Treatment for 85-Year-Old Man with Metastatic Prostate Cancer with Bone and Lymph Node Metastases
An 85-year-old man with metastatic hormone-sensitive prostate cancer involving bone and lymph nodes should receive continuous androgen deprivation therapy (ADT) combined with either abiraterone acetate plus prednisone or enzalutamide, along with mandatory bone-protective therapy (denosumab or zoledronic acid). 1, 2
Initial Systemic Therapy
Primary Hormonal Treatment
Continue ADT indefinitely through either bilateral orchiectomy or LHRH agonist/antagonist therapy, which forms the foundation of all metastatic prostate cancer treatment. 1, 2
When initiating LHRH agonists, administer a short-course antiandrogen (e.g., bicalutamide) for 4 weeks to prevent disease flare from the initial testosterone surge. 3, 2
Intensified First-Line Therapy
For an 85-year-old patient, prioritize novel hormonal agents over chemotherapy due to better tolerability:
Abiraterone acetate plus prednisone or enzalutamide should be offered as first-line intensification with ADT, as both demonstrate improved survival with favorable benefit-harm balance. 3, 1
Docetaxel chemotherapy (75 mg/m² every 3 weeks) combined with ADT is an alternative for fit patients, but given the patient's age (85 years), the toxicity profile makes hormonal intensification preferable unless he has high-volume symptomatic disease and excellent performance status. 1, 4
The distinction matters: Enzalutamide plus ADT showed particular efficacy in patients with bone and lymph node metastases (HR 0.31 for radiographic progression), making it especially appropriate for this presentation. 5
Mandatory Bone-Protective Therapy
Skeletal-Related Event Prevention
All patients with bone metastases must receive bone-protective agents to prevent pathologic fractures, spinal cord compression, and need for bone surgery or radiation. 1, 2, 6
Denosumab 120 mg subcutaneously every 4 weeks is superior to zoledronic acid in delaying skeletal-related events (HR 0.82, P=0.0002), though neither improves overall survival. 1, 2
Alternative: Zoledronic acid 4 mg intravenously every 3-4 weeks if denosumab is contraindicated or unavailable. 3, 2
Critical Monitoring and Supportive Care
Spine Surveillance
Obtain baseline MRI of the spine to detect subclinical cord compression in all patients with vertebral metastases, as this is a medical emergency requiring immediate intervention. 2, 6
Perform urgent MRI for any new neurological symptoms (weakness, sensory changes, bowel/bladder dysfunction). 2
Metabolic Monitoring
Monitor bone densitometry for ADT-induced osteoporosis, as long-term androgen suppression accelerates bone loss beyond that caused by metastases alone. 1, 2
Screen for metabolic syndrome complications including cardiovascular risk factors, diabetes, and lipid abnormalities, which are exacerbated by ADT. 1
Obtain baseline PSA and serial PSAs at 3-6 month intervals after ADT initiation, with periodic conventional imaging to assess disease response. 3
Symptomatic Management
For painful bone metastases, single-fraction 8 Gy external beam radiation provides equivalent pain relief to multi-fraction regimens (30 Gy in 10 fractions) with greater convenience. 1, 2, 6
Ensure adequate hydration and monitor for dehydration, as ADT combined with hormonal agents increases risk of nausea, diarrhea, and vomiting. 7
Treatment Upon Progression to Castration-Resistant Disease
Sequencing After Hormonal Therapy Failure
When disease progresses despite castrate testosterone levels (<50 ng/dL):
If the patient received abiraterone first-line, switch to enzalutamide (or vice versa), though cross-resistance is common. 3, 4
For symptomatic progression after hormonal therapy, docetaxel 75 mg/m² every 3 weeks remains standard chemotherapy if performance status permits. 1, 4
Post-Docetaxel Options
Cabazitaxel chemotherapy for patients who progress after docetaxel, though toxicity risk is substantial in elderly patients. 3, 4
Radium-223 (55 kBq/kg every 4 weeks for 6 cycles) is the only bone-directed therapy proven to improve overall survival (3.6-month improvement) in patients with symptomatic bone-predominant castration-resistant disease without visceral metastases. 6, 7
177Lu-PSMA-617 for PSMA-expressing tumors after prior ARPI and docetaxel. 4
PARP Inhibitor Consideration
- If genetic testing reveals BRCA1/2 alterations, olaparib monotherapy shows OS benefit after prior ARPI or ARPI followed by docetaxel. 4
Common Pitfalls to Avoid
Age-related considerations for an 85-year-old:
Do not automatically exclude chemotherapy based solely on chronological age—assess functional status, comorbidities, and patient preferences. 8
However, recognize that novel hormonal agents (abiraterone, enzalutamide) offer better tolerability than docetaxel in elderly patients while maintaining efficacy. 3, 8
Bone-protective therapy errors:
Do not use older beta-emitting agents (Strontium-89, Samarium-153) as they provide only pain palliation without survival benefit and carry higher myelosuppression risk compared to radium-223. 6
Remember that bone-protective agents (denosumab, zoledronic acid) prevent skeletal events but do not shrink bone metastases—they are adjunctive, not primary anticancer therapy. 6
Monitoring failures:
Do not wait for neurological symptoms to image the spine—subclinical cord compression requires proactive surveillance MRI. 2
Recognize that bone metastases in prostate cancer are predominantly osteoblastic, making radiographic "shrinkage" assessment problematic—increased sclerosis on CT may represent treatment response, not progression. 6
Prognosis
Median survival for metastatic castration-resistant prostate cancer is less than 2 years, with time to castration resistance averaging 14-30 months from ADT initiation. 1
Early aggressive combination therapy (ADT plus novel hormonal agents or docetaxel) in the hormone-sensitive phase improves prognosis compared to sequential monotherapy. 1, 9