Mediastinal Seminoma Treatment & Management
- Author: Shabir Bhimji, MD, PhD; Chief Editor: Jeffrey C Milliken, MD more...
Seminomas generally affect young males in their second or third decade of life. For localized seminomas, the current treatment is radiation therapy. Surgery is reserved for patients with residual masses after successful treatment with radiation therapy, chemotherapy, or both. Because most patients are young, an aggressive approach with newer, multimodality treatments should be the intent in all patients.
The current therapy for seminomas depends on presenting features at the time of diagnosis and staging. Treatment usually involves a combination of radiotherapy, systemic chemotherapy, and surgery.
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 irradiation of the mediastinum and supraclavicular regions. The neck region is included in the radiation field 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.
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. Chemotherapy is administered in four to six 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 three 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 that its limitations and toxicity are understood.[9, 10]
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 analogues, such as carboplatin and iproplatin, are now available. These agents induce greater response than cisplatin does but may be more myelosuppressive.
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, though 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.
Combination of radiation therapy with chemotherapy
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 receives chemotherapy consisting of cisplatin, bleomycin, and etoposide. After the patient has recovered (4-6 weeks), radiation is administered at a dose of 40-60 Gy for 4-6 weeks. A computed tomography (CT) scan is then obtained to assess the response of the tumor to treatment. If only a small mass remains, it is excised.
Surgery is not the prime treatment modality, and more than 50% of patients are deemed to have unresectable tumors. For this reason, surgery is usually reserved for only small mediastinal masses in asymptomatic patients. Even in this situation, surgery has been associated with a high rate of recurrence and must therefore be accompanied by some form of adjuvant therapy, even if the resection appears to be complete.
When complete excision is not possible, a biopsy is performed to confirm the diagnosis, and an alternative treatment is started. Because these tumors are quite responsive to radiation, performing high-risk surgery (with its potential for injuring mediastinal structures) is unnecessary.
Surgery should not be undertaken without a tissue diagnosis, for two reasons. First, seminomas respond poorly to surgery and have a high rate of recurrence. Second, the mediastinal mass may be a lymphoma (more common in young males) instead of a seminoma, and lymphomas usually respond to chemotherapy. Furthermore, if the patient has severe tracheomalacia from prolonged compression of the trachea by the tumor, anesthesia is not recommended. Finally, if the patient has metastatic disease or numerous medical conditions, surgery is best avoided.
Preparation for surgery
Generally, most patients with seminomas are young, healthy males who have minimal comorbid disorders. The preoperative workup for patients with mediastinal tumors involves CT, pulmonary function tests, and nutritional status assessment. Because the mass in the mediastinum has the tendency to compress the airways and make intubation difficult, knowing the extent of airway compromise before the operation is extremely important. Bronchoscopy must be performed if bronchomalacia is possible. If the airway is compromised, anesthesia must be induced with the patient in a semi-Fowler position and a long endotracheal tube that can bypass the obstructed site must be used.
Strict airway maintenance is required whenever patients with large anterior mediastinal tumors are sedated. A rigid bronchoscopy cart must always be available during this procedure. All anesthesia must be reversed before extubating the patient. Some patients may require longer intubation and may be extubated slowly, after the administration of steroids and bronchodilators. An arterial line, a Foley catheter, and a dose of preoperative antibiotic are required.
If the mass has produced symptoms of superior vena cava compression, magnetic resonance imaging (MRI) can be ordered. MRI does not require contrast and can help identify the site and extent of obstruction. In all patients with superior vena cava obstruction, lower-extremity intravenous (IV)access must be available. Some surgeons also recommend that standby cardiopulmonary bypass be available when patients have tracheal compromise or superior vena cava syndrome.
Depending on the mass location, excision via a thoracotomy can be performed; however, the typical and preferred incision for anterior mediastinal tumors is the median sternotomy. The sternum is divided from the suprasternal notch to the xiphoid, and all bleeding from the sternum is stopped. Once hemostasis has been achieved, the tumor is palpated in the anterior mediastinum prior to any resection. Structures such as the superior vena cava, pericardium, innominate vein, pleura, and phrenic nerves are identified.
Because seminomas are sensitive to radiation, unnecessary resection of vital structures must be avoided. When the entire mass is not resectable, adjuvant radiation therapy is required. Once the mass (or appropriate portions thereof) is resected, complete hemostasis is obtained and mediastinal drainage tubes are inserted. Surgical clips are placed in the area where the mass was excised to allow for the radiation field to be mapped later. If the pleural space was inadvertently entered, chest drainage tubes are also placed. The sternum is closed with wires, and the patient is awakened from anesthesia.
The typical patient with an anterior mediastinal mass is observed in the intensive care unit for a few hours and, if hemodynamically stable with minimal chest drainage, is transferred to a monitored floor. Postoperative chest radiographs are obtained in every patient to view the placement of the drainage tubes and endotracheal tube (if present) and to assess for pneumothorax.
IV fluids are kept to a minimum, and adequate pain control is maintained. Most drainage tubes are removed on postoperative day 2, and the patient is encouraged to ambulate. Daily chest radiographs are not required after the mediastinal drains have been removed, but they are obtained after the chest tubes are removed in order to evaluate for the presence of pleural fluid or pneumothorax. The average hospital stay after a routine median sternotomy exploration is approximately 2-4 days.
The complications of radiation therapy are well known and predictable. Rapidly dividing cells are affected most significantly; these include cells of the dermis and the gastroitnestinal 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 after delivery of radiation to the chest. This complication usually occurs 2 weeks after the start of radiation therapy and subsides 1-2 weeks after completion.
All patients may have radiographic evidence of radiation-induced pneumonitis, but fewer than 5% of patients may be clinically symptomatic. Life-threatening pneumonitis occurs in fewer than 1% of patients.
Late complications may include bone deformities, cataracts, sterility, lung fibrosis, chromosomal damage, and, perhaps, an increased risk of cancer. Although radiation-induced myocarditis and pericarditis are rare, the risks are directly related to the amount of cardiac tissue near the field of treatment.
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. It 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.
Because surgery is usually performed for small tumors, complication rates are much lower. The usual complications of a median sternotomy include incision pain, atelectasis, injury to the phrenic nerve and/or vascular structures, and postoperative bleeding.
A common complication is airway compression from the mediastinal mass. During anesthesia, intubation may prove to be very difficult. Additionally, some patients may not be able to be weaned off the respirator because the prolonged compression of the airways may have caused tracheobronchomalacia. These patients may remain intubated for prolonged periods and may even require stenting of the airways.
When aggressive surgical resection is undertaken for a seminoma, injury to the phrenic nerve(s) can result in diaphragm paralysis; however, in young, healthy patients, the complication rates are negligible, and most patients have an uneventful recovery.
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 radiography after treatment is a medical dilemma. If CT reveals 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.
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