Is the SelectMDx (Prostate Cancer Diagnostic Test) accurate in detecting prostate cancer and predicting the Gleason score?

SelectMDx Test Accuracy for Prostate Cancer Detection and Gleason Score Prediction

SelectMDx is a promising urinary biomarker test that shows comparable accuracy to multiparametric MRI in detecting prostate cancer and predicting Gleason score, but it is not currently included in major clinical guidelines as a recommended test for routine use in prostate cancer detection. 1, 2

Understanding SelectMDx

• SelectMDx is a urine-based molecular test that measures mRNA expression of DLXI and HOXC6 genes to predict the likelihood of clinically significant prostate cancer 1, 2
• It is designed to help identify patients at risk for high-grade prostate cancer (Gleason score ≥7) before proceeding to invasive biopsy procedures 3
• The test aims to reduce unnecessary biopsies while maintaining high detection rates for clinically significant prostate cancer 3

Accuracy of SelectMDx

For Prostate Cancer Detection:

• SelectMDx demonstrates a pooled sensitivity of 81% and specificity of 69.8% for detecting prostate cancer 2
• The negative predictive value (NPV) is approximately 85%, indicating good reliability in ruling out cancer 2
• In comparison, multiparametric MRI shows similar sensitivity (80.8%) but slightly better specificity (73.4%) 2

For Gleason Score Prediction:

• SelectMDx was specifically validated for detecting Gleason score ≥7 (ISUP Grade Group 2-5) prostate cancers 3
• The test shows promising results in identifying patients with high-grade disease, with a sensitivity of 87.1% for clinically significant prostate cancer 4
• When combined with clinical risk factors, SelectMDx can help stratify patients according to their risk of harboring aggressive disease 5

Comparison with Other Diagnostic Methods

• SelectMDx outperforms PCA3 (another urinary biomarker) in predicting multiparametric MRI outcomes with an area-under-the-curve of 0.83 compared to 0.65 for PCA3 5
• There is a positive association between SelectMDx score and PI-RADS grade, with statistically significant differences in SelectMDx scores between PI-RADS 3 and 4 (p<0.01) and between PI-RADS 4 and 5 (p<0.01) 5
• When used in combination with mpMRI, SelectMDx can further refine patient selection for biopsy 6, 4

Clinical Impact and Utility

• In real-world clinical practice, patients with positive SelectMDx results are five times more likely to undergo biopsy than those with negative results 3
• Using both high-risk SelectMDx and PI-RADS scores of 4/5 as criteria for biopsy could potentially reduce unnecessary biopsies by 87%, while still detecting 64% of prostate cancers 6
• In cases of PI-RADS 3 lesions with negative SelectMDx, unnecessary biopsies could be reduced by 42%, with only a 9% risk of missing high-grade prostate cancer 2

Current Guideline Recommendations

• The NCCN Guidelines for Prostate Cancer Early Detection do not specifically recommend SelectMDx as part of routine screening 1
• Current guidelines recommend several biomarker tests for consideration before biopsy, including percent free PSA, 4Kscore, or Prostate Health Index (PHI) 1
• For patients with prior negative biopsies, guidelines recommend consideration of percent free PSA, 4Kscore, PHI, PCA3, or ConfirmMDx 1

Limitations and Considerations

• Most studies on SelectMDx have relatively small sample sizes and are from single institutions, which may limit generalizability 6
• There is a risk of overfitting in some of the proposed predictive models 6
• The Gleason scoring system itself has inherent limitations in predicting cancer aggressiveness, as it is based on subjective histopathological assessment 1, 7
• SelectMDx is not FDA approved but is considered a laboratory-developed test, similar to some other prostate cancer biomarkers 1

Optimal Use Strategy

• SelectMDx appears most valuable as part of a sequential testing approach, particularly after an initial negative mpMRI 4
• A proposed algorithm would be to perform biopsy for all cases with PI-RADS 4-5 scores, and to consider SelectMDx testing for those with PI-RADS 1-3 scores to determine the need for biopsy 4
• This approach could optimize the balance between detecting clinically significant prostate cancer and avoiding unnecessary biopsies 2, 4