External beam radiotherapy remains the most commonly used radiotherapy treatment for prostate cancer due to widespread availability, familiarity with the technique, and difficulties with brachytherapy. It has not been shown to be inferior to radical prostatectomy or brachytherapy techniques in terms of cancer control or toxicities but there are theoretical advantages to other strategies.
Radical EBRT
Pre-Treatment Considerations
All patients with high risk disease should receive neo-adjuvant androgen deprivation for 6 months as per the TROG and Bolla trials which demonstrate improved survival with this approach. It is more controversial in patients with intermediate risk disease. I would consider androgen deprivation for those with multiple intermediate risk factors (PSA 10-20 AND Gleason 3+4 = 7 OR with Gleason 4+3 alone).
Controversies
Dose Escalation
Older dose schedules were between 66 to 70 Gy. Higher doses were shown to be possible and safe in numerous randomised trials. Meta-analysis performed in Brazil has shown an absolute reduction in biochemical failure by 10% (35% -> 25%) when all risk groups were included and the benefit is present in all risk groups. There is no evidence of an overall survival advantage. Most centres are moving to higher dose schedules (78 Gy most commonly) and further studies into dose escalation are being performed.
The alternative method of dose escalation is to use HDR or LDR brachytherapy as the boost.
Regional Nodes
Two randomised studies have evaluated treatment of regional nodes (RTOG 9413 and GETUG). These both demonstrated no difference in progression free or overall survival with whole pelvic RT versus prostate alone treatment. These studies were hampered by their timing (3DCRT or IMRT is now standard) and the non-routine use of androgen deprivation. A modern study examining nodal RT in conjunction with androgen deprivation for high risk disease patients is underway.
Given the results of these trials I would not advocate for nodal RT unless regional lymphadenopathy is present.
Hypofractionation
Prostate cancer is thought to have a low 𝜶/β ratio. Therefore, higher dose per fraction should be associated with an improved tumour kill rate. This has been evaluated in three randomised studies that showed no significant benefit to hypofractionation with short follow up and old treatment techniques and dosages. The largest study (Lukka et al suggested a trend towards improved outcomes with conventional fractionation. Further studies are underway but this treatment can not be recommended in the current setting.
Dose
The typical dose is 74 - 78 Gy in 37-39 fractions, delivered to the prostate and surrounding tissue. If treated, the regional nodes should receive 50 Gy in 25 fractions. Involved regional nodes should be boosted to 60 Gy if possible.
Volume
The prostate is always included. Depending on risk, 0 - 2 cm of the seminal vesicles should also be included.
- 0 cm for low risk
- 1 cm for intermediate risk
- 2 cm for high risk
Toxicities
Early toxicities include skin reaction, fatigue, dysuria, frequency, diarrhoea and rectal bleeding.
Late effects include:
- Skin changes (tone, texture, telangiectasia)
- Hair loss
- Reduced bladder volume < 5%
- Incontinence < 5%
- Impotence (50%)
- Radiation proctitis (10-20%, most commonly rectal bleeding and increased bowel frequency, rarely ~ 1% have severe debilitating complications)
- Hip fracture < 1%
- Second malignancies (age dependent)
