Adjuvant and Early Salvage RT: More Data to Support Early Salvage RT
Paul Sargos, MD
By Daniel Spratt, MD, University of Michigan
Until recently, nearly all guidelines around the world endorsed the discussion of the biochemical control benefit of adjuvant radiation therapy (ART) post-radical prostatectomy (RP) in men with pT3 disease and/or a positive surgical margin. However, ART consistently has been shown to increase post-operative side effects, and some men who receive ART would have been cured by RP alone. This has led to a very low utilization rate of ART in many countries, even for men at high risk of recurrence.
Over the past decade, it has become increasingly clear that early salvage RT (eSRT), when delivered at low PSA levels (~0.2 ng/mL), results in very good long-term tumor control. Furthermore, there does not appear to be survival benefit to the addition of androgen deprivation therapy (ADT) to early SRT, and newer expensive advanced molecular PET/CT imaging modalities have very low detection rates at such low PSA levels, making them of limited value at PSAs 0.1-0.2 ng/mL. Thus, use of eSRT is an attractive option, as – if it results in comparable tumor control to ART – it is likely to result in lower rates of toxicity than ART, as well as the routine use of ADT and PET/CT imaging may be of lower yield compared to late SRT at higher PSAs.
In 2019 the results of RAVES and RADICALS were presented in abstract form, as well as the pooled ARTISTIC meta-analysis of RAVES, RADICALS and GETUG-AFU-17 Phase III randomized trials that all compared ART vs. eSRT. These prior presentations demonstrated no evidence of any biochemical control benefit of ART over eSRT with intermediate-term follow-up, but there was higher toxicity with ART. Importantly, no subgroup of patients appeared at this time to benefit more from ART, and many men who were randomized to the eSRT have yet to need eSRT given they have not yet experienced a biochemical recurrence post-RP.
The toxicity and QOL results from the GETUG-AFU-17 trial, A Phase III Randomised Trial Comparing Adjuvant versus Early Salvage Radiotherapy, Both Combined with Short-term Androgen Deprivation Therapy, following a Radical Prostatectomy: Initial Results of the GETUG-AFU 17 Study [NCT00667069], were presented for the first time by Paul Sargos, MD. This trial unfortunately was stopped early due to poor accrual but still managed to enroll 424 of the intended 718 patients between 2008-2016. They enrolled patients with pT3-4 and positive margins, pNx or pN0, with post-operative PSA ≤0.1 ng/mL, who were then randomized ≤6 months after RP to ART or observation with eSRT, combined with six months of ADT. Similar to the prior trials mentioned, after a median follow-up of 6.3 years, 53% of men in the eSRT arm had a biochemical recurrence prompting eSRT. They showed that acute toxicities were similar between arms, but late grade >2 toxicities, essentially incontinence and sexual dysfunction, were significantly higher with ART (20%) comparted to eSRT (8%, p<0.001).
After writing this article, the results of RAVES, RADICALS, GETUG-AFU-17, or the ARTISTIC meta-analysis have been published in The Lancet and Lancet Oncology, which confirm that there is now strong evidence that eSRT may be the preferred approach over ART for patients well-represented in these trials (most commonly Gleason 7 and pT3a disease).
A Phase III Randomised Trial Comparing Adjuvant versus Early Salvage Radiotherapy, Both Combined with Short-term Androgen Deprivation Therapy, following a Radical Prostatectomy: Initial Results of the GETUG-AFU 17 Study [NCT00667069] was released onDemand on Saturday, October 24 in the Science Center, as part of Scientific session (SS) 05.
Published on: October 27, 2020