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Early Testicular Cancer By John LeBas
When testicular cancer is found early—that is, when the tumor is confined to the testicle—the cancer is almost always curable. In fact, patients treated at this disease stage can typically expect to lead full lives with few long-term effects from the cancer or its treatment on their fertility or health. Much of this success in curing testicular cancer has resulted from treating potential metastasis of the primary tumor. Physicians at The University of Texas M. D. Anderson Cancer Center continue to refine treatment approaches for early-stage testicular cancer to achieve an optimal outcome for each patient. “There have been significant advances in how chemotherapy, surgery, and radiation are integrated to produce an optimal outcome for patients with early testicular tumors,” said Lance C. Pagliaro, M.D., an associate professor in the Department of Genitourinary Medical Oncology at The University of Texas M. D. Anderson Cancer Center. “This involves a balance between minimizing the long-term risk of recurrence and minimizing the long-term risks of treatment side effects.” Early-stage testicular cancer characteristics In the United States, about 7,000 men each year are newly diagnosed with testicular cancer, most commonly of germ cell origin. About half of those germ cell tumors are seminomas; the rest are single- and mixed-histology non-seminomas. About 95% of patients are cured with surgery alone or surgery followed by chemotherapy or radiation therapy, and the chance of a cure is highest when the tumor is confined to the testis (clinical stage I). For confined tumors, only one testicle is usually removed (orchiectomy). After orchiectomy, a decision about whether to give further treatment is made based on the likelihood that an apparently confined tumor may have actually already metastasized. Some patients are considered to have high-risk clinical stage I disease, in which histologic characteristics of the tumor indicate a higher chance of metastasis. For both seminoma and non-seminoma, evidence of lymphovascular invasion indicates that a tumor is at high risk of spread; in addition, the presence of embryonal carcinoma in non-seminomas increases the risk of spread. Patients with such tumor characteristics are candidates for immediate adjuvant (postorchiectomy) treatment or careful observation, in which further treatment is delayed unless testing reveals evidence of metastasis. The standard adjuvant treatment options depend on the disease type, which is determined by pathologic examination of the tumor after orchiectomy, and alternative treatment options for each type have emerged. The refinement of available treatments has not only decreased occurrence but also allowed fertility to be preserved in a majority of clinical stage I testicular cancer patients—important since the disease usually develops in late adolescence or early adulthood. “However, we have not eliminated the risk that fertility will be damaged. Also, there are long-term risks of chemotherapy, such as cardiovascular disease and second malignancies,” Dr. Pagliaro said. “Therefore, the burden of these risks becomes the paramount consideration in selecting adjuvant intervention or observation for selected patients.” Seminomas The standard adjuvant therapy for stage I seminoma is radiation therapy. In recent years, treatment fields have been refined to limit the side effects of radiation therapy. While the chance of affecting fertility is low with radiation, there is still a higher risk of second malignancies as compared to the normal population. Two main approaches have been developed as alternatives to radiation therapy after orchiectomy for seminomas: Chemotherapy. Patients receive one dose of carboplatin chemotherapy. This approach kills micrometastases or isolated cancer cells throughout the body, but there is limited knowledge about the long-term risks. Observation. This approach decreases the likelihood of unnecessary adjuvant therapy through the careful monitoring of selected patients. Only if metastasis is clinically detected will therapy be given. The disadvantage of observation is that patients must adhere to a rigorous, long-term follow-up schedule—and failure to do so can ultimately result in unchecked disease progression.
