Stages of Testicular Cancer

Learn how testicular cancer is staged — from carcinoma in situ to Stage III - and how Texas Oncology tailors treatment based on cancer type and progression.

Non-Seminoma: Stage I Non-Seminoma: Stage II Non-Seminoma: Stage III Seminoma: Stage I Seminoma: Stage II Seminoma: Stage III

Non—Seminoma: Stage I

Overview

Patients with stage I testicular cancer of non-seminoma type have a primary cancer that is limited to the testes and is curable in more than 95% of cases.

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 I 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.

Standard approach: retroperitoneal lymph node dissection and surveillance

Currently, surgical orchiectomy and retroperitoneal lymph node dissection is considered to be the standard approach to treatment of stage I non-seminoma in adults, but not in children. The major advantage of retroperitoneal node dissection is accuracy of staging. Following surgery, patients undergo surveillance, which consists of monthly checking of cancer markers and chest x-rays for the first year and slightly less frequent evaluations in the second year. Patients that experience a cancer recurrence are treated with chemotherapy.

In clinical studies, 15% of patients with a negative lymph node dissection (no evidence of spread) experienced cancer recurrence, usually in the lungs. Recurrences usually occur within 18 months of surgery and most patients are subsequently cured with combination chemotherapy. In patients with stage I cancer confirmed by retroperitoneal lymph node dissection, the presence of lymphatic or venous invasion in the primary cancer appears to predict for a greater chance of cancer relapse.

Alternative approach: no retroperitoneal lymph node dissection, surveillance, and chemotherapy for those who relapse

Since virtually all patients with stage I non-seminoma that relapse after orchiectomy can be cured with combination chemotherapy, some doctors believe it is not necessary to perform a retroperitoneal lymph node dissection. Patients who elect this approach are treated with orchiectomy, but do not undergo retroperitoneal lymph node dissection. Instead, they have frequent follow-up visits with their doctor (surveillance) including chest x-rays, evaluations of cancer markers and, during the first year, abdominal CT scan every 2 months. Since approximately 25% of patients initially diagnosed with stage I cancer who are treated with orchiectomy and careful observation will in fact have a stage II cancer with spread to the retroperitoneal lymph nodes, careful follow-up and prompt administration of chemotherapy for relapse is important.

In a large clinical study involving 105 patients with clinical stage I disease (no retroperitoneal lymph node dissection), not including patients with choriocarcinoma, the relapse rate following treatment with orchiectomy alone was 26%. All cancer recurrences occurred within 2 years of diagnosis and 24 of the 27 patients with recurrent cancer were cured with chemotherapy. Relapses have, however, been reported more than 5 years after the orchiectomy in patients who did not undergo a retroperitoneal lymph node dissection. The option of no lymph node dissection is considered only if a CT scan and cancer markers are negative.

Alternative approach: no lymph node dissection and adjuvant chemotherapy

Patients with clinical stage I non-seminoma may also elect to receive treatment with chemotherapy following orchiectomy and avoid a retroperitoneal lymph node dissection. Two courses of bleomycin, etoposide and Platinol® (BEP) have been given to patients with clinical stage I disease who were considered at high risk of relapse based on the presence of vascular invasion and aggressive histology. In these studies, 95-98% of patients were cured. These results may be better than results achieved in patients treated with orchiectomy followed by surveillance, with chemotherapy reserved only for patients who relapse.

The number of patients treated with adjuvant chemotherapy is too small to draw conclusions about the risk of chemotherapy-induced secondary malignancies, impact on fertility or risk of late relapse. It is unclear if the 3 approaches to treatment are equivalent or one is superior to another. It is clear, however, that the differences will be small and hard to detect without an extremely large clinical trial performing a direct comparison of the 3 approaches.

