Chris Parker, MD, discusses the clinical implications of STAMPEDE and how radiotherapy fits into the treatment paradigm for these patients.
Chris Parker, MD
Radiotherapy should be a standard treatment option for patients with newly diagnosed metastatic prostate cancer who have a low metastatic burden, said Chris Parker, MD.
In the multi-arm, phase III STAMPEDE trial, one arm of which was presented at the 2018 ESMO Congress, patients were randomized to receive either the standard of care or the standard of care plus radiotherapy. Standard treatment consisted of lifelong androgen deprivation therapy or docetaxel, and radiotherapy began ≤8 weeks after randomization or the introduction of docetaxel. The primary endpoints of the trial were failure-free survival (FFS) and overall survival (OS).
In the general cohort, radiotherapy improved FFS (HR, 0.68; 95% CI, 0.68-0.84), but not OS (HR, 0.92; 95% CI, 0.80-1.06). However, in a subgroup analysis of patients with low metastatic burden (n = 819), OS was improved by 32% (HR, 0.68; 95% CI, 0.52-0.90).
Additionally, there was no benefit observed in patients with high metastatic burden (HR, 1.07; 95% CI, 0.90-1.28).
In an interview with OncLive, Parker, who is the lead author of the study and a consultant clinical oncologist at The Royal Marsden NHS Foundation Trust in the United Kingdom, discussed the clinical implications of STAMPEDE and how radiotherapy fits into the treatment paradigm for these patients.Parker: Men with metastatic prostate cancer have always been managed with systemic treatment only. They have not had specific treatment of the prostate unless they had symptoms of progressive disease. In terms of radiation therapy and surgery, it was palliation only. In some preclinical models, it looks like when you treat the primary cancer, the metastases actually slow down and you can improve survival. That was the hypothesis we wanted to test in this trial of men with newly diagnosed metastatic prostate cancer. Metastatic disease is, sadly, incurable and the average survival is around 4 years. There is clearly scope to improve that considerably. Radiotherapy is a very simple treatment and it is very well tolerated, so if it works, it is an important addition to treatment. The trial included just over 2000 patients and they were randomized to receive drug therapy alone or drug therapy plus radiation to the prostate. The primary endpoint was OS, and it was significantly improved by radiotherapy. The hazard ratio was 0.9. However, we did a prespecified subgroup analysis according to metastatic disease burden. In patients with high metastatic disease burden, the trial was completely negative. In patients with low metastases, we saw a benefit—about a 30% improvement in OS. I should perhaps start by saying some people are skeptical about subgroup analyses in general, but this particular subgroup finding is robust, and one can be confident about it. Our group meets the standard criteria in evaluating subgroup effects. In the future, prostate radiotherapy should be a standard treatment option for men with newly diagnosed metastatic prostate cancer and a low metastatic burden.
There is a second interesting message as well, and that includes men with pelvic node-positive prostate cancer. They were not included in the trial, but if you think about it, prostate radiotherapy improved survival in men with distant metastases; it should surely improve survival in men with regional metastases.
There is a third, more speculative message. That is, we have proven the principle that radiotherapy to the primary tumor improves survival. It is quite possible that this approach will be applicable to metastatic disease in other cancers.
Our findings are sufficient to change clinical practice. When patients come to the clinic with newly diagnosed metastatic prostate cancer with low metastatic burden, they should receive radiotherapy. Going forward, there are a couple of other questions we should ask. Is there potential for radiotherapy to oligometastases? Also, can we expand this to other solid tumors?
Parker CC, ND James, C Brawley, et al. Radiotherapy (RT) to the primary tumour for men with newly diagnosed metastatic prostate cancer (PCa): survival results from STAMPEDE (NCT00268476). In: Proceedings from the 2018 ESMO Congress; October 19-23, 2018; Munich, Germany. Abstract LBA5.