Plasma miR371 as Reliable Biomarker for Testicular Cancer Surveillance

Testicular Cancer: Testicular CancerTesticular germ cell tumors (GCT) often present in clinical Stage I (CSI), requiring careful surveillance to monitor for relapse. However, the lack of reliable biomarkers has posed a challenge in identifying early signs of relapse. New research presented at the 2023 ASCO Annual Meeting focused on plasma miR-371a-3p (miR371), a potential biomarker demonstrating high sensitivity and specificity in advanced non-teratoma GCT. The recent long-term follow-up analysis aimed to evaluate the operating characteristics of miR371 in detecting early relapse in CSI GCT patients (J Clin Oncol 2023; doi: 10.1200/JCO.2023.41.16_suppl.5006). The study, conducted with patients enrolled in the British Columbia provincial biobank, included those with available plasma samples after radical orchiectomy. The qualitative assessment of plasma miR371 was performed using RT-PCR. Lucia Nappi, MD, PhD, and her research team evaluated the sensitivity, specificity, negative and positive predictive values (NPV, PPV), and area under the curve (AUC) to determine the predictive power of miR371 in detecting tumor recurrence. Additionally, the post-orchiectomy miR371 status was correlated with relapse-free survival (RFS) in the patients. In total, 101 patients were included in the analysis, with a median follow-up of 41 months. Among them, 35 patients (34.6%) had disease relapse. miR371 was found to be positive in 22 out of the 35 relapsed patients. The specificity and PPV of miR371 were both 100 percent, indicating a lack of false-positive results. The sensitivity was determined to be 62.8 percent, while the NPV reached 83.5 percent. The AUC value was calculated to be 0.81, indicating a promising diagnostic performance. Notably, the patients with a positive post-orchiectomy miR371 had significantly shorter RFS compared to those with a negative miR371 result. The median RFS for the miR371-positive group was only 3.5 months, highlighting the potential of miR371 as an early indicator of relapse. The hazard ratio for relapse in miR371-positive patients was 16.9. Moreover, the sensitivity of miR371 correlated with tumor burden, time between relapse and miRNA testing, and histology with non-seminoma tumors demonstrating higher sensitivity compared to seminoma tumors. To discuss the implications of the study and the miR371 expression as a biomarker, Oncology Times chatted with lead study author, Lucia Nappi, MD, PhD, a medical oncologist and senior research scientist at the Vancouver Prostate Centre. Oncology Times: What are the implications of these findings for clinical practice? Nappi: “Our data confirmed a very high-positive predictive value and specificity (100%) and a high-negative predictive value (83%) in patients without evidence of tumor recurrence or at a very early stage of the tumor. This means that a positive miR371 after the orchiectomy almost certainly predicts the occurrence of a relapse, while a negative result rules out a recurrence of cancer in 83 percent of the patients. If these data are validated in a larger patient sample, we could think of using this biomarker after the orchiectomy to plan the treatment (e.g., surveillance vs. surgery) or during the surveillance to diagnose a very early tumor recurrence and, therefore, use less toxic treatment options.” Oncology Times: What further research is needed to fully understand the potential of miR371 expression as a biomarker for detecting early relapse in patients with testicular germ cell tumors? Nappi: “The main limitations of our study are the limited number of patients analyzed and the lack of longitudinal blood samples for most of the patients. Clinical trials enrolling a larger number of patients with pre-defined time points for longitudinal blood samples collection will overcome these limitations and be used to validate the operating characteristics of miR371 in detecting minimal residual disease or early relapse in CSI testis cancer patients. “There are two clinical trials currently opened and actively enrolling patients that will define the accuracy of miR371 in detecting early relapse and the timing of miR371 positivity during the surveillance. The SWOG S1823 trial (NCT04435756) is opened in >200 centers in the U.S. and in Canada through the Canadian Cancer Trials Group and has enrolled 725 of the 956 planned patients. The first interim analysis is expected next year. “The Children's Oncology Group AGCT 1523 trial (NCT03067181) has an optional biomarker correlative component that will also analyze the serum miRNAs profile of pediatric and adult patients with testicular cancer with early or advanced stage of disease, on surveillance, or receiving chemotherapy. Other studies using the miR371 status post-orchiectomy for treatment planning are under development, such as a clinical trial that will allocate patients to either surveillance or primary [retroperitoneal lymph node dissection] RPLND based on post-orchiectomy miR371.” Oncology Times: How might the use of miR371 expression as a biomarker impact the management of patients with testicular germ cell tumors in terms of surveillance protocols and treatment decisions? Nappi: “The miR371 has many potential clinical applications if its operating characteristics will be confirmed in the before-mentioned clinical trials. First, miR371-positive patients immediately post-orchiectomy could be treated with less long-term toxic regimens, such as surgery. We have several clinical trials that demonstrate the high activity of primary RPLND in patients with Stage IIA seminomas and we already had data for early-stage non-seminoma patients. Surgery is associated with relapse-free survival of 70 percent and a specific cancer survival that approaches 100 percent with the incredible advantage to spare long-term toxicity (associated with chemotherapy or radiation therapy) to a patient population characterized by a very long life expectancy. “Second, a high specific biomarker can reduce the risk of overtreatment in patients who have clinical suspicious findings of tumor (i.e., low elevated tumor markers or borderline enlarged retroperitoneal lymph nodes) but have no cancer. Third, miR371 integrated with the current clinical diagnostic tools could be used to detect residual post-chemotherapy disease discriminating between residual active germ cell malignancy (miR371-positive) fibrosis (miR371-negative, stable, or decreasing lesions on CT scan) or teratoma (miR371-negative, growing lesions on CT scan). And fourth, especially in seminoma patients, miR371 could completely substitute CT scans for active surveillance, decreasing the exposure to ionizing radiation.” Dibash Kumar Das is a contributing writer.

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.