What is the role of radiotherapy in the management of metastatic carcinoma of the prostate?

Radiotherapy for Metastatic Carcinoma Prostate

Radiotherapy plays a crucial role in metastatic prostate cancer management, particularly for palliating bone pain with a single 800 cGy fraction for non-vertebral metastases, while radiopharmaceuticals like radium-223 are indicated for patients with symptomatic bone metastases and no known visceral disease. 1

Palliative External Beam Radiotherapy

• External beam radiotherapy is highly effective for pain palliation in bone metastases from prostate cancer, with complete relief achieved in 42% of patients and partial relief in 35% 2
• A short course of 800 cGy in a single fraction is as effective and less costly than 3000 cGy in 10 fractions for non-vertebral metastases 1
• For painful bone metastases from castration-refractory disease, fractioning of 1×8 Gy or 10×3 Gy may be used with equal pain-relieving efficacy 1
• Pain relief typically occurs within 24-48 hours of treatment and can be maintained until death in approximately 67% of patients 3

Radiopharmaceuticals

• Radiopharmaceuticals are effective for patients with widespread metastatic disease, particularly when they are no longer candidates for effective chemotherapy 1
• Radium-223 dichloride (Xofigo) is FDA-approved for castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastatic disease 4
• Unlike beta-emitting palliative radiopharmaceuticals, radium-223 emits high-energy alpha particles with shorter path, reducing toxic effects on adjacent tissue 1
• Radium-223 significantly improves overall survival (median 14.9 vs 11.3 months) and prolongs time to first skeletal-related event (median 15.6 vs 9.8 months) compared to placebo 1
• Other radiopharmaceuticals commonly used include strontium-89 (89Sr) and samarium-153 (153Sm) 1

Emerging Role in Oligometastatic Disease

• Stereotactic body radiotherapy (SBRT) is effective for oligometastatic prostate cancer, providing high local control and delaying the need for systemic therapy 5
• Prostate radiotherapy shows survival benefit in patients with low metastatic burden, particularly those with ≤3 bone metastases without visceral metastasis 6
• The magnitude of benefit decreases continuously as the number of bone metastases increases, with benefit most pronounced up to 3 bone metastases 6

Half-Body Irradiation

• High-dose radiation therapy given as a single fraction to upper and lower halves of the body can provide effective palliation for widespread metastatic disease 3
• This approach appears particularly effective in tumors with slow doubling time such as prostate cancer 3

Combination Approaches

• For patients with bone pain resistant to palliative radiotherapy and conventional analgesics, intravenous bisphosphonates (e.g., pamidronate) should be considered 1
• Bisphosphonates can reduce skeletal-related events despite the predominantly osteoblastic nature of prostate cancer metastases 7

Practical Considerations and Pitfalls

• Radium-223 is well-tolerated with low rates of grade 3/4 hematologic toxicity (3% neutropenia, 6% thrombocytopenia, 13% anemia) 1
• The safety of using chemotherapy after radium-223 has not been established, and preliminary data suggest combination with standard doses of docetaxel should not be undertaken 1
• Despite SBRT effectiveness in oligometastatic disease, the high rate of distant metastasis progression (mean 16.2 months) highlights the importance of proper patient selection 5
• Patients with castration-refractory disease should be managed in collaboration with dedicated palliative care services 1

In summary, radiotherapy remains a cornerstone in managing metastatic prostate cancer, offering effective pain palliation with external beam approaches and survival benefits with newer targeted radiopharmaceuticals like radium-223 for appropriate patients.