New data from the multi-arm STAMPEDE trial confirm the hypothesis that local treatment of the primary prostate tumour might not only improve local control, but also slows progression of metastatic disease. In fact, in prostate cancer patients with a low metastatic burden, radiotherapy to the prostate was found to be associated with a significant 32% reduction in the risk of death. In contrast, men with a higher metastatic burden did not derive a survival benefit from this approach. For men with newly diagnosed oligometastatic prostate cancer, these data will likely be practice changing and may also be relevant for men with pelvic node positive, non-metastatic disease (N1M0) where addition of radiotherapy to drug treatment could be curative.
The current standard treatment for newly diagnosed men with metastatic prostate cancer consists of drug treatment alone. Although outcomes have improved, patients still die from metastatic prostate cancer within around five years. As such, there is a need for more effective treatment options in this setting. The multi-arm, multi-stage STAMPEDE study included a randomised phase III comparison to test whether radiotherapy to the prostate improves the OS in men with newly diagnosed metastatic prostate cancer. This was based on the hypothesis that primary tumours could contribute to the overall disease progression and a shorter survival in men with metastatic prostate cancer.
The study included 2,061 patients with a median age 68 years who were newly diagnosed with metastatic prostate cancer. They were randomly allocated to standard of care (SoC) treatment, consisting of lifelong androgen deprivation therapy plus early docetaxel from 2016 or to SoC plus radiotherapy to the prostate. The radiotherapy schedule was 55Gy/20f daily over 4 weeks or 36Gy/6f weekly over 6 weeks.
In the overall intent-to-treat (ITT) population, prostate radiotherapy significantly improved the failure-free survival of patients (HR[95%CI]: 0.68[0.68-0.84]) but not the OS (HR 0.92, 95% CI 0.80, 1.06). However, in a prespecified subgroup analysis taking into account the metastatic burden of patients, a significant OS benefit was seen in patients with a low disease burden. In these 819 patients, the 3-year OS rate was 73% with SoC as compared to 81% in the radiotherapy arm. This translates into a statistically significant 32% reduction in the risk of death in favour of the radiotherapy containing treatment arm (HR[95%CI]: 0.68[0.52-0.90]; p= 0.007). Among the 1,120 patients with a higher metastatic burden, the addition of radiotherapy to the primary tumour did not impact the survival with comparable 3-year survival rates (54% with SoC and 53% with SoC plus radiotherapy; HR[95%CI]: 1.07[0.90-1.28]; p= 0.420). For this analysis, higher burden of disease was defined as having four or more bone metastases with at least one metastasis outside the axial skeleton and/or the presence of visceral metastases.
Radiotherapy to the prostate was well tolerated with only 5% of patients having grade 3/4 adverse events during treatment and 4% following treatment. There was a small increase in risk of bladder and bowel toxicity, but these were modest but these side effects are certainly outweighed by the survival benefit
In summary, prostate radiotherapy significantly improves the survival of men with metastatic prostate cancer and a low disease burden. As such, prostate radiotherapy added to standard drug treatment, should now be a standard treatment option for men with oligometastatic disease. In addition, the results of this study are also relevant to men with pelvic node positive but non-metastatic disease (N1M0) where addition of radiotherapy to drug treatment could be curative. On a critical note, one needs to consider that notwithstanding the fact that the study at hand was a large, randomised phase 3 trial, only 18% of the patients received early docetaxel and none received early abiraterone, although these treatments are now part of standard treatment in fit men.
Parker C, James N, Brawley C, et al. Radiotherapy (RT) to the primary tumour for men with newly-diagnosed metastatic prostate cancer (PCa): Survival results from STAMPEDE (NCT00268476). Presented at ESMO 2018; Abstract LBA5_PR.