This tab covers radiation delivery concepts (fractionation, particle therapy) and palliative radiation. The EBRT/brachytherapy modalities, dose escalation, EBRT + ADT trials, and toxicity/PSA-failure definitions are detailed in the Management of Localized Prostate Cancer tab.
Hypofractionation
The total dose is divided into fractions; hypofractionation delivers fewer, higher-dose fractions over a shorter course. Prostate cancer is thought to be especially sensitive to the dose delivered per fraction (low α/β ratio), so a few high-dose treatments may produce more cell kill than many 2-Gy fractions — potentially allowing a lower total dose with similar control and less normal-tissue injury. Phase III trials have delivered 2.6–3.1 Gy per fraction with low morbidity; extreme fractionation (6.7–10 Gy) shows good early biochemical control but limited follow-up. Safe delivery requires accurate setup and conformal planning.
Heavy-Particle Therapy
A form of 3D conformal radiation using neutrons or protons, which are harder to produce and control. Particles travel differently in tissue and exhibit a Bragg peak — a sharp dose cutoff at the end of the particle's range (sparing tissue beyond it). Neutrons may cause more normal-tissue damage than photons. Protons are expensive and have not demonstrated a clinical benefit over modern IMRT — planning studies show reduced low-to-medium (but not high) doses to nearby organs, with no head-to-head outcome comparison; control and morbidity are likely similar to IMRT.
Palliative Radiotherapy
- Bone metastases: a single-fraction regimen (800 cGy × 1) is preferred for uncomplicated non-spinal bone metastases — as effective as protracted regimens, more cost-effective, and less time-consuming. Pathologic fracture is infrequent (prostate metastases are primarily blastic). Consider prophylactic surgical fixation (orthopedic referral) for an intramedullary lytic lesion ≥50% of the bone's cross-sectional diameter, a cortical lytic lesion ≥ the bone diameter, or a lytic lesion >2.5 cm in axial length; give post-operative radiation after fixation.
- Spinal cord compression — the most serious complication of bone metastasis and a medical emergency, usually epidural from a vertebral body. Presentation: back pain (~95%), focal neurologic deficit, and bladder/bowel changes. MRI is the diagnostic modality of choice. Give corticosteroids immediately (dexamethasone load 4–10 mg, then 4–24 mg every 6 h); definitive treatment is radiation, surgery, or both. Favor surgery before radiation when the tissue diagnosis is unknown, the area was previously irradiated, or there is a pathologic fracture with instability/bony cord compression.
Molecular Therapies and Radiation
Inhibiting DNA-repair proteins (e.g. DNA-PK, ATM) with chemical or short-interfering RNA (siRNA) sensitizes cells to radiation; the main challenge for RNA-interference therapy is selective, cell-type-specific delivery to avoid sensitizing surrounding normal tissue.
Self-Test
1. What is the dose of palliative radiation for bone metastases? A single fraction of 800 cGy.
2. What are the indications for surgical fixation of a bone metastasis? An intramedullary lytic lesion ≥50% of the bone's cross-sectional diameter, a cortical lytic lesion ≥ the bone diameter, or a lytic lesion >2.5 cm in axial length.