The odds of testicular cancer recurrence are 10 times higher if an investigational liquid biopsy biomarker is detectable after orchiectomy — strongly outperforming standard recurrence predictors in stage I disease, according to a prospective study of 196 men.

When plasma levels of the biomarker, called miR‑371, were undetectable within 6 weeks of orchiectomy, recurrence-free survival was 89% at 2 years, vs only 32% with detectable levels.

“In stage I testicular cancer, post-orchiectomy 371 is superior to existing biomarkers for recurrence, and it has the potential to optimize patient selection for adjuvant chemotherapy,” said lead investigator Ben Tran, MBBS, a genitourinary medical oncologist at the Peter MacCallum Cancer Centre in Melbourne, Australia.

Tran presented the results of the study, dubbed CLIMATE, at the ASCO Genitourinary Cancers Symposium 2026.

MiR‑371 is a microRNA involved in early fetal development; it is largely silenced after birth but reexpressed in seminomas and most nonseminomatous germ cell tumors, except teratomas.

Testing is investigational in the US, but in March 2025, the FDA granted the German company mir|detect a Breakthrough Device Designation for a commercial assay it developed and now markets in Europe.

Following orchiectomy for stage I testicular cancer, men typically undergo active surveillance with CT scans and current, but poorly predictive, serum biomarkers.

Those with high-risk pathologic features are also considered for adjuvant cisplatin-based chemotherapy, but only a minority will recur, Tran said. As a result, most men face the risks of chemotherapy — tinnitus, hearing loss, and secondary cancers decades later, among others — with no benefit.

The hope with miR-371, Tran said, is to identify men who truly need adjuvant chemotherapy while sparing the rest.

To assess the potential, his team enrolled 200 patients (median age, 33 years) at 12 centers in Australia and New Zealand within 6 weeks post-orchiectomy; 196 patients had assays run on baseline blood samples by the time of data cutoff.

The researchers focused their analysis specifically on plasma miR-371 after early testing showed that it performed better than serum measurement. At baseline, miR-371 was detected in 42 (21%) plasma samples.

Over a median follow-up of 18.9 months, there were 40 recurrences, including in 10 (9%) of 117 patients with seminomas and 30 (38%) of 79 patients without seminomas.

In addition to the 10-fold increase in recurrence risk when miR-371 was present at baseline (hazard ratio, 10.28; P < .001), the biomarker proved more accurate at predicting recurrence than conventional pathologic markers of high-risk disease.

Among patients with seminoma, miR‑371 outperformed both tumor size above 4 cm (area under the curve [AUC], 0.86 vs 0.57; P = .02) and Boorman risk group (AUC, 0.86 vs 0.61; P = .03). In the group without seminomas, the biomarker outperformed the presence of lymphovascular invasion (AUC, 0.73 vs 0.58; P = .04) and embryonal carcinoma (AUC, 0.73 vs 0.53; P < .001).

The team is now analyzing miR-371’s performance as a serial measurement in the study population.

Reviewing the results, study discussant Samuel Funt, MD, called miR-371 “the most promising lead to date” for predicting stage I recurrence but stressed that questions remain.

“Are we ready to go back Monday and use this biomarker in the management of clinical stage I testis cancer patients? I would say no,” said Funt, a genitourinary medical oncologist at Memorial Sloan Kettering Cancer Center in New York City.

“There are too many barriers, questions, and potential pitfalls to support its routine use in clinic today,” Funt said. “The assay is being run across a variety of institutions, and each institution uses its own cutoffs [and] analyzes different analytes, and this variability is a barrier.”

However, this study and others do support moving forward with interventional trials, Funt said, adding that he is “eagerly anticipating” the additional CLIMATE data on the role of serial testing.

A European trial, DRKS-00019223, has already reported a predictive AUC of about 0.99 for serial sampling with the German test. However, it didn’t lead to significantly earlier relapse detection than imaging and/or standard serum marker elevations.

CLIMATE was funded by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group and others. Tran disclosed research support, consulting, and/or honoraria from Pfizer, Merck, Amgen, and other companies. Funt reported research support, consulting, travel funding, and/or ownership interests in UroGen Pharma, AstraZeneca, and Roche, among others.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com