@jeff1963 It’s important to remember what a Gleason score is —> It’s one pathologist’s educated, expert opinion of what is seen under a microscope in the biopsied tissues.

But, being more an art than it is a science, what one pathologist sees as a 3+3, another might see as a 3+4. (Which is why it’s so important to get 2nd opinions on any test, biopsy, or scan that requires a doctor’s opinion or interpretation.)

With a 3+3, all of the cell structures that the pathologist can see under a microscope are all “3” cell structures. What happens with a 6(3+3) Gleason score, is that there may also be some sub-microscopic “4” cell structures that are too small to see, but in time grew large enough to be a visible cell structure in the biopsy samples taken. So, what was a 3+3 eventually becomes a 3+4 as those cells multiply. But, this is not a metastases (i.e., growth distant from the prostate). The “4” cell structures were always there; just too small to see.

In this PCRI presentation, Dr. Scholz mentions that if there is a metastasis of a Gleason 6, that in clinical trials those were shown to have been initially misdiagnosed:
> https://youtu.be/NV8QHzbgamI