Publication

Multicentre optimization and validation of a 2-gene mRNA urine test for detection of clinically significant prostate cancer prior to initial prostate biopsy

J Urol 2019;202:256-63.  https://www.ncbi.nlm.nih.gov/pubmed/31026217

 

What was studied?

This European, prospective, multicentre study optimised and validated SelectMDx for detection of clinically significant prostate cancer in patients undergoing an initial biopsy.

 

What were the main outcomes?

The SelectMDx clinical model was optimised to have a high sensitivity and negative predictive value (NPV) for detection of clinically significant prostate cancer (ISUP grade ≥2). The optimised model included: urinary HOXC6 and DLX1 mRNA levels, age, DRE outcome and PSA density.

NPV

SelectMDx had a high NPV of 95% for the detection of clinically significant prostate cancer (ISUP grade ≥2). This means that the risk of missing clinically significant cancer in case of a negative test is only 5%. Of note, the NPV was 99% for ISUP grade ≥4 prostate cancer (unpublished data).

If SelectMDx would have been used for initial biopsy decisions in men with a PSA <10 ng/ml, 53% of excess biopsies* could have been avoided.

biopsies avoided

*excess biopsies: biopsies that would have identified ISUP grade 1 or no cancer

 

The diagnostic accuracy of SelectMDx was better than that of the Prostate Cancer Prevention Trial (PCPT) risk calculator.

AUC

SelectMDx

PCPT risk calculator

 

0.85

0.76

AUC: area under the receiver operating characteristic curve

 

When the optimised SelectMDx test was applied to the validation cohort in the initial validation study by Van Neste et al1, the results were comparable showing a NPV of 98%. This shows that SelectMDx is robust across different patient cohorts.

  

What was concluded?

SelectMDx showed a high NPV of 95% for the detection of clinically significant prostate cancer. This demonstrates the potential of the test to improve the detection of clinically significant PCa by avoiding approximately half of excess biopsies. These results confirm the use of SelectMDx to help guide initial biopsy decisions.

 

How was the study performed?

This was a multicentre, prospective study performed in The Netherlands, France and Germany. It included men scheduled for initial biopsy:

- training cohort (PSA <10 ng/ml: N=805)

- validation cohort (all PSA levels: N=916, PSA <10 ng/ml: N=715)

 

A post-DRE urine sample was collected. Urinary HOXC6 and DLX-1 mRNA levels were measured and combined with other PCa risk factors in a clinical model predicting clinically significant PCa (ISUP grade ≥2) on biopsy. All patients underwent a prostate biopsy.

The clinical model was optimised in the training cohort (PSA <10 ng/ml) to have a high NPV and sensitivity for detection of clinically significant prostate cancer. This optimised SelectMDx model was then validated in the validation cohort and outcomes were compared with those of the PCPT risk calculator.

 

1. Van Neste L, et al. Detection of high-grade prostate cancer using a urinary molecular biomarker-based risk score. Eur Urol 2016;70:740-748

Editor comment

The current study confirms the validity of biomarkers and, specifically, SelectMDx in the identification of clinically significant prostate cancer in a cohort of European patients. The routine implementation of this test in the clinical practice would allow to spare more than 50% of prostate biopsies and their side effects at the cost of missing only 5% of clinically significant diseases.  This would also have positive implications for a reduction of the risk of overdiagnosis as well as healthcare system expenditures. Since the introduction of novel imaging modalities such as multiparametric MRI will play an important role in the diagnostic pathway of prostate cancer, further studies are needed to assess how these tools should be integrated in this setting.

Photo Dr. Giorgio Gandaglia
Dr. Giorgio Gandaglia
Vita-Salute San Raffaele University, Milan, Italy

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