The current therapy for seminomas depends on presenting features at the time of diagnosis and staging. Treatment usually involves a combination of surgery, radiotherapy, and systemic chemotherapy.^[2]

In the past, primary treatment with radiation often yielded survival rates of 50-60%. The standard radiotherapy protocols call for 40-50 Gy delivered by external beam radiation to the mediastinum and supraclavicular regions. The neck region is included in the field of radiation because of the tendency of seminomas to initially spread to the cervical lymph nodes. Some oncologists also incorporate the axilla in the radiation field when the cervical nodes are enlarged. The radiation therapy is administered at a daily dose of 45-60 Gy over a period of 6 weeks. A failure of radiation therapy is believed to be due to the development of distant metastases rather than local recurrences. Combination treatment with radiation and surgery is not logical because both are aimed at achieving local control only. Because these tumors are bulky at presentation, the radiation may not encompass the entire tumor.

The complications of radiation are well known and predictable. Rapidly dividing cells are affected most significantly; these include cells of the dermis and the GI tract. Patients may present with nausea, vomiting, general malaise, poor wound healing, eczema, and ulcerations. The most frequent adverse effect is esophagitis, which occurs in most patients following radiation to the chest. This complication usually occurs 2 weeks after the start of radiation and subsides 1-2 weeks after completion.

All patients may have radiographic evidence of radiation-induced pneumonitis, but less than 5% of patients may be clinically symptomatic. Life-threatening pneumonitis occurs in less than 1% of patients.

Late complications may include bone deformities, cataracts, sterility, lung fibrosis, chromosomal damage, and, perhaps, an increased risk of cancer. Although rare, the risks of radiation-induced myocarditis and pericarditis are directly related to the amount of cardiac tissue near the field of treatment.

In the last decade, significant improvements in survival have been achieved with multimodal chemotherapy regimens involving bleomycin, cisplatin, and etoposide. Cisplatin-based chemotherapy has induced complete responses in a small number of patients with seminomas.^[3] Chemotherapy is administered in 4-6 cycles, and intermittent pulmonary function tests are performed in all patients because of the toxicity of bleomycin to the lungs. At present, cisplatin forms the basis of most combination chemotherapeutic regimens that are active against seminomas.

Other agents used for chemotherapy are vinblastine, cyclophosphamide, and dactinomycin. The response rates are difficult to compare with most other study results because many of the studies on these 3 agents were not randomized. In addition, the patient populations have been heterogeneous, and the chemotherapeutic regimens have been different.

Chemotherapy clearly exerts a biologic effect in patients with advanced disease. Whenever possible during clinical trials, patients should be treated with either newer agents or a combination of agents. At this time, chemotherapy is sufficiently justified for use in patients with advanced disease, provided its limitations and toxicity are understood.

Cisplatin is an important agent in the treatment of seminomas and is generally administered in combination with other agents in divided doses over 3-5 days. Cisplatin is recognized as an excellent agent because of its superior activity and its only modest myelosuppression. It generally acts in synergy with other chemotherapeutic agents. For this reason, it forms the basis of most combination regimens. In addition, cisplatin can be administered with thoracic radiation without undue toxicity.

Various platinum analogs, such as carboplatin and iproplatin, are now available. These agents induce greater response but may be more myelosuppressive than cisplatin.

Both vincristine and vinblastine have been used to treat seminomas. These agents act as mitosis inhibitors by binding to microtubules and causing arrest in the metaphase. Although these alkaloids share a similar structure, they have a wide spectrum of clinical activity and toxicity. They are almost always used in combination with other chemotherapeutic agents.

Etoposide, an epipodophyllotoxin, has only mild activity as a single agent but because of its synergy with other agents is always used in combination regimens. This agent shows phase-specific activity for cells in the dividing phase. The correct dosing is still being debated, but most authorities recommend long-term administration for weeks.

Ifosfamide is a non–cell-specific alkylating agent that is replacing cyclophosphamide in many studies. It can be used in higher doses than cyclophosphamide, although hemorrhagic cystitis is still a major adverse effect. It can also cause renal and hepatic dysfunction. Ifosfamide is generally administered intravenously.

Bleomycin belongs to the antibiotic classification of chemotherapeutic drugs. It is derived from Streptomyces and causes breaks in the DNA molecule. Bleomycin is used in combination therapy and is usually administered parenterally. Although it has a number of adverse effects, the most well known is pulmonary fibrosis.

Most chemotherapeutic agents are associated with adverse effects, and some have specific organ toxicity. Most produce nausea, vomiting, and flulike syndromes.

Cisplatin can cause renal dysfunction, and renal parameters must be constantly monitored. Cisplatin is also associated with ototoxicity, neurotoxicity, anaphylaxis, a Raynaud-type phenomenon, and local vesication.

Ifosfamide can cause myelosuppression, renal and hepatic dysfunction,hemorrhagic cystitis, alopecia, and confusion.

Etoposide can also cause myelosuppression and has been associated with bronchospasm, hypotension, and ileus.

Bleomycin can cause fever and pulmonary fibrosis.

Recent clinical trials have demonstrated excellent results when multimodality chemotherapy is combined with radiation for large, localized mediastinal seminomas or extensive residual disease. In these cases, the patient is administered chemotherapy consisting of cisplatin, bleomycin, and etoposide. After the patient has recovered (4-6 wk), radiation is administered at a dose of 40-60 Gy for 4-6 weeks. A CT scan is then obtained to assess the response of the tumor to treatment. If only a small mass remains, it is excised.

After radiation and/or chemotherapy, CT scans are delayed for 6 weeks to allow maximum reduction of the mass. Regular blood workups are obtained to assess the effects of chemotherapy on the bone marrow, kidneys, and liver. Residual disease as seen on radiographs following treatment is a medical dilemma. If CT scans reveal a residual mediastinal mass, surgery is offered; however, some patients still have viable seminomas or teratomas after excision.

If a small mediastinal mass remains after nonsurgical therapy, it must be excised; however, this treatment is not a universal protocol. Some oncologists instead prefer to monitor these masses with serial CT scans, a course that carries a risk of recurrent disease.