铂耐药男性生殖细胞肿瘤的治疗选择：当前标准与未来方向

Germ cell cancers (GCCs) represent the most common malignant tumours among men up to the age of 40 years. GCCs are characterised by high cure rates of >99% for localised stage I disease, but even at advanced metastatic stages, 67%-96% of patients can be cured with multimodal treatment approaches. The high curability owes to an exceptional responsiveness to cisplatin-based chemotherapy.

However, about 30% of patients with metastatic disease eventually relapse after first-line multimodality treatment. At first relapse, salvage treatment still cures approximately 50% of patients. Platinum-based chemotherapy remains the standard of care in this setting, administered either as conventional-dose cisplatin-based regimens or as high-dose carboplatin-based combination chemotherapy.

Across multiple large retrospective cohorts, high-dose chemotherapy has repeatedly been associated with superior progression-free and overall survival compared with conventional-dose approaches, although definitive prospective evidence is awaited.

Patients suffering second or multiple relapses are considered platinum-resistant and face a very dismal prognosis with a life expectancy generally limited to less than 12 months. The mainstay of treatment in this setting is still conventional cytotoxic chemotherapy since no molecularly targeted treatments have shown clinically meaningful activity, to date.

However, Claudin-6 (CLDN6)-directed approaches appear the most promising avenue of new treatment options in this situation. In this narrative review, we outline established and emerging treatment opportunities for this rare but challenging clinical scenario of platinum-resistant GCCs.

This review provides a focused and up-to-date synthesis of therapeutic options for multiply relapsed, platinum-refractory GCCs, with a particular emphasis on late-line treatment sequencing and emerging biomarker-driven strategies, including CLDN6-directed therapies. New treatment options for germ cell cancer when standard chemotherapy no longer works Germ cell cancers (GCCs) are highly curable tumours, even when they have spread. Most patients respond very well to standard cisplatin-based chemotherapy.

However, a small group of patients experience several relapses and eventually develop resistance to platinum-based treatment. In this situation, treatment options are limited and long-term survival is rare. This review summarises the available therapies for patients with platinum-refractory GCCs. High-dose chemotherapy can still help some patients, but its success decreases after multiple relapses.

Standard combination chemotherapies may temporarily shrink the tumour, but responses usually do not last. Modern treatments such as targeted drugs or immunotherapy have shown very limited benefit to date. A promising new approach targets a protein called Claudin-6 (CLDN6), using innovative treatments such as antibody drug conjugates or CAR-T cells. These early results offer hope for future therapeutic progress.