Testicular Tumour Size and Rete Testis Invasion as Prognostic Factors for the Risk of Relapse of Clinical Stage I Seminoma Testis Patients Under Surveillance: a Systematic Review by the Testicular Cancer Guidelines Panel

CONTEXT: Patients with clinical stage I (CS I) seminoma testis with large primary tumours and/or rete testis invasion (RTI) might have an increased risk of relapse. In recent years, these risk factors have frequently been employed to decide on adjuvant treatment. OBJECTIVE: To systematically review the literature on tumour size and RTI as risk factors for relapse in CS I seminoma testis patients under surveillance. EVIDENCE ACQUISITION: Relevant databases including Medline, Embase, and the Cochrane Library were searched up to November 2016. Randomised controlled trials (RCTs) or quasi-RCTs, prospective observational studies with controls, retrospective matched-pair studies, and comparative studies from well-defined registries/databases were included. The primary outcome was the rate of relapse and relapse-free survival (RFS). The risk of bias was assessed by the Quality in Prognosis Studies tool. EVIDENCE SYNTHESIS: After assessing 3068 abstracts and 80 full-text articles, 20 studies met the inclusion criteria. Although evidence to justify a cut-off of 4cm for size was lacking, it was the most frequently studied. The reported hazard ratio (HR) for the RFS for tumours >4cm was 1.59-2.8. Accordingly, the reported 5-yr RFS ranged from 86.6% to 95.5% and from 73.0% to 82.6% for patients having tumours ≤4 and >4cm, respectively. For tumours with RTI present, the reported HR was 1.4-1.7. The 5-yr RFS ranged from 86.0% to 92.0% and 74.9% to 79.5% for patients without versus those with RTI present, respectively. A meta-analysis was considered inappropriate due to data heterogeneity. CONCLUSIONS: Primary tumour size and RTI are associated with the risk of relapse in CS I seminoma testis patients during surveillance. However, in the presence of either risk factor, the vast majority of patients are cured by orchiectomy alone and will not relapse. Furthermore, the evidence on the prognostic value of size and RTI has significant limitations, so prudency is warranted on their routine use in clinical practice. PATIENT SUMMARY: Primary testicular tumour size and rete testis invasion are considered to be important prognostic factors for the risk of relapse in patients with clinical stage I seminoma testis. We systematically reviewed all the literature on the prognostic value of these two postulated risk factors. The outcome is that the prognostic power of these factors in the published literature is too low to advocate their routine use in clinical practice and to drive the choice on adjuvant treatment in clinical stage I seminoma testis patients.