrospective cohort study , pca3 , confidence interval , cancer , oncology
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 ( PC a) 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 ( THBS 1) 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 THBS 1, 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 PC a, the specificity of the model was 62%, while % fPSA had a specificity of 23%. For high grade (Gleason score ≥ 7 in prostatectomy specimen) PC a, 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 ( THBS 1 and CTSD ) and % fPSA can improve PC a diagnosis and may reduce the number of unnecessary prostate biopsies because of its improved specificity for PC a when compared to % fPSA alone.