Corbisiero started England's last two Tests against South Africa and New Zealand and was favourite to do the same against the Scots in four weeks' time.
"His knee's a mess. I couldn't tell you if he's going to play next week or not, and that's been the case since I've been back at the club," said London Irish director of rugby Brian Smith.
"We picked Alex and we expected Alex to play - we've been doing that a lot lately.
"It's very frustrating for us and it's very frustrating for Corbs.
"He's got degenerative knee issues. England have got to manage it, we're certainly doing our bit to manage it and wherever he ends up in the future, it's going to need to be managed."
Corbisiero has played more games for England than relegation-threatened Irish so far this season - a fact that isn't lost on a frustrated Smith.
"You've got to manage the club versus country relationship and we're doing our bit.
"He's played one and a half games for us this season.
"He's a world-class loosehead and it's very disappointing. We've put a lot of resources into that position and we haven't had much value so far this season.
"We certainly hope to get some but the Six Nations is looming and, the way it's gone lately, he's been right for England and not right for London Irish. That hurts him and it hurts us.
"There's not much of a decision to make when a bloke's knee's blown up and he feels he can't play. You can't put a gun to his head and say 'get on the paddock'.
"He's an honest person, he's a good bloke and he's been with London Irish a long time. He desperately wants to play for us.
"It's a very frustrating situation, particularly when you see him play so well for England - that's pretty hard to swallow."