The data comparing observation and chemotherapy have evolved slowly, since a follow-up period of 20–30 years is needed to accurately assess recurrence rates, rates of second malignancies, and the cardiovascular effects of therapy. Clinical trials have supported the use of platinum-based chemotherapy agents such as carboplatin, said Dr. Pagliaro. For example, he cited a recent European study1 of patients randomly assigned to receive adjuvant carboplatin or radiation therapy after orchiectomy for stage I seminoma. The study found that each group experienced similar recurrence rates. Long-term follow-up is needed, but based on the results of this study and others like it, adjuvant carboplatin is now sometimes given for one or two cycles instead of radiation therapy to treat stage I seminoma. “The role of platinum-based chemotherapy has been well established, and the high cure rates for seminoma suggest that we are doing well with the treatments we have available,” Dr. Pagliaro said. “But there continues to be vigorous debate about how much chemotherapy is appropriate and whether it might be better for some patients to be carefully observed for recurrence before receiving further treatment after orchiectomy. What we are really trying to determine is which approach will produce the best outcome for each patient in terms of limiting both recurrence and effects of therapy.” Non-seminomas The standard adjuvant therapy for stage I non-seminoma testicular cancer is actually a second surgery—prophylactic retroperitoneal lymph node dissection (RLND). In this surgery, the lymph nodes most likely to be the initial sites of metastasis are removed. The advantage of RLND is that metastasis can be completely removed if it is confined to the retroperitoneal lymph nodes, increasing the chance of a cure; the disadvantage is that RLND can result in damage to nerves that control ejaculation and fertility. To reduce risk to fertility, surgeons at M. D. Anderson perform nerve-sparing RLND, a procedure that is available at only a handful of centers. This surgery attempts to preserve the sympathetic nerve trunks responsible for maintaining ejaculation and fertility, and the techniques have been improved in recent years. “We have developed a better understanding of the retroperitoneal pattern of spread and where the sympathetic nerve trunks are. This helps us properly select patients in a way that doesn’t appear to be reducing the cure rate,” said Louis L. Pisters, M.D., a professor in the Department of Urology. The nerve-sparing approach has increased the likelihood that normal ejaculation will be preserved following surgery. RLND is performed for patients who have early-stage non-seminoma with no clinical signs of spread (i.e., those with apparently confined tumors who might have micrometastases in the lymph nodes). For patients with lymphovascular invasion in the primary tumor or other histologic characteristics of high-risk disease, the surgery is not considered appropriate or feasible because the amount of metastatic tumor is likely too great, Dr. Pisters said. Likewise, radiation therapy is not appropriate for high-risk stage I non-seminoma since this tumor is not as sensitive to radiation as seminoma. Instead of RLND or radiation therapy, patients at M. D. Anderson who have high-risk early-stage non-seminoma usually receive adjuvant chemotherapy or are carefully observed for metastasis before receiving any therapy. The standard chemotherapy is two courses of combined bleomycin-etoposide-cisplatin (BEP), a regimen that lowers the risk of recurrence from 50% in high-risk non-seminoma to about 2% but increases the risk of second malignancies and cardiovascular disease. Separate European studies2,3 have found that one course of BEP instead of two may result in a similar reduction of recurrence risk with less toxicity, but no randomized study comparing one versus two courses has been conducted. A study of 745 men in Sweden and Norway compared one course of BEP to observation (with patients assigned to therapy in a risk-adaptive fashion) and showed that the chemotherapy significantly reduced risk of recurrence3. “These data have prompted a re-evaluation of combination chemotherapy involving platinum-based agents as a preferred option over RLND for adjuvant intervention in patients who are known to be at high risk for recurrence,” Dr. Pagliaro said. Following adjuvant therapy After initial treatment, non-seminoma germ cell tumors are most likely to recur in the 2 to 3 years following initial therapy. Seminomas can recur much later, and patients should be evaluated regularly for at least 10 years, Dr. Pagliaro said. Most patients, however, will never experience a recurrence. 1 Oliver RT, Mason MD, Mead GM, et al. Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial. Lancet. 2005;366(9482):293-300. For more information, call Dr. Pagliaro at 713-792-2830 or visit the Genitourinary Cancer Center Web page. Other articles in OncoLog, October 2009 issue: Home/Current Issue | Previous Issues | Articles by Topic | Patient Education ©2009 The University of Texas M. D. Anderson Cancer Center |
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