Well, Detective Conan is going on twenty years strong without having to recourse to spin-offs or increasingly over-the-top villains, so in theory, I suppose a comic could just limp on indefinitely if there's an audience, haha.
It's obviously a professional published manga, but its run is still damn impressive.
I don't write comics, though I do read them, and I know it bums me out to find one that just burnt out halfway through, especially if there is a big mystery, quest, or romance involved. If it's more an episodic series with little overarching plot, it's still sad to see the series peter out, but not quite as frustrating.
I think on a semi-professional (but not financially supporting) scale, a lot of web-comic artists reach a point where real life starts to become more demanding, and they reach a fork in the road: quit their job and do comics full time, or give up on their comic/website/whatever and put their time into their jobs, spouses, and kids. And if they aren't already making decent money off their comic, the choice is made for them.
On a personal level, and as for writing in general... I had a story I posted online that took me ten years to finish. I had 200 subscribers on a fairly small website where that was a robust number, and by the time I finally posted the last chapter, the number of people still reading was... six.
I don't blame the other 200, I was a TERRIBLE updater! I went over a year without updating on at least one occasion, I think twice. Going 4 or 5 months between chapters wasn't uncommon. Actually, it was a miracle it only took me ten years to finish it. I'm amazed I had any readers at all whatsoever by the end (though my updating schedule picked up with the last 50k of the story with a new stricter writing regimine).
Comics, of course, as very different creatures. There's so much more potentially for infinitally fractaling subplots, and the ability to keep a reader engaged for years on end without driving them insane, which you don't have with novels (you're pushing your luck, George R. R. Martin and Clive Barker).