320 - Initial Results of a Multi-Institutional Phase 1/2 Trial of Focal Dose-Escalated Salvage High Dose Rate Brachytherapy for Radiorecurrent Prostate Cancer (F-SHARP)

A. A. Solanki¹, W. Adams², K. Baldea³, A. M. Block¹, A. Farooq³, A. Garant⁴, A. Gorbonos³, G. Gupta³, R. Joel¹, H. Kang¹, M. L. Mysz⁵, M. Quek³, C. Quick¹, T. N. Showalter⁶, J. S. Welsh¹, M. Woods³, R. Yoo¹, W. Small Jr¹, and M. M. Harkenrider¹; ¹Department of Radiation Oncology, Stritch School of Medicine, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL, ²Biostatistics Core, Clinical Research Office, Loyola University Chicago, Maywood, IL, ³Department of Urology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, ⁴Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, ⁵Loyola University Medical Center, Maywood, IL, ⁶University of Virginia, Charlottesville, VA

Purpose/Objective(s): A third of patients with biochemical recurrence (BCR) after radiation (RT) have intraprostatic radiorecurrence (IPR) on PSMA PET/CT. Patients with IPR have worse metastasis-free survival (MFS) - a surrogate for progression to lethal prostate cancer (pCa). There are limited prospective data on the best management of this growing population. We hypothesized that a dose-escalated focal salvage high dose rate (HDR) brachytherapy approach to treat IPR would be safe and effective. Materials/

Methods: F-SHARP is a multi-institutional phase I/II trial of focal dose-escalated salvage HDR for IPR conducted at 3 centers. Eligibility criteria included a history of localized pCa treated with any form of definitive RT, and biopsy-proven IPR with no regional or distant metastasis. All patients had a PET/CT. Patients received up to 30 Gy in 1-2 fractions (Fx) to a focal target, prioritizing OAR constraints. Primary objective was to determine the acute RT-related grade =3 CTCAE v4.03 GU and GI toxicity rates. Secondary endpoints included all-grade acute and late toxicity, QoL (IPSS and EPIC-26), and biochemical/radiographic disease control and survival measures. Generalized estimating equations were used for toxicity and QoL analyses. The Kaplan-Meier method was used to estimate PSA-relapse-free survival (PSA-RFS), radiographic progression-free survival (rPFS), and MFS. Cox proportional hazards models were used for univariable and multivariable analyses.

Results: From 2017-2023, 62 patients were enrolled. Prior RT included conventional/hypofractionated photons (60%), LDR (24%), protons (11%), and SBRT (3%). Median BCR PSA was 4.7 ng/mL (Range: 2.2-20.3) and time from prior RT was 8 years (Range: 1.4-26.5). Median tumor D98 was 23 Gy (IQR: 20-27), for 1 Fx (n= 24) and 32 Gy (IQR: 30-34) for 2 Fx (n= 38). 5 patients had concurrent hormone therapy (HT). Median follow-up was 26.1 months (95% CI: 21-36). There were no grade =3 acute or late toxicities. Acute/late grade 2 GU toxicity occurred in 58%/63%. Acute/late grade 2 GI toxicity occurred in 2%/3%. Acute/late grade 2 sexual toxicity occurred in 16%/32%. The table shows the proportions of patients with a minimal clinically important decline in each QoL measure. There was no difference between 1 and 2 Fx for the risk of toxicity or worsening QoL (all p > 0.05). 3-year PSA-RFS was 59%, rPFS was 65%, and MFS was 91%. 5 patients required palliative HT. There was no difference between 1 and 2 Fx for any of these events (all p > .05). Patients with PSA =10 ng/mL were more likely to experience any event (HR = 3.9, 95% CI: 1.2 to 12.2; p = .02).

Conclusion: Re-irradiation is a growing indication for RT in pCa. Dose-escalated focal salvage HDR is safe and has encouraging early efficacy. At this time, there is no difference in efficacy or toxicity between 1 vs. 2 Fx. Investigations into clinical/transcriptomic prognostic factors and patterns of failure are ongoing.

Table 1

	IPSS	Urinary Irritation	Urinary Incontinence	Bowel	Sexual
3 months	21%	33%	12%	35%	14%
2 years	16%	37%	30%	48%	22%