Current pharmacotherapy for testicular germ cell cancer

ABSTRACT

Introduction: With the implementation of platinum-based chemotherapy, germ cell tumors (GCTs) became a model for a curable solid tumor, with survival rates of 95% in all patients with >80% survival in metastatic stages.

Areas covered: Herein, the authors review the current standards of adjuvant chemotherapy for stage I GCTs as well as first-line and salvage treatments for metastatic disease. Novel approaches for refractory disease are also reviewed.

Expert opinion: Active surveillance should be considered for all stage I patients and is the preferred approach for stage I seminoma. In stage I non-seminomas with vascular invasion, one cycle of bleomycin, etoposide, and cisplatin (BEP) substantially reduces the relapse risk. For most advanced GCTs, BEP remains the first-line standard of care. For poor prognosis disease treatment, stratification according to tumor marker decline is recommended. The role of primary high-dose chemotherapy (HDCT) for selected very high-risk patients remains to be prospectively evaluated. Salvage HDCT at relapse seems superior to conventional chemotherapy, retrospectively. The treatment of multiply relapsed disease remains challenging. The gemcitabine/oxaliplatin/paclitaxel (GOP) protocol is considered the standard for refractory disease. However, overall, outcomes are poor and new treatment approaches are urgently needed with targeted therapies so far failing to yield relevant clinical activity.

KEYWORDS:

• Active surveillance
• cisplatin
• platinum-based chemotherapy
• tumor marker decline
• high-dose chemotherapy

Article Highlights

• Stage 1 seminoma should be managed by active surveillance. Due to its modest efficacy, carboplatin currently has a limited role in adjuvant therapy and if used a dose of AUC7 is recommended. Depending on results of ongoing clinical trials (i.e. the ABC-study; NCT02341989), BEP may also become an option for adjuvant treatment in seminoma.

• Treatment with one cycle of BEP reduces the relapse risk (absolute risk approx. 50%) by 90% in stage 1 nonseminoma patients with lymphovascular invasion. Patients without this risk factor should preferably be managed by active surveillance.

• Standard treatment for metastatic GCT remains three cycles BEP for good risk disease and four cycles for intermediate- and poor-risk patients.

• In poor-risk patients, inadequate tumor marker decline is a negative prognostic marker requiring early treatment intensification.

• For relapsed metastatic GCT, either standard-dose chemotherapy (four cycles of TIP or GIP) or high-dose chemotherapy (high-dose carboplatin/etoposide followed by autologous stem cell transplantation) is given. Meta-analyses suggest the superiority of HDCT, which therefore should be the preferred approach in this setting, as long as results of the currently ongoing randomized phase III TIGER trial comparing 1^st-salvage conventional versus high-dose chemotherapy are pending.

• Patients with platinum-resistant disease and/or multiple relapses are difficult to treat. In this setting, combination chemotherapy with gemcitabine, oxaliplatin, and paclitaxel (GOP) is the most effective therapy. GOP followed by surgical resection of all residual disease can induce long-term remissions in a fraction (<20%) of patients.

• For platinum-refractory disease novel therapeutic approaches like tyrosine-kinase inhibitors or immunotherapy have so far failed to demonstrate relevant antitumor activity.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.