Current serum tumor markers (STMs) for testicular germ cell tumor (GCT) are limited by low sensitivity. Growing evidence supports the use of circulating miR-371a-3p as a superior marker for malignant (viable) GCT management. We evaluated the real-world application of serum miR-371a-3p levels in detecting viable GCT among patients undergoing partial or radical orchiectomy.
Serum samples were collected from 69 consecutive patients pre-orchiectomy. Performance characteristics of serum miR-371a-3p were compared with conventional STMs (AFP/ꞵ-hCG/LDH) between viable GCT patients and those without viable GCT on orchiectomy pathology. Relative miR-371a-3p levels were correlated with clinical course. Kruskal-Wallis test and linear and ordinal regression models were used for analysis.
For detecting viable GCT, combined conventional STMs had a specificity of 100%, sensitivity of 58%, and area under the curve (AUC) of 0.79. The miR-371a-3p test showed a specificity of 100%, sensitivity of 93%, and AUC of 0.978. Median relative expression of miR-371a-3p in viable GCT patients was >6,800-fold higher than in patients lacking viable GCT. MiR-371a-3p levels correlated with composite stage (CS) (p=0.006), and, among CS I patients, independently associated with embryonal carcinoma percentage (p=0.0012) and tumor diameter (p<0.0001). Six patients received orchiectomy after chemotherapy and were correctly predicted to have presence or absence of viable GCT by the miR-371a-3p test.
If validated, the miR-371a-3p test can be used in conjunction with conventional STMs to aid clinical decision-making. A positive miR-371a-3p test in patients after preoperative chemotherapy or with solitary testes could potentially guide subsequent orchiectomy or observation.
The Journal of urology. 2020 Aug 28 [Epub ahead of print]
Rohit R Badia, Dreaux Abe, Daniel Wong, Nirmish Singla, Anna Savelyeva, Nathan Chertack, Solomon L Woldu, Yair Lotan, Ryan Mauck, Dan Ouyang, Xiaosong Meng, Cheryl M Lewis, Kuntal Majmudar, Liwei Jia, Payal Kapur, Lin Xu, A Lindsay Frazier, Vitaly Margulis, Douglas W Strand, Nicholas Coleman, Matthew J Murray, James F Amatruda, John T Lafin, Aditya Bagrodia
Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas., Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas., Quantitative Biomedical Research Center, Department of Population & Data Sciences, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas., Dana-Farber/Boston Children's Cancer and Blood Disorder Center, Boston, Massachusetts., Department of Pathology, University of Cambridge, UK., Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Departments of Pediatrics and Medicine, Keck School of Medicine, University of Southern California.