(UroToday.com) The 2024 American Urological Association (AUA) annual meeting featured a session on testicular cancer, and a presentation by Dr. Julian Chavarriaga discussing miRNA as a liquid biomarker to detect malignancy in small testicular masses. Secondary to the widespread use of scrotal ultrasound, approximately 1-4% of individuals undergoing scrotal ultrasounds are found with incidental small (≤ 2cm) testicular masses, with the vast majority being benign (∼13-21% malignant). Distinguishing between malignant and benign small testicular masses remains a challenge, as neither serum tumor markers nor imaging methods offer reliable predictive capabilities. This study, presented at AUA 2024 by Dr. Chavarriaga, assessed the potential of miRNAs, as liquid biomarkers for predicting germ cell tumors in small testicular masses.
Pre-orchiectomy serum/plasma samples, drawn between 1 day and <6 months before surgery, were analyzed using different miRNA extraction methods (qRT-PCR, DdPCR) and platforms across three research laboratory facilities in three different centers (Portugal, Vancouver, and Toronto). The primary endpoint of this study was the association between miRNA (miR-371a-3p) and the presence of germ cell tumors. Additionally, the authors analyzed miRNAs 372, 373, and 367 aiming to improve the diagnostic performance of miRNA to predict germ cell tumors in small testicular masses. Area under the receiver operating characteristic curve was used to calculate and establish optimal thresholds for miRNAs. Comparison of pre-orchiectomy miRNA and surgical pathology was done using the Wilcoxon rank-sum test.
From 2009 to 2023 there were 65 patients identified with small testicular masses who had banked serum/plasma prior to orchiectomy. This cohort included 41 patients with confirmed germ cell tumors, 20 with benign histology, and four patients who had been on surveillance for >12 months and were deemed to have benign small testicular masses. The median age was 38 years (IQR 29-46), median tumor size was 1.4 cm (IQR 0.9 – 1.9), 77% underwent radical orchiectomy, and 12% underwent partial orchiectomy:
Of the patients with germ cell tumors 27 (67.5%) had seminoma and 13 (32.5%) had nonseminomatous germ cell tumors. Of the benign tumors 31% were sex cord-stromal (6 Leydig and 2 Sertoli cell tumors). The first lab used magnetic beads-based for extraction on serum, with miR371a-3p showing a sensitivity of 67.5%, specificity of 100%, PPV of 100%, and NPV of 62.5%. The area under the receiver operating characteristic curve was 0.774. Dr. Chavarriaga and colleagues then examined plasma with a qRT-PCR extraction kit in the second research laboratory. With a Ct mean threshold of >28, miR371a-3p showed a sensitivity and specificity of 92.3% and 85%, and an area under the receiver operating characteristic curve of 0.932 (95% CI 0.826-0.998; p < 0.0001):
Other miRNAs were not informative.
Dr. Chavarriaga concluded his presentation by discussing miRNA as a liquid biomarker to detect malignancy in small testicular masses with the following take-home messages:
- This is the largest series of small testicular masses with banked blood/serum to date
- miR-371a-3p exhibits remarkable sensitivity and accuracy in detecting germ cell tumors
- Isolation of exosomal/micro vesicle miRNA and the lack of preamplification in the DdPCR might have led to inferior performance, and there is need for further external and internal validation (ongoing work)
- This prospective initiative of miRNA in serum/plasma/semen in small testicular masses is ongoing
Presented by: Julian Chavarriaga, MD, University of Toronto, Toronto, Canada
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 American Urological Association (AUA) Annual Meeting, San Antonio, TX, Fri, May 3 – Mon, May 6, 2024.