Bone metastases features may predict radiotherapy benefit in prostate cancer
medwireNews: The number and location of bone metastases, as determined by conventional imaging, are associated with the survival benefit of prostate radiotherapy (RT) in men with newly diagnosed metastatic prostate cancer, STAMPEDE trial data show.
Noel Clarke (The Christie NHS Foundation Trust, Manchester, UK) and co-investigators say that “[p]rostate RT was associated with greater overall and failure-free survival [FFS] in patients with only nonregional lymph node [NRLN] metastasis (M1a) or 3 or fewer bone metastases without visceral metastasis.”
The exploratory analysis included data for 1939 individuals (median age 68 years) randomly assigned to receive standard of care (androgen deprivation therapy with or without docetaxel) or standard of care plus prostate RT (55 Gy in 20 daily fractions over 4 weeks or 36 Gy in 6 weekly fractions over 6 weeks) within the STAMPEDE trial’s metastasis M1 RT comparison.
Of these, 82% had bone metastases with or without additional NRLN metastasis, 9% had NRLN metastases only, and 9% had visceral or other metastases.
Clarke and co-authors report in JAMA Oncology that the overall survival (OS) benefit from RT decreased significantly with increasing numbers of bone metastases, with no significant benefit beyond three metastases.
For people with one, two, or three metastases, however, prostate RT was associated with absolute improvements in 3-year estimated OS of 8.5%, 6.2%, and 5.8%, respectively, when compared with no RT.
FFS, defined as the time to biochemical failure, local progression, or prostate cancer death, also decreased significantly with increasing metastases number, with absolute improvements in estimated 3-year FFS rates of 21.5%, 10.1%, 14.2%, and 8.8% in patients with one, two, three, and four bone metastases, respectively.
The researchers also note that there was “a strong indication” of OS benefit from prostate RT among individuals with M1a disease. These individuals had a 7.0% absolute improvement in 3-year OS and a 22.0% improvement in FFS with versus without prostate RT.
By contrast, the addition of prostate RT to standard of care showed no significant OS or FFS benefit among patients with any visceral or other metastasis.
Using this information, Clarke and team created a classification for metastatic burden, with low burden defined as patients with M1a disease or with three or fewer bone metastases without visceral metastasis and high burden defined as all other patients.
They found that individuals with low metastatic burden had a significant 38% lower risk for death and a significant 43% lower risk for a failure event than those with high burden.
The investigators conclude: “Taken together, our study reinforces the predictive role of nonosseous metastatic sites within the metastatic burden criteria.”
They add: “The criteria for low metastatic burden based on conventional imaging, predictive of survival benefit from prostate RT in men with newly diagnosed [metastatic prostate cancer], should now also include men with M1a disease.”
In an accompanying comment, Bridget Koontz (Duke University School of Medicine, Durham, North Carolina, USA) and Thomas Hope (University of California, San Francisco, USA) say the “new analysis of STAMPEDE M1 RT data is important because it provides additional information about who should be offered prostate RT.”
They believe the study “provides confirmation that focusing more aggressive therapies targeting the bulkier sites of disease can improve survival when the systemic burden of disease is low.”
However, the commentators continue: “More work is yet to be done to understand the role of metastasis-directed therapy and the influence of better imaging on quantifying the burden of disease and predicting benefit of RT for metastatic prostate cancer.”
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