A multicenter prospective validation study of the 3-cm cut-off in stage I seminoma (S3MIPT).

TPS435 Background: Testicular germ cell tumors (TGCT) are the most common solid malignancy in men aged 15 to 35, and Seminoma histology can account for up to half of the cases. Since the latest edition of the American Joint Committee on Cancer (AJCC) staging manual (8th edition, 2018), it is recommended that, only in pure Seminoma, the pT1 category should be subdivided according to tumor size: pT1a for tumors < 3 cm or T1b for tumors ≥ 3 cm. This change was based on large retrospective data that suggested almost a doubling of the risk of relapse at 3-years in pT1b versus pT1a, with a Hazard Ratio of 1.87, 95% confidence interval (CI) 1.15-3.06. So far, there has been no prospective validation for these staging changes and there are no known implications of its use in clinical practice. Furthermore, these changes are exclusive for AJCC since the Union for International Cancer Control (UICC), another widely used staging system, did not change from previous editions (i.e., no pT1 subdivision in pure Seminoma). Tumor size was already recognized as a risk factor for relapse (if tumor size > 4 cm) but not formally used for staging before. Of concern, these are mostly young patients, and despite exceptionally good long-term survival rates, in stage I Seminoma, the general estimation of relapse is about 15% but can surpass 30% — therefore accurate prognostic information is particularly important. This study aims to validate the 3 cm cut-off in stage I Seminoma introduced by AJCC 8th edition. Additionally, the study will allow for the evaluation for current trends of adjuvant options (namely surveillance vs active treatment). Methods: S3MI-PT, or Seminoma 3 cm cut-off Prospective Trial, is a multicenter prospective observational validation study that aims to include at least 300 patients (the estimate includes a 10% loss to follow-up rate as TGCT studies are historically difficult to accrue). Eligibility criteria: male patients ≥ 18 years old diagnosed with clinical stage I pure Seminoma histology (pT1N0M0S0), whose orchiectomy must have occurred after January 2018, the AJCC 8th ed. implementation date, who are willing to sign the informed consent. Demographic and clinical data will be collected, that includes, age at diagnosis, tumor size, rete testis invasion, values for TGCT markers, adjuvant treatment options (surveillance or active treatment) and relapse, if applicable. Exclusion criteria: non-pure Seminoma TGCT staged pT2-T4, pN1-N3, M1, S1-3. Primary endpoint is relapse-free survival at 3 years in pT1a versus pT1b, with two-sided P < 0.05 used to determine statistical significance with a 95% CI, by Kaplan-Meier method. S3MI-PT has been approved by the Ethics Committee. The study is actively enrolling, and all individuals and institutions interested in collaborating can do so by request.