What testosterone level is considered castrate-resistant prostate cancer?

Castration-Resistant Prostate Cancer Testosterone Threshold

Castration-resistant prostate cancer (CRPC) is defined as disease progression despite androgen deprivation therapy (ADT) and a castrate level of testosterone less than 50 ng/dL (less than 1.7 nmol/L). 1

Diagnostic Criteria for CRPC

The diagnosis of CRPC requires both biochemical/clinical progression and documented castrate testosterone levels:

Testosterone Threshold

• Serum testosterone must be less than 50 ng/dL (< 1.7 nmol/L) to meet the definition of castrate-resistant disease 1
• This threshold should be confirmed by laboratory testing in all patients with suspected CRPC progression 1
• Patients must maintain castrate testosterone levels throughout CRPC treatment with continued ADT (LHRH agonist/antagonist or surgical castration) 1

Evidence of Disease Progression

CRPC progression can manifest in three ways while maintaining castrate testosterone levels 1:

1. Biochemical (PSA) progression: Continuous rise in serum PSA with values identified at minimum 1-week intervals, minimal PSA value of 2.0 ng/mL, with at least 3 values measured 4 weeks apart 1

2. Radiographic progression: Development of new lesions or progression of pre-existing disease on conventional imaging (CT, MRI, bone scan) 1

3. Clinical progression: Development or worsening of cancer-related symptoms 1

Critical Clinical Considerations

Why the 50 ng/dL Threshold Matters

• The 50 ng/dL cutoff was established by the Prostate Cancer Clinical Trials Working Group and has been consistently used across all major clinical trials that established current treatment standards 1
• This threshold is retained despite recognition that intratumoral androgen levels may not correlate with serum testosterone and can be sufficient to stimulate tumor growth even at castrate serum levels 1
• Laboratory variation exists in testosterone measurement, but the 50 ng/dL threshold remains the standard for clinical decision-making and trial eligibility 1

Common Pitfalls to Avoid

• Do not diagnose CRPC based on rising PSA alone without confirming castrate testosterone levels, as some patients may have inadequate testosterone suppression from ADT 1
• Continue ADT indefinitely in all CRPC patients to maintain castrate testosterone levels, even when adding additional systemic therapies 1
• For patients on combined androgen blockade (GnRH analog plus antiandrogen), evaluate for antiandrogen withdrawal response before confirming CRPC diagnosis, particularly if the antiandrogen produced a PSA decline lasting more than 3 months 1

Prognostic Implications of Testosterone Levels

• Among patients meeting CRPC criteria (testosterone < 50 ng/dL), those with very low testosterone levels (< 5 ng/dL) may have different treatment responses compared to those with testosterone 5-50 ng/dL 2
• Patients with testosterone ≥ 5 ng/dL appear more likely to benefit from AR-targeted therapies, while those with testosterone < 5 ng/dL may derive slightly greater benefit from abiraterone compared to enzalutamide 2
• However, the primary diagnostic threshold remains < 50 ng/dL for all clinical and guideline purposes 1