Blood Tests Show Promise for Testicular Cancer Monitoring and Treatment Decisions

New blood tests show promise for predicting testicular cancer recurrence and treatment outcomes, according to recent research. The findings suggest these biomarkers could help personalize care for patients with early-stage disease and guide treatment decisions for those with resistant tumors.

People diagnosed with stage 1 testicular germ cell tumour are often treated with surgery alone and then closely monitored through active surveillance. While most will have strong long-term outcomes, around one in four patients will see their cancer return within five years. The new study found the blood-based marker miR-371 could be used to detect tiny amounts of remaining cancer after testicular surgery.

In separate research focusing on young adults with germ cell tumors for whom standard chemotherapy doesn't work well, blood samples from 69 patients receiving high-dose chemotherapy and 26 patients receiving standard chemotherapy were analyzed using shallow whole genome sequencing. In circulating tumor DNA (cfDNA), researchers assessed tumor fraction (TF) and copy number alterations (CNAs).

Tumor fraction exceeded the detection threshold in 75% of patients treated with high-dose chemotherapy. A high tumor fraction was strongly associated with poorer survival, both in patients receiving high-dose and standard-dose chemotherapy. miR‑371a‑3p proved more informative than the established biomarker for detecting the presence of disease, but it was not a good predictor of survival.

Specific genetic alterations (a high frequency of 3p gain, 9q and 11q gains, and 6q loss) were more common in patients receiving high-dose chemotherapy who had a poor prognosis. Patients whose tumors exhibited abnormalities consistent with extra-embryonic histology (yolk sac tumor and choriocarcinoma) had worse survival outcomes. High-dose chemotherapy appears to be more effective than standard chemotherapy in patients with a high tumor fraction.

In the Netherlands, approximately 30 children are diagnosed with a germ cell tumor each year, as well as around 850 young men with testicular germ cell tumors. Testicular cancer is the most common cancer in young men aged 15 to 35. In one in ten of these young adults, standard chemotherapy doesn't work well enough. Despite treatment with high-dose chemotherapy, half of this group ultimately dies.

Meanwhile, research on long-term health outcomes in testicular cancer survivors found that morbidity varies with National Comprehensive Cancer Network (NCCN)-endorsed chemotherapy regimens. The study examined 798 long-term survivors treated with contemporary NCCN-endorsed regimens of four cycles of etoposide/cisplatin (EPx4) or 3 or 4 cycles of bleomycin/etoposide/cisplatin (BEPx3/BEPx4). The median age at follow-up was 45 years (median of 11 years postchemotherapy).

Compared with BEPx3, survivors receiving EPx4 had significantly increased odds of worse renal impairment, ototoxicity, and neuropathy (adjusted odds ratios, 1.55, 1.48, and 1.77, respectively). A reduced estimated glomerular filtration rate (eGFR) was seen in 41% of survivors and was associated with cumulative cisplatin dose and with increased odds of developing hypertension (odds ratios, 2.01, 2.84, and 20.0 for 60 to 89, 45 to 59, and 30 to 44 mL/min/1.73m2, respectively).

Significantly increased odds of developing hyperlipidemia and/or cardiovascular disease were seen in association with moderate-to-severe eGFR reductions (30 to 44 mL/min/1.73m2; odds ratios, 6.10 and 7.09, respectively). Similar cumulative burden of morbidity scores were seen after EPx4 vs BEPx3, but scores were worse after BEPx4 or 4 cycles of etoposide/ifosfamide/cisplatin (adjusted odds ratios, 1.77 and 2.24, respectively). There were strong correlations for self-reported global physical health with cumulative burden of morbidity score and chemotherapy regimen.

Further research is required before the blood test approaches can be implemented in clinical practice. The next step is to confirm these findings in a larger group of people, including blood samples from children with germ cell tumors. Researchers now plan to validate these results in a larger cohort of adolescents and children with germ cell tumors, within an international collaboration.