To clarify, it's not the best choice for serving applications where Apache works as anything but a proxy.

For what's best, take your pick of any framework that entirely decouples the application directory structure from the routes and keeps the logic for it all completely internalized. All logic for how URI's are handled should be within the application configuration or code. Something written in the target language will probably provide far more benefits than whatever is lost through Apache.

Whether Apache is in the path to your application is irrelevant, whether Apache does anything except note that a request should be handled by another application and hand the entire request off without change is not.

Generally the application itself. Listening on an http port or a unix socket is pretty easy in most modern languages. Then use a normal HTTP server like apache to listen to incoming connections and proxy them on to whatever port on localhost your application is listening to.