Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada
Lucia Nappi , Neetu Saxena , Sara Pautasso , Sylwia Mazurek , Guliz Ozgun , Catarina Kollmannsberger , Max Trottier Chi , Antoine Morin Coulombe , Maryam Soleimani , Kim N. Chi , Bernhard J. Eigl , Peter C. Black , Alan I. So , Martin Gleave , Sean Kern , Siamak Daneshmand , Nabil Adra , Lawrence H. Einhorn , Craig R. Nichols , Christian K. Kollmannsberger
Background: Clinical Stage I (CSI) is the most common presentation of germ cell testicular tumors (GCT) and patients are usually managed with active surveillance, in absence of reliable biomarkers of relapse. Circulating plasma miR371a-3p (miR371) has demonstrated high sensitivity and specificity in advanced non teratoma GCT. However, its operating characteristics and power to detect early relapse are still undefined. Methods: CSI GCT patients enrolled in the British Columbia provincial biobank with available plasma samples after radical orchiectomy were included in this study. Plasma miR371 was qualitatively assessed by RT-PCR. Sensitivity, specificity, negative and positive predictive values (NPV, PPV) and AUC in predicting tumor recurrence were evaluated in the post-orchiectomy blood samples and/or during the follow-up prior to or at the time of the clinically evident relapse. Relapse free survival (RFS) was correlated to post-orchiectomy miR371 status. Results: One-hundred-one patients were analyzed, 35 (34.6%) experienced a disease relapse with a median follow-up of 41 months. miR371 was positive in 22/35 of the relapsed patients. The specificity and PPV were 100% (95% CI: 94.5 - 100 for both), sensitivity 62.8% (95% CI: 44.9 - 78.5), NPV 83.5% (95%CI: 76.7 - 88.6) and AUC 0.81 (95% CI: 0.71 - 0.91). No false positive results were observed. The RFS of the patients with positive post-orchiectomy miR37 was significantly shorter (median: 3.5 months vs. not reached; p<0.0001) compared to the patients with a negative post-orchiectomy miR371 (HR: 16.9; 95% CI: 2.1 - 135.7; p<0.0001). miR371 sensitivity correlated with tumor burden, time between tumor relapse and miRNA testing and histology (nonseminoma > seminoma). Conclusions: miR371 has high specificity and PPV in detecting GCT at an early stage and could be used to predict GCT relapse during surveillance and to guide treatment selection after orchiectomy. Further studies have been planned for validation of miR371 clinical utility.
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Abstract Disclosures
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