3358 - PSMA PET Response Dynamics after 177Lu-PSMA Radiopharmaceutical Therapy and External Beam Radiotherapy
Presenter(s)
A. K. Rao1, H. P. Bagshaw1, M. K. Buyyounouski1, and M. Marar1,2; 1Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, 2Department of Radiology, Stanford University School of Medicine, Stanford, CA
Purpose/Objective(s): Patients with metastatic castrate-resistant prostate cancer (mCRPC) undergoing 177Lu-PSMA radiopharmaceutical therapy (RPT) may benefit from external beam radiotherapy (EBRT) for local disease control and symptom palliation. PSMA PET molecular imaging is used for patient selection and has prognostic value within the 177Lu-PSMA Theragnostics paradigm. This study aims to characterize PSMA PET response to focal EBRT administered in conjunction with 177Lu-PSMA, which has not previously been reported.
Materials/Methods: This single institution retrospective study included mCRPC patients who received EBRT within 6 months of a 177Lu-PSMA treatment course (>2 cycles) between February 2022 and December 2025. PSMA PET characteristics for tumors treated with EBRT were analyzed using MIM software (v7.3.3) for the subset of patients who were treated with 3D technique, completed a full 6 cycle 177Lu-PSMA course, and had PSMA PET scans at least 2 months and 6 months after EBRT.
Results: A total of 40 patients underwent 72 EBRT courses and 190 cycles of 177Lu-PSMA. EBRT most commonly treated spine (N=30, 41.7%) and pelvis (N=21, 29.2%) tumors and included 3D technique (N=44, 61.1%) and IMRT/SBRT/SRS technique (N=28, 38.9%). Post-EBRT PSMA PET was compared to pre-EBRT PSMA PET for 9 3D technique EBRT courses in 8 patients (Table). Baseline PET occurred at a median 1.4 months pre-EBRT (range 0.3 to 4.4) and at pre-RPT (Treatments 1-7), mid-RPT (Treatment 8), or post-RPT (Treatment 9) intervals. Median percent change in PSMA PET SUVmax for EBRT-treated tumors was -69.1% (range -94.3 to -8.9) and -43.9% (range -93.4 to +77.4) at 1st and 2nd post-EBRT imaging timepoints.
Conclusion: EBRT was associated with sustained tumor response on serial PSMA PET imaging in most patients undergoing 6 cycles of 177Lu-PSMA. Forthcoming analyses correlating PSMA PET response dynamics with tumor control and symptom palliation can further optimize combined EBRT and RPT in mCRPC.
Table. EBRT characteristics| EBRT course (patient) | EBRT timing relative to 177Lu-PSMA | Days between most recent 177Lu-PSMA and EBRT START | Days between EBRT END to next 177Lu-PSMA | EBRT site | Dose (Gy) / fractions | Months between EBRT and 1st post-EBRT PSMA PET | % change in lesion SUVmax from baseline PSMA PET to 1st post-EBRT PSMA PET | Months between EBRT and 2nd post-EBRT PSMA PET | % change in lesion SUVmax from baseline PSMA PET to 2nd post-EBRT PSMA PET |
| 1 (A) | Pre-Cycle 1 | N/A | 16 | Spine | 20/5 | 5.6 | -76.0 | 10.5 | -33.6 |
| 2 (B) | Pre-Cycle 1 | N/A | 16 | Pelvis | 20/5 | 5.9 | -74.3 | 9.2 | -19.9 |
| 3 (C) | Pre-Cycle 1 | N/A | 17 | Pelvis | 8/1 | 5.1 | -69.1 | 9.6 | -82.8 |
| 4 (D) | Pre-Cycle 1 | N/A | 93 | Pelvis | 20/5 | 5.7 | -18.4 | 11.6 | -67.0 |
| 5 (E) | Pre-Cycle 1 | N/A | 162 | Pelvis | 12/3 | 3.5 | -11.4 | 9.1 | -77.1 |
| 6 (B) | Between Cycles 1 and 2 | 27 | 15 | Spine | 8/1 | 4.4 | -77.7 | 7.7 | -43.9 |
| 7 (F) | Between Cycles 1 and 2 | 28 | 10 | Pelvis | 20/5 | 2.7 | -94.3 | 15.3 | -93.4 |
| 8 (G) | Between Cycles 4 and 5 | 140 | 40 | Spine | 20/5 | 4.4 | -22.9 | 8.6 | +77.4 |
| 9 (H) | Post-Cycle 6 | 175 | N/A | Lung | 30/10 | 5.8 | -8.9 | 9.9 | +23.8 |