Did you also tried to unpack ISO?
I mean extract all files from ISO.
Make once again ISO from extracted files.
Some ISO's after unpacking can take even 50% less space after unpacking.
E.g. Heroes of the Pacific (SLES_534.41) ISO takes ~4,6 GB.
Files of that game after unpacking ISO should take ~2,5 GB.
Now for test you can make an ISO from these unpacked files.
New ISO should take only ~2,5 GB, not ~4,6 GB as it was originally.
I don't remember if it was called fake LBA or something else,
but not all games will support this method.