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Non-Seminoma: Stage III


Patients with stage III non-seminoma have cancer that has spread outside the retroperitoneal lymph nodes. The majority of patients are cured with standard multi-agent chemotherapy.

A variety of factors ultimately influence a patient’s decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase a patient’s chance of cure, or prolong a patient’s survival. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.

The following is a general overview of the treatment of stage III testicular non-seminoma. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.

Most new treatments are developed in clinical trials. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Clinical trials are available for most stages of cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. To ensure that you are receiving the optimal treatment of your cancer, it is important to stay informed and follow the cancer news in order to learn about new treatments and the results of clinical trials.

Since patients with stage III non-seminoma have widespread cancer, the treatment of choice is systemic chemotherapy. However, patients with cancer involving the brain are typically treated with both chemotherapy and simultaneous whole-brain radiation. Chemotherapy is a treatment modality that utilizes anti-cancer drugs. When chemotherapy is delivered systemically, it can kill cancer cells throughout the body, including cancer cells that reside in areas outside of the original location of the cancer. The most frequently utilized chemotherapy combinations include bleomycin, etoposide and Platinol® (BEP) for 3 courses or etoposide and Platinol® (EP) for 4 courses in good-prognosis patients. Other chemotherapy regimens may produce similar results, but are not as commonly used.

The expected outcome following Platinol®-based combination chemotherapy can be predicted based on the extent of the cancer. This is an important consideration because patients likely to have a poor outcome may want to consider participation in clinical trials evaluating new treatment approaches in an attempt to improve their chance of cure.

Risk of Cancer Recurrence Following Treatment with Standard Chemotherapy
Good < 1,000 < 5,000 < 1.5 ULN 90%
Intermediate 1,000-10,000 5,000-10,000 1.5-10xULN 75%
High >10,000 >50,000 >10xULN 40%

*Disease-free survival (DFS) refers to the number of patients surviving without a cancer recurrence following treatment.

The table above outlines the risk levels for patients with different levels of tumor markers in their blood following treatment with standard chemotherapy. Only 10% of “good-risk” patients experienced a cancer recurrence following treatment with standard chemotherapy. However, 25% of “intermediate-risk” patients and 60% of “high-risk” patients experienced a cancer recurrence after treatment with standard chemotherapy. Patients who fall in the intermediate and high-risk categories may wish to consider other treatment options to help reduce their risk of a cancer recurrence.

One such treatment option involves high-dose chemotherapy (HDC) with stem cell transplant. High-dose chemotherapy with autologous blood stem cell support has been successful in producing long-term complete remissions in patients with refractory cancer. High-dose chemotherapy (HDC) kills more cancer cells than lower-dose conventional chemotherapy. Unfortunately, HDC also kills more normal cells, especially the blood-producing stem cells in the bone marrow. Stem cells are immature cells produced in the bone marrow that eventually develop into red blood cells, which provide oxygen to tissues; white blood cells, which fight infection; or platelets, which aid in blood clotting. The treatment strategy utilizing stem cell transplant is an attempt to restore the blood-producing stem cells after HDC has reduced them to dangerously low levels. When stem cells reach critically low levels from HDC, complications such as anemia, infection and bleeding can occur. Thus, it is imperative to restore stem cell levels as quickly as possible. Autologous stem cell transplants involve the collection of a patient’s own stem cells prior to chemotherapy treatment. These stem cells are frozen and then infused back into the patients after treatment to “rescue” the bone marrow.

Recently, physicians in Germany further evaluated HDC with stem cell transplant as initial therapy for high-risk patients. The study involved 146 patients who received HDC and stem cell transplant. These patients were then directly compared to similar patients who received conventional-dose therapy. The results of this study indicated that 72% of patients who were treated with HDC and stem cell transplant experienced a 3-year cancer-free survival, compared to 59% of patients who were treated with conventional chemotherapy.

Role of Surgery

In selected cases, surgery should be used after chemotherapy to remove residual masses to determine if viable cancer cells remain, since such a finding is an indication for further chemotherapy. Surgical removal of residual masses is also necessary to prevent regrowth of teratomas and growth of non-germ cell elements present in some of these masses. Results from one study have indicated that regardless of the initial histology, there is a significant risk of residual teratoma or carcinoma in residual masses after chemotherapy. Neither the size of the initial tumor nor the degree of cancer shrinkage while on therapy appears to accurately identify patients with residual teratoma or carcinoma. This has led some physicians to recommend surgery with resection of all residual masses apparent on scans, even in patients who have normal markers after responding to chemotherapy.

Chemotherapy Before Orchiectomy for Life-Threatening Disease

In some cases, chemotherapy is initiated prior to orchiectomy because of life-threatening spread of cancer. When this is done, orchiectomy after chemotherapy is advisable in order to remove the primary cancer. This is because there is a blood-testes barrier to chemotherapy. There are two places in the body where chemotherapy cannot penetrate, the brain and the testes. The blood-testes barrier prevents chemotherapy from reaching the testicle, thereby resulting in a high incidence of residual cancer in the testicle after completion of a full course of chemotherapy. In other words, all cancer outside the testes can be eliminated with a full course of chemotherapy, but there could still be cancer in the testes.

Strategies to Improve Treatment

The progress that has been made in the treatment of testicular cancer has resulted from improved development of chemotherapy and radiation treatments in patients with more advanced stages of cancer and participation in clinical trials. Future progress in the treatment of testicular cancer will result from continued participation in appropriate clinical trials. Currently, there are several areas of active exploration aimed at improving the treatment of stage III non-seminoma testicular cancer.

Supportive Care: Supportive care refers to treatments designed to prevent and control the side effects of cancer and its treatment. Side effects not only cause patients discomfort, but also may prevent the optimal delivery of therapy at its planned dose and schedule. In order to achieve optimal outcomes from treatment and improve quality of life, it is imperative that side effects resulting from cancer and its treatment are appropriately managed. For more information, go to Supportive Care.

High-Dose Chemotherapy with Stem Cell Support: Different high-dose chemotherapy regimens are being evaluated in patients with high-risk cancers. In one study of high-dose Platinol®, etoposide and Ifex® supported by peripheral blood stem cells, the long-term survival was 80%.

New Chemotherapy Regimens: Development of new multi-drug chemotherapy treatment regimens that incorporate new or additional anti-cancer therapies for use as treatment is an active area of clinical research carried out in phase II clinical trials.

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Testicular Cancer FACT SHEET

Testicular cancer is one of the most treatable and survivable types of cancer if detected early. Testicular cancer occurs when cells in a testicle become cancerous. A disease most often associated with young men, testicular cancer is often diagnosed in men ages 20 to 34. The disease is essentially unpreventable as most risk factors are present at birth, and men with no known risk factors can also be diagnosed with testicular cancer. However, if detected and treated in early stages when the cancer is only in the testicle, testicular cancer patients have a 99% chance of survival after five years. Most cases of testicular cancer are initially identified by the patient, making self-observation critical to early detection.

Eddie Maraboto

Patient Story: Eddie Maraboto

"Being a nurse and having worked in a hospice and helping my mom and grandfather through their cancer, I’ve been involved in oncology care. Right away, I saw the team environment at Texas Oncology and found it reassuring."