3240 - Single-Dose Radiotherapy (SDRT) with Dominant Intraprostatic Lesion Simultaneous Integrated Boost (SIB-DIL) in Unfavorable Intermediate Risk Prostate Cancer: Preliminary Results from a Phase II Trial

Purpose/Objective(s): The dominant intraprostatic lesion (DIL) is the most common site of local recurrence. We hypothesized that a simultaneous integrated boost (SIB) to the DIL would be feasible and safe, potentially improving local control rates in unfavorable intermediate risk patients. We report on acute and late treatment-related toxicity and preliminary PSA outcomes after whole gland 24Gy single dose radiotherapy (SDRT) with a ⁶⁸Ga-PSMA PET-derived concomitant boost of up to 30 Gy.

Materials/Methods:: Between February 2021 and December 2024, 87 patients with unfavorable intermediate prostate cancer were enrolled in an IRB-approved phase II study to receive 24 Gy SDRT with a DIL-SIB identified by ⁶⁸Ga-PSMA PET/CT and MRI planning. Organ motion mitigation was achieved with placement of an endorectal air-filled balloon (150 cc) and a Foley catheter. The PTV included the prostate gland and lower 2/3 of the seminal vesicles with a 2 mm margin. Online tracking with endo-urethral beacon transponders ensured treatment delivery within the 2 mm threshold. Treatment planning was based on 10MV FFF VMAT with a dose prescription of 24Gy to the PTV with dose escalation of the boost volume to 26.4 Gy, 28.8 Gy and 30 Gy. Organ at risk (OAR) sparing was achieved with a 20% reduction of dose to the urethra, rectal wall, urogenital diaphragm and bladder. The neurovascular bundles were also spared whenever feasible. Acceptable SIB coverage was = 80% of the prescribed dose while fulfilling all protocol dose/volume constraints. Genito-urinary (GU) and gastro-intestinal (GI) toxicity were graded according to the NCI CTCAE v.4, and QoL was assessed by EPIC and IPSS questionnaires. Tumor response was assessed by PSA every 3 months during year 1 and very 6 months thereafter. Reassessment MRI were performed at 12 and 24 months. ⁶⁸Ga-PSMA scans were acquired In case of PSA failure.

Results: DIL-SIB doses were 26.4Gy, 28.8Gy and 30Gy in 9, 8 and 70 patients, respectively. Median CTV was 58 cm³ (range 32-110). Median DIL volume was 5.5 cm³ (range 0.3-20.8), representing a median of 9.4% of the total CTV (range 0.6%-36.8%). Acute grade =2 GU and GI toxicities were 45.9% and 21.6%, respectively. There were no cases of grade =3 acute toxicities. With a median follow-up of 19 months (range, 3-46), late G1 GU and GI toxicities were 40.2% and 12.6%, respectively while late G2 GU and GI toxicities were 5.7% and 1%, respectively. No grade =3 late GI or GU toxicities were observed. Median PSA at 36 months for the entire group was 0.23 ng/mL (range 0.02-0.55). So far, 3 of 87 (3.4%) patients experienced a Phoenix definition biochemical failure, two in the 26.4Gy group (1 with a ⁶⁸Ga-PSMA avid DIL recurrence, 1 with systemic progression) and 1 in the 30Gy group (with systemic progression but no ⁶⁸Ga-PSMA evidence of DIL relapse).

Conclusion: These early trial outcomes indicate that a ⁶⁸Ga-PSMA-PET-guided 30 Gy SIB-DIL in addition to a whole gland 24Gy SDRT can be consistently and safely delivered, while maintaining unchanged dose volume constraints for the organs at risk.