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The testicles are 2 egg-shaped glands located inside the scrotum (a sac of loose skin that lies directly below the penis). The testicles are held within the scrotum by the spermatic cord, which also contains the vas deferens and vessels and nerves of the testicles.
The testicles are the male sex glands and produce testosterone and sperm. Germ cells within the testicles produce immature sperm that travel through a network of tubules (tiny tubes) and larger tubes into the epididymis (a long coiled tube next to the testicles) where the sperm mature and are stored.
Almost all testicular cancers start in the germ cells. The two main types of testicular germ cell tumors are seminomas and nonseminomas. These 2 types grow and spread differently and are treated differently. Nonseminomas tend to grow and spread more quickly than seminomas. Seminomas are more sensitive to radiation. A testicular tumor that contains both seminoma and nonseminoma cells is treated as a nonseminoma.
Testicular cancer is the most common cancer in men 20 to 35 years old.
Anything that increases the chance of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. Talk with your doctor if you think you may be at risk. Risk factors for testicular cancer include:
These and other signs and symptoms may be caused by testicular cancer or by other conditions. Check with your doctor if you have any of the following:
The following tests and procedures may be used:
The prognosis (chance of recovery) and treatment options depend on the following:
Testicular cancer can usually be cured in patients who receive adjuvantchemotherapy or radiation therapy after their primary treatment.
Certain treatments for testicular cancer can cause infertility that may be permanent. Patients who may wish to have children should consider sperm banking before having treatment. Sperm banking is the process of freezing sperm and storing it for later use.
See the PDQ summary on Sexuality and Reproductive Issues for more information.
The process used to find out if cancer has spread within the testicles or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment.
The following tests and procedures may be used in the staging process:
Cancer can spread through tissue, the lymph system, and the blood:
When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph system or blood.
The metastatic tumor is the same type of cancer as the primary tumor. For example, if testicular cancer spreads to the lung, the cancer cells in the lung are actually testicular cancer cells. The disease is metastatic testicular cancer, not lung cancer.
In stage 0, abnormalcells are found in the tiny tubules where the sperm cells begin to develop. These abnormal cells may become cancer and spread into nearby normal tissue. All tumor marker levels are normal. Stage 0 is also called carcinoma in situ.
In stage I, cancer has formed. Stage I is divided into stage IA, stage IB, and stage IS and is determined after an inguinal orchiectomy is done.
Stage II is divided into stage IIA, stage IIB, and stage IIC and is determined after an inguinal orchiectomy is done.
Stage III is divided into stage IIIA, stage IIIB, and stage IIIC and is determined after an inguinal orchiectomy is done.
Recurrenttesticular cancer is cancer that has recurred (come back) after it has been treated. The cancer may come back many years after the initial cancer, in the other testicle or in other parts of the body.
Different types of treatments are available for patients with testicular cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.
For nonseminoma, all of the following must be true:
For seminoma, all of the following must be true:
For nonseminoma, at least one of the following must be true:
There is no poor prognosis grouping for seminoma testicular tumors.
Surgery to remove the testicle (inguinal orchiectomy) and some of the lymph nodes may be done at diagnosis and staging. (See the General Information and Stages sections of this summary.) Tumors that have spread to other places in the body may be partly or entirely removed by surgery.
Even if the doctor removes all the cancer that can be seen at the time of the surgery, some patients may be given chemotherapy or radiation therapy after surgery to kill any cancer cells that are left. Treatment given after the surgery, to lower the risk that the cancer will come back, is called adjuvant therapy.
Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.
Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping the cells from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.
See Drugs Approved for Testicular Cancer for more information.
Surveillance is closely following a patient's condition without giving any treatment unless there are changes in test results. It is used to find early signs that the cancer has recurred (come back). In surveillance, patients are given certain exams and tests on a regular schedule.
High-dose chemotherapy with stem cell transplant is a method of giving high doses of chemotherapy and replacing blood-forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient or a donor and are frozen and stored. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body’s blood cells.
Stem Cell Transplant
Stem cell transplant (Step 1). Blood is taken from a vein in the arm of the donor. The patient or another person may be the donor. The blood flows through a machine that removes the stem cells. Then the blood is returned to the donor through a vein in the other arm.
