Many years ago I spoke with some of the investigators on NLST. One of them said something like "we always were expecting to find that 5 mm lesion that would grow large and dangerous in the next round but we never found one." Someone at the table pressed on this question -- wouldn't every 30 mm lesion be 5 mm at one point? and he softened a bit saying, "ok there might have been one, but the point is that this didn't really happen." This experience is reflected in LUNG-RADS now where, in a screening population, sub-6mm nodules are just ignored. But going behind the scenes, my impression is that *when the trial was designed* they thought that annual screening would allow them to catch some of these tumors when they were very small and still progressing, but this didn't materialize as expected.
Possible that there's some telephone game happening here, lung screening is not my main thing, but that's what I took from these conversations.
OK, putting that history aside. You expect that if you screen every 5 years, you will catch at least as much per screen as if you screen annually, because you are "accumulating" more of those slower growing tumors. So it stands to reason that a different version of NLST that screened every 5 years instead of every year would have also been positive, probably more positive and with more signal. The problem now is that you have to wait 20 years for results, and nobody wants that. Even if you were going to wait 20 years for results, nobody wants to find p=0.07 at the end and you all look around and say, "if only we listened to Dr. X and screened every year, it would definitely have been positive now."
