It all depends on if some program needs it. For the core system As well as for flatpaks.
In my handy little cheatsheet around the end i got the 3 relevant commands to update, clean unneeded dependances and cache:
flatpak update
flatpak uninstall --unused
rm -rfv /var/tmp/flatpak-cache-*
To get further insight what needs what you can use the flatpak app warehouse.
As a side note: most of the flatpak apps require gnome. Current runtime is 47, many apps are also 46 which is still supported. 45 does not receive security updates anymore, if anything needs it the app has not been updated from the developer for a long time.