ASCO 2018: Circulating miR-371a-3p for the Detection of Low Volume Viable Germ Cell Tumor: Expanded Pilot Data, Clinical Implications and Future Study

Chicago, IL ( Testicular cancer remains a highly curable disease with an established treatment algorithm. However, there are a subset of patients with recurrent disease for whom management can result in significant clinical impact – overtreatment in this population has important long-term complications, as many of these patients are young me with long life expectancy.

One particular area that still requires better definition and patient selection is the patient with a post-chemotherapy residual mass. Patients treated with chemotherapy who have a residual mass, oftentimes in the retroperitoneum, potentially harbor residual viable disease – however, the remainder of men have fibrosis (which does not require treatment) or teratoma (which does require treatment, due to risk of growing teratoma syndrome or malignant teratoma). Unfortunately, we have no good way to identify the patients that require treatment beyond clinical parameters which suggest higher risk of viable disease. In seminoma, PET imaging may be able to assist in the evaluation, but there is no great radiographic options in NSGCT.

Similarly, while active surveillance in clinical stage 1 disease has become a mainstay of therapy, particularly in North America, patients with slowly growing retroperitoneal masses face a similar conundrum. Being able to better select patients with true viable disease may help minimize overtreatment.

One such promising biomarker is a micro-RNA miR-371a-3p (miR371) extracted from plasma of patients. Obviously, as a blood based marker, this would make decision making much more straightforward. Early preclinical work has been promising.

In this study, 77 patients’ blood samples with GCT were analyzed by RT-PCR and relative expression calculated by the 2-ΔΔCt method with appropriate negative and positive controls. The goal of the study was identify the sensitivity and specificity of miR371 to the presence of relapsed/residual NTVGCT (non-teratoma viable GCT).

Of the 77 patients, there were 94 blood samples. The breakdown of the patients analyzed were: 42 Clinical stage 1 (CS1) and 35 metastatic (of whom 24 had post-chemotherapy residual disease PCRD). Among CSI patients, 9 relapses occurred.

Looking at miR371 results:
In the CS1 population: miR371 was positive in 8/9 patients with confirmed relapses. Among those without relapses, 9 had borderline enlarged nodes but 8 had negative miR371.

image 8

For the metastatic pts, miR371 was positive in 19/21 pts pre-chemotherapy and became negative in all post-chemotherapy. 3 miR371 negative pts (1 CSI and 2 metastatic) had pathologically confirmed primary teratoma.

image 8b

miR371 was negative in all the pts with PCRD (n = 24) and no residual NTVGCT was detected in any of those patients by either pathology (n = 17) or clinical follow-up (n = 7).

image 8c

Based on this, the sensitivity and specificity were 96% and 98%, respectively across the entire cohort of samples in detecting the presence of relapse or residual NTVGCT. Both internal (Cohort #2) and external (Vancouver Prostate Cancer Centre) validation studies have been performed with excellent concordance. Further details were not provided regarding the internal and external validation studies.

However, once main weakness is its inability to detect teratoma – which may still impact management and require intervention. The authors accept this weakness, but it still remains a very strong biomarker of viable disease.

Author(s): Lucia Nappi, Brock O Neil, Siamak Daneshmand, Robert James Hamilton, Ricardo Romao Nazario Leao, Marisa Thi, Kim N. Chi, Martin Gleave, Bernhard J. Eigl, Peter C. Black, Alan I. So, Daniel Khalaf, Christian K. Kollmannsberger, Craig R. Nichols

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA
email news signup