How would you deliver salvage prostate bed radiation in a patient with a neobladder?

In a situation like this, I think the risks of an adverse event are higher and the chance of cure lower than the average patient. Thus, the anticipated behavior of the cancer will play a strong role in the decision about whether to treat or not. Factors like the Gleason score, risk factors for a recurrence, the PSA doubling time, and the overall health of the patient are always important, but perhaps even more so in this case. In an elderly patient with multiple comorbidities, a focally positive margin of Gleason 3+4 who had a long disease-free interval and a long PSA doubling time, I would probably observe; whereas for a young, healthy patient with high-risk or very high risk disease and a PSA doubling time of <10 months, I would try to treat.

I'd start by trying to find the source of the PSA elevation with imaging (MRI and/or fluciclovine PET). Maybe you'll get lucky and it will be far enough away from the neobladder that you could give a full dose at least to this small focus. Assuming you find nothing or the source is located close to the neobladder, I think you are limited in the dose you can deliver. I have treated the prostate bed to 45 Gy in 1.8 Gy fractions, but I avoid treating the full circumference of the neobladder to that dose to the greatest extent possible, even if it means compromising coverage of the region behind the pubic symphysis. Most recurrences on imaging in this region are adjacent to the vesicourethral anastomosis, and I would limit the superior margin here if that is the case. If you can find a target to boost, I would limit the point dose to the neobladder to 54 Gy in 1.8-2 Gy fractions. Since this dose is low, and unlikely to be curative, I would add ADT for ~6 months for Gleason 7 and longer for Gleason 8-10.