Do guidelines recommend imaging surveillance in patients with low Prostate-Specific Antigen (PSA) levels while on Androgen Deprivation Therapy (ADT)?

Imaging Surveillance for Prostate Cancer Patients on ADT with Low PSA

Yes, guidelines strongly recommend regular imaging surveillance in patients with castration-resistant prostate cancer (CRPC) on ADT even when PSA levels are low, as PSA alone is not a reliable indicator of disease progression. 1

Rationale for Imaging Despite Low PSA

• PSA is an unreliable sole marker for monitoring response in CRPC patients on ADT
• Disease progression can occur despite low or stable PSA values
• Conventional imaging techniques (CT and bone scan) are necessary to properly assess response/progression, particularly for bone metastatic disease

Guideline Recommendations

The European Society for Medical Oncology (ESMO) guidelines explicitly state:

• "In patients with CRPC on systemic treatment, regular imaging studies should be done to monitor disease response/progression" [Level V, Grade B] 1
• "It is not adequate to rely on PSA alone to monitor response in men with CRPC" 1

Similarly, the National Comprehensive Cancer Network (NCCN) guidelines recommend:

• For patients who develop CRPC, "imaging tests may be indicated to monitor for signs of distant metastases" 1
• "Factors affecting the frequency of imaging include individual risk, age, overall patient health, PSA velocity, and Gleason grade" 1

Imaging Modalities to Consider

1. Conventional Imaging:

   • CT scan - to investigate distant metastases
   • Bone scintigraphy - especially for patients with signs or symptoms of bone metastases 1

2. Advanced Imaging (when conventional imaging is inconclusive):

   • PSMA PET/CT - highest accuracy for detecting prostate cancer metastases with superior sensitivity (75-77%) and specificity (97-99%) for lymph node metastases 2
   • MRI - particularly for suspected spinal cord compression in patients with vertebral metastases 1

Special Considerations

• Urgent MRI of the spine is very strongly recommended in men with CRPC with vertebral metastases and neurological symptoms [Level III, Grade A] 1
• MRI of the spine is recommended to detect subclinical cord compression in men with CRPC with vertebral metastases [Level III, Grade B] 1

Monitoring Schedule

While specific intervals are not universally defined, monitoring should be based on:

• Risk stratification
• PSA velocity
• Previous treatment history
• Symptoms

Important Caveats

1. PSA levels and PSMA imaging: Detection rates with PSMA PET/CT are lower when PSA is <0.3 ng/mL under ADT (28.6% detection rate), compared to PSA levels between 0.3-2.0 ng/mL (85.7% detection rate) 3

2. ADT effects on imaging: ADT may affect PSMA expression and detection on PET/CT imaging, which should be considered when interpreting results 4

3. Early intervention benefits: Early ADT at PSA levels <2 ng/mL has been associated with improved cancer-specific survival compared to delayed ADT at PSA ≥2 ng/mL in patients with localized or locally advanced prostate cancer who received radiation therapy following radical prostatectomy 5

In conclusion, while PSA monitoring is important, it should not replace regular imaging surveillance in patients with prostate cancer on ADT, as disease progression can occur despite low PSA levels. This approach ensures timely detection of disease progression and appropriate therapeutic adjustments to improve patient outcomes.