Quoting the unbound.conf man page:
prefetch: <yes or no>
If yes, message cache elements are prefetched before they expire
to keep the cache up to date. Default is no. Turning it on
gives about 10 percent more traffic and load on the machine, but
popular items do not expire from the cache.
There is no explanation of "popular items". This is always the time where you'll have to look into the source code (so I did this). It's not simple to say this as the situation between "ordinary" DNS and "mesh" DNS is somewhat different, however, at first glance, it seems that all DNS queries are prefetched when they are close to TTL expiration. One could consult total.num.prefetch and compare it to total.num.queries to get some experimental data (unbound-control).
edit See also: [Unbound-users] About the prefetch switch used in the unbound.conf.
This explanation makes it clear that prefetching might not have an effect with caching enabled. It may be a valid point to argue for disabling Pi-hole's cache. However, mind that DNSSEC will not be available without a cache as the cache is integral to DNSSEC validation. The validation requires the use of a whole set of RRsets. The only way to have all those RRsets is to put them in the cache or you'd generate a ton of requests each time. This would surely be disadvantageous.