Treatment of Seminoma Stage I-III
Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor (08/2018)
Treatment of Stage I Seminoma
A stage I seminoma is a primary cancer that is limited to the testes and is curable with surgical orchiectomy alone in more than 95% of individuals.
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?
Treatment of Stage II Seminoma
Stage II testicular seminoma involves the testis and the retroperitoneal lymph nodes and is curable with surgery, and adjuvant treatment with radiation and or systemic therapy. 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
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.
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.
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.1Chemotherapy 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
Treatment of Seminoma Stage III
Patients with Stage III seminoma have cancer that has spread outside the testes and retroperitoneal lymph nodes and is curable in more than 90% of individuals.
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
Treatment of Refractory/Recurrent Seminoma
Patients can have a recurrence of cancer after initial therapy and/or be refractory to chemotherapy following treatment. Outcomes for patients with recurrent cancer depend on the extent of disease, prior therapy and the interval from primary treatment. Many patients with recurrent disease remain curable.
Patients with Cancer Recurrence after Surgery or Radiation Therapy
Patients who experience a cancer recurrence after treatment with orchiectomy and/or radiation therapy are typically treated with chemotherapy. The most frequently administered chemotherapy combinations include bleomycin, etoposide and Platinol® (BEP) for 3 courses or etoposide and Platinol® (EP) for 4 courses in good-prognosis patients. Over 90% of patients who relapse after surgery or radiation therapy can be cured with chemotherapy.
Treatment of Patients who Fail Initial Chemotherapy
Patients who fail Platinol®-based chemotherapy require treatment with different chemotherapy regimens. Currently available chemotherapy regimens can induce long-term complete remissions in approximately 25% of patients with cancer that persisted or recurred following initial Platinol®-based treatment. Patients who experienced a complete response to initial chemotherapy and those without extensive disease have the most favorable outcomes.
High-dose chemotherapy with autologous blood stem cell support has also been successful in producing long-term complete remissions in patients with refractory testicular 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.
A large clinical study involving 150 patients evaluated high-dose chemotherapy with Platinol®, etoposide and Ifex®. Overall, 29% of patients survived without cancer recurrence following treatment, which may be greater than expected with non stem cell supported conventional-dose therapy.
In another recent clinical trial, researchers evaluated a treatment strategy that utilized two sequential doses of high-dose chemotherapy followed by autologous stem cell transplants in patients as initial therapy following their recurrence. Three years following this treatment, almost 60% of these patients survived cancer free. Not one patient died from complications related to high-dose treatment.
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.
Stage I Seminoma: 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.
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
High-Dose Chemotherapy And Stem Cell Transplant: Different high-dose chemotherapy regimens are being evaluated in patients with refractory disease. There are also trials of sequential administration of more than one high-dose regimen.
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.
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.
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.