3352 - Safety of Spine Radiotherapy Delivered within 6 Months of Lu-177 PSMA Radioligand Therapy in Metastatic Prostate Cancer
Presenter(s)
J. Y. Qian, R. A. Weber, A. Sabbagh, M. Pagadala, J. Janopaul-Naylor, C. B. Jackson, H. Nagar, Y. Yamada, D. J. Gorovets, and B. S. Imber; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
Purpose/Objective(s): Lutetium-177 prostate-specific membrane antigen (Lu-177 PSMA) radioligand therapy (RLT) and radiotherapy (RT) are commonly used in metastatic androgen pathway modulation resistant (mAPMR) prostate cancer, yet safety data for concurrent or close-sequence use are limited. We hypothesized that spine RT within 6 mos of Lu-177 PSMA RLT has acceptable rates of severe toxicity.
Materials/Methods: We performed a single-institution retrospective study of patients with mAPMR prostate cancer who received both Lu-177 PSMA RLT and spine RT (conventional RT [cRT] or stereotactic body RT [SBRT]) within 6 mos between 2019-2025. RT targets, doses, sequencing relative to RLT (before, during, or after), and time between modalities were recorded. The primary safety endpoint was CTCAE v5.0 grade =3 adverse events (G3+ AE). Fisher’s exact tests compared G3+ AE by number of spine levels treated, sequencing, and RLT cycles received.
Results: Fifty-four patients (median age 68 yrs [range 52-82]) were included. Median prior systemic therapy lines was 3 (IQR 2-4) and included taxanes (100%), olaparib (24%), platinum (17%), and radium-223 (15%); patients who received endocrine therapy (both ADT and ARPI) and 3 other lines of systemic therapy were defined as heavily pretreated (35%). Prior to RLT, PSMA-avid disease was present in bone (98%), lymph nodes (65%), and viscera (41%). Median RLT cycles given was 2 (range 1-6).
A median of 4 spinal levels (IQR 2–7) were irradiated; 56% received SBRT (most common SBRT doses: 30 Gy/5 fx, 30 Gy/3 fx, 40 Gy/5 fx; for cRT: 20 Gy/5 fx). Median interval between modalities was 47 days. RT was delivered before, during, and after RLT in 52%, 15%, and 33%, respectively. With a median follow-up of 126 days, G3+ AE occurred in 18/54 (33%), and all were hematologic: anemia 14/54 (26%), thrombocytopenia 2/54 (4%), bicytopenia 1/54 (2%), and pancytopenia 1/54 (2%). Of these 18 patients, 14 required transfusions and 2 additionally had G3+ rectal bleeding (rectal D0.1cc: 3.5 Gy [20 Gy/5 fx]; 10.7 Gy [40 Gy/5 fx]). No G3+ vertebral fracture, myelopathy, neuropathy, or esophagitis was observed. G3+ AE rates were significantly higher in patients receiving =3 vs 1–2 RLT cycles (50% vs 18%, p=0.02). Toxicity rates did not differ by RT sequencing (before vs during/after RLT: 25% vs 42%, p=0.25), number of spine levels treated (1–2 vs =3: 25% vs 37%, p=0.53), or by use of SBRT (any SBRT vs no SBRT: 33% vs 33%, p=1).Conclusion: In this cohort treated with spine RT and Lu-177 PSMA RLT, severe toxicity was primarily hematologic with no high-grade spine RT-site complications. G3+ AE were associated with cumulative RLT exposure rather than RT sequencing or extent of spine treatment, supporting the safety of integrating these modalities. Longer follow-up is needed to fully characterize the safety conclusion. Prospective studies should validate these findings and optimize RT/RLT sequencing.