Factors which affect decision making

Physicians have been surveyed to determine which therapy they would select. Half chose surgery and half chose chemotherapy. However, 82% of medical oncologists chose chemotherapy and 83% of urologists chose surgery. Medical oncologists are experts in the delivery of chemotherapy and urologists perform surgery. This survey demonstrated that physicians often make decisions based on their experience and comfort level with the procedure they perform. Thus, the treatment offered for a stage I testicular cancer patient may depend on the type of physician the patient sees. The management of stage I testicular cancer is still evolving. This survey demonstrates the importance of having all treatment information presented in an objective fashion and for the need to seek the opinion of more than one physician, preferably in a different subspecialty.

Questions to ask your physician

What are the advantages, disadvantages and side effects of a retroperitoneal lymph node dissection?
What are the chances of my disease coming back without lymph node dissection or chemotherapy?
How frequently do I need to have CT scans if I do not receive adjuvant chemotherapy treatment?
What are the long-term side effects of adjuvant chemotherapy?

Strategies to improve outcomes

Clinical trials for patients with stage I non-seminoma testicular cancer are limited to determining the initial extent of treatment necessary for optimal results and what the factors are that favor one approach over another. It will be important to determine which treatment approach produces the fewest long-term side effects in patients with stage I non-seminoma.

Non—Seminoma: Stage II

Overview

Patients with stage II non-seminoma have cancer that involves the testicle and the retroperitoneal lymph nodes and is curable in over 90% of cases

The following is a general overview of the treatment of stage II 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.

There are several treatment options for patients with stage II non-seminoma based on the extent of the disease at diagnosis. All include surgical removal of the cancer with orchiectomy and pelvic lymph node dissection or adjuvant therapy.

Lymph node dissection and surveillance

Because surgical removal of the cancer cures the majority of patients and chemotherapy can cure most patients whose cancer returns following surgery, a surgical orchiectomy and retroperitoneal lymph node dissection followed by close surveillance is the standard treatment. Surveillance consists of monthly checkups, physical examination, chest x-ray, and cancer marker tests (AFP, BHCG and LDH) with CT scans every 2 months. This option of surgery and careful surveillance, reserving chemotherapy to only treat cancer recurrences, is usually advised for patients who have fewer than 6 lymph nodes involved with cancer at retroperitoneal lymph node dissection, none of which are greater than 2 centimeters (about one inch) in diameter and cancer that is without evidence of venous or lymphatic invasion. Such patients have a cancer recurrence rate of approximately 20-30% if treated with surgery alone and most are curable with standard combination chemotherapy containing Platinol^® when recurrence occurs. By utilizing this approach, the majority of patients are cured and 70-80% of patients will not require chemotherapy.

Lymph node dissection and adjuvant chemotherapy

It is important to understand that some patients with non-seminoma already have small amounts of cancer that have spread beyond what was removed surgically and cannot be detected with any of the currently available tests. Undetectable areas of cancer are referred to as micrometastases. The presence of micrometastases causes cancer recurrence following treatment with surgery alone. An effective treatment is needed to cleanse the body of micrometastases in order to improve a patient’s potential for cure. The delivery of cancer treatment following local treatment with surgery is referred to as adjuvant therapy and may include chemotherapy or radiation therapy.

Following orchiectomy and lymph node dissection, some patients will experience cancer recurrence if they are not treated with adjuvant therapy. By routinely administering adjuvant chemotherapy after surgery, the chance of cancer recurrence can almost be completely eliminated. The choice of receiving adjuvant chemotherapy is influenced by the risk of cancer recurrence and the preferences of the patient concerning surveillance.

Tumors larger than 2 centimeters, involvement of more than 6 lymph nodes with cancer and evidence of vascular invasion of the primary tumor are all associated with an increased risk of cancer recurrence. The relapse rate after retroperitoneal lymph node dissection has been reported to be approximately 60% in patients who had microscopic evidence of vascular invasion in the primary tumor. Patients whose tumor markers do not return to normal following the removal of retroperitoneal lymph nodes are also at a high risk for cancer recurrence. These patients may elect to be treated with adjuvant chemotherapy to reduce their risk of recurrence.

