Proton Beam Therapy for Testicular Seminoma: Clinical Outcomes and Toxicity From the Proton Collaborative Group Prospective Registry

Introduction: Testicular seminoma predominantly affects young men, and while photon-based radiotherapy achieves excellent disease control, concerns about late effects, including secondary malignancies, have driven interest in proton beam therapy (PBT) as a way to improve dose conformality and spare normal tissue. Prospective clinical data for PBT in seminoma, however, remain scarce. Methods: We reviewed 19 consecutive patients with histologically confirmed testicular germ cell tumors treated with PBT between 2010 and 2024 from the Proton Collaborative Group (PCG) multi-institutional prospective registry. Primary endpoints included overall survival (OS), progression-free survival (PFS), local control, and toxicity graded per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: All 19 patients (19/19, 100%) completed their prescribed radiation course without interruption (median dose 32.8 GyRBE; median 17 fractions). Among 10 patients (10/19, 53%) with evaluable follow-up (median 23.9 months), two-year OS and PFS were both 100% in non-metastatic patients (n=9), with 100% local control (9/9) across the evaluable cohort. One death (1/2 metastatic patients) occurred in a patient with metastatic disease at presentation. Acute toxicities were predominantly grade 1-2 (fatigue, nausea, radiation dermatitis), and all resolved without treatment interruption. No treatment-related grade ≥3 adverse events (0/19) or secondary malignancies were observed. Late toxicities were observed in two of 19 patients (2/19, 11%), with only one late event (grade 1 urinary urgency) attributable to radiation in the non-metastatic cohort. No secondary malignancies were observed during 28.8 person-years of follow-up, comparing favorably to predicted excess rates of two to eight per 100 person-years reported for photon-based approaches. Conclusions: These results support PBT as a feasible and well-tolerated option for testicular seminoma. A longer follow-up is needed to assess secondary malignancy risk reduction.