Low Metastatic Burden May Point to Radiation Benefit For Newly Diagnosed Prostate Cancer

STAMPEDE findings shed light on the use of radiotherapy for men with newly diagnosed metastatic prostate cancer beginning androgen deprivation therapy

medwireNews: Men with a new diagnosis of metastatic prostate cancer who have a low metastases burden may benefit from the addition of radiotherapy to lifelong androgen deprivation therapy given alone or with upfront docetaxel, suggest STAMPEDE results.

The primary endpoint of overall survival (OS) in the full intention-to-treat population of the phase III trial did not demonstrate a significant advantage with use of 36 Gy given in six weekly fractions or 55 Gy divided into 20 daily fractions over 4 weeks, with a hazard ratio (HR) of 0.92 compared with no radiotherapy, delegates were told at the ESMO 2018 Congress in Munich, Germany. The study was simultaneously published in The Lancet.

However, the 1032 men who were randomly assigned to receive radiation did achieve significantly better failure-free survival compared with the 1029 controls, with a HR of 0.76, said presenting author Christopher Parker, from the Royal Marsden Hospital in London, UK.

Moreover, the researchers identified a significant 3-year OS benefit with radiation among the 40% of participants who had a low metastatic burden (81 vs 73%, HR=0.68), whereas no such association was found for the 54% of men with a high metastatic burden. Six percent of patients had an unknown metastases burden.

For men with a low metastatic burden, receipt of radiation also conferred a greater likelihood of achieving 3-year secondary endpoints of progression-free survival (HR=0.78) and prostate cancer-specific survival (HR=0.65), the STAMPEDE investigators say.

Radiation was “well tolerated”, with grade 3 or 4 events reported by 5% of patients during treatment and a further 4% after radiotherapy was completed. In all, 39% of radiation-treated patients experienced at least one grade 3 event, as did 38% of those given only the standard of care treatment.

“Prostate radiotherapy should be a standard treatment option for men with newly diagnosed disease with a low metastatic burden”, Christopher Parker therefore concluded.

The STAMPEDE trial used the CHAARTERED trial definition of metastases, where four or more bone sites outside the vertebrae and pelvis, and/or visceral metastases was considered a high metastatic burden and all other assessed patients classified as low.

Christopher Parker and colleagues write that there is “uncertainty regarding the optimal definition of low metastatic burden” in prostate cancer, but say the STAMPEDE trial had “almost identical” results when the LATITUDE trial definition of absence of visceral metastases and fewer than three bone sites was applied.

“Exploratory analyses of a broader cohort of patients in the STAMPEDE study will inform the definition of oligometastic disease with the aim of refining patients’ selection for prostate radiotherapy", they say.

Recognising that current definitions of metastatic disease are based on computed tomography and bone scans, they highlight that “[c]aution will be required in extrapolating these results to patients imaged with more sensitive techniques”.

“For example, patients with low metastatic burden on conventional imaging should not be denied prostate radiotherapy because they have additional lesions identified on a [positron emission tomography] scan”, the authors say.

 

References  

Parker CC, James ND, Brawley C.D, et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial Lancet; Advance online publication 21 October 2018.
https://doi.org/10.1016/S0140-6736(18)32486-3  

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) . ESMO 2018 Congress, 19-23 October, Munich, Germany (LBA5_PR). 

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