A CAP-USAF Cat E just made O-6, so it's not impossible. Same formula as anywhere else: PME, AAD, work the boss recognizes and appreciates. The aforementioned O-6 select spent WAY more time on his Reserve job than several Cat Es combined, took great care of his people, and totally deserved the promotion.
Most Cat Es that make O-5 will do so based off their career/strats/OPRs prior to leaving a more active position. There's plenty of PRF-fodder work to do as a CAP-USAF dude; most don't want to do it because that's why they're a Cat E in the first place.
I've been told explicitly that as long as you can get 20 good years in 21 or 22 (?) years you won't get booted as a twice passed over Major. There was something about it that could mess you up, but most of us wouldn't fall into that.