High and inside.

Top Line: HIgh risk prostate cancer benefits from higher dose, so how high can we go with SBRT?

The Study: Here’s a single institution, phase 1 dose escalation trial from UTSW of 5-fraction SBRT for high risk prostate cancer including whole gland treatment with simultaneous integrated boost and elective nodal treatment. Patients (n=55) had grade group ≥ 4, PSA ≥ 20, or clinical/radiographic T3+ disease. All patients had mpMRI, rectal hydrogel spacer, and intraprostatic fiducial markers. They received neoadjuvant (10-20 weeks) and concurrent GnRH agonist/antagonist and bicalutamide. Bicalutamide was stopped after SBRT and the GnRH agonist/antagonist was continued for a total of 2 years. Alpha-blockers were used during SBRT and 4mg dexamethasone was given prior to each treatment. The prostate and proximal 1cm SVs plus a 3 mm margin were prescribed 47.5 Gy in 5 fractions. Dose escalation was tested for both the pelvic nodes (22.5Gy → 25Gy) and the intraprostatic lesion (50Gy→ 52.5Gy→ 55 Gy), and it was successful through all dose levels without dose-limiting toxicity. The average volume covered by the prescription dose was 93% for the pelvic nodes, 94% for prostate + SV, and 88% for the SIB. Of note, OAR constraints (listed in the supplement) were prioritized over PTV coverage. The authors noted that the urethral constraint limited SIB PTV coverage in the higher dose cohorts. The rate of acute grade 2 GI toxicity was 13% and grade 2 GU toxicity was 25% with no grade 3+ toxicity. There was also no signal of a significant increase in toxicity across dose-escalation cohorts. The rate of late grade 2 GI toxicity was 7% and grade 2 GU toxicity was 20%. There was 1 grade 3+ late urinary retention requiring TURP. This appears to be the highest reported SBRT dose used for prostate cancer. While some may debate the benefit of rectal hydrogel spacer, the outcomes of dose escalation trials like this (compared to their pre-spacer predecessors) might not be possible without the added safety cushion.

TBL: This phase 1 trial delivered 25 Gy elective nodal radiation, 47.5 Gy to the prostate, and 55 Gy to gross disease all in 5 fractions with no major dose limiting toxicity. | Hannan, Int J Radiat Oncol Biol Phys 2021