Clinical outcomes of de novo versus relapsed early metastatic testicular seminoma treated with contemporary radiation therapy.

BACKGROUND: Chemotherapy (CHT) or radiation therapy (RT) are first line treatments for clinical stage II testicular seminoma (CS-II). Historically, clinical stage I (CS-I) seminoma was also treated with CHT or RT, but in the past two decades practice has shifted towards active surveillance for CS-Iwith RT or CHT reserved for patients with progression to CS-II. Limited data exist on contemporary RT techniques and patient stratification, i.e. de novo (CS-II at orchiectomy) vs. relapsed (CS-II diagnosed during surveillance after orchiectomy for CS I). We investigated outcomes in CS-II patients treated with RT in the modern era across two institutions.METHODS: A retrospective review identified 73 patients treated with RT for CS-II A or B seminoma between 2001-2022. Recurrence free survival (RFS) was calculated by the Kaplan-Meier method and univariate analyses were performed with Log-Rank or Cox proportional hazard regression. Recurrence was defined as biopsy-proven metastatic seminoma after RT completion. Second malignancies were defined as a biopsy-proven malignancy originating in the prior RT field.RESULTS: Thirty-eight (52%) patients presented with de novo CS-II while 35 (48%) patients had relapsed CS-II. Median follow-up was 4.8 years (IQR: 2.3 - 8.1). Five-year RFS was 82% overall (92% in relapsed patients and 73% in de novo patients). Relapsed CS-II disease had lower recurrence rates following RT compared to de novo CS-II disease. All recurrences occurred outside the prior RT field and were salvaged. Disease-specific survival was 100%. Two second malignancies occurred (prostate, colorectal cancer at 67 months and 119 months post-RT, respectively).CONCLUSION: In patients with CS-II seminoma treated with modern RT, there were no in-field recurrences. Presentation with de novo CS-II is associated with out-of-field recurrence. Subject to further larger-scale validation, our results suggest that compared to CS-II at time of relapse, de novo CS-II may portend more aggressive or micrometastatic disease beyond the retroperitoneum, raising the possibility of benefit from chemotherapy after radiation.