Presenter(s)
J. Starner, A. Coelho, S. E. Sim, and L. Potters; Northwell, New Hyde Park, NY
Purpose/Objective(s): Despite widespread adoption of SBRT for localized prostate cancer, consensus on optimal dosing is lacking. This knowledge gap is striking given that focal dose escalation improves outcomes. We present long-term prospective data from a dose-escalation trial addressing whether whole-gland SBRT dose intensification enhances tumor control without unacceptable toxicity.
Materials/Methods: Between 2011–2016, we conducted a prospective dose-escalation trial (Protocol NSLIJ-0839, IRB-approved). Patients with localized intermediate-risk prostate cancer were assigned to sequential dose cohorts of 40 Gy, 45 Gy, or 50 Gy in 5 fractions delivered every other day with mandatory safety review before each escalation step. All plans underwent physician peer review and physics verification of dose constraints, with fiducial markers and MRI fusion used for target delineation. No patients received a rectal spacer, and androgen deprivation therapy was not utilized. Treatment used IMRT/VMAT with 6–10 MV photons under daily CBCT image guidance. Patients were monitored with PSA every 3–6 months and structured toxicity assessments at 1, 3, and 6 months, then annually, with minimum 30-month follow-up required. Endpoints included PSA nadir, biochemical recurrence (Phoenix definition), and toxicity (CTCAE v6.0). Welch's t-tests were used for continuous variables and Fisher's exact test for categorical comparisons (p<0.05).
Results: 23 of 29 enrolled patients were eligible, distributed as 40 Gy (n=9), 45 Gy (n=8), and 50 Gy (n=6), with median follow-up of 97 months (range 31–172). Mean PSA nadir showed significant stepwise reduction from 0.55 ng/mL at 40 Gy to 0.10 ng/mL at 45 Gy (p=0.008) and 0.05 ng/mL at 50 Gy (p=0.004), plateauing between 45 and 50 Gy (p=0.295). Dichotomized analysis revealed mean nadir of 0.08 ng/mL for =45 Gy versus 0.55 ng/mL for 40 Gy (p=0.006). Biochemical recurrence differed significantly: 33% (3/9) at 40 Gy versus 0% (0/14) at =45 Gy (p=0.04). Five-year biochemical relapse-free survival was 67% and 100%, respectively. Toxicity analysis revealed no dose-related increase in adverse events. Grade =2 genitourinary toxicity was equivalent across cohorts at 56%, 63%, and 67% for 40, 45, and 50 Gy (p=0.92). No grade =3 events occurred. Time to grade 2 toxicity was comparable across cohorts (all p>0.1).
Conclusion: Dose escalation from 40 to 50 Gy in 5-fraction SBRT yielded clear therapeutic benefit: biochemical recurrence was 33% at 40 Gy versus 0% at =45 Gy with lower PSA nadirs. No grade =3 toxicity occurred despite follow-up approaching 8 years without rectal spacer use. These findings extend the principle that dose escalation improves prostate cancer control into the ultra-hypofractionated setting, while the toxicity profile at 50 Gy suggests the therapeutic ratio remains favorable at higher biological doses. Although limited by sample size, these data support further investigation to define optimal SBRT dosing across risk groups.