What is biochemical recurrence of prostate cancer post prostatectomy?

Biochemical Recurrence of Prostate Cancer Post-Prostatectomy

Biochemical recurrence after radical prostatectomy is defined as an initial serum PSA ≥0.2 ng/mL with a second confirmatory level >0.2 ng/mL. 1

Standard AUA Definition

The American Urological Association (AUA) established this standardized definition to address the extraordinary variability that previously existed in the literature, where 53 different definitions were identified across 145 studies. 1

Key components of the definition:

• Initial threshold: PSA must reach ≥0.2 ng/mL 1, 2
• Confirmation required: A second PSA measurement must be >0.2 ng/mL to confirm the elevation and eliminate laboratory error 1, 3
• Timing: The first post-operative PSA should be obtained at 6 weeks to 3 months after surgery to allow adequate washout time 2

Rationale for the 0.2 ng/mL Threshold

After radical prostatectomy, PSA should become undetectable within 6 weeks since the source of PSA production has been removed. 1, 3 Any detectable PSA implies residual prostate tissue and most likely residual or recurrent prostate cancer. 1

The 0.2 ng/mL cutpoint was selected because:

• It was the most commonly used definition in the literature (35 of 145 studies) 1
• It represents the optimal balance between sensitivity for detecting true recurrence and specificity to avoid false positives from benign remnant tissue 2
• PSA values between 0.2-0.4 ng/mL most accurately correlate with clinical failure 1, 3

Alternative Definitions and Their Limitations

While the AUA recommends 0.2 ng/mL, some evidence suggests higher thresholds may be more predictive:

• PSA ≥0.4 ng/mL followed by another increase showed the strongest association with systemic progression (HR 36, R² 0.92) and best explained metastatic disease development 4, 5
• At the 0.4 ng/mL threshold, 74% of patients experience continued PSA increase over 5 years, compared to only 61% at 0.2 ng/mL 4
• Lower thresholds (0.2 ng/mL) increase sensitivity but may lead to earlier intervention in patients who might not progress 1

However, the AUA definition remains the standard for data reporting and comparison purposes, even though the clinical decision to initiate treatment depends on multiple factors beyond a specific PSA threshold. 1

Clinical Significance

Biochemical recurrence is not synonymous with clinical progression. 6 While a rising PSA universally precedes metastatic progression and prostate cancer-specific mortality, it is not a surrogate for these endpoints. 6 The natural history of PSA-defined biochemical recurrence is highly variable. 6

Important distinctions:

• Approximately one-third of patients develop detectable PSA within 10 years after radical prostatectomy 7
• A small percentage (8.8%) may have detectable but stable PSA for 10+ years without clinical failure 3
• PSA kinetics (doubling time, velocity) help differentiate local from distant recurrence 3

Monitoring Protocol

After detecting biochemical recurrence:

• Repeat PSA in 1-3 months to confirm elevation and calculate PSA doubling time 3
• Refer immediately to the primary treating specialist for any confirmed detectable or rising PSA 2
• Salvage radiotherapy should be offered when PSA is rising without evidence of distant metastases, with better outcomes when PSA <2.0 ng/mL at treatment initiation 2

Critical Pitfall to Avoid

Do not use the ASTRO radiation therapy criteria for post-prostatectomy patients. 1 The ASTRO definition (3 consecutive PSA rises after nadir) applies only to radiation therapy, where residual prostatic epithelium can produce PSA. 1 After prostatectomy, the prostate is removed, so any detectable PSA indicates disease recurrence, requiring a different definition. 1