What is the management of metastatic prostatic Acinar adenocarcinoma?

Management of Metastatic Prostatic Acinar Adenocarcinoma

For patients with metastatic prostatic acinar adenocarcinoma, the standard first-line treatment should be androgen deprivation therapy (ADT) combined with docetaxel, abiraterone, enzalutamide, or apalutamide, as these represent four separate standards of care with proven survival benefits. 1

First-Line Treatment Options

• ADT through bilateral orchiectomy (surgical castration) or LHRH agonists/antagonists (medical castration) forms the backbone of treatment for metastatic prostate cancer 2
• For patients with high-volume disease (HVD) who are candidates for chemotherapy, ADT plus docetaxel should be offered 1
• For patients with low-volume disease (LVD) who are candidates for chemotherapy, docetaxel plus ADT should not be offered 1
• The recommended docetaxel regimen is six doses administered at 3-week intervals at 75 mg/m² either alone or with prednisolone 1
• ADT plus abiraterone with prednisolone is another standard of care option with proven survival benefits 1
• ADT plus enzalutamide or ADT plus apalutamide are also standard treatment options for metastatic disease 1

Combined Androgen Blockade (CAB)

• CAB (ADT plus a nonsteroidal antiandrogen) may provide a small survival benefit (1-5% absolute reduction in mortality at 5 years) compared to ADT alone, but with increased toxicity 2, 1
• In a large Japanese retrospective study, CAB showed improved progression-free survival compared to castration monotherapy (11.6 vs 7.1 years) 1
• For patients with metastatic disease specifically, CAB was associated with a 6-month improvement in overall survival and a 10-month improvement in progression-free survival versus castration alone 1
• Among patients receiving CAB, those treated with bicalutamide had significantly longer PFS than those treated with flutamide (45.24 vs 38.85 months) 1

Intermittent vs Continuous ADT

• For metastatic disease, continuous ADT is recommended over intermittent ADT 2
• While intermittent ADT may be offered to patients with high-risk biochemically recurrent nonmetastatic prostate cancer, it has not been studied in combination with additional cytotoxic or hormonal agents for metastatic disease 1
• Patients should be informed that intermittent ADT may offer quality-of-life benefits during off-treatment intervals but could potentially impact survival 1

Novel Hormonal Agents

• For patients who progress to castration-resistant prostate cancer (CRPC), additional options include abiraterone or enzalutamide for asymptomatic/mildly symptomatic patients 2
• Darolutamide, an androgen receptor inhibitor, is indicated for metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel 3
• When starting LHRH agonist therapy, an antiandrogen should be given for 3-4 weeks initially to prevent testosterone flare 2

Monitoring and Follow-up

• PSA measurements should be performed every 3-4 weeks initially to assess response to therapy 4
• Regular imaging follow-up with CT scans and bone scintigraphy should be considered to assess treatment response 4
• For patients on darolutamide, monitor for signs and symptoms of coronary artery disease, as ischemic heart disease is a potential adverse effect 3

Important Clinical Considerations

• Regular exercise has been shown to reduce fatigue and improve quality of life in men on ADT 2
• Antiresorptive bone therapy has not shown a benefit in the setting of noncastrate bone metastases for skeletal-related event risk reduction 1
• Patients on ADT should be monitored for common side effects including sexual dysfunction, hot flashes, fatigue, and metabolic changes 5, 6
• For rare histological variants like acinar with ductal and mucinous features, the same treatment principles apply, though these may show different sensitivity to ADT 7

Treatment Algorithm

1. Confirm metastatic disease through appropriate imaging
2. Initiate ADT (surgical or medical castration)
3. Based on disease volume and patient factors:
   • High-volume disease: Add docetaxel (if chemotherapy candidate)
   • Consider adding abiraterone, enzalutamide, or apalutamide as alternatives
4. Monitor PSA response every 3-4 weeks initially
5. Perform regular imaging to assess treatment response
6. Upon progression to castration resistance, consider second-line hormonal agents or chemotherapy