@dan06 It's certainly quite possible that a low grade cancer with a limited number of mutations can accumulate additional mutations and evolve into a more aggressive species. This paper might be of interest
https://www.nature.com/articles/s41467-020-18843-5

@dan06 It is both new mutations either de-novo or type 6 cells and missed lesions since a random biopsy misses 99% of the prostate. An MRI followed by fusion biopsy gives a higher probability of sampling existing lesions, but even this will miss many. Progression from 3+4 to 4+3 can occur without new mutations. A 4+3 is when 50%+ are type 4 cells. Since 4 cells are more aggressive the percentage increases as they divide faster than type 3 cells.

@dan06
When I had my proton radiation I asked my R/O if he just radiates the MRI/Fusion biopsies areas or entire prostate.

His reply: "I treat the entire prostate and margins with radiation." "I do this because we may have missed something with the biopsies or the MRI/Fusions. P.C. can be present even at microscopic level that we don't see, or did not do a biopsy on."

Made since and for those of us that had radiation as initial treatment for me glad I has such an experienced and knowledgably R/O. And was, and is, at a major medical institution who specialize in proton radiation for over 20 years. He only does prostate radiation and he said half of all prostate treatments for P.C. he has done at UFHPTI. 20 years of experience and a lot of knowledge learned from direct experience on treating P.C.