Easy as 1-2-3.

Top Line: Is bone metastasis burden really predictive of the survival benefit of prostate radiation in men with M1 disease?

The Study: In 2018, the STAMPEDE trial's comparison showed no overall improvement in survival with the addition of prostate radiation to ADT for men with metastatic prostate cancer. However, among the subset of men with “low burden” metastatic disease, 3-year overall survival was significantly improved from 73 → 81%. Low burden M1 disease was defined as < 4 bone mets and no visceral mets on standard imaging. But is the 1-3 bone met definition kinda arbitrary like the old 1-3 brain mets rule for SRS? This exploratory analysis of STAMPEDE sought to specifically determine 1) if the number of bone mets on bone scan is a clinically relevant predictor of the benefit of prostate radiation in men with M1 disease and 2) if a higher threshold of mets exists that still benefits from radiation. They found that, indeed, bone met count as a continuous variable was inversely associated with the overall and failure-free survival benefit of prostate radiation. And the 1-3 bone mets rule turned out to be pretty accurate. Men with 1, 2, and 3 mets had a clear benefit from prostate radiation with 8.5%, 6.2%, and 5.8% absolute improvements in 3-year overall survival and 21.5%, 10.1%, and 14.2% improvements in FFS, respectively. These benefits were less clear with 4-7 mets and clearly absent with >7 mets. A similar benefit was also noted in the subset of men (9%) who had non-regional lymph node-only M1 disease. This data led the authors to revise the STAMPEDE definition of “low burden” disease to: 1-3 bone metastases (regardless of location) and/or non-regional lymph node mets, both in the absence of visceral metastases. This study also leads one to wonder about the importance of node count and the potential added benefit of radiation directed at all sites of low burden M1 disease.

TBL: Men with prostate cancer with 1-3 bone mets and/or non-regional lymph node mets derive an overall and failure-free survival benefit from the addition of prostate-directed radiation to standard ADT. | Ali, JAMA Oncol 2021