Objective: In this review, we summarize the current state of the art of primary mediastinal germ cell tumours (PMGCTs) and we highlight challenges and future research directions for this disease.
Background: PMGCTs account for 1-3% of all germ cell malignancies and for 15% of adult anterior mediastinal cancers. In 60-70% of cases PMGCTs are represented by nonseminomatous germ cell tumours (GCTs), and in 30-40% of cases by seminomas. Even if PMGCTs share histological and biochemical characteristics with gonadal GCTs, they have peculiar clinical and biological features. Nonseminomatous PMGCTs have a poor prognosis, with a 5-year overall survival (OS) rate of 40-50% after platinum-based chemotherapy and surgery, and a long-term OS of only 10% after salvage treatment. Due to the rarity of this disease, no level 1 evidence is available from randomised trials for PMGCTs. The combination of bleomycin, etoposide, and cisplatin (BEP) or etoposide, ifosfamide and cisplatin (VIP) for 4 cycles are recommended as first line treatment options for nonseminomatous PMGCTs. Surgery of the residual disease after chemotherapy is fundamental in the treatment of nonseminomatous PMGCTs. PMGCTs have high TP53 pathway gene alterations, while targetable gene alterations are rarely identified, thus challenging the advance of precision medicine in this field.
Methods: We performed a narrative review of international literature published in English on PMGCTs, focusing the attention on clinical trials, international guidelines and translational studies.
Conclusions: Treatment of patients with PMGCTs is challenging and should be performed in experienced centers. International collaborations should become a priority to ensure optimal patient management. Clinical investigation of new therapeutic options remains an important unmet clinical need, and inclusion of patients in clinical trials should be encouraged. Liquid biopsy is a new promising strategy in PMGCTs.
Keywords: Primary mediastinal germ cell tumours (PMGCTs); extragonadal germ cell tumours (EGCTs); nonseminoma; seminoma.
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