I believe an epic questline does lead back to the island. But that's definitely not the same instance as the one you begin in.
Once you left, you can't go back. If you need to complete the collection quests there, you can do so in Greater Faydwer or any other later beginners zone.
Indeed, when you go after Darathar you go back to a special instance of the Isle. Great quest line, btw... you definitely learn your way around Norrath!