Radiotherapy Raised to New Standard in Newly Diagnosed Prostate Cancer With Low Metastatic Burden

Chris Parker, MD

When added to standard of care therapy, radiotherapy to the prostate improves overall survival (OS) in men newly diagnosed with metastatic prostate cancer who have a low metastatic disease burden.

In the multiarm STAMPEDE trial, prespecified subgroup analysis of the men with low metastatic disease burden demonstrated a 32% improvement in OS in those who received radiotherapy plus standard of care medical therapy compared with men who received standard of care treatment alone,1 reported Chris Parker, MD, at the 2018 ESMO Congress.

Radiotherapy conferred no survival benefit in the men with a high metastatic disease burden, said Parker, clinical oncologist, The Royal Marsden NHS Foundation Trust, Sutton, UK.

Although outcomes have improved, men still typically die from metastatic prostate cancer within approximately 5 years, so more effective treatment is needed, he said. “We wanted to know if radiotherapy to the prostate might not only improve local control but also slow progression of metastatic disease.

“Until now men with metastatic prostate cancer have always been treated with drugs. It was thought that if the cancer had spread elsewhere, then there was no point in treating the prostate itself with surgery or radiotherapy,” said Parker. “Going forward, prostate radiotherapy should now be a standard treatment option for men with newly diagnosed metastatic prostate cancer with a low metastatic burden.”

STAMPEDE enrolled 2061 patients (median age 68 years) from the UK and Switzerland who were newly diagnosed with metastatic prostate cancer. They were randomly assigned to standard of care treatment consisting of lifelong androgen deprivation therapy or to standard of care plus radiotherapy to the prostate. Early docetaxel was added to the standard of care regimen in 2016. The radiotherapy schedule was 55Gy/20F daily over 4 weeks or 36Gy/6F weekly over 6 weeks.

Prostate radiotherapy improved failure-free survival (HR 0.68, 95% CI 0.68-0.84) but not OS (HR 0.92, 95% CI 0.80-1.06) in the entire cohort of patients.

In the prespecified subgroup analysis, radiotherapy to the prostate improved OS by 32% in the 819 men with a low burden of metastatic disease (HR 0.68, 95% CI 0.52-0.90). The absolute improvement in OS in this group at 3 years was 81%.

OS was not improved with radiotherapy in the 1120 men with higher metastatic burden. Higher burden of disease in prostate cancer is defined as 4 or more bone metastases with at least 1 lesion outside the axial skeleton and/or visceral metastases.

Radiotherapy to the prostate was well tolerated. Five percent of patients had grade 3-4 adverse events during treatment and 4% following treatment. “There was a small increase in risk of bladder and bowel side effects but these were modest. The side effects are certainly outweighed by the survival benefit,” said Parker. “It’s worth saying that prostate radiotherapy is a simple treatment, it’s very well tolerated, and it’s widely available in any cancer center throughout the world.”

Men with regional nodal metastases but not metastatic disease were not included in STAMPEDE, Parker noted. “However, if prostate radiotherapy can improve survival for men with distant metastases, we can be very confident that it would improve survival for men with regional nodal disease,” he said. “There aren’t any trials addressing that question and currently many of these men receive drugs alone. So going forward, prostate radiotherapy should be a standard treatment for these men as well.”

The principal that treating the primary tumor can improve survival in men with metastatic disease should be tested in patients with oligometastatic disease, low burden metastatic disease, or other types of cancer, he added.

Ignacio Duran, MD, from Hospital Universitario Marques de Valdecilla in Santander, Spain, offered his perspective on the findings. He said that although prostate cancer is normally diagnosed as a localized disease in the Western world, 10% of men will present for the first time with metastatic prostate cancer. “Ten percent is a relevant number of gentlemen who are diagnosed every year with newly metastatic prostate cancer,” he said. “We were mentally used to handling these patients in a different way. That way was patting down the main fuel for prostate cancer, which is testosterone. More recently we have added new treatments to that, docetaxel or abiraterone acetate, but we have never considered treating the local tumor in a context of a widespread disease. This is what I think is revolutionary.”

The next step is to determine if combining radiation to the prostate with docetaxel and abiraterone will further improve survival, he said.

Parker CC, James ND, 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 by: ESMO 2018; October 19-23; Munich, Germany. LBA5.

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