SPPORT complex.

Top Line: Should men receiving salvage prostate fossa radiation also receive ADT and pelvic nodal radiation?

The Study: RTOG 9601 and GETUG 16 have evaluated the role of long and short course ADT with salvage radiation for prostate cancer. The SPPORT trial not only evaluated the role of ADT but also that of pelvic lymph node radiation. In SPPORT, 1792 men with a detectable PSA between 0.1 and 2.0 after radical prostatectomy were enrolled. They were staged with bone scan and CT. Disease characteristics included positive margins in 50%, pT3b disease in 15%, and Gleason 8-9 disease in 17%. The median time since prostatectomy was just over 2 years, and the median PSA at enrollment was 0.35. Standard treatment consisted of 64.8-70.2 Gy to the prostate fossa. Patients were randomized to the addition of short course ADT (arm 2) or short course ADT and pelvic lymph node radiation (45 Gy). ADT consisted of a combination of an antiandrogen (flutamide or bicalutamide) and a LHRH agonist for 4-6 months with roughly ⅔ receiving 6 months. SPPORT used the Phoenix definition (PSA ≥2 above nadir) to define biochemical failure, and freedom from progression (FFP) was the primary endpoint. At 5 years, the addition of both short course ADT and pelvic lymph node RT incrementally improved FFP, which was 70.9% with prostate fossa RT alone, 81.3% with the addition of ADT, and 87.4% with both ADT and pelvic lymph node RT.  Factors associated with worse FFP were PSA >1, Gleason 8+, seminal vesicle involvement. The rate of distant metastasis and prostate cancer death was lower in arm 3 compared to arm 1. You may recall an exploratory analysis of RTOG 9601 found that those with a lower pretreatment PSA had less benefit from ADT. In SPPORT, a post-hoc analysis found that even those with PSA <0.35 had significantly higher FFP in arms 2 and 3. Another post-hoc analysis found no difference in FFP with 4 v 6 months ADT. So, what about the use of the Phoenix definition for biochemical failure? The rate of biochemical failure using Phoenix was 25.7% in arm 1, 18.0% in arm 2, and 14.8% in arm 3. When an alternative definition was used (PSA≥0.4), the rate of biochemical failure was 43.4% in arm 1, 29% in arm 2, and 23.1% in arm 3. So, even though the rates of failure are considerably higher with a different definition, the differences between arms persisted. While acute grade 2+ toxicity was higher with ADT and pelvic node RT (44% v 36% with ADT v 18% with fossa RT alone), late toxicity was comparable with the exception of late grade 2 heme toxicity. Is a decrease in biochemical failure enough to merit routine short course ADT and pelvic lymph node RT for men receiving salvage radiation? Hopefully, genomic classifiers may inform the former while molecular imaging will address the latter.

TBL: The addition of short course ADT and pelvic lymph coverage reduces the rate of PSA progression among men receiving salvage prostate radiation. | Pollack, Lancet 2021