A large randomized clinical trial, SAKK 09/10, found that a salvage radiation dose of 64 Gy over 32 treatments had equivalent biochemical outcomes compared to 70 Gy over 35 treatments.
They treated 350 patients from 2011 to 2014 at 28 hospitals in Germany, Switzerland, and Belgium. They were treated with either 3D-CRT (44%) or more modern radiation techniques. None had positive lymph nodes. Key patient characteristics were as follows:
- Biochemically recurrent after prostatectomy (median PSA= 0.3 ng/ml)
- Positive margins in 45%
- Gleason score ≥ 8 in 18%
- No detectable tumors
After 6.2 years of follow-up, outcomes were as follows:
- Freedom from biochemical progression (FFBP) was enjoyed by 65% of those who got 64 Gy vs 73% of the 70 Gy group. This difference is not statistically different (p=0.11).
- Local recurrences (only) occurred in 9% of the 64 Gy group vs 2% of the 70 Gy group. This difference is statistically significant (p= 0.005)
- Regional recurrences (only) occurred in 11% of the 64 Gy group vs 17% of the 70 Gy group. This difference is not statistically significant (p= 0.11)
- Distant recurrences (any) occurred in 15% of the 64 Gy group vs 15% of the 70 Gy group.
- In an earlier report, acute urinary toxicity of Grade 2 or greater occurred in 14% of the 64 Gy group vs 18% of the 70 Gy group (not different)
- In an earlier report, acute rectal toxicity of Grade 2 or greater occurred in 17% of the 64 Gy group vs 18% of the 70 Gy group (not different)
- Late urinary toxicity of Grade 2 or greater occurred in 29% of the 64 Gy group vs 30% of the 70 Gy group (not different)
- Late rectal toxicity of Grade 2 or greater occurred in 12% of the 64 Gy group vs 22% of the 70 Gy group (different)
- Patient-reported outcomes were not different between the two dose regimens.
- Using the expanded prostate bed delineation guidelines may improve local control.
- As PSMA PET/CT becomes more widely available, it will be possible to detect more loco-regional cancer for boost doses, and eliminate salvage treatment from patients who already have small distant metastases.
- The use of genomic tests, like Decipher, may aid in selecting patients in whom higher doses are needed. In a subset analysis, among Decipher "high risk" patients, FFBF was 51% for 70 Gy vs 39% for 64 Gy patients.
- There is a clinical trial at UCLA that will determine whether raising the biologically effective dose (BED) using SBRT (34 Gy/ 5 fractions) gives good outcomes compared to historical controls. The BED is equivalent to 85 Gy if given in fractions of 1.8 Gy.
- There is a clinical trial in France that will determine whether adjuvant hormone therapy intensification with Erleada improves results.
- Keeping in mind that very few patients in this trial had Gleason scores of 8-10, and none had detectable gross tumors at or near the prostate, those patients may still be good candidates for dose intensification (as well as adjuvant ADT).