Main Session
Sep
29
PQA 06 - Genitourinary Cancer, Gynecological Cancer, and Health Care Access and Engagement
3238 - Safety and Clinical Outcomes of Combining Radiotherapy with Lutetium-177-PSMA Therapy in Metastatic Castrate-Resistant Prostate Cancer
Presenter(s)
Patrick Carriere, MD, PhD - MD Anderson Cancer Center, Houston, TX
P. P. Carriere1, G. Lee1, P. T. Tran1, S. Cho2, D. S. Surasi2, G. Ravizzini2, A. Zurita-Saavedra3, O. R. Mawlawi4, A. Salem2, P. Pilie3, P. G. Corn3, S. Ramirez1, and C. J. Hassanzadeh1; 1Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 3Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 4Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX
Purpose/Objective(s):
Lutetium-177 [177Lu]PSMA-617 (LuPSMA)– improves outcomes in metastatic castration-resistant prostate cancer (mCRPC). During LuPSMA therapy, patients may require external beam radiation therapy (RT) for symptomatic or progressive lesions. The safety of RT delivered in close temporal proximity to LuPSMA remains unclear with the potential for risks from cumulative dose. We sought to evaluate the safety, toxicity, and outcomes among patients receiving RT for palliation and local control.Materials/Methods:
This retrospective institutional review board approved study of patients with mCRPC treated from 2022–2025 who received =1 cycle of LuPSMA and =1 RT course delivered concurrently within 90 days of LuPSMA. Toxicities were graded per CTCAE v5.0 and recorded per RT course. The primary endpoint was grade =2 toxicity, with cumulative incidence estimated at 90 days from LuPSMA initiation. Secondary endpoints included progression free survival (PFS) and overall survival (OS) from the first LuPSMA cycle. Logistic regression evaluated predictors of grade =2 toxicity. Kaplan-Meier and univariate Cox proportional hazards models assessed PFS and OS.Results:
Of 126 patients who received LuPSMA, 26 patients received RT with LuPSMA within 90 days. EBRT was most commonly delivered to osseous sites (50%), followed by combined bone and visceral targets (46%), with rare treatment to visceral sites alone (4%). Median age was 66 years (IQR 62–72). Median number of LuPSMA cycles was 3 (IQR 2–6). Eighteen patients (40%) received RT within 30 days of LuPSMA, one (2%) received concurrent therapy, and the remainder (27%) within 90 days. Median RT dose was 25 Gy (IQR 20-30) in 5 fractions (IQR 5-10). Grade =3 toxicity occurred in 1/26 patients (4%), consisting of pain flare requiring surgical intervention. No radiation-associated myelitis events were observed, including among patients receiving spinal RT. The 90-day cumulative incidence of grade =2 toxicity was 30.8%, with pain being the most common grade 2 toxicity. On regression analysis, RT timing relative to LuPSMA and number of cycles were not significantly associated with grade =2 toxicity (p>0.05). At a median follow-up of 9.7 months (IQR 5.7-15.2), median OS was not reached and median PFS was 10.9 months (IQR 3.8-11). On exploratory univariate Cox analysis, completion of all six LuPSMA cycles, presence of bone plus visceral metastases vs bone only, and RT timing were not significantly associated with OS or PFS.Conclusion:
In this single-institution cohort, RT combined with LuPSMA was well tolerated. Early survival outcomes were favorable, though time-to-event analyses were limited by small sample size and event number. These findings support the safety of integrated multimodality treatment and provide clinical reassurance for delivering RT in proximity to LuPSMA.