What is the recommended treatment and prognosis for a patient with infiltrating prostatic adenocarcinoma, acinar type with bone metastasis?

Treatment and Prognosis for Metastatic Prostate Adenocarcinoma (Acinar Type) with Bone Metastases

Immediate First-Line Treatment

Continuous androgen deprivation therapy (ADT) combined with docetaxel chemotherapy is the recommended first-line treatment for fit patients with metastatic hormone-naïve prostate cancer with bone metastases 1, 2.

• ADT should be achieved through either bilateral orchiectomy or LHRH agonist/antagonist therapy 2.
• When using LHRH agonists, administer a short-course antiandrogen (e.g., bicalutamide) to prevent disease flare from the initial testosterone surge 2.
• Docetaxel should be given at 75 mg/m² every 3 weeks for patients fit enough for chemotherapy 1.
• Alternative first-line options include ADT plus novel hormone agents (abiraterone, enzalutamide, apalutamide, or darolutamide) for patients who cannot tolerate chemotherapy 3.
• Triplet therapy (ADT + docetaxel + abiraterone or darolutamide) represents the most aggressive approach for fit patients with de novo metastatic disease 3.

Mandatory Bone-Targeted Therapy

All patients with bone metastases should receive bone-protective agents to prevent skeletal-related events (SREs) 2, 4.

• Denosumab 120 mg subcutaneously every 4 weeks is superior to zoledronic acid in delaying SREs (HR 0.82, P=0.0002) 2.
• Alternative: Zoledronic acid 4 mg intravenously every 3-4 weeks 1, 2, 4.
• Neither agent improves overall survival, but both prevent pathologic fractures, spinal cord compression, and need for bone surgery or radiation 2, 4.
• Ensure adequate renal function monitoring before each dose, as both agents carry nephrotoxicity risk 4.

Palliative Radiation for Symptomatic Lesions

For painful bone metastases in the pelvis or ribs, a single 8 Gy fraction of external beam radiation provides equivalent pain relief to multi-fraction regimens 1, 2.

• Single-fraction treatment is more convenient and cost-effective than 10 fractions of 3 Gy (30 Gy total) 2.
• Reserve radiation for symptomatic sites or impending pathologic fractures 1.

Critical Monitoring Requirements

Implement spine surveillance and metabolic monitoring from treatment initiation 2.

• Obtain MRI of the spine to detect subclinical cord compression in all patients with vertebral metastases 1, 2.
• Perform urgent MRI immediately if any neurological symptoms develop (weakness, sensory changes, bowel/bladder dysfunction) 1, 2.
• Monitor bone densitometry for osteoporosis in all patients on long-term ADT 1, 2.
• Screen for metabolic syndrome complications including cardiovascular risk factors, diabetes, and lipid abnormalities 2, 5.
• Recommend regular exercise to reduce fatigue and improve quality of life 1.

Treatment Upon Progression to Castration-Resistant Disease

When disease progresses despite castrate testosterone levels (median time 14-30 months), treatment escalation follows a specific sequence 1, 6.

For Asymptomatic/Mildly Symptomatic Castration-Resistant Prostate Cancer (CRPC):

• First-line: Abiraterone or enzalutamide 1, 3.
• Alternative: Radium-223 for bone-predominant disease without visceral metastases (improves overall survival: median 14.9 vs 11.3 months, HR 0.70) 1.

For Symptomatic CRPC:

• Docetaxel 75 mg/m² every 3 weeks remains the standard chemotherapy 1.
• PSA rise alone does not define docetaxel failure; continue if no clinical progression 1.

Post-Docetaxel Options:

• Cabazitaxel provides survival benefit and is superior to switching between abiraterone and enzalutamide due to cross-resistance 1, 7.
• Enzalutamide or abiraterone (if not previously used) 1.
• Radium-223 for bone-predominant disease without visceral metastases 1.
• 177Lu-PSMA-617 for PSMA-expressing tumors after taxane and androgen receptor axis inhibitor failure 3.
• Olaparib for patients with BRCA1/2 alterations 3.

Prognosis

Median survival for metastatic castration-resistant prostate cancer is less than 2 years 1.

• Time to castration resistance averages 14-30 months from ADT initiation 1.
• More than 90% of CRPC patients have bone metastases 1.
• Prognosis improves with early aggressive combination therapy (ADT + docetaxel or novel hormones) in the hormone-sensitive phase 1, 3.
• Bone metastases are the major cause of mortality, morbidity, and poor quality of life 1.

Common Pitfalls to Avoid

• Do not delay ADT initiation in patients with symptomatic metastatic disease 1.
• Do not use intermittent ADT as first-line for metastatic disease; continuous ADT is superior for survival 1.
• Do not interpret increased bone sclerosis on CT as progression; treated bone metastases often become more densely sclerotic, which is a common false-positive finding 1.
• Do not rely solely on PSA in patients on ADT, as hormonal therapy reduces PSA production independent of disease status 1.
• Do not use bone scan flare phenomenon (temporary worsening on imaging after treatment initiation) as evidence of progression 1.
• Do not combine radium-223 with standard-dose docetaxel; preliminary data suggest increased toxicity 1.