Four RCTs confirmed an improvement in BCR-free survival with adjuvant radiation for high risk patients (pT3, PSM) vs observation (this includes Bolla 2012 Lancet)
- 10 yr BCR free survival about 53 – 60 % vs 30 – 41 %, all significant
- 10 yr OS – generally not significant
- Whilst this suggests adjuvant radiation will benefit some men – it does mean that 30 – 40 % will be cured / not have BCR at 10 years – and therefore be overtreated
Therefore, an interest developed in early salvage radiation as an alternative.
Three RCTs have been performed (RAVES, RADICALS, GETUG) and a meta-analysis done (ARTISTIC)
- No significant difference in progression free survival at 5 – 6 year follow up in all 3 trials
- 5 year progression free survival 89 vs 88 %
- Lower urinary toxicity and stricture rates in salvage radiation group
- Only 40 % of those in salvage group had received radiation (60 % has not met criteria)
- Salvage radiation given at a median 0.24 ng/mL – lower than commonly used in practice
- Proportion of ‘high risk’ patients in trials (at least two of pT3/R1/GS 8+) was low, about 10 – 20 %– and conversely probably underpowered to show a difference in these groups
- Radiation techniques got better during trials – more recent patients likely better radiation / less toxicity
Because of the low number of ‘high risk’ patients in the above trials, EAU still suggests that patients with 2/3 of positive margins, pT3 disease, and Gleason 8+, be considered for adjuvant radiation (for other patients – standard of care is salvage radiation).
pN1 disease
All data is retrospective – but suggests a benefit in terms of overall survival for men treated with adjuvant ADT, and probably an improvement again for combination therapy with EBRT and ADT (EBRT to nodes/fossa).
However, a small percentage of men (less than a third) will remain recurrence free in the long term, up to 10 years – these are generally patients with low volume (1 or 2 positive nodes only).
EAU recommendations:
- Offer adjuvant ADT
- Offer adjuvant ADT + EBRT
- Offer observation if only 1 or 2 nodes positive, and initial PSA < 0.1 ng/mL