ASCO GU 2020: Developments in Rare Urologic Malignancies: Are biomarkers going to change the future of testicular cancer?

San Francisco, CA (UroToday.com) At ASCO GU 2020, Lucia Nappi, MD, outlined the role of micro-RNAs as a new biomarker in germ cell tumors (GCTs).

Micro-RNAs are small non-coding RNAs regulating oncogenes and tumor suppressor gene expression. miR371a-3p and miRNA-302/367 clusters are overexpressed in >90% of GCTs, both seminoma and non-seminomas. They are extremely specific (expressed in GCTs and pregnancy only), and not expressed in teratoma. They are well correlated with clinical stage and demonstrate rapid decrease and disappearance after successful treatment.

There have been several studies demonstrating the high performance of miRNAs in GCTS (Table 1).

Table 1 – miRNA performance in studies:

high performance of mirnas in gcts confirmed across several studies

MiRNA371 has been shown to outperform standard CT scan and biomarkers to detect viable GCT, with an AUC of 0.96, sensitivity of 96%, and specificity of 100%, PPV of 100% and NPV of 98% (Figure 1). TO this date, they have presented the attributes of an ideal biomarker (Figure 2).

Figure 1 – miRNA371 outperforms CT and standard biomarkers:

mir371 outperforms standard ct scan and biomarkers to detect viable gct

Figure 2- Is miRNA371 the ideal biomarker?

ideal biomarkers

Dr. Nappi then presented the future S1823 trial which is a clinical utility validation study pf the miRNA371. It is a prospective observational cohort study assessing miRNA371 for outcome prediction in patients with newly diagnosed GCT (Figure 3). Eligible patients are those with clinical stage 1 and stage 2A GCT after orchiectomy. The primary endpoints are establishing a PPV of miRNA371 in predicting active GCT in early stages of real world GCT patients. Additionally, the goal is to establish by how much time (if at all) does miRNA371 expression detection precedes current clinical identification of active germ cell malignancy (imaging and classical markers).

Figure 3 – S1823 miRNA371 clinical utility validation study:

s1823 trial proposal

The potential clinical applications of miRNA in GCTs is substantial, from selecting patients for adjuvant treatment, to identifying patients for curative treatments, and selecting patients for surgery, as seen in Figure 4. According to Dr. Nappi, miRNA371 will be critical in all patient stages (Figure 5).

Figure 4 – Clinical applications of mRNAs in GCTs:

potential clinical applications of mrnas in gcts

Figure 5 – What the future might hold for miRNA371:

towards a mirnas based care model in gcts

Dr. Nappi concluded her talk by stating that miRNAs are potentially useful biomarkers to be used in GCTs and have the ability to change the management of GCTs. They have shown clinical validity in pilot studies, and currently large clinical trials are planned to validate their clinical utility in equivocal clinical settings.

Presented by: Lucia Nappi, MD, PhD, Medical Oncologist and Senior Research Scientist, BC Cancer Agency, British Columbia, Canada

Written by: Hanan Goldberg, MD, Urology Department, SUNY Upstate Medical University, Syracuse, NY, USA, Twitter: @GoldbergHanan, at at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California.

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