What is the recommended treatment for a 75-year-old patient with metastatic prostate cancer?

Treatment of Metastatic Prostate Cancer in a 75-Year-Old Patient

For a 75-year-old patient with metastatic prostate cancer, continuous androgen deprivation therapy (ADT) combined with either docetaxel chemotherapy (if fit enough), abiraterone, enzalutamide, or apalutamide represents the standard first-line treatment, with bilateral orchiectomy or LHRH agonist/antagonist as the backbone ADT approach. 1, 2, 3

Primary Treatment Algorithm

Step 1: Assess Fitness for Combination Therapy

For patients fit enough to receive chemotherapy:

• ADT plus docetaxel (75 mg/m² every 3 weeks for 6 cycles) is recommended as first-line treatment for metastatic hormone-naïve disease 1, 2, 4
• This combination is particularly indicated for high-volume disease (defined as visceral metastases and/or ≥4 bone lesions with ≥1 beyond vertebral bodies/pelvis) 3
• Docetaxel should be administered with prednisone 5 mg orally twice daily continuously 4

For patients not candidates for chemotherapy or with lower-volume disease:

• ADT plus abiraterone (1000 mg daily) with low-dose prednisone (5 mg twice daily) 1, 3
• ADT plus enzalutamide 1, 3
• ADT plus apalutamide 3

Step 2: Select the ADT Backbone

Bilateral orchiectomy or LHRH agonist/antagonist are equally effective options 1:

LHRH agonist (e.g., leuprolide, goserelin):

• Must add antiandrogen coverage (bicalutamide, flutamide, or nilutamide) for at least 7 days, preferably 3-4 weeks, to prevent testosterone flare 2, 5
• This is critical in patients with extensive symptomatic bone metastases to prevent spinal cord compression 5
• Testosterone flare can exacerbate symptoms and cause disease progression 6

LHRH antagonist (e.g., degarelix):

• Provides rapid testosterone suppression within 3 days without initial surge 5
• Does not require antiandrogen coverage 6
• Preferred for patients with severe symptoms requiring immediate testosterone reduction 5

Bilateral orchiectomy:

• Achieves castrate testosterone levels within 12-24 hours 5
• Most cost-effective but irreversible and carries psychological burden 1
• Consider for patients with severe symptoms needing most rapid relief 5

Step 3: Combined Androgen Blockade Consideration

Adding a nonsteroidal antiandrogen (bicalutamide, flutamide, nilutamide) to castration provides modest survival benefit 1:

• Meta-analyses show 1-5% absolute reduction in mortality at 5 years 3
• Benefit appears only after 5 years of follow-up 1
• Increases gastrointestinal, ophthalmologic, and hematologic adverse effects 1
• For metastatic disease specifically, combined androgen blockade showed 6-month improvement in overall survival and 10-month improvement in progression-free survival versus castration alone 3
• Steroidal antiandrogens should not be offered as they show inferior outcomes 1

Continuous vs. Intermittent ADT

Continuous ADT is recommended over intermittent ADT for metastatic disease 1, 3:

• The phase III SWOG-9346 trial demonstrated that intermittent ADT was not non-inferior to continuous therapy for overall survival in metastatic disease 1, 7
• Intermittent ADT showed 7% increase in prostate cancer deaths, though balanced by more non-prostate cancer deaths in continuous ADT arm 1
• Intermittent ADT is not recommended for metastatic hormone-naïve prostate cancer outside clinical trials unless significant intolerance to hormone therapy exists 2

Age-Specific Considerations for 75-Year-Old Patients

Elderly patients (≥65 years) treated with docetaxel experience higher rates of specific toxicities 4:

• Anemia (71% vs 59% in younger patients) 4
• Infection (37% vs 24%) 4
• Nail changes (34% vs 23%) 4
• Anorexia (21% vs 10%) 4
• Weight loss (15% vs 5%) 4

However, age alone should not preclude combination therapy if the patient is otherwise fit 4, 8:

• Median survival in patients ≥65 years treated with docetaxel plus cisplatin was 12.1 months (95% CI: 9.3-14 months) 4
• Close monitoring is essential for elderly patients receiving combination therapy 4

Monitoring Requirements

Initial assessment:

• Bone scan and CT scan (or MRI) of abdomen and pelvis 2
• Baseline PSA, testosterone, complete blood count, liver function tests 1

Ongoing monitoring:

• PSA measurements every 3-4 weeks initially to assess response 3
• Clinical assessment and management of side effects at each visit 2
• Verify testosterone suppression to <50 ng/dL (ideally <20 ng/dL or <0.7 nmol/L) 1, 9
• Bone densitometry and metabolic syndrome screening for patients on long-term ADT 1, 2

Supportive Care Measures

Mandatory interventions:

• Regular exercise reduces fatigue and improves quality of life 1, 2
• Bone-targeted therapy (denosumab or zoledronic acid) for patients at high risk of skeletal-related events once castration-resistant 1, 2
• Single fraction external beam radiotherapy for palliation of painful bone metastases 1, 2
• MRI of spine to detect subclinical cord compression in patients with vertebral metastases 1, 2

Critical Caveats

Hepatic impairment:

• Avoid docetaxel in patients with bilirubin >ULN or AST/ALT >1.5 × ULN with alkaline phosphatase >2.5 × ULN 4
• These patients have increased risk of severe neutropenia, febrile neutropenia, infections, and toxic death 4

Neutropenia monitoring:

• Do not administer docetaxel to patients with neutrophil counts <1500 cells/mm³ 4
• Prophylactic G-CSF may be used to mitigate hematological toxicities 4

Neuroendocrine differentiation:

• PSA is not a reliable indicator in patients with neuroendocrine features 2
• These patients should receive chemotherapy in addition to ADT 1, 2