The results of a large clinical trial comparing adjuvant chemotherapy to surveillance demonstrated that 2 courses of Platinol^®-based chemotherapy (either Platinol^®, Velban^®, bleomycin (PVB) or Velban^®, bleomycin, cyclophosphamide, Platinol^® (VAB VI)) prevented cancer recurrences in more than 95% of patients with stage II non-seminoma. There was a 49% recurrence rate in patients assigned to surveillance; however, almost all of these patients could be effectively treated with chemotherapy at the time of relapse. This study suggests that although adjuvant therapy will almost always prevent recurrences, the alternative approach of surveillance with chemotherapy only for patients who relapse results in an equivalent overall cure rate.

Neoadjuvant chemotherapy with delayed surgery for large volume disease

Neoadjuvant therapy consists of chemotherapy or radiation therapy that is administered prior to surgery with the intent of shrinking the cancer so that it is easier to remove. Some patients have large cancers and it may be difficult to remove the entire cancer with surgery. Treatment with neoadjuvant chemotherapy may decrease the size of the cancer, thereby allowing for easier and more complete removal with surgery. Standard chemotherapy regimens include bleomycin, etoposide and Platinol^® (BEP) for 3 courses or a regimen of etoposide and Platinol^® for 4 courses.

If patients do not achieve a complete response from neoadjuvant chemotherapy, surgical removal of residual cancer is performed. The timing of such surgery requires clinical judgment, but typically occurs after 3 or 4 cycles of combination chemotherapy and normalization of tumor markers. The chance of finding residual cancer after chemotherapy is dependent on the histology of the primary tumor. Patients whose primary tumor contained teratomatous elements have a higher probability of having residual teratoma or carcinoma in the lymph nodes than do patients whose primary tumor contains only embryonal cancer. However, one study has reported that regardless of initial histology, there is a significant risk of residual teratoma or carcinoma in residual masses after chemotherapy. Therefore, some physicians think that neither the size of the initial cancer nor the degree of shrinkage accurately identifies patients likely to have residual teratoma or carcinoma. This has led some physicians to recommend surgery with resection of all residual masses apparent on CT scans in patients who have normal cancer markers after responding to chemotherapy. If patients have persistent non-seminomatous germ cell malignant cancer in the surgically removed mass, additional chemotherapy is required.

Chemotherapy before orchiectomy for life-threatening disease

In some cases, cancer has spread to other areas of the body and has become life threatening. In these instances, chemotherapy is initiated prior to orchiectomy. 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.

The standard chemotherapy regimens based on controlled studies consist of 3 cycles of bleomycin, etoposide and Platinol^® (BEP) or 4 cycles of etoposide and Platinol^® using a 5-day etoposide schedule.

Adjuvant therapy and no lymph node dissection for low volume disease

In some clinical trials, primary chemotherapy has been administered to patients with small volume cancers in an effort to avoid lymph node dissection. Although clinical trials directly comparing lymph node dissection to chemotherapy have not been performed, it appears that primary chemotherapy, when compared to primary retroperitoneal node dissection, produces similar cure rates in patients with clinical stage II non-seminoma.

Questions to ask your physician

Based on my situation, what is the best treatment option?
What are the risks of delaying treatment compared to getting adjuvant chemotherapy?
What are the risks of lymph node dissection?

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. The main issues for treatment of stage II non-seminoma involve studies to determine the optimal timing for intervention with chemotherapy and the role of retroperitoneal node dissection.

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.

Non—Seminoma: Stage III

Overview

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.

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.

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
Risk	AFP	BHCG	LDH	5-yr DFS*
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.

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.

Seminoma: Stage I

Overview

Patients with Stage I seminoma have a primary cancer that is limited to the testes and is curable in more than 95% of individuals.

The primary treatment of Stage I seminoma is surgical removal of the cancer by orchiectomy. Following surgery, patients may receive chemotherapy or radiation therapy to reduce the risk of cancer recurrence, or close surveillance to detect recurrence at an early stage.

