We report a case study, highlighting how a novel testis-cancer-specific circulating serum miRNA biomarker (a combined miR-371a-3p and miR-372-3p assay) has the potential to detect testicular cancer relapse prior to clinical evidence of disease as determined by standard diagnostics (axial imaging and serum tumor markers).
A 43-year-old man with clinical stage I seminoma had undergone orchiectomy at an outside institution and elected to follow up with routine surveillance managed by our clinic. For the first 18 months post-surgery, conventional serum tumor markers (AFP, β-hCG, and LDH) remained consistently normal, and scheduled CT scans showed no signs of disease recurrence. At 24 months post-orchiectomy, a routine surveillance CT scan revealed a 4 cm retroperitoneal mass, consistent with relapse. The patient had been enrolled in our prospectively accruing miRNA serum collection study, and post hoc analysis of the serum at the 21-month mark (i.e. prior to detection by standard testing) was positive. Importantly, the patient’s conventional serum tumor markers were within normal limits at the time. The patient went on to receive first-line chemotherapy, given the bulky relapse not amenable to surgical resection with primary retroperitoneal lymph node dissection (RPLND), and achieved a complete response.
Early Detection and Treatment Implications
This case illustrates the potential clinical benefit of incorporating novel miRNA biomarkers into testicular cancer surveillance. Detecting a recurrence earlier, when tumor burden is lower, allows multiple potential treatment options. In particular, primary RPLND may be an option in the setting of low-volume retroperitoneal-only disease and, accordingly, avoidance of first-line chemotherapy. In the case above, had the miRNA assay results been included in routine surveillance (at 21 months), the patient’s relapse may have been detected at a smaller size. For non-bulky (< 3cm) seminoma retroperitoneal masses, treatment options include targeted radiation therapy and primary RPLND along with first-line chemotherapy. However, bulky recurrences necessitate multi-agent chemotherapy, which is associated with the potential for significant acute and long-term side effects. Hence, earlier identification and intervention, guided by an accurate biomarker, might allow certain patients to avoid chemotherapy.
An additional potential benefit to including miRNA in future surveillance protocols is the possibility that it can be used to augment the need for frequent axial imaging. Although MRIs can be considered for surveillance of testicular cancer, regular CT scans carry cumulative radiation exposure and often require contrast, which can be nephrotoxic and associated with significant allergic reactions in some patients. If a miRNA test could confidently indicate relapse or a high likelihood of no relapse, imaging frequency could be tailored based on the test results, as we present in the manuscript for consideration. In our patient’s case, the miR-371a-3p and miR-372-3p assay was the first sign of relapse, and perhaps an earlier CT scan would have identified a smaller mass and afforded him the option of either primary surgery or radiation instead of chemotherapy.
Growing Role of miRNA Markers in Testicular Cancer
This case adds to a growing body of evidence that miRNA markers have a promising role in testicular cancer care. In recent years, multiple studies have shown that serum miR-371a-3p is highly sensitive for the detection of active germ cell tumors, often detecting disease that conventional serum tumor markers miss. Particularly in seminoma patients, who rarely have elevated serum tumor markers, miR-371a-3p has demonstrated significant potential in research settings. The marker has consistently correlated with tumor presence and burden, and in a significant subset of patients, rising miR-371a-3p levels have preceded radiologic relapse by a few months. This “lead time” can be critical. Our case, along with previous studies, exemplifies a future in which germ cell tumor relapses could be detected earlier by incorporating miRNA testing into surveillance.
In conclusion, the case discussed underscores both the potential benefits and challenges of bringing novel miRNA biomarkers into routine practice. Circulating miR-371a-3p and miR-372-3p suggested a disease recurrence that standard surveillance methods eventually found months later – a powerful proof-of-concept for biomarker-augmented surveillance. Had we been able to act on that information in real time, the patient might have avoided the morbidity of first-line chemotherapy. While hurdles like teratoma detection and assay standardization remain, miRNA assays seem poised to become an integral part of testicular cancer surveillance, bridging gaps left by conventional markers and possibly improving patient care. Our case study offers a glimpse of how the future of testicular cancer surveillance might evolve from a standard schedule to a miRNA-informed schedule, helping to ensure that no relapse goes undetected and that recurrence is caught as early as possible.
Written by: Adam Levin,2 Jonathan Huynh,3 Vincent D’Andrea,1 Richard S. Matulewicz1
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
- Cornell University, Ithaca, New York, NY
- Icahn School of Medicine at Mount Sinai, New York, NY