Main Session
Sep
29
PQA 06 - Genitourinary Cancer, Gynecological Cancer, and Health Care Access and Engagement
3378 - Oncologic Outcomes and Toxicity of PULSAR-Based Stereotactic Ablative Radiotherapy (SAbR) with Immunotherapy in Metastatic Urothelial Carcinoma
Presenter(s)
Yash Soni, MD, BS - UT Southwestern Medical Center, Dallas, TX
Y. S. Soni1, B. Tortelli1, R. Hannan2, A. Garant1, D. X. Yang1, R. D. Timmerman1, N. B. Desai3, and X. D. Li4; 1Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, 2UT Southwestern Medical Center, Dallas, TX, 3University of Texas Southwestern Medical Center, Dallas, TX, 4Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
Purpose/Objective(s):
Personalized ultrafractionated stereotactic adaptive radiotherapy (PULSAR) delivers SAbR in temporally separated pulses designed to enhance immune priming. We evaluated oncologic outcomes and toxicity among patients with metastatic urothelial carcinoma (mUC) receiving immunotherapy with either PULSAR-based or conventionally delivered SAbR.Materials/Methods:
We performed a single-institution retrospective cohort study of mUC patients who received SAbR in combination with immunotherapy between 2016 and 2025. PULSAR was defined as SAbR delivered in temporally separated pulses =1 week apart. Conventional SAbR was delivered in standard schedules (1–2 fractions per week). Oncologic outcomes included local control (LC) and progression-free survival (PFS). PFS was defined as time from SAbR initiation to disease progression at any site or death. SAbR and immunotherapy-related toxicities were graded according to CTCAE v5.0. Time-to-event outcomes were estimated using Kaplan-Meier methods and compared using log-rank testing.Results:
Forty-two patients (12 PULSAR vs 30 conventional SAbR) were identified, with similar age (71 vs 69 years), ECOG performance status (PS <=1, 92% vs 80%), visceral disease (42% vs 37%), prior systemic therapy (median 1.5 vs 1.0). and total radiation dose (36 vs 35 Gy) between groups. Treatment intent distribution showed directional imbalance (p = 0.22). PULSAR was more delivered with consolidative intent (50% vs 23%). Conventional SAbR was more delivered for progression (57% vs 42%) or palliation (20% vs 8%). More patients in the PULSAR cohort received enfortumab vedotin in combination with immunotherapy (50% vs 7%, p = 0.004). Treatment duration was longer with PULSAR (median 42 vs 11.5 days, p < 0.001). Local control was high in both cohorts (100% PULSAR, 97% conventional). Grade =3 radiation-related toxicity was uncommon (0 PULSAR, 2 conventional). Grade =3 immune-related adverse events occurred in 3 PULSAR and 4 conventional patients, all outside radiation treatment fields. Median PFS was 10.1 months with PULSAR and 3.77 months with conventional SAbR (log-rank p = 0.22). Multivariable analyses for PFS were not performed given the small sample size and significant imbalance in key baseline variables.Conclusion:
In this single-institution retrospective cohort, PULSAR-based SAbR in combination with immunotherapy demonstrated high local control and low rates of high-grade toxicity, without evidence of inferior oncologic outcomes compared with conventional SAbR. Differences in PFS should be interpreted cautiously given non-random treatment selection, imbalance in treatment intent and different systemic therapy exposure. Nonetheless, these findings support the feasibility of PULSAR-based SAbR delivered with immunotherapy and provide hypothesis-generating evidence to inform prospective evaluation of such combinations in controlled studies.