I see that Astrid was actually the "strong figure" who put DB back on track. Maybe they didn't their thing "right" when she was in charge, but she might have been their first credible leader in who knows how long. However, even more powerful figure emerged, and, if the Dovahkiin listener is actually canon (and not killing all the killable characters in DB), the guild will have a new renaissance with many shadowy people pouring in. I hope many of those are other than random unnamed students. ;P
You could think that, if murdering the DB was canon, Babette and possibly Cicero would still be left. (Even though Babette surviving was just a gameplay mechanic, it could easily be turned into canon. She's also virtually immortal, so there's a possible character for the next game as well.) The return of the Night Mother could still have happened, just with a different Listener. Might've been Babette, for example.
Then there's the possibility that DB was still alive elsewhere, too. Just barely, like in Skyrim before they brought the Night Mother there. They might just be keeping so low profile that even the Skyrim branch doesn't know about their existence. Or, at least, the ideology about DB should be alive in the minds of many potential assassins throughout Tamriel, even if the cult itself wasn't. Maybe someday the Night Mother would approach one of those, or something. The point is, I still see there's future for them, were they all in Skyrim killed by Dovahkiin or strengthened by him.
Besides, they're so popular amongst players that the writers wouldn't just write them out, you know.
And, who's to say the next TES game will be chronologically later than Skyrim was? They could jump back to Third Era or in the beginning of the Fourth Era as far as we know. Unlikely, I admit, but should be considered a possibility (as far as I know...).