What is the treatment approach for a patient with prostate cancer and bone lesions in the pelvis and ribs?

Treatment of Prostate Cancer with Bone Metastases to Pelvis and Ribs

For prostate cancer with bone metastases to the pelvis and ribs, initiate continuous androgen deprivation therapy (ADT) as the foundation of treatment, add docetaxel chemotherapy if the patient is fit enough, implement bone-targeted therapy with denosumab or zoledronic acid to prevent skeletal-related events, and use single-fraction radiation therapy (8 Gy) for painful lesions. 1, 2

Systemic Therapy Approach

First-Line Hormonal Therapy

• Continuous ADT is the cornerstone first-line treatment for metastatic hormone-naïve prostate cancer, achieved through either bilateral orchiectomy or LHRH agonist/antagonist 1, 3
• When initiating LHRH agonists, administer a short-course antiandrogen (e.g., bicalutamide) to prevent disease flare from the initial testosterone surge 1, 3
• Continue androgen suppression even after progression to castration-resistant disease 1

Addition of Chemotherapy

• ADT plus docetaxel 75 mg/m² every 3 weeks is recommended as first-line treatment for metastatic hormone-naïve disease in men fit enough for chemotherapy 1, 4
• This combination has demonstrated superior outcomes compared to ADT alone in hormone-sensitive metastatic disease 1
• Docetaxel should be infused over 1 hour every 3 weeks, with prednisone 5 mg orally twice daily administered continuously 4

Bone-Targeted Therapy

Prevention of Skeletal-Related Events

• In patients with bone metastases from castration-resistant prostate cancer (CRPC) at high risk for skeletal-related events (SREs), either denosumab 120 mg subcutaneously every 4 weeks or zoledronic acid 4 mg intravenously every 3-4 weeks should be initiated 1
• Denosumab demonstrated superiority over zoledronic acid in delaying time to SREs (HR 0.82, P=0.0002), though neither agent improves overall survival 1
• Zoledronic acid must be infused over no less than 15 minutes to reduce renal toxicity risk 5

Mandatory Monitoring and Prophylaxis

• All patients must receive calcium and vitamin D supplementation before starting bone-targeted therapy 1
• Dental examination is mandatory prior to initiating denosumab or zoledronic acid due to osteonecrosis of the jaw risk (seen in both agents) 1
• Monitor serum calcium levels closely, as denosumab carries higher hypocalcemia risk (13% vs 6% with zoledronic acid) 1
• For zoledronic acid, assess serum creatinine before each treatment and avoid use if creatinine clearance <30 mL/min 5

Radiation Therapy for Symptomatic Bone Lesions

Palliative Radiation

• A single 8 Gy fraction of external beam radiation is recommended for palliation of painful bone metastases in the pelvis or ribs 1, 2
• Single-fraction 8 Gy provides equivalent pain relief to 10 fractions of 3 Gy (30 Gy total) but is more convenient and cost-effective 1, 2
• Up to 80% of patients achieve pain relief with palliative radiation 2, 6

Radiopharmaceuticals for Widespread Disease

• Radium-223 dichloride is recommended for men with bone-predominant, symptomatic metastatic CRPC without visceral metastases, as it significantly improves overall survival (median 14.9 vs 11.3 months) 1, 2
• Radium-223 emits high-energy alpha particles with shorter path length, reducing toxicity to adjacent bone marrow compared to beta-emitters like strontium-89 or samarium-153 2
• Alternative radioisotopes (strontium-89, samarium-153-EDTMP) can be considered for painful bone metastases from castration-refractory disease when radium-223 is unavailable 1, 2

Treatment Algorithm for Castration-Resistant Disease

Asymptomatic or Mildly Symptomatic CRPC

• Abiraterone acetate or enzalutamide are recommended first-line options for asymptomatic/mildly symptomatic chemotherapy-naïve metastatic CRPC 1
• Sipuleucel-T is an alternative option in this population, though with lower level of evidence 1

Symptomatic CRPC

• Docetaxel 75 mg/m² every 3 weeks is recommended for symptomatic metastatic CRPC 1
• Radium-223 is specifically indicated for bone-predominant symptomatic disease without visceral metastases 1

Post-Docetaxel Progression

• After docetaxel failure, recommended options include abiraterone, enzalutamide, cabazitaxel, or radium-223 (if no visceral disease) 1
• All these agents have Level I evidence supporting their use in the post-docetaxel setting 1

Critical Monitoring Requirements

Spinal Cord Compression Surveillance

• MRI of the spine to detect subclinical cord compression is recommended in men with CRPC with vertebral metastases 1
• Urgent MRI is very strongly recommended for any patient with vertebral metastases who develops neurological symptoms 1

Long-Term ADT Monitoring

• Monitor for osteoporosis using bone densitometry in men on long-term ADT 1
• Screen for metabolic syndrome complications including cardiovascular risk factors 1
• Regular imaging studies should be performed to monitor disease response/progression in patients with CRPC on systemic treatment 1

Common Pitfalls to Avoid

• Do not use bisphosphonates or denosumab in hormone-naïve metastatic prostate cancer, as they are not recommended outside of castration-resistant disease 1
• Avoid docetaxel doses of 100 mg/m² in previously treated patients, as this is associated with increased hematologic toxicity, infection, and treatment-related mortality 4
• Do not administer docetaxel to patients with bilirubin >ULN or AST/ALT >1.5× ULN with alkaline phosphatase >2.5× ULN due to severe toxicity risk 4
• Never discontinue ADT after progression to castration-resistant disease; continue androgen suppression indefinitely 1