Something I’ve found helpful is to detect the country from the submitting IP (I use Maxmind GeoIP), and watch for trends. Over the years I’ve found some countries with a 100% spam rate (or at least, 100% unconstructive), and I redirect submissions from countries with high spam rates into a manual review area. I’m sure that will be controversial, but it’s had the biggest impact on reducing my spam fighting workload.
Beyond that, I also have a lot of keyword filters for common spam phrases, which I tweak whenever something gets through.
I also tried IP lookups with Project Honeypot and some other spam blacklists, but I ultimately turned them off for too many false positives.