Germ Cell Tumors of the Testis Treatment

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Inguinal exploration with cross-clamping of the spermatic cord vasculature and delivery of the testis into the field is the mainstay of exploration for a possible testis tumor. If cancer cannot be excluded by examination of the testis, radical orchiectomy is warranted. Scrotal approaches and open testicular biopsies should be avoided. Further therapy depends on the histologic characteristics of the tumor as well as the clinical stage.

A. Low-Stage Seminoma (I, II-A)
Seminoma is exquisitely radiosensitive. Ninety-five percent of all stage I seminomas are cured with radical orchiectomy and retroperitoneal irradiation (usually 2500-3000 cGy). This low dose of radiation is usually well tolerated, with minimal, if any, gastrointestinal side effects.

Low-volume retroperitoneal disease also can be treated effectively with retroperitoneal irradiation with an average 5-year survival rate of 87%. Prophylactic mediastinal radiation is no longer employed because this may cause considerable myelosuppression and thus compromise the patient’s ability to receive chemotherapy if required. Chemotherapy should be used as salvage therapy for patients who relapse following irradiation.

B. High-Stage Seminoma (II-B, III)
Patients with bulky seminoma and any seminoma associated with an elevated AFP should receive primary chemotherapy. Seminomas are also sensitive to platinum-based regimens, as are their NSGCT counterparts. Some of the successful regimens include cisplatin, etoposide, and bleomycin (PEB); vinblastine, cyclophosphamide, dactinomycin, bleomycin, and cisplatin (VAB-6); and cisplatin and etoposide. All seminomas receive low-risk chemotherapy regimens, which currently consist of cisplatin and etoposide (4 cycles) or 3 cycles of PEB.

Ninety percent of patients with stage III disease achieve a complete response with chemotherapy. Residual retroperitoneal masses following chemotherapy are often fibrosis (90%) unless the mass is well circumscribed and in excess of 3 cm, under which circumstances approximately 40% of patients harbor residual seminoma. In such cases surgical excision is warranted.

C. Low-Stage Nonseminomatous Germ Cell Tumors
Standard treatment for stage A disease in the United States has included retroperitoneal lymph node dissection (RPLND). However, because three-fourths of patients with clinical stage A disease are cured by orchiectomy alone and the morbidity of RPLND is not negligible, other alternatives have been explored. These options include surveillance and modified RPLND.

Surveillance in stage A NSGCT was proposed because, as mentioned previously, 75% of patients with clinical stage A disease have, in fact, pathologic stage A disease. In addition, infertility related to disruption of sympathetic nerve fibers is common following RPLND. Clinical staging has been markedly improved in the presence of CT scanning and LAG. And finally, effective chemotherapy regimens have been developed for relapse. Patients are considered candidates for surveillance if the tumor is an NSGCT confined within the tunica albuginea, the tumor does not demonstrate vascular invasion, tumor markers normalize after orchiectomy, radiographic imaging shows no evidence of disease (chest x-ray [CXR], CT), and the patient is considered reliable.

Surveillance should be considered an active process on the part of both the physician and the patient. Patients are followed monthly for the first 2 years and bimonthly in the third year. Tumor markers are obtained at each visit, and CXR and CT scans are obtained every 3-4 months. Follow-up continues beyond the initial 3 years. Most relapses occur, however, within the first 8-10 months. With rare exceptions, patients who relapse can be cured by chemotherapy or surgery, or both.

Retroperitoneal lymph node dissection has been the preferred treatment of low-stage NSGCTs in the United States until recently. A thoracoabdominal or midline transabdominal approach may be used, and all nodal tissue between the ureters from the renal vessels to the bifurcation of the common iliac vessels is removed. Patients with negative nodes or N1 disease do not require adjuvant therapy, whereas the recommendation for those with N2 disease is to receive 2 cycles of chemotherapy because their relapse rate approaches 50%.

While effective in surgically staging and potentially curing a subset of patients, RPLND is associated with significant morbidity, especially with respect to fertility in young men. With a standard RPLND, sympathetic nerve fibers are disrupted, resulting in loss of seminal emission. Currently a modified RPLND has been developed that preserves ejaculation in up to 90% of patients. By modifying the dissection below the level of the inferior mesenteric artery to include only the nodal tissue ipsilateral to the tumor, important sympathetic fibers from the contralateral side are preserved, thus maintaining ejaculation.

D. High-Stage Nonseminomatous Germ Cell Tumors
Patients with bulky retroperitoneal disease (> 3-cm nodes or 3 or more 1-cm cuts on CT scan) or metastatic NSGCT are treated with primary platinum-based combination chemotherapy following orchiectomy. If tumor markers normalize and a residual mass is apparent on imaging studies, resection of that mass is mandatory, because 20% of the time it will harbor residual cancer, 40% of the time it will be teratoma, and 40% of the time it will be fibrosis (Figure 23-2). In patients with residual cancer in the resected tissue, the histologic picture is usually embryonal cell carcinoma, but malignant teratoma is seen in less than 5% of cases. Malignant teratoma is unresponsive to chemotherapy, and only 15% of patients survive following surgical resection. If tumor markers fail to normalize following primary chemotherapy, salvage chemotherapy is required (cisplatin, etoposide, bleomycin, ifosfamide). Even if patients attain a complete response after chemotherapy (normal tumor markers, no mass on CT scan or CXR), some investigators advocate an RPLND because viable germ cell tumor may be seen in up to 10% of cases

Although the treatment plan described cures up to 70% of patients with high-volume disease, there are patients who fail to respond. Also, the potential complications from chemotherapy including sepsis, neuropathy, renal toxicity, and death must be considered. It is thus apparent that it is important to be able to discriminate between patients who are likely to respond to standard chemotherapy (low risk) and those who may require more aggressive regimens (high risk). In a multivariant analysis only 3 parameters, the serum LDH, the serum hCG, and the total number of sites of metastasis provided unique information in predicting response to chemotherapy. The rate of decline of serum tumor markers during chemotherapy has also been used to predict response in patients with advanced disease.

RELATED STORIES:
Germ Cell Tumors of the Testis Clinical Findings   Pathology - Germ Cell Tumors of the Testis   Germ Cell Tumors of the Testis Prognosis   Germ Cell Tumors of the Testis Differential Diagnosis   Classification - Germ Cell Tumors of the Testis   Patterns of Metastatic Spread - Germ Cell Tumors of the Testis

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