Long-course ADT plus radiotherapy provides survival benefit after prostatectomy
Long-course androgen depravation therapy extended metastasis-free survival compared with short-course ADT when added to radiotherapy after radical prostatectomy, results of the randomized phase 3 RADICALS-HD trial showed.
The findings, presented at ESMO Congress, also revealed no significant improvement in metastasis-free survival (MFS) among men with prostate cancer who received short-course ADT plus radiotherapy after surgery compared with those who received only radiotherapy.
Background
The addition of ADT to initial radical treatment for prostate cancer is known to improve patient outcomes, according to Chris C. Parker, BA, BM, BChir, MD, FRCR, MRCP, senior lecturer and honorary consultant in clinical oncology and prostate cancer translational research at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust.
“We also know that, at least in men with high-risk disease, longer-term ADT is more effective than short-term ADT,” he said during a presentation. “However, the role of ADT is uncertain in men receiving postoperative radiotherapy after radical prostatectomy, and current guidelines are largely silent on the matter, although ESMO guidelines say ADT may be offered to men having salvage radiotherapy.”
To achieve some clarity, Parker and colleagues examined the effect of adding ADT to postoperative therapy on MFS, in addition to comparing the efficacy of short- vs. long-course ADT in this setting.
Methodology
RADICALS-HD included 2,839 men randomly assigned — prior to receiving postoperative radiotherapy — to no ADT, 6 months of ADT (short-course) or 26 months of ADT (long-course). Patients underwent a second randomized assignment into groups that included no ADT vs. short-term ADT or short-term ADT vs. long-term ADT.
MFS served as the study’s primary endpoint. Secondary endpoints included time-to-salvage ADT, OS and treatment-related toxicity.
Median follow-up was 9 years.
Key findings
The analysis showed short-course ADT plus radiotherapy significantly improved MFS compared with long-course ADT plus radiotherapy (HR = 0.77; 95% CI, 0.61-0.97; 10-year EFS rates, 72% vs. 78%).
Investigators observed delayed time to salvage ADT (HR = 0.73; 95% CI, 0.59-0.91) between the two groups, with no significant improvement in OS (HR = 0.88; 95% CI, 0.66-1.17).
Researchers reported no significant improvement in MFS among those who received radiotherapy alone compared with short-course ADT plus radiotherapy (HR = 0.89; 95% CI, 0.69-1.14; 10-year EFS rates, 79% vs. 80%). Results showed delayed time to salvage ADT (HR = 0.54; 95% CI, 0.42-0.7) between the groups, with no significant improvement in OS (HR = 0.88; 95% CI, 0.65-1.19).
Clinical implications
“When added to postoperative radiotherapy after radical prostatectomy, long-course hormone therapy — compared with short-course — improved metastasis-free survival,” Parker said. “Short-course hormone therapy — compared with no hormone therapy — did not meaningfully improve metastasis-free survival.”
The results, Parker added, appeared consistent across all prespecified subgroups.
References:
Perspective
Back to TopCurrent recommendations in the ESMO guidelines are rather vague, stating that the addition of 6 months to 2 years of additional hormonal treatment may be offered to patients after radical prostatectomy. The results of RADICALS-HD have been eagerly awaited to help clarify this situation.
It's clear from the results that some patients will benefit from short-term ADT vs. no ADT and some from long-term ADT vs. short-term ADT. The next question is how to personalize this therapy. One approach is through genomics — as it has been shown that having a higher genomic classifier score is associated with increased benefit from the addition of hormonal treatment to salvage radiotherapy — but the difference was not statistically significant, and the test is expensive.
What may be even more promising for the prediction of the benefit of adding ADT is artificial intelligence based on pathology slides, as reported by Spratt and colleagues at this year’s ASCO Genitourinary Cancers Symposium.
Until these predictive tests are validated and available, we will have to consider a combination of clinical factors to decide whether to provide additional ADT to these patients. A meta-analysis of subgroups from the relevant clinical trials may help further characterize clinical factors and their combinations for clinical treatment.
Some patients with very high-risk disease after surgery may benefit from further intensification with novel androgen receptor pathway inhibitors. Our goal should be optimal treatment intensification, but only for patients who need it.
References:
Feng FY, et al. JAMA Oncol. 2021;doi:10.1001/jamaoncol.2020.7671.
Spratt DE, et al. Abstract 223. Presented at: ASCO Genitourinary Cancers Symposium; Feb. 17-19, 2022; San Francisco.
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Parker CC, et al. Abstract LBA9. Presented at: European Society for Medical Oncology Congress. Sept. 9-13, 2022; Paris.