Which test is better to determine if a man needs a biopsy, Confirm MDx (Confirm Molecular Diagnostics) or Select MDx (Select Molecular Diagnostics)?

Comparing ConfirmMDx and SelectMDx for Determining Need for Prostate Biopsy

Neither ConfirmMDx nor SelectMDx can be definitively recommended over the other as both tests have different purposes and applications in determining the need for prostate biopsy. 1

Test Characteristics and Applications

ConfirmMDx

• Tissue-based multiplex epigenetic assay that assesses hypermethylation of promoter regions of GSTP1, APC, and RASSF1 in core biopsy tissue samples 1
• Specifically designed for men with prior negative biopsies who are being considered for repeat biopsy 1
• Added to NCCN guidelines in 2016 for men contemplating repeat biopsy 1
• Has demonstrated a high negative predictive value in validation studies 1, 2
• In a field observation study, only 4.3% of men with negative ConfirmMDx results underwent repeat biopsies, suggesting potential to reduce unnecessary procedures 2

SelectMDx

• Urine-based molecular test that measures mRNA expression of genes (DLXI, HOXC6) to predict likelihood of clinically significant prostate cancer 1, 3
• Can be used before initial biopsy to help identify patients at risk for high-grade prostate cancer 4, 5
• Validation studies suggest it could avoid 38% of unnecessary biopsies while missing only 10% of high-grade prostate cancers 5
• Not specifically mentioned in NCCN guidelines for routine screening 4
• Has demonstrated cost-effectiveness in European healthcare systems by reducing unnecessary biopsies and overtreatment 6

Clinical Decision-Making Considerations

When to Consider ConfirmMDx

• Most appropriate for patients who have already had at least one negative biopsy but have persistent clinical suspicion of prostate cancer 1
• NCCN guidelines specifically include ConfirmMDx as an option for men contemplating repeat biopsy 1
• Particularly useful when trying to determine if a repeat biopsy is necessary after a prior negative result 1, 2

When to Consider SelectMDx

• More appropriate for biopsy-naïve patients with elevated PSA who are deciding whether to undergo an initial biopsy 3, 5
• Can be used to reduce unnecessary initial biopsies and minimize detection of low-grade prostate cancer 5
• May be particularly valuable in settings where MRI availability is limited or expensive 5

Comparative Effectiveness

• No head-to-head studies directly comparing ConfirmMDx and SelectMDx are available in the provided evidence 1
• The NCCN guidelines panel emphasizes that no biomarker test can be recommended over any other 1
• Test selection should be based on the clinical context (initial vs. repeat biopsy) rather than assuming superiority of one test over another 1

Potential Pitfalls and Caveats

• Results of any biomarker test should be used as part of discussions between clinician and patient to assist in biopsy decisions, not as the sole determinant 1
• The optimal order of biomarker tests and imaging (such as multiparametric MRI) remains unknown 1
• Interpretation of multiple tests in individual patients can be challenging, especially when results are contradictory 1
• Neither test eliminates the need for biopsy in all cases - they are tools to refine patient selection 1, 7

Algorithm for Test Selection

1. For patients considering initial biopsy:

   • Consider SelectMDx as it is designed for biopsy-naïve patients 3, 5
   • May be combined with multiparametric MRI for optimal results 5

2. For patients with prior negative biopsy:

   • Consider ConfirmMDx as it is specifically validated and recommended by NCCN for the repeat biopsy setting 1
   • Has demonstrated ability to reduce unnecessary repeat biopsies 2

3. For all patients:

   • Consider biomarker testing in conjunction with other clinical factors (PSA, PSA density, digital rectal exam findings) 1
   • Discuss that these tests aim to reduce unnecessary biopsies while still identifying clinically significant prostate cancer 1, 5