First interim analysis of SWOG S1823: Operating characteristics of circulating microRNA 371a-3p (miR371) in predicting active germ cell malignancy (aGCM) in patients (pts) with early-stage testicular cancer.

LBA5003 Background: Circulating miR371 has been reported in retrospective studies as a biomarker with high accuracy for predicting aGCM. However, large prospective data of miR371 in identifying early stage disease are missing. S1823/GCC.1 (NCT04435756) is an international prospective cohort study designed to define the operating characteristics of plasma miR371 in detecting tumor relapse in pts with early stage aGCM managed with active surveillance (AS). Methods: Serial plasma samples for miR371 assessment were obtained within 56 days from new diagnosis of GCM (baseline) and every 6-12 months (according to risk of relapse) during AS, for maximum 3 years or until relapse. Samples most proximate to relapse were analyzed. Control pts were histology-matched 2:1 to cases. miR371 was measured by RT-PCR and expression was analyzed both qualitatively and quantitatively. Sensitivity, specificity, positive and negative predictive value (PPV and NPV) were evaluated to define miR371 operating characteristics. Results: 948 eligible pts were enrolled from June 2020 to May 2024 (median f/u= 32.7 months). The CSI and IIA pts managed with AS (n=630) formed the cohort of interest. At the time of data cutoff, 103 pts (16.3% overall; 14.7% of seminoma; 19.3% of nonseminoma) had relapsed. Results are from the 224 pts selected for the pre-specified interim analysis. PPV/NPV for the whole cohort was 0.66 (95% CI: 0.51, 0.80)/0.90 (95% CI: 0.88, 0.92), for seminoma 0.58 (95% CI: 0.36, 0.80)/ 0.92 (95% CI: 0.90, 0.94), for nonseminoma 0.75 (95%CI: 0.58, 0.92)/0.86 (95% CI: 0.83, 0.89). Sensitivity increased with stage at relapse (IIA,IIB, IIC/III) (p = 0.07) (Table). Conclusions: S1823 achieved the primary objective of defining the operating characteristics of plasma miR371 during AS. In aggregate, S1823 results showed high specificity and NPV suggesting potential clinical utilities of miR371 in managing pts with germ cell tumors. Future miR371-informed interventional trials to integrate miR371 in clinical practice are either underway or planned. Clinical trial information: NCT04435756 . Operating characteristics of miR371. Group N (Cases; Controls) Sensitivity (95% CI) Specificity (95% CI) Median time to relapse (mo) 1 Median miR371 at relapse (log RQ) 2 Overall 224 (69; 155) 0.54 (0.42, 0.65) 0.94 (0.90, 0.97) 5.8 17.17 Seminoma 108 (33; 75) 0.52 (0.35, 0.69) 0.93 (0.88, 0.99) 7.4 16.89 Nonseminoma 116 (36; 80) 0.56 (0.39, 0.72) 0.94 (0.88, 0.99) 5.3 17.50 Low-risk 184 (48; 136) 0.52 (0.38, 0.66) 0.93 (0.89, 0.98) 6.6 17.15 Moderate-risk 40 (21, 19) 0.57 (0.36, 0.78) 0.95 (0.85, 1.00) 4.1 17.27 Stage at Relapse 3 IIA 23 0.39 (0.19, 0.59) — 6.8 16.89 IIB 28 0.57 (0.39, 0.76) — 5.7 17.32 IIC/III 16 0.69 (0.46, 0.92) — 5.3 17.37 1 From orchiectomy; 2 Amongst miR371+ cases; RQ: relative expression; 3 Stage at relapse unavailable for 2 pts whose r