The bills ran a handful of pistol this weekend. Their offense is not based from the pistol set. The NFL is a pass happy league but theres a reason scouts still look for pro style offenses.
In college, many WRs run their routes regardless of the defense, one reason why WRs dont have huge rookie years in the NFL typically. Thats bc in the NFL WRs need to adjust their routes based on shifting coverages.
Now the same goes for QBs who ahve the read the defense on the fly and know the WRs route. This is one reason why teams prefer college QBs who run these types of offenses with success.
Its hard to do to begin with, let alone learn it for the first time at the pro level.
Many spread sets, including the pistol are one read systems making it easy on everyone.