What fractionation regimen do you use for combination EBRT and HDR for high-risk prostate cancer?

There is a range of appropriate HDR boost fractionation options.

The 2018 NCCN Guidelines list the following options:

45-50.4 Gy + 10.75 Gy x 2

37.5 Gy (2.5 Gy fractions) + 12-15 Gy

RTOG 0815 (allows brachy boost as an option): 45 Gy +10.5 Gy x 2

RTOG 0924 (allows brachy boost as an option): 45Gy+ 15Gy x 1

The data for 15Gy x 1 is mostly strongly supported by the long term follow up from Gerard Morton's group. They compared 45Gy+ 10Gy x 2 vs 37.5Gy (2.5Gy fractions) + 15Gy showed similar PSA control and a low rate of long term toxicity with 15 Gy x 1 boost regimen‚.

So I think that a 15 Gy boost after 45 Gy is a very reasonable HDR boost fractionation as would a two fraction boost of 10.5 Gy.

The best evidence for fractionation schedule in combination with 15 Gy HDR boost is the 37.5 Gy in 15 fraction schedule. In my practice at UVA, I start with the prostate HDR boost (15 Gy in 1 fraction), which allows me to place prostate-rectal spacer at time of brachytherapy. Then, I use 45 Gy in 1.8 Gy fractions if I am treating pelvic lymph nodes or 37.5 Gy in 15 fractions if I am not.  Of course, the best thing to do is to enroll these patients on RTOG 0924, which I try to do as much as possible. I agree with @Dr. First Last.