Login to Access Video or Poster Abstract: MP28-05
Sources of Funding: None

Introduction

Increased prostate volume due to benign disease leads to many false-positive PSA results and consequently to negative prostate biopsies. Previous research indicated that cancer-related protein biomarkers discovered by a genetic-guided approach using a Pten knock-out mouse model could improve prostate cancer diagnosis. The objective of this study was to evaluate if the protein biomarkers are capable of distinguishing benign disease from prostate cancer in men with enlarged prostates.

Methods

We conducted a retrospective study of men with a total PSA of 2.0-10 ng/ml, negative DRE and enlarged prostate volume (?35 ml). Serum samples were collected from men before undergoing prostate biopsy at the Martini-Klinik Hamburg, Germany. All samples were taken between 2011 and 2016 following written patient consent. Serum concentration of CTSD, ICAM1, THBS1, OLFM4, TIMP1, and HYOU1 was measured using immunoassays. In addition, total and free PSA were analyzed to calculate %fPSA using the ADVIA Centaur immunoassay system.

Results

Of the 474 men included in this study, 236 men had a negative biopsy and 238 were diagnosed with prostate cancer. %fPSA discriminated among biopsy-positive and negative patients with an AUC = 0.650 (P <0.001; 95% CI = 0.600-0.699). Logistic regression analysis revealed that the combination of the two proteins CTSD and THBS1 yielded an AUC = 0.834 (P <0.001; 95% CI = 0.797-0.871); and when combined with %fPSA, it resulted in an even higher AUC = 0.845 (P <0.001; 95% CI = 0.810-0.880). At 90% sensitivity for prostate cancer, the specificity of the combination including CTSD, THBS1 and %fPSA was 60% indicating that 141 of 236 negative biopsies could have been avoided (see Figure 1). Independent training on samples collected before March 2013 and testing on the samples thereafter also resulted in a high AUC =0.872 (P <0.001; 95% CI = 0.826-0.918) showing reproducibility of the method.

Conclusions

In patients with elevated PSA, negative DRE and enlarged prostate, the method presented is significantly more accurate than %fPSA alone in determining the absence of prostate cancer. The implementation of the method in clinical practice has the potential to significantly lower the rate of prostate biopsies which are negative for cancer by more than 50%.

Funding

None