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Please explain the terminology of "first bone metastasis"

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Posted 7/30/2017 7:58 PM (GMT 0)
Could one of you smart guys please explain the difference? Not terribly important, but I am stumped. (someone kindly posted the link somewhere awhile back, but only now I am reading it):
First, their definition: "bone metastasis–free survival (BMFS)"
Then the one that stumped me, page 1:
"median BMFS was 25.2 months and median time to first bone metastasis was 40.8 months" What is the difference???
www.cancernetwork.com/oncology-journal/treatment-nonmetastatic-castration-resistant-prostate-cancer
Treatment of Nonmetastatic Castration-Resistant Prostate Cancer
Oncology Journal, Prostate Cancer, Prostate Cancer
By Jia Luo, MD, Tomasz M. Beer, MD, and Julie N. Graff, MD
April 15, 2016
Posted 7/30/2017 9:02 PM (GMT 0)
These are the endpoints for the trial of Denosumab, the RANK-L drug that you refer to in the article:

The primary end point of BMFS (determined by time to first occurrence of bone metastasis [symptomatic or asymptomatic] or death resulting from any cause, whichever occurred first) and secondary end points of time to first bone metastasis (symptomatic or asymptomatic), excluding deaths

Thus the time to bone metastasis includes death from any cause (including prostate cancer) and the secondary endpoint of time to bone metastasis specifically excludes those with death of any cause. Those who died of any cause before bone metastasis was identified, even if metastasis was elsewhere in the body, were not "Metastatic" for the purposes of this trial of bone only mets measurement. The second group was winnowed by death of any cause, metastasis to other locations, loss to follow up and whatever other issues are out there. It is thus a different and smaller group than group one, the BMFS endpoint which includes every participant. It also includes those who die, regardless of cause. Death itself was the equal of bone metastasis, in other words for the first endpoint which makes the median shorter than the group that ignored death from any cause and measured only those who survived all causes.
This is the study:

]http://ascopubs.org/doi/full/10.1200/jco.2012.44.6716

Post Edited (tarhoosier) : 7/30/2017 3:08:44 PM (GMT-6)
Posted 7/30/2017 10:18 PM (GMT 0)
Dr. Walsh puts it another way....Average mortality after the first bone met is revealed is 5 years....That means half the patients live longer than 5 years and half live less..At the 10 year point, the mortality rate is 95%...This was written before the new drugs Zytiga and Xtandi came into wide use..I suspect you can now add an average of 2 years to those mortality figures...
Posted 7/30/2017 11:25 PM (GMT 0)
I read your question as WHY the difference. Why would median time to first bone met be so much more than median to bone met free survival. Thus my answer above.
Posted 7/30/2017 11:52 PM (GMT 0)
"BMFS was defined as the time to first occurrence of bone metastasis or death from any cause. "

So median time to first bone met was only among those who survived long enough to have an observable first bone met.

However, none of that article applies to you.

The article said...
...bone scan as well as computed tomography (CT) of the chest, abdomen, and pelvis—remain negative for metastatic lesions, this disease state is known as nonmetastatic castration-resistant prostate cancer (CRPC). ...The most common site of disease metastasis is bone, followed by lymph nodes, lungs, and liver.

So when the article says "metastatic," it means both pelvic lymph nodes (N1) or bones (M1) and other distant sites.
Posted 7/31/2017 12:26 PM (GMT 0)
Thanks guys, all clear now.
Posted 7/31/2017 5:43 PM (GMT 0)
Oh Revered Tall One:
To make an unimportant point on an unimportant thread, while I do understand what you mean by "none of that article applies to you," I would say that it can be a general sort of guide in that my lymph node mets only showed up on the nano-iron (Combidex) scan and not on any subsequent scans (I did not have any of the new, sensitive scans yet).
Thus, once I become castrate resistant, my situation might well be similar to that of some of the trial participants, I would think.
Posted 7/31/2017 5:54 PM (GMT 0)
Then it applies to you even less. Everyone analyzed in the studies included in the review article eventually had mets large enough to be discovered by bone scans/CT, which is far more advanced than you are. Non-met CRPC is not a common situation and there is no reason to believe you will someday fall into that category. It is far more likely that larger mets will precede castration resistance.
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