I've had a bunch of Pi cards, running on SD without problems. But a single one suddenly developed a super-hot SD card, this was a brand new Pi which I was just setting up. Got the card out, and that one and the next Pi got a USB SSD and are now using those. That was a bit scary. But as mentioned I've also been running Pi with micro SD as Cups servers for years, with no problems at all.
Sample size of 1, but I ran an RPi4 just fine on a USB thumb drive for about a year.
Still upgraded to an SSD later because I wanted even more storage space (and SSD seemed to have better random IOPS than a thumb-drive), but I'd say go for it.
I don't really know. I assume they would be slower than SSDs though, but I have never measured USB flash. The SSBs get some 300MB/sec on my Pi 4 boards.