The following is a general overview of treatment for Stage I seminoma. Cancer treatment may consist of surgery, radiation, chemotherapy, targeted therapy, or a combination of these treatment techniques. Combining two or more of these treatment techniques–called multi-modality care–has become an important approach for increasing a patient’s chance of cure and prolonging survival.

In some cases, participation in a clinical trial utilizing new, innovative therapies may provide the most promising treatment. Treatments that may be available through clinical trials are discussed in the section titled Strategies to Improve Treatment.

Circumstances unique to each patient’s situation influence which treatment or treatments are utilized. The potential benefits of multi-modality care, participation in a clinical trial, or standard treatment must be carefully balanced with the potential risks. The information on this Web site is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision-making process with their treating cancer physician.

Adjuvant therapy

It is important to understand that a few patients with Stage I seminoma already have small amounts of cancer that have spread into the lymph nodes and cannot be detected with any of the currently available tests. Undetectable areas of cancer are referred to as micrometastases. The presence of micrometastases causes cancer recurrence following treatment with surgery alone. An effective treatment is needed to cleanse the body of micrometastases in order to improve a patient’s duration of survival and potential for cure. The delivery of cancer treatment following local treatment with surgery is referred to as “adjuvant” therapy and may include chemotherapy or radiation therapy.

Following surgical orchiectomy (removal of the affected testicle), approximately 15% of patients with a Stage I seminoma will experience cancer recurrence if they are not treated with additional therapy. By administering relatively low doses of chemotherapy and/or radiation therapy to the retroperitoneal and inguinal lymph nodes after surgery, the chance of cancer recurrence can almost be completely eliminated.

Historically, most patients have been given radiation treatment following orchiectomy; however, recent clinical trials suggest that chemotherapy may be more advantageous. One of these clinical studies involved 125 patients who received either one or two courses of chemotherapy with Paraplatin^® (carboplatin) after orchiectomy.¹ Cancer recurred in 8.6% of patients who received one course of Paraplatin; all were cured with further chemotherapy. None of the patients who received two courses of Paraplatin experienced a cancer recurrence. In another study, 107 patients with Stage I seminoma received two courses of Paraplatin after orchiectomy; during an average of six years of follow-up, none of the patients experienced a cancer recurrence.² These studies suggest that adjuvant treatment with two doses of Paraplatin is as effective as radiation therapy, and may be better tolerated.

Treatment of patients with surgery and surveillance

An acceptable alternative to adjuvant therapy is to give no additional treatment after surgery and to perform surveillance. The principle of surveillance is to perform frequent evaluations after surgery in order to detect an early cancer recurrence and then initiate further treatment. Evaluations consist of chest X-rays, CT scans, and checking for cancer markers.

A review of previously published studies found that 17% of seminoma patients managed by surveillance experienced a cancer recurrence. Nearly all of these patients were cured with subsequent treatment.³

The advantage of surveillance is that the 85% of patients who are not destined to relapse are not exposed to radiation, which is associated with a low but definite risk of developing a second cancer, or chemotherapy. However, prolonged surveillance is necessary, because 20% of relapses occur four or more years after diagnosis. The size of the primary cancer may be an important prognostic factor, as patients with cancers larger than 6 centimeters (2 ½ inches) have a higher risk of relapse without adjuvant radiation therapy.

In summary, adjuvant radiation, chemotherapy or surveillance are all appropriate treatment options. Adjuvant treatment may be the option of choice for patients with a higher risk of cancer recurrence, such as those with vascular invasion observed on examination under the microscope or for patients who have primary cancers over 5 cm (2 inches) in size. Adjuvant chemotherapy may also be a consideration for those who do not want to risk the potential long-term side effects of radiation therapy (second cancers) or the anxiety associated with the frequent surveillance testing after surgery to detect early recurrences of cancer.

Questions to ask your physician

What is my risk of cancer relapse without adjuvant therapy?
What are the short-term and long-term side effects of adjuvant therapy given to prevent relapses?
How frequently do I need to have surveillance examinations if I choose not to have adjuvant therapy?

