The Oncologist, Vol. 2, No. 3, 183–184,
June 1997
© 1997 AlphaMed Press
SPECIAL FEATURE
BRIEF REPORT |
Remaining Issues in Germ Cell Tumors
Lawrence H. Einhorn, M.D.
Indiana University, 550 University Boulevard, University Hospital, Room 1730, Indianapolis, IN 46202-5250
Testis cancer has become a model for a curative neoplasm. The past two decades have witnessed major surgical and medical advances that have significantly improved the cure rate and simultaneously decreased morbidity from therapy. Cisplatin combination chemotherapy truly revolutionized the cure rate as no other regimen has ever done in any solid tumor.
Despite the advances of the last two decades, there are still remaining clinical issues which are outlined below.
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POST-CHEMOTHERAPY SURGICAL DECISIONS
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The indication for post-chemotherapy surgery in patients with non-seminomatous germ cell tumors has been controversial. The goal of the surgery is to resect residual teratoma and/or carcinoma. If a patient achieves a radiographic complete remission, at Indiana University, no surgery is offered.
The more complicated issue is what to do when patients have multiple anatomical sites of persistent disease post-chemotherapy. There is evidence that if a two- or three-stage operation is done, and there is only necrosis in the retroperitoneal lymph node dissection, the probability of there being anything other than necrosis above the diaphragm is extremely low.
Another complicated area is what should be done in patients who have greater than 90% radiographic regression in a clinical scenario where the probability for teratoma is very low (e.g., no teratoma in the orchiectomy specimen). This is an evolving field and there are no definitive solutions for this complicated group of patients.
Finally, patients that have bulky pure seminoma will virtually never normalize their CT scan after completion of chemotherapy. It has been the policy at Indiana University to not do surgery; instead, the patients are watched with serial CT scans and no intervention is done unless there is evidence of radiographic progression.
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PROGRESSIVE UNRESECTABLE TERATOMA
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Most patients who have poor (advanced) germ cell tumors represent a struggle of chemotherapy versus cancer. However, some patients have biologic as well as radiographic reasons for incurability. These are patients who have bulky unresectable teratoma in multiple sites. Standard chemotherapy or radiotherapy has been unsuccessful in these patients and new strategies are clearly needed.
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MANAGEMENT OF ADVANCED DISEASE
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An international consensus has been reached with new definitions for poor risk disease. This will include serologic markers (i.e., HCG >50,000; alphafetoprotein >10,000), or LDH values greater than 10 times the upper limit of normal. In addition, this will include any patient with primary mediastinal non-seminomatous germ cell tumor, or bone, liver or CNS metastases. Previous randomized studies in the United States for advanced disease included BEP versus the same chemotherapy, but with double dose (40 mg/m2 per day for five consecutive days) cisplatin and BEP versus VIP. Unfortunately, neither of these approaches improved the cure rate and, instead, were both associated with increased toxicity. The current intergroup study will address the issue of very high-dose chemotherapy with peripheral blood stem cell rescue. The control arm will consist of four courses of BEP, and the experimental arm will be two courses of BEP followed by two courses of very high-dose chemotherapy.
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LATE RELAPSE
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Testicular cancer is a rapidly proliferating and uniquely chemosensitive tumor. It is now recognized that approximately 2%-3% of patients who are disease-free at two years will experience a late relapse and about half of those will be beyond five years. This is often manifested by a rising alphafetoprotein on a routine determination. Unfortunately, with very rare exceptions, these patients are not curable with chemotherapy. Proper management for these patients is to find where their disease is radiographically and attempt to surgically resect their disease.
It is a luxury in germ cell tumors to address the above issues rather than the fundamental issue of successful primary chemotherapy for disseminated disease. Testicular cancer has been a success story and, hopefully, these and other remaining issues will be appropriately addressed and answered as we approach the year 2000.
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