What are the next steps for a patient with castration-sensitive prostate cancer on Abiraterone acetate (abiraterone) with rising Prostate-Specific Antigen (PSA) levels and symptoms of Lower Urinary Tract Symptoms (LUTS)?

Management of Rising PSA and LUTS in a Patient with Prostate Cancer on Abiraterone

The patient with rising PSA (from 8 to 27) and LUTS while on abiraterone acetate for prostate cancer should be referred to a urologist for evaluation of disease progression to castration-resistant prostate cancer (CRPC) and consideration of alternative therapies such as enzalutamide.

Assessment of Disease Progression

The significant PSA rise from 8 to 27 ng/mL while on abiraterone acetate strongly suggests disease progression to castration-resistant prostate cancer. This requires prompt evaluation and management changes:

1. Confirm CRPC status:

   • Verify castrate levels of testosterone (<50 ng/mL) 1
   • Document PSA progression (increase ≥25% over nadir with absolute increase ≥2 ng/mL) 1
   • The presence of LUTS with rising PSA suggests symptomatic disease progression

2. Evaluate LUTS symptoms:

   • Use validated symptom score questionnaire (IPSS) to assess severity 1
   • Determine if symptoms are storage or voiding predominant
   • Assess bother and quality of life impact 1

Diagnostic Workup

A comprehensive diagnostic evaluation should include:

1. Urinalysis to rule out infection 1
2. Post-void residual measurement to assess bladder emptying 1
3. Uroflowmetry to evaluate voiding function 1
4. Prostate imaging (transrectal ultrasound) to assess prostate volume and rule out obstruction 1
5. Urethrocystoscopy if hematuria is present or to evaluate for bladder outlet obstruction 1
6. Imaging studies to assess for metastatic disease progression:
   • Bone scan if not recently performed
   • CT/MRI to evaluate for soft tissue metastases

Treatment Approach

Based on the rising PSA and presence of LUTS, treatment should address both cancer progression and urinary symptoms:

For Cancer Progression:

1. Switch to alternative anti-androgen therapy:

   • Enzalutamide 160 mg daily is indicated for CRPC 2
   • Consider referral for clinical trials of newer agents

2. Consider additional systemic therapies based on patient's performance status and prior treatments:

   • Docetaxel chemotherapy if good performance status and symptomatic disease 1
   • Radium-223 if bone metastases are present

For LUTS Management:

1. Alpha-blocker therapy (alfuzosin, doxazosin, silodosin, tamsulosin, or terazosin) for rapid symptom relief 1

   • These medications provide symptom improvement within days to weeks
   • Choice should be based on patient age, comorbidities, and side effect profiles 1

2. 5-alpha reductase inhibitors if prostate volume >30cc:

   • Consider adding if alpha-blocker alone is insufficient 1
   • Note that 5-ARIs decrease PSA by approximately 50%, which must be considered when monitoring cancer 1

Follow-up Plan

1. Short-term follow-up (4-6 weeks):

   • Assess response to alpha-blocker therapy for LUTS
   • Monitor PSA response to new anti-androgen therapy

2. Medium-term follow-up (3 months):

   • Reassess LUTS using IPSS questionnaire 1
   • Evaluate PSA trend on new therapy
   • Consider urodynamic studies if symptoms persist 1

3. Long-term monitoring:

   • Regular PSA monitoring every 3 months
   • Imaging studies as clinically indicated
   • Adjust therapy based on response

Important Considerations

• PSA monitoring limitations: PSA may not accurately reflect disease status in all patients with CRPC, especially after multiple lines of therapy
• Drug interactions: Be aware of potential interactions between LUTS medications and cancer therapies
• Quality of life impact: Both cancer progression and LUTS significantly affect quality of life and should be addressed simultaneously
• Palliative care: Consider early palliative care involvement for symptom management if disease is progressing rapidly

The rising PSA while on abiraterone is concerning for treatment failure, and the presence of LUTS may indicate local disease progression. Prompt urologic evaluation and consideration of alternative therapies are essential to maintain quality of life and optimize survival outcomes.