Strategies to improve treatment

The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Future progress in the treatment of testicular cancer will result from the continued evaluation of new treatments in clinical trials.

Patients may gain access to better treatments by participating in a clinical trial. Participation in a clinical trial also contributes the cancer community’s understanding of optimal cancer care and may lead to better standard treatments. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. Areas of active investigation aimed at improving the treatment of Stage I seminoma include the following:

Adjuvant Therapy vs. Surveillance: Current clinical trials for patients with Stage I seminoma are focused on determining who will benefit from adjuvant therapy and who will benefit from surgery alone followed by careful surveillance and treatment with chemotherapy when relapse occurs.

References

1 Dieckmann KP, Brüggeboes B, Pichlmeier U, Küster J, Müllerleile U, Bartels H. Adjuvant treatment of clinical stage I seminoma: is a single course of carboplatin sufficient? Urology. 2001;55:102-6.

2 Reiter WJ, Brodowicz T, Alavi S et al. Twelve-year experience with two courses of adjuvant single-agent carboplatin therapy for clinical stage I seminoma. Journal of Clinical Oncology. 2001;19:101-4.

3 Groll RJ, Warde P, Jewett MA. A comprehensive review of testicular germ cell tumor surveillance. Critical Reviews in Oncology/Hematology. 2007;64:182-97.

Seminoma: Stage II

Overview

Patients with Stage II testicular seminoma have a curable cancer that involves the testis and the retroperitoneal lymph nodes. Retroperitoneal lymph node involvement is further characterized by the number of nodes involved and the size of involved nodes. Patients with Stage II seminoma are often divided into “bulky” and “non-bulky” for treatment planning.

The primary treatment of Stage II seminoma is surgical removal of the cancer by orchiectomy followed by adjuvant therapy to reduce the risk of cancer recurrence.

The following is a general overview of treatment for Stage II seminoma. Cancer treatment may consist of surgery, radiation, chemotherapy, targeted therapy, or a combination of these treatment techniques. Combining two or more of these treatment techniques–called multi-modality care–has become an important approach for increasing a patient’s chance of cure and prolonging survival.

Adjuvant therapy

It is important to understand that some patients with Stage II seminoma already have small amounts of cancer that have spread into the lymph nodes and cannot be detected with any of the currently available tests. Undetectable areas of cancer that remain after surgery are referred to as micrometastases. The presence of micrometastases causes cancer recurrence following treatment with surgery alone. An effective treatment is needed to cleanse the body of micrometastases in order to improve a patient’s duration of survival and potential for cure.

The delivery of cancer treatment following local treatment with surgery is referred to as “adjuvant” therapy and may include chemotherapy or radiation therapy. Following orchiectomy, 15-50% of patients will experience cancer recurrence if they are not treated with adjuvant therapy. By administering chemotherapy or radiation therapy to the retroperitoneal and inguinal lymph nodes after surgery, the chance of cancer recurrence can almost be completely eliminated. The choice of receiving radiation therapy or chemotherapy is influenced by side effects, convenience and whether the cancer is bulky.

Non-bulky cancers

Patients with non-bulky disease have cancers involving the lymph nodes that are less than 5 centimeters (2 inches) in greatest dimension measured on a computed tomography (CT) scan. The standard treatment for non-bulky cancers consists of radiation to the retroperitoneal lymph nodes following surgical orchiectomy. This results in a cure rate of more than 90%. One of the controversies in management of Stage II seminoma is how much surveillance is necessary in patients who have received radiation therapy since the recurrence rate is so low.

Bulky disease

Patients with bulky disease have cancers involving the lymph nodes that are greater than 5 centimeters (2 inches) in greatest dimension when measured on a CT scan. Standard therapy for bulky disease utilizes a Platinol^® (cisplatin)-based combination chemotherapy regimen or radiation therapy to the abdominal and pelvic lymph nodes following surgical orchiectomy. In the past, patients with bulky disease were treated with radiation therapy and orchiectomy; however, one frequent cause of treatment failure in patients with bulky disease receiving radiation therapy was cancer recurrences outside the field of radiation. Because cancers recurred outside the radiation field, doctors began using chemotherapy, which is a systemic treatment capable of killing cancer cells throughout the body.

