Prognostic Significance of Germline <i>DICER1</i> Pathogenic or Likely Pathogenic Variants in Outcomes of Ovarian Sertoli-Leydig Cell Tumor.

Abstract

Sertoli-Leydig cell tumors (SLCTs) are rare sex cord-stromal tumors, representing <0.5% of all ovarian tumors. We analyze the role of germline <i>DICER1</i> status in outcomes of ovarian SLCT. Patients with SLCT were enrolled in the International Pleuropulmonary Blastoma/<i>DICER1</i> Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Medical records were systematically abstracted, and those with known germline <i>DICER1</i> status were selected for analysis. Of 162 patients with SLCT, 60% had a germline <i>DICER1</i> pathogenic or likely pathogenic (P/LP) variant. The adjusted 3-year recurrence-free survival (RFS) was 87.2% (95% CI, 79.4 to 95.8) for patients with a germline <i>DICER1</i> P/LP variant compared with 78.1% (95% CI, 66.4 to 91.9) for those without a germline <i>DICER1</i> P/LP variant (<i>P</i> = .043). The adjusted 3-year and 5-year overall survival (OS) was 93.9% (95% CI, 87.3 to 100.0) for those with a germline <i>DICER1</i> P/LP variant compared with the 3-year OS of 91.3% (95% CI, 83.4 to 100.0) and the 5-year OS of 78.2% (95% CI, 63.8 to 95.9) for those without a germline <i>DICER1</i> P/LP variant (<i>P</i> = .021). Among patients with a germline <i>DICER1</i> P/LP variant, the risk of a subsequent, nonrecurrent event was 36.2% (95% CI, 21.4 to 48.1) within 10 years. Previous/concurrent and subsequent neoplasms were rare among those without a germline <i>DICER1</i> P/LP variant. This cohort study of patients with SLCT demonstrated that those with germline <i>DICER1</i> P/LP variants had superior RFS and OS even when adjusting for other prognostic factors. Beyond prognostic implications of a germline <i>DICER1</i> P/LP variant, germline testing helps identify patients at risk of subsequent neoplasms, including metachronous SLCT.