What laboratory tests and imaging studies can determine if prostate cancer has spread?

Laboratory Tests and Imaging Studies to Detect Prostate Cancer Spread

The most comprehensive approach to determine if prostate cancer has spread includes PSA testing, bone scan, CT/MRI of abdomen and pelvis, and PSMA PET/CT imaging when available, as these provide the highest diagnostic accuracy for detecting metastatic disease.

Initial Laboratory Tests

• Prostate-specific antigen (PSA) is the most sensitive and clinically useful method for monitoring patients following definitive therapy for prostate cancer. A detectable value following radical prostatectomy or an increasing level following radiation therapy indicates recurrent or residual disease 1
• Complete blood count and chemistry profile, including alkaline phosphatase, should be performed as part of the initial workup to assess for the presence of regional or distant metastases 2
• Elevated alkaline phosphatase may indicate bone metastases and should prompt further investigation with bone imaging 2

Imaging Studies for Metastatic Spread

Standard Imaging Approach

• Chest radiograph or CT scan should be performed to evaluate for lung metastases 2
• Bone scan is indicated in patients with:
  • PSA levels >10 ng/mL 3
  • Gleason grade 4 or 5 disease 3
  • Bone pain 3
  • Elevated alkaline phosphatase 2
  • Locally advanced tumor (T3Nx or T1-4N1-3) 3
• CT or MRI scan of the abdomen and pelvis should be performed to assess:
  • Local tumor invasion 2
  • Lymph node involvement 2
  • Spread to visceral organs 2
• Abdominal and pelvic CT scan is specifically recommended for patients with:
  • T2a stage disease or higher 3
  • PSA concentration >15 ng/mL 3
  • Gleason score ≥7 3

Advanced Imaging Techniques

• PSMA PET/CT is now recommended as the preferred imaging modality when available, particularly for high-risk disease 2
• PSMA PET/CT has significantly higher accuracy than conventional imaging for detecting:
  • Lymph node metastases (sensitivity 73.7% vs 38.9% for MRI, specificity 97.5% vs 82.6%) 4
  • Bone metastases (sensitivity 98.0% vs 73.0% for bone scan, specificity 96.2% vs 79.1%) 4
  • Visceral metastases 2

Pattern of Spread Assessment

• Prostate cancer spread should be classified according to the following patterns 2:
  • Locally recurrent disease in the prostate or prostate bed
  • Nodal spread within the pelvis (lymph nodes >1.0 cm)
  • Nodal spread beyond the pelvis
  • Bone disease with or without nodal disease
  • Visceral disease (lung, liver, adrenal, or CNS sites) 2

Molecular and Biomarker Testing

• Molecular biomarkers in metastatic lesions can be assessed through:
  • Directed biopsy of metastatic sites 2
  • Blood-based assays of circulating tumor cells 2
  • Cell-free nucleic acids (RNA or DNA) 2
• Tumor sequencing may reveal actionable mutations that can guide treatment decisions 2
• Testing for mutations in genes such as BRCA1, BRCA2, ATM, CHEK2, or PALB2 may have implications for treatment and genetic counseling 2

Common Pitfalls and Caveats

• CT scans, ultrasound, and MRI cannot always accurately predict the true depth of local invasion 2
• Conventional imaging (CT and bone scan) has limited sensitivity for detecting small metastases 2
• A single negative imaging study does not definitively rule out metastatic disease, especially with high clinical suspicion 3
• The rate of increase in serum PSA can help distinguish between local recurrence and metastatic disease 1
• Time interval between different imaging modalities should ideally be less than 1 month to avoid heterogeneity in results 4

Algorithm for Metastatic Workup Based on Risk

1. For intermediate-risk disease (particularly with Gleason grade group 3):

   • Cross-sectional abdominopelvic imaging
   • Bone scan
   • PSMA PET/CT if available 2

2. For high-risk localized or locally advanced disease:

   • PSMA PET/CT (preferred if available)
   • At minimum: cross-sectional abdominopelvic imaging and bone scan 2

3. For suspected recurrence after treatment:

   • PSA monitoring (rate of rise helps distinguish local vs. distant recurrence)
   • PSMA PET/CT when available
   • CT/MRI for abdominal/pelvic lymph nodes
   • Bone scan for skeletal assessment 1