What's the next step for a patient with rising Prostate-Specific Antigen (PSA) levels from <0.04 to 0.13 after finishing Lupron (leuprolide) and external beam radiation therapy (XRT), and previously treated with Abiraterone (abiraterone) and Prednisone (prednisone)?

Management of Rising PSA After Prostate Cancer Treatment

The next step for this patient with rising PSA levels from <0.04 to 0.13 after completing Lupron and radiation therapy should be to confirm the PSA rise with a repeat PSA test in 4-6 weeks to establish a consistent pattern of increase before initiating further treatment. 1, 2

Understanding the Current Situation

The patient's PSA history shows:

• Diagnosed with prostate cancer in 02/2022
• Treatment included Lupron (started 2/17/2022, last dose 2/12/2024)
• Abiraterone with prednisone (started 2/25/2022)
• External beam radiation therapy (XRT) to prostate
• PSA levels:
  • 11/06/2023: <0.04
  • 02/12/2024: <0.04
  • 05/13/2024: <0.04
  • 11/20/2024: 0.06
  • 5/27/2025: 0.13

Diagnostic Algorithm

1. Confirm PSA Rise

   • Repeat PSA test in 4-6 weeks to verify the trend 1, 2
   • Ensure consistency in laboratory testing (same assay method)
   • Calculate PSA doubling time once 3 values are available 1

2. Risk Assessment Based on PSA Kinetics

   • Calculate PSA doubling time (PSADT) using at least 3 measurements 1
   • PSADT <6 months indicates aggressive disease with higher risk of metastasis 1, 2
   • Current rise from <0.04 to 0.13 over approximately 6 months suggests moderate velocity

Management Options After Confirmed Rise

If PSA Rise is Confirmed:

1. Imaging Studies

   • Order bone scan and CT/MRI to evaluate for metastatic disease
   • Consider PSMA-PET scan if available (more sensitive for detecting early recurrence)
   • Even with low PSA levels, imaging is warranted as some patients can progress to metastatic disease despite low PSA 3

2. Treatment Options Based on Imaging Results:

   If No Evidence of Metastasis:

   • Resume ADT with Lupron (leuprolide) 2
   • Consider adding back abiraterone with prednisone 4
   • The STAMPEDE trial showed significant benefit of adding abiraterone to ADT in high-risk non-metastatic prostate cancer 4

   If Metastatic Disease is Detected:

   • Resume ADT with Lupron
   • Restart abiraterone with prednisone 4
   • Consider adding enzalutamide if not previously used 4

Important Considerations

1. PSA Flare Phenomenon

   • Be aware that restarting abiraterone can cause a temporary PSA flare (seen in 8.7% of patients) before eventual response 5
   • PSA may increase by up to 63% before declining 5

2. Monitoring After Treatment Restart

   • Monitor PSA every 4-8 weeks initially to assess response 1
   • Continue regular imaging studies every 3-6 months, especially if PSA continues to rise despite treatment

3. Atypical Progression

   • In rare cases (approximately 22%), metastasis can occur without significant PSA elevation 3
   • Consider periodic imaging even with modest PSA rises in high-risk patients

4. PSA Interpretation Pitfalls

   • Post-radiation PSA interpretation differs from post-surgical interpretation 1
   • PSA "bounces" can occur 18-36 months after radiation therapy and may not represent true recurrence 1
   • The current rise appears to be occurring after hormone therapy withdrawal, which is more concerning

Conclusion

The rising PSA trend from <0.04 to 0.13 after completing Lupron therapy warrants close attention. While the absolute values remain low, the consistent upward trend suggests biochemical recurrence. Confirmation with repeat testing is essential before initiating treatment. Once confirmed, resumption of ADT with consideration of adding abiraterone is appropriate, guided by imaging results to rule out metastatic disease.