Last time I was on submission, I got plenty of complimentary rejections, but I didn't make it to even one acquisition meeting or one step "up the food chain"... So many possible stages for things to fall apart on.
I've been through this twice with agent repped books via my current agent, and twice with another agent circa 1988--1991. I think the worst pain you ever feel is when you come to the end of the sub trail with a book that you and your agent adores. You're bolstered up during the entire process with a glimmer of hope, thinking that just one editor will feel the same way about it and go to bat for you. But when 18 of the most powerful and influential editors give it the ax, something inside of you dies and you begin mumbling to yourself. "If these giants rejected me outright, then there's no hope for this--this book really is shit."
That's where you could be wrong. That's the time when you have to administer the chest thump and begin CPR. Not on your book per se. But on you. (I swear, I'm going to devise a triage thread for orphaned books!) If you believe in that book, you'll hit the sub trail again. With a vengence. It ain't easy, but it CAN be fun, and you can get some very helpful feedback from editors who take the time to analyze your story and shoot the shite with you.
The Lupus Strain received 37 rejections before it was offered a contract.
Gate Walker pulled 19 rejections before it hit. (Agent didn't even like this book). It was offered another contract soon after.
Planet Janitor ran through 41 rejections before it sold. Even received a nice little advance on this one, but I voided the contract before it went to print. It's now sitting with another small press who is half way through it and loving it. I do expect a sale on this one.
I'm just saying it's not the end. When and if you do get an offer from a small or independent publisher, YOU'VE GOT TO WORK THAT CONTRACT. Don't be afraid to change or add clauses. Or you can have your agent rip it a new one. And for gawd's sakes, ask for an advance EVERY TIME--something reasonable and within their budget. You just might get it! It also demonstrates your self-value.
Your alternative is to back-burner the manuscript for a year or so. In that time, you can change the title, rename the characters, tweak the plot, revise and polish. You can use a pseudonym, if it makes you feel any better. The point is, you're going back out into the world with that book in stealth mode. It should be significantly reworked to the point where it's not instantly recognizable, just in case in lands on the same editor's desk. (Important: huddle with your agent if you choose this route--you can decide on precisely what to do. He/she will also know if editor positions have been changed in a year's time, and that means new eyes on an old manuscript.
Just never say it's the end. You've got options.
Tri