Radiation is generated and delivered from linear accelerator – photons delivered to target using modern techniques of IMRT (multileaf collimator), VMAT (continuous rotation around patient) and image guiding (fiducial markers, tattoos, daily cone beam CT).
Roles of EBRT in prostate cancer:
- Curative intent treatment of organ confined disease
- Adjuvant or salvage treatment post prostatectomy
- Palliative treatment of painful metastases, at risk bony sites, or bleeding primary
- Treatment of prostate in low volume metastatic disease
- ?Metastasis directed treatment or treatment of oligorecurrent disease
Conventional curative primary dose is 78 Gy in 39 # with 2 Gy / dose.
Hypofractionated treatment to 60 Gy in 20 # has been proven equivalent in large RCTs.
SABR (ultrahypofractionation) with high doses (7 – 8 Gy / dose, for 5 #, 35 – 40 Gy total) has emerging evidence for equivalent biochemical control and early evidence of similar toxicity (late toxicity data not available).
Contra-indications / precautions for EBRT
- Prior pelvic radiation therapy
- Active IBD
- Bilateral hip replacements
- Scleroderma, SLE, connective tissue disorders – higher risk of complications
- Significant obstructive LUTS
- ?Pacemakers – historic – generally OK
ADT with radiation
Mechanisms of synergistic effect:
- Induces apoptosis
- Inhibits VEGF and angiogenesis
- Blocking the AR stops DNA repair
- Increases oxygenation, blood flow and radiosensitivity
- Reduction of tumour size
- Eradicates untreated micrometastatic disease
Guidelines:
- 4 – 6 months ADT with intermediate risk disease
- 2 – 3 years ADT with high risk disease
Evidence for ADT with XRT – multiple RCTs for 6 months ADT with intermediate risk disease:
- Biochemical recurrence 15 vs 30 %
- Progression 4 % vs 12 %
- Prostate cancer specific mortality 1.3 vs 6 %
Also level 1 evidence that 2 years ADT for high risk disease improves overall survival and BCR vs 6 months ADT.
ADT can be neoadjuvant, adjuvant or concurrent.
Treating the nodes
EAU – there is no clear evidence for prophylactic irradiation of the pelvic lymph nodes.
Some studies have shown small improvements in progression free survival with small increases in toxicity – “insufficient to change practice”.
AUA – “offer” lymph node radiation in high risk disease
POP-RT trial showed improvements in DFS/PFS/BCR (no OS benefit) in high risk patients – AUA submits this trial was only trial to standardise high risk patients and using modern EBRT and ADT regimes
cN1 disease should be treated with whole pelvic radiotherapy – can boost the involved node (and ADT).
Rectal spacers
Aims to reduce rectal toxicity during EBRT for prostate cancer by increasing distance between rectum and prostate.
Hydrogels – injectable viscous semiliquid compounds made mostly of water, with structure given by hydrophilic polymer matrix
Polyethylene glycol (PEG) – SpaceOAR
- Single use system with concurrent mixing of precursor and accelerator – fixed volume
Hyaluronic acid – Barrigel
- Ready to inject – can use variable volumes in different locations
Gradual metabolism and complete absorption of the spacers occur within 12 months.
Contra-indications:
- T4 disease, particularly posterior extension
- Bleeding diathesis or coagulopathy
- Inability to have TRUS or be placed in lithotomy
Complications
- Mild perineal discomfort
- Inability to place spacer
- Rectal erosion, ulceration – 1 % – severe
- Prostatic abscess and fistula
Evidence
- Confirmed reduction in rectal dose – reduction of V70 (volume of rectum receiving 70 Gy) of more than 25 %
- EAU says meta-analysis showed 5 – 8 % reduction in volume receiving high dose
- No proven reduction in acute rectal toxicity, but reduction in patient reported and grade 2+ rectal toxicity at 2 – 3 years
Role in ultra-hypofractionation still unclear.
Fiducial markers
3 gold containing seeds. Inert. Permanent. Safe to be placed at time of spacer.
Complications of EBRT
Early:
- Fatigue
- Urinary frequency and storage symptoms
- Bowel frequency, cramping and pain
Late:
- Rectal toxicity – frequency, incontinence, bleeding, urgency
- Radiation cystitis and haematuria
- Storage LUTS with reduced bladder capacity
- Urethral stricture
- Erectile dysfunction and ejaculatory dysfunction
- Second malignancy – risk increases after 10 years
- Pelvic fracture – increased long term risk
Review article (Eur J Urol) here
