Definition of Biochemical Relapse in Oncology
Biochemical relapse is defined as a rise in tumor-specific biomarkers (such as PSA in prostate cancer or paraproteins in multiple myeloma) in the absence of clinical signs or symptoms of disease, with specific thresholds varying by cancer type and primary treatment modality. 1
Prostate Cancer: Post-Radical Prostatectomy
The American Urological Association defines biochemical recurrence as a serum PSA ≥0.2 ng/mL with a second confirmatory level ≥0.2 ng/mL. 1, 2, 3
Key Implementation Details:
- Timing of first PSA measurement: Obtain between 6-8 weeks post-surgery to allow complete PSA clearance and resolution of inflammation-related elevations 3
- Confirmation requirement: Any detectable PSA must be repeated to eliminate laboratory error 1
- Date of failure: Defined as the date of the first detectable PSA level once confirmed 1
- Washout period: Minimum 6 weeks before obtaining first postoperative PSA value 1
Critical Context:
The 0.2 ng/mL threshold represents the most commonly used definition (used in 35 of 145 studies reviewed), balancing sensitivity for early detection against specificity to avoid false positives from benign tissue remnants 1, 3. While higher thresholds (0.4 ng/mL) improve specificity and may better predict metastatic relapse risk, the 0.2 ng/mL standard provides optimal sensitivity and generalizability across different PSA assays 1, 3.
Important caveat: This definition identifies biochemical failure but does NOT indicate when to initiate salvage therapy—treatment decisions require additional risk stratification 1
Prostate Cancer: Post-Radiation Therapy
The ASTRO (American Society for Therapeutic Radiology and Oncology) definition requires 3 consecutive PSA rises after nadir, with the date of failure being the midpoint between nadir and the first of 3 consecutive rises. 1
Alternative Definition:
- Phoenix definition (Definition N): PSA elevation >2 ng/mL above the nadir PSA level 4
Critical Differences in Outcomes:
The choice of definition dramatically affects reported outcomes and treatment comparisons. Using the Phoenix definition versus ASTRO results in 13% better biochemical relapse-free survival at 5 years but 12% worse survival at 10 years 4. This means the ASTRO definition suggests radiation therapy is inferior to surgery, while the Phoenix definition suggests equivalence—highlighting why standardized definitions are essential for clinical decision-making. 4
Major Limitation:
The ASTRO definition fails to specify time intervals between consecutive PSA increases and does not use PSA nadir as a risk factor, despite its close relationship to disease progression 1
Multiple Myeloma
Biochemical relapse in multiple myeloma is defined by IMWG (International Myeloma Working Group) criteria as a rise in serum or urine paraprotein in the absence of clinical signs or symptoms of myeloma. 1
Key Distinction from Clinical Relapse:
- Biochemical relapse: Rising paraproteins without symptoms or organ dysfunction
- Clinical relapse: Evidence of CRAB criteria (hypercalcemia, renal dysfunction, anemia, lytic bone lesions) or other myeloma manifestations 1
Treatment Triggers for Biochemical Relapse:
Immediate treatment is indicated for: 1
- High-risk cytogenetics
- Extramedullary disease
- Early relapse after transplant or initial therapy
- Rapid rise in myeloma markers
Close observation is appropriate for: 1
- Slowly progressive disease
- Asymptomatic patients
- Standard-risk cytogenetics
Common Pitfalls to Avoid
- Laboratory variability: PSA assays can vary by 20-25% between laboratories—use the same assay for longitudinal monitoring 3
- Single elevated values: Always confirm with repeat testing before declaring biochemical recurrence 1, 3
- Premature imaging: Conventional imaging has extremely low yield when PSA <5 ng/mL in prostate cancer; PSMA PET is preferred for detecting occult disease at lower PSA levels 2, 3
- Treatment threshold confusion: Biochemical recurrence definitions identify disease activity but do not automatically trigger treatment—additional risk stratification is required 1, 2
- Cross-modality comparisons: Exercise extreme caution when comparing surgery versus radiation outcomes due to treatment-specific PSA kinetics and definition variations 1, 4
Variability in the Literature
A comprehensive AUA review identified 166 different definitions of biochemical recurrence across prostate cancer treatments, with 53 variations for radical prostatectomy alone 1. This lack of standardization means slight definition changes can alter reported biochemical disease-free survival by 16-18% at 5-10 years. 1