Pharmacotherapeutic treatment of germ cell tumors: standard of care and recent developments

ABSTRACT

Introduction: Testicular germ cell tumors are the most common malignancy among men aged 40 and less. Since the introduction of cisplatin-based combination chemotherapy, germ cell tumors are among the most curable solid tumors with cure rates of 95% in all patients and > 80% in metastatic disease.

Areas covered: Current standards and future developments in GCT treatment, including adjuvant chemotherapy, first line treatment for metastatic disease, and salvage regimens in case of relapse and refractory disease.

Expert opinion: Maintaining therapeutic success while further reducing treatment-related toxicity is paramount. Cancer-specific survival in localized disease approximates 100%. Therefore, orchidectomy followed by active surveillance is the preferred approach for all seminomas and non-seminomas lacking lymphovascular invasion. Non-seminomas with lymphovascular invasion should be offered adjuvant treatment with one cycle of bleomycin, etoposide and cisplatin (BEP). The BEP regimen remains standard of care for metastatic disease, while the role of primary high-dose chemotherapy in case of inadequate tumor-marker decline or presence of high-risk features (i.e. mediastinal origin, non-pulmonary visceral metastases) remains to be elucidated. Several curative salvage chemotherapy combinations are available, i.e. TIP, VeIP, GIP or high-dose carboplatin and etoposide. GOP is the current option of choice in cisplatin-refractory patients. Novel targeted agents failed to improve treatment outcome so far.

KEYWORDS:

• Testicular cancer
• germ cell tumor
• chemotherapy
• salvage treatment
• high-dose chemotherapy
• cisplatin-refractory disease

Article highlights.

• After inguinal orchidectomy, clinical stage I seminomas should preferably be managed by active surveillance, clinical stage I nonseminomas lacking lymphovascular invasion should undergo active surveillance, positive patients should be offered one cycle of BEP.

• According to the International Germ Cell Consensus Classification criteria, for good risk patients three cycles of BEP, and for intermediate and poor risk patients four cycles of BEP, remains the standard of care. In nonseminoma patients, secondary resection of all residues sized ≥1cm is strongly recommended to reduce the risk of relapse.

• For patients failing first-line systemic treatment, curative salvage treatment options include conventional dose treatment with four cycles of TIP, GIP, VIP or VeIP, or high-dose chemotherapy consisting of three cycles of carboplatin plus etoposide followed by autologous stem cell transplantation.

• Treatment of choice for patients failing cisplatin-based chemotherapy is the triple combination gemcitabine and oxaliplatin together with paclitaxel (GOP) followed by secondary resection of all residues. Patients failing GOP have a very unfavorable prognosis and no further standard treatment exists.

• Due to the importance of multimodal treatment approaches including high-dose systemic and technically challenging surgical treatments to maintain treatment success in this highly curable disease, patients should referred to expert uro-oncology centers.

• Molecularly targeted treatment approaches do not play a role in the management of germ cell tumors to date. Immune-checkpoint inhibition by targeting the programmed death 1/programmed death ligand 1 axis is currently under investigation.

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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.