In the application I referred to, PGO was also used. However, that only applies ...

pclmulqdq on Oct 17, 2021 | parent | context | favorite | on: Bubble sort slower with -O3 than -O2 with GCC

In the application I referred to, PGO was also used. However, that only applies -Os to cold code, and if what you're doing is very branchy, it can help even in the hot path.