What are the options for metastasis-directed therapy in patients with oligometastatic prostate cancer?

Metastasis-Directed Therapy Options in Oligometastatic Prostate Cancer

Stereotactic ablative body radiotherapy (SABR) is the preferred metastasis-directed therapy for patients with oligometastatic prostate cancer, particularly those with ≤3 metastases, as it can delay the need for systemic therapy while maintaining quality of life. 1

Definition of Oligometastatic Disease

Oligometastatic prostate cancer is generally defined as having a limited number of metastases, with consensus (85% of experts) defining it as ≤3 synchronous metastases in bone and/or lymph nodes 1. This state represents a transitional phase between localized and widespread metastatic disease where targeted therapies may be beneficial.

Metastasis-Directed Therapy (MDT) Options

1. Stereotactic Ablative Body Radiotherapy (SABR)

• Primary option for oligometastatic lesions
• Advantages:
  • High local control rates (>90% at 1-2 years) 1
  • Minimal toxicity (14% grade 2,3% grade 3) 1
  • Can be delivered in 1-5 fractions
  • Non-invasive
• Evidence from randomized trials:
  • STOMP trial: Improved ADT-free survival (21 vs 13 months) with no significant toxicity 1
  • ORIOLE trial: Demonstrated progression-free benefits 1

2. Surgical Options

• Salvage lymph node dissection (sLND)
  • For patients with nodal-only recurrence
  • Can include extended bilateral pelvic lymph node dissection
  • May improve second-line systemic therapy-free survival 1
  • Higher morbidity compared to SABR
  • Consider only in highly selected patients

3. Combined Approaches

• MDT + short-term androgen deprivation therapy (ADT)
  • Recommended in a minority of selected patients 1
  • May improve disease control compared to MDT alone

Clinical Scenarios for MDT Application

1. Synchronous (De Novo) Oligometastatic Disease

• Detected at time of initial diagnosis
• Treatment options:
  • Standard: ADT plus docetaxel or novel hormonal agents 2
  • Consider: Local treatment of primary tumor + MDT to metastases in selected patients 1
  • 62% of experts recommend MDT with short-term ADT in selected patients 1

2. Metachronous (Recurrent) Oligometastatic Disease

• Detected after treatment of primary tumor
• Higher risk of progression compared to synchronous disease (HR 4.50) 3
• Treatment options:
  • MDT to delay initiation of systemic therapy
  • MDT + short-term ADT (recommended by 46% of experts for selected patients) 1

3. Oligoprogressive Disease

• Limited sites progressing despite otherwise effective systemic therapy
• SABR can extend progression-free survival by approximately 9 months 1
• Can delay need to switch systemic therapy by approximately 12.6 months 1

Patient Selection Factors

1. Number of metastases: ≤3 metastases shows best outcomes 1
2. PSA doubling time: <4 months predicts worse outcomes 3
3. Location of metastases:
   • Bone metastases: SABR preferred
   • Lymph node metastases: Either SABR or sLND
4. Prior treatments and response
5. Performance status and comorbidities

Imaging Considerations

• Advanced imaging (PET/CT) detects more lesions than conventional imaging 1
• Common PET tracers:
  • 11C-choline PET
  • PSMA-PET (higher sensitivity)
• Appropriate imaging is crucial for accurate staging and treatment planning

Pitfalls and Caveats

1. Underestimation of disease burden:

   • Conventional imaging may miss micrometastases
   • Consider more sensitive imaging modalities before MDT

2. Patient expectations:

   • MDT is not curative but aims to delay systemic therapy and improve quality of life
   • Progression is expected in most patients within 1-3 years 4

3. Toxicity considerations:

   • While generally well-tolerated, SABR can cause site-specific toxicities
   • Surgical approaches have higher morbidity than radiation-based MDT

4. Evidence limitations:

   • Most data comes from small phase II trials and retrospective series
   • No definitive overall survival benefit has been demonstrated
   • Current recommendations are based on progression-free and ADT-free survival benefits

Treatment Algorithm

1. Confirm oligometastatic status:

   • Advanced imaging (PSMA-PET preferred if available)
   • ≤3-5 metastatic lesions

2. Assess patient factors:

   • PSA doubling time (worse if <4 months)
   • Performance status
   • Prior treatments

3. Select MDT approach:

   • For most patients: SABR to all visible metastases
   • For selected patients with nodal-only disease: Consider sLND
   • Consider adding short-term ADT in higher risk patients

4. Follow-up:

   • PSA monitoring
   • Repeat imaging when clinically indicated
   • Be prepared to initiate systemic therapy when needed

MDT represents a promising approach for selected patients with oligometastatic prostate cancer, with the potential to delay systemic therapy while maintaining quality of life. However, patients should understand that this is typically not a curative approach but rather one that may extend the time to requiring systemic treatments.