Ben Tran, MBBS, FRACP, on miR-371 as a marker of MRD in testicular cancer

In the following video, Ben Tran, MBBS, FRACP, discusses initial findings from the CLIMATE trial, which assessed the clinical utility of miR-371a-3p (miR-371) as a marker of minimal residual disease (MRD) in clinical stage 1 testicular germ cell tumor (CS1 TGCT). The initial results suggested that circulating miR-371 may serve as a clinically useful biomarker to stratify recurrence risk in patients with CS1 TGCT undergoing active surveillance.¹

Tran is a medical oncologist at Peter MacCallum Cancer Centre in Melbourne, Australia.

In this prospective cohort study conducted across Australia and New Zealand, investigators enrolled approximately 200 patients with stage I testicular cancer managed with orchiectomy followed by surveillance. Tran explained that while most patients are cured with surgery alone, a subset will experience recurrence and require curative-intent chemotherapy. Current clinical risk stratification tools have limited precision, resulting in some patients—particularly those deemed high risk—receiving adjuvant chemotherapy unnecessarily and being exposed to avoidable toxicity. To address this unmet need, the CLIMATE trial evaluated the role of circulating miR-371 as a biomarker of MRD. Blood samples were collected at baseline and serially every 3 months to assess associations with recurrence outcomes.

Overall, baseline miR-371 demonstrated a positive predictive value of 62% and a negative predictive value of 91% in predicting recurrence. Notably, miR-371 outperformed existing clinical biomarkers in both seminoma and non-seminoma populations. Recurrence-free survival outcomes further underscored its discriminatory ability: at 24 months, recurrence-free survival was 32% among patients with detectable baseline miR-371 compared with 89% among those with undetectable miR-371, corresponding to a hazard ratio of 10.28 (P < .001).

According to Tran, these findings suggest potential clinical utility for miR-371 in guiding surveillance strategies. A negative result may provide reassurance of low recurrence risk, potentially enabling de-escalation of imaging intensity, particularly in seminoma. For example, clinicians may feel more comfortable adopting less frequent CT imaging schedules, such as those evaluated in the TRISST study (NCT00589537), which include scans at 6, 18, and 36 months.² However, the role of miR-371 in informing adjuvant treatment decisions remains uncertain.

REFERENCES

1. Tran B, Lewin JH, O’Haire S, et al. Initial results from CLIMATE, a prospective cohort study assessing the clinical utility of miR-371a-3p (miR-371) as a marker of minimal residual disease (MRD) in clinical stage 1 testicular germ cell tumour (TGCT): ANZUP 1906. Presented at: 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium. February 26-28, 2026. San Francisco, California. Abstract 586. https://www.asco.org/abstracts-presentations/256658

2. Joffe JK, Cafferty FH, Murphy L, et al. Imaging Modality and Frequency in Surveillance of Stage I Seminoma Testicular Cancer: Results From a Randomized, Phase III, Noninferiority Trial (TRISST). J Clin Oncol. 2022;40(22):2468-2478. doi:10.1200/JCO.21.01199