If I don't recognize your number, I immediately send it to voicemail. If it's something I need to worry about, I call back.
My hope is that eventually spam callers will catch on to the fact that they've had no hits on my number and drop me from the list. I assume that no amount of interaction I have with them will get me off the list, so I simply choose not to interact with them.
Broadly speaking, you could also probably set up Do Not Disturb settings on your device, and I'd love it if we could filter calls unless they're from specific people during a specific time (e.g. family calls during work).
Long term, the best way we fight this is with our vote. The current FCC administration seems uninterested in this problem, and I think voting in a new administration may provide different results. Engage with your federal representatives as well!