There are PSP games that use raw addressing outside the ISO filesystem? It is common enough on the PS2 and not unheard of on the PS1 (where it usually gets termed LBA addressing or something like that, probably where the name originated) but I had not heard it was the case on the PSP, give or take some of the binary stuff.
To second Gemini's statement: I have only experience with a single game, which uses OS calls to create a virtual file out of raw offsets in the ISO. (Ex: sound + image data have been packed together in a single file, maybe for the sake of making things harder for us?) So opening the file is not efficient because the file itself is too big, but the game mounts a chunk of memory as a file through standard OS calls.
(The game is Super Robot Taisen A(dvance) Portable. You can mark it as such.
A way to see this happen is to de-ISO the file structure (through UMDGen, standard stuff) and to try to open the main directory to launch the game (from ppsspp). If it starts, then you don't have this problem. If it doesn't start, then the game does not use only the files, but also the offsets in the ISO.
Again, I'm just rehashing stuff I was explained by a good guy.
Don't credit me for that.