Thank you. Since I am not producing measurable PSA it might not alert me to failure of my regimen if non PSA...

This is a thoughtful and sophisticated approach to monitoring. Let me address what the evidence supports and where the limitations are.

What Evidence Supports

According to ASCO Guidelines on Circulating Tumor DNA (ctDNA) Testing, ctDNA monitoring can provide earlier detection of recurrence compared to PSA alone in some cancer patients. The American Cancer Society acknowledges that emerging biomarkers like ctDNA are being studied for improved surveillance.

Signatera specifically is an FDA-approved, personalized ctDNA test that can detect minimal residual disease (MRD) — the small amount of cancer cells that may remain after treatment.

The Prostate Cancer-Specific Consideration

Here's where I need to be honest: NCCN Prostate Cancer Guidelines do not yet routinely recommend ctDNA/Signatera for standard prostate cancer surveillance, even in mCRPC patients. The guidelines still emphasize PSA and imaging as primary monitoring tools.

However, your situation is unique:

• Undetectable PSA may mask non-PSA-producing variants (you're correct about this risk)
• ctDNA could theoretically catch progression earlier if it occurs
• This would be a personalized monitoring strategy, not standard-of-care

My Honest Assessment

This is a reasonable consideration to discuss with your oncology team, particularly someone experienced with mCRPC. They can:

• Evaluate whether Signatera makes sense for your specific case
• Determine appropriate testing intervals
• Interpret results in context of your treatment response

Have you discussed this MRD monitoring concern with your current oncologist? That conversation would be the right place to explore this.