MEN WITH newly diagnosed metastatic prostate cancer do not typically receive treatment to the primary tumor with radiation or surgery. A new analysis of the STAMPEDE trial found that radiation administered to the prostate can improve overall survival in men with newly diagnosed metastatic prostate cancer if they have a low metastatic disease burden. The study showed no survival benefit in men with a higher metastatic disease burden.
These results from a preplanned analysis of the multiarm, multistage STAMPEDE study were presented at the European Society for Medical Oncology (ESMO) 2018 Congress1 and published online in The Lancet to coincide with the presentation.2
“Going forward, prostate radiation should be a standard treatment option for men with newly diagnosed metastatic prostate cancer and a low metastatic disease burden.”— Christopher C. Parker, MD
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“Until now, men with metastatic prostate cancer were only given drugs. We thought that if the cancer had spread, there was no point in treating the prostate itself with surgery or radiation,” explained lead author Christopher C. Parker, MD, of The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom. “In animal models, it has been shown that if you treat the primary tumor, the metastases slow down and animals live longer. We wanted to see if this would be true in men with metastatic prostate cancer, and we hypothesized that the benefit would likely be greater in men with a lower metastatic disease burden.”
He continued, “We think these are robust and reliable findings. Going forward, prostate radiation should be a standard treatment option for men with newly diagnosed metastatic prostate cancer and low metastatic disease burden. Furthermore, we believe the results can be extrapolated to men with pelvic nodal disease alone, for whom androgen-deprivation therapy alone is no longer adequate treatment.”
THE ANALYSIS Dr. Parker presented was from a randomized phase III comparison embedded in the multiarm, multistage STAMPEDE trial to evaluate whether radiotherapy to the prostate improves overall survival in men with newly diagnosed metastatic prostate cancer. The hypothesis was that untreated primary tumors could contribute to overall disease progression and shorter survival in men with metastatic prostate cancer.
The study included 2,061 patients from the United Kingdom and Switzerland who were newly diagnosed with metastatic prostate cancer. The median age was 68 years; the median prostate-specific antigen level was 97 ng/mL; and 18% received early docetaxel treatment at the investigator’s discretion. Metastatic disease burden was characterized as low in 40% and high in 54%, with 6% unknown.
Participants were randomly allocated to standard-of-care treatment consisting of lifelong androgen-deprivation therapy with or without early docetaxel or the same standard of care plus radiation to the prostate. Radiotherapy consisted of two different schedules: daily (55 Gy in 20 fractions for 4 weeks) or weekly (36 Gy in 6 fractions for 6 weeks) based on investigator’s choice.
Radiation to the prostate improved failure-free survival (defined as biochemical failure, local failure, or death) by 34% but did not improve overall survival in the whole group of patients. There were 391 deaths reported in the control arm and 370 in the radiotherapy arm. Three-year survival rates were 62% in the control arm and 65% for the radiotherapy arm.
“The side effects are certainly outweighed by the survival benefit.”— Christopher C. Parker, MD
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High vs Low Metastatic Burden
A HIGHER BURDEN of disease in prostate cancer was defined as ≥ 4 bone metastases, with at least 1 metastasis outside the axial skeleton and/or visceral metastases. The remainder of patients were characterized as having lower disease burden.
The prespecified subgroup analysis showed that radiation to the prostate improved overall survival by just over one-third (32%) in the 819 men with a low burden of metastatic disease. Three-year overall survival rates were 81% in the radiation therapy arm vs 73% for standard of care—an absolute benefit of 8% that was statistically significant (P = .007).
By contrast, no improvement in overall survival was seen with radiation to the prostate in 1,120 men with a higher metastatic burden. Three-year overall survival was 53% vs 54%, respectively.
RADIOTHERAPY TO the prostate was well tolerated, with 5% of patients experiencing grade 3 or 4 adverse events during treatment and 4%, after treatment.
“At this point, the majority of local events seem to be acute radiation toxicity, and there have been few serious late local events from disease progression. More may emerge with longer-term follow-up…. There was a small increase in the risk of bladder and bowel side effects, but they were modest. The side effects are certainly outweighed by the survival benefit,” Dr. Parker said.
Interpreting the Results
“PROSTATE RADIOTHERAPY improves the survival of men with metastatic prostate cancer who have a low disease burden,” Dr. Parker reported. He recommended: “Prostate radiotherapy, in addition to drug treatment, should now be a standard treatment option for men with oligometastatic disease.”
According to Dr. Parker, prostate radiotherapy is a simple technique, widely available, and relatively inexpensive. “It should be easy to implement this treatment,” he noted. He added that study results are also relevant to men with pelvic node–positive nonmetastatic disease (N1, M0), where the addition of radiotherapy to drug treatment could be curative.
“Patients with regional nodal metastasis were not included in our trial, but radiation therapy should be considered standard for men with pelvic nodal disease,” Dr. Parker said.
“Radiation to the primary tumor should also be tested in other cancers in patients with low-volume [oligometastatic] disease,” he stated. ■
DISCLOSURE: The study was funded by Cancer Research UK and the Medical Research Council. The protocol platform is also supported by Astellas, Clovis Oncology, Janssen, Novartis, Pfizer, and Sanofi-Aventis. Dr. Parker is on the advisory board of Bayer and has received speaker fees from Janssen.
1. Parker CC, James ND, Brawley C, et al: Radiotherapy to the primary tumour for men with newly-diagnosed metastatic prostate cancer: Survival results from STAMPEDE. ESMO 2018 Congress. Abstract LBA5. Presented October 21, 2018.
2. Parker CC, James ND, Brawley CD, et al: Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): A randomised controlled phase 3 trial. Lancet. October 21, 2018 (early release online).
Robert G. Bristow, MD, PhD
FORMAL DISCUSSANT Robert G. Bristow, MD, PhD, of the Manchester Cancer Research Centre, Manchester, United Kingdom, called this trial “an exemplar.”
“Radiation to the prostate should be considered standard of care in the setting of hormone-sensitive...!-->!-->