Management of Advanced Germ Cell Tumours.

Background: Male germ cell tumours are an exemplar of a highly curably malignancy and represent the most frequent solid malignancy among men under the age of 40. The majority of cases are detected while the tumour is confined to the testicle where cure rates exceed 99%. Even in cases of metastatic disease expansion, cure rates remain extraordinary compared to other malignancies, owing to the unique sensitivity of most germ cell tumour components to cisplatin-based chemotherapy.

Summary: The treatment of metastatic germ cell tumours is adapted to (i) primary histology (seminoma versus non-seminoma or mixed germ cell tumour), (ii) disease spread (clinical stage IIA/B versus IIC/III), and (iii) clinical risk according to the International Germ Cell Cancer Collaborative Group classification. Across all metastatic stages, the combination of bleomycin, etoposide, and cisplatin is most commonly used. In non-seminomas, post-chemotherapy residual mass resection is the second cornerstone of treatment. Among patients who relapse after first-line chemotherapy, platinum-based conventional dose or high-dose chemotherapy regimens can still achieve cure in 50% of patients. Outcomes for patients with multiple relapses, however, remain dissatisfactory and novel treatment approaches are urgently needed. High cure rates demand cautious consideration of possible long-term side effects. Novel strategies are being explored to mitigate the risk of long-term morbidity without lowering the outstanding cure rates.

Key messages: (i) Advanced germ cell tumours are highly curable with cisplatin-based combination chemotherapy and often surgical post-chemotherapy residual mass resection. (ii) Novel de-escalation strategies and survivorship programs aim to mitigate the risk of long-term treatment side effects. A lack of effective molecularly targeted treatment approaches pinpoints the need for novel treatments for multiply relapsed, platinum-resistant disease.