What are the treatment options for a patient with prostate cancer that has metastasized to the hip bone and is experiencing progressive symptoms?

Symptoms of Prostate Cancer with Metastases to the Hip Bone and Progressive Symptoms

Patients with prostate cancer metastatic to the hip bone commonly experience bone pain, pathological fractures, spinal cord compression, and limited mobility, requiring prompt treatment with docetaxel chemotherapy plus prednisone as first-line therapy for castration-resistant disease, along with zoledronic acid to prevent skeletal-related events.

Common Symptoms of Bone Metastases

Pain Symptoms

• Bone pain is the most prominent symptom, typically:
  • Localized to the hip area
  • Persistent and progressive in nature
  • Often worse at night or during weight-bearing activities
  • Initially responsive to analgesics but eventually becoming refractory 1
  • May radiate to the lower back, groin, or down the leg

Skeletal-Related Events (SREs)

• Pathological fractures (hip fractures are common due to weakened bone integrity)
• Spinal cord compression if metastases extend to vertebrae
• Need for surgery to bone to prevent or treat fractures
• Need for radiation therapy to alleviate pain 1

Functional Limitations

• Decreased mobility and difficulty walking
• Reduced ability to bear weight on the affected side
• Impaired activities of daily living
• Decreased quality of life 1

Systemic Symptoms

• Fatigue and weakness
• Weight loss
• Anemia (due to bone marrow involvement)
• Hypercalcemia (elevated calcium levels) in advanced cases 1

Diagnostic Evaluation

Imaging Studies

• MRI is recommended for detailed assessment of bone metastases and to detect subclinical cord compression in men with back pain 1
• CT and MRI are the modalities of choice for routine response assessment 1
• Bone scan to identify the extent of metastatic disease
• Plain radiography may show osteoblastic (bone-forming) lesions typical of prostate cancer 1

Laboratory Tests

• PSA levels (typically elevated)
• Alkaline phosphatase (often elevated with bone metastases)
• Complete blood count to assess for anemia
• Serum calcium levels to check for hypercalcemia 1

Treatment Approaches

First-Line Systemic Therapy

• Docetaxel (75 mg/m² every 3 weeks) with prednisone (5 mg twice daily) is the standard first-line chemotherapy for castration-resistant prostate cancer with bone metastases 1, 2
  • Provides survival benefit (median survival 19.2 months vs 16.3 months with mitoxantrone)
  • Improves quality of life in approximately 25% of patients
  • Reduces PSA levels by ≥50% in about half of patients 1

Bone-Targeted Therapy

• Zoledronic acid (4 mg IV every 3-4 weeks) is recommended to:
  • Reduce risk of skeletal-related events by 36% 1, 3
  • Provide durable pain palliation 1
  • Delay the first skeletal-related event by >5 months 1
• Denosumab is an alternative bone-targeted agent 4

Radiation Therapy

• External beam radiotherapy for painful bone metastases:
  • Single fraction of 8 Gy has equal pain-reducing efficacy to multifraction schedules 1
  • Pain relief occurs in 70-80% of patients, with complete relief in one-third 1
  • Pain relief may occur rapidly, with 40% of responders showing benefit within 10 days 1

Radioisotope Therapy

• Strontium-89 or Samarium-153 should be considered for patients with painful bone metastases from castration-resistant disease 1
  • More effective than placebo in reducing pain
  • Can prolong time to further bone pain 1

Management Algorithm

1. Initial Pain Management:

   • Optimize analgesics according to WHO pain ladder
   • Consider external beam radiotherapy (single 8 Gy fraction) for localized pain 1

2. Systemic Therapy:

   • For castration-resistant disease: Docetaxel 75 mg/m² every 3 weeks with prednisone 5 mg twice daily 1, 2
   • Monitor for side effects including neutropenia, fatigue, alopecia, diarrhea, and neuropathy 1

3. Bone-Targeted Therapy:

   • Add zoledronic acid 4 mg IV every 3-4 weeks 1, 3
   • Monitor renal function before each dose
   • Consider dental examination before starting therapy to prevent osteonecrosis of jaw 4

4. For Refractory Pain:

   • Consider radioisotope therapy with strontium-89 or samarium-153 1
   • MRI of spine to detect subclinical cord compression in patients with vertebral metastases and back pain 1

Important Considerations and Pitfalls

• Early Intervention: SRE reduction is greatest in patients without pain, suggesting patients should not wait for symptoms before starting bone-targeted therapy 1

• Monitoring Complications: Regular assessment for spinal cord compression is critical - this is a medical emergency requiring urgent MRI and immediate dexamethasone (16-24 mg/day) 1

• Treatment Limitations: Radioisotope therapy can cause bone marrow suppression, which may limit subsequent chemotherapy options 1

• Renal Function: Monitor renal function closely in all patients receiving zoledronic acid, as renal toxicity is a potential complication 3

• Pain Assessment: Pain should be systematically assessed using validated tools to guide treatment decisions and evaluate response 1