Adjuvant radiotherapy has no benefit following radical prostatectomy

Prof Noel Clarke - The Christie NHS Foundation Trust, Manchester, UK

The RADICALS study was designed in around 2004, 2005, to address the question of treatment for patients who had had radical prostatectomy who had high risk features. There were two components to the trial, one was to address the issue of radiotherapy with hormone therapy, androgen deprivation therapy, known as RADICALS-HD, and the second question was to address the issue of the timing of radiotherapy, whether it should be given immediately or whether it should be given in a delayed manner, that was RADICALS-HT or hormonal timing.

In my presentation on behalf of the RADICALS investigators at the ESMO meeting 2023 I was reporting the long-term results of RADICALS radiotherapy timing. We had previously reported the RADICALS results for this part of this trial at ESMO 2020 and published those findings in The Lancet Oncology. They had looked at the effect of treatment, early/late, in patients looking at their treatment failure rate, predominantly looking at PSA failure or other events such as metastasis, prostate cancer death and so on. What was shown in that first analysis was that patients who had been treated with salvage radiotherapy on failure had just the same benefit as those patients treated immediately following their radical prostatectomy. The important finding there was that a very high proportion of men didn’t need any treatment at all. What we also found was that the complication rate, most notably rectal and bladder toxicity, was higher when patients were treated with the adjuvant therapy by comparison with those who were delayed.

Now, in the follow-up, which is the long-term report which was, for a large-scale trial of just under 1,400 patients, we were able to report on overall survival and metastasis-free survival which is a direct surrogate of overall survival. What we found was that the results that we presented in the earlier ESMO study based on biochemistry were borne out by metastasis free survival and overall survival. In other words, salvage treatment for PSA failure was as effective as adjuvant treatment but approximately 40% or so of the patients needed treatment and the rest of them didn’t. So, this saved a huge amount of treatment for men who didn’t need therapy.

What we also found was that the side effects were, in the long-term, sustained. In other words, if a patient had developed post-treatment bladder-related problems or post-treatment rectal symptoms, then they continued out at the ten year time interval.

So the conclusion, which I think really settles this issue of whether patients should have radiotherapy after radical prostatectomy, is this: that they don’t need treatment unless they show signs of failure subsequently. If they do, then there is potential benefit.