@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

@jeff1963 ❝In other words, if Gleason 6 keeps growing, can it eventually metastasize?❞

Yes, but for "normal" prostate cancer, you'd see a rise in PSA first as a warning, and a then a rising Gleason score (e.g. 4+3) before that happened.

Not all prostate cancer is "normal," though, and that's why the 2012 recommendation against routine PSA screening turned out to be so tragically wrong.

Neuro-endocrine prostate cancer is very rare, but it can metastatise while expressing very little PSA (< 2.0, sometimes < 1.0).

Some prostate cancer can also be hyperactive (my word, not science's), escaping the prostate almost immediately, before there are any detectable tumours or enlargement in the prostate itself and setting up shop somewhere else.

The majority of prostate cancer cases (about 95%, I think) follow the well-known path of growing slowly in the prostate and taking years or decades to metastatise, if ever. But since prostate cancer is such a common disease, that still leaves thousands of people with de-novo advanced prostate cancer like mine, which might have been prevented with regular PSA screening.