In a clinical study comparing 19 patients treated with chemotherapy to 16 patients treated with radiation therapy, the results indicated that none of the patients treated with chemotherapy experienced cancer recurrences, whereas 9 of the 16 patients treated with radiation therapy experienced recurrences.¹ Chemotherapy without radiation may be the better treatment alternative for patients with bulky disease. Standard chemotherapy based on carefully controlled clinical studies consists of 3 cycles of bleomycin, etoposide and Platinol (BEP) or 4 cycles of etoposide and Platinol (EP).²

After completion of therapy, a residual mass in the location of the original cancer is often detected by CT, magnetic resonance imaging (MRI), or positron emission tomography (PET) scans. A residual mass may represent scar formation or inadequately treated cancer, and is best evaluated by PET scan at least 6 weeks after completing chemotherapy. If the PET scan is negative, routine follow up is indicated. If the PET scan is positive, there may be residual cancer and a biopsy is considered useful in order to determine the most appropriate course of action.²

Strategies to improve treatment

Adjuvant Therapy: Clinical trials are attempting to define the optimal role of chemotherapy and radiation therapy for patients with Stage II disease. Researchers are also attempting to decrease the short and long-term side effects of chemotherapy without decreasing survival.

References:

1 Warde P, Gospodarowicz M, Panzarella T et al. Management of stage II seminoma. Journal of Clinical Oncology. 1998;16:290-294.

2 National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Testicular Cancer. V.2.2008. © National Comprehensive Cancer Network, Inc. 2008. NCCN and NATIONAL COMPREHENSIVE CANCER NETWORK are registered trademarks of National Comprehensive Cancer Network, Inc.

Seminoma: Stage III

Overview

Patients with Stage III seminoma have spread of cancer outside the testes and retroperitoneal lymph nodes and are curable in more than 90% of cases.

The following is a general overview of treatment for Stage III seminoma. Cancer treatment may consist of surgery, radiation, chemotherapy, targeted therapy, or a combination of these treatment techniques. Combining two or more of these treatment techniques–called multi-modality care–has become an important approach for increasing a patient’s chance of cure and prolonging survival.

Since patients with Stage III testicular seminoma have widespread cancer, the treatment of choice is systemic chemotherapy. The most frequently utilized chemotherapy combinations include bleomycin, etoposide and Platinol^® (cisplatin) (BEP) for 3 courses or etoposide and Platinol (EP) for 4 courses in good-prognosis patients.¹ The cure rate following either of these regimens is approximately 90%.

After completion of therapy, a residual mass in the location of the original cancer is often detected by computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) scans. A residual mass may represent scar formation or inadequately treated cancer, and is best evaluated by PET scan at least 6 weeks after completing chemotherapy. If the PET scan is negative, routine follow up is indicated. If the PET scan is positive, there may be residual cancer and a biopsy is considered useful in order to determine the most appropriate course of action.¹

Strategies to improve treatment

New Adjuvant Chemotherapy Regimens: The goal of developing new chemotherapy regimens is to decrease short- and long-term side effects without compromising the chance of cure. Several new chemotherapy drugs show promising activity for the treatment of testicular cancer. The combination of cyclophosphamide and Paraplatin^® (carboplatin) chemotherapy appears to be as effective as Platinol, etoposide, and bleomycin combinations without the severity of side effects.²

References:

1 National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Testicular Cancer. V.2.2008. © National Comprehensive Cancer Network, Inc. 2008. NCCN and NATIONAL COMPREHENSIVE CANCER NETWORK are registered trademarks of National Comprehensive Cancer Network, Inc.

2 Amato RJ, Millikan R, Daliani D, Wood L, Logothetis C, Pollack A. Cyclophosphamide and carboplatin and selective consolidation in advanced seminoma. Clinical Cancer Research. 2000;6:72-7.