Stem cell transplant (Step 2). The patient receives chemotherapy to kill blood-forming cells. The patient may receive radiation therapy (not shown).
Stem cell transplant (Step 3). The patient receives stem cells through a catheter placed into a blood vessel in the chest.
Information about clinical trials is available from the NCI Web site.
For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.
Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.
Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.
Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.
Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.
Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.
Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.
Men who have had testicular cancer have an increased risk of developing cancer in the other testicle. A patient is advised to regularly check the other testicle and report any unusual symptoms to a doctor right away.
Long-term clinical exams are very important. The patient will probably have check-ups frequently during the first year after surgery and less often after that.
Treatment of stage I testicular cancer depends on whether the cancer is a seminoma or a nonseminoma.
Treatment of seminoma may include the following:
Treatment of nonseminoma may include the following:
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I malignant testicular germ cell tumor. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.
Treatment of stage II testicular cancer depends on whether the cancer is a seminoma or a nonseminoma.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II malignant testicular germ cell tumor. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.
Treatment of stage III testicular cancer depends on whether the cancer is a seminoma or a nonseminoma.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III malignant testicular germ cell tumor. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.
Treatment of recurrenttesticular cancer may include the following:
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent malignant testicular germ cell tumor. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.
For more information from the National Cancer Institute about testicular cancer, see the following:
For general cancer information and other resources from the National Cancer Institute, see the following:
This information is provided by the National Cancer Institute.
This information was last updated on July 3, 2014.
Estimated new cases and deaths from testicular cancer in the United States in 2014:
Testicular cancer is a highly treatable, usually curable, cancer that most often
develops in young and middle-aged men. Most testicular cancers are germ cell tumors. For treatment planning, germ cell tumors are broadly divided
into seminomas and nonseminomas because they have different prognostic and treatment algorithms. For patients with seminoma (all
stages combined), the cure rate exceeds 90%. For patients with low-stage
seminoma or nonseminoma, the cure rate approaches 100%.
Risk factors for testicular cancer include the following:
Surgical correction of an undescended testis (orchiopexy) before puberty appears to lower the risk of testis cancer, but this isn't certain.
The five histopathological subtypes of testicular germ cell tumors include:
Tumors that are 100% seminoma are considered seminomas. All other tumors, including those that have a mixture of seminoma and nonseminoma components, are considered and should be
managed as nonseminomas. Most nonseminomas consist of a mixture of the different germ-cell tumor subtypes. Tumors that appear to have a seminoma histology but are accompanied by an elevated
serum level of alpha-fetoprotein (AFP) should be treated as nonseminomas because seminomas do not produce AFP.
Alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (beta-hCG), and lactase dehydrogenase (LDH) play an important role as serum tumor markers in the staging and monitoring of germ cell tumors and should be measured prior to removing the involved testicle. For patients with nonseminomas, the degree of tumor-marker elevation after the cancerous testicular has been removed is one of the most significant predictors of prognosis. Serum tumor markers are also very useful for monitoring all stages of nonseminomas and for monitoring metastatic seminomas because elevated marker levels are often the earliest sign of relapse.
AFP: Elevation of serum AFP is seen in 40% to 60% of men with nonseminomas. Seminomas do not produce AFP. Men who have an elevated serum AFP should be considered to have a mixed germ cell tumor (i.e., nonseminomatous germ cell tumors [NSGCT]) even if the pathology shows a pure seminoma, unless there is a more persuasive explanation for the elevated AFP, such as liver disease.
Beta-hCG: Elevation of the beta subunit of hCG is
found in approximately 14% of the patients with stage I pure seminoma prior to orchiectomy and in about half of patients with metastatic seminoma. Approximately 40% to 60% of men with nonseminomas have an elevated serum beta-hCG.
Significant and unambiguously rising levels of AFP and/or hCG are an indication of relapsed germ cell tumor in most cases and are an indication for treatment even in the absence of radiological evidence of metastatic disease. Nonetheless, tumor-marker elevations do need to be interpreted with caution. For example, false-positive hCG levels can result from cross reactivity of the assay with luteinizing hormone, in which case an intramuscular injection of testosterone should result in normalization of hCG values. There are also clinical reports of marijuana use resulting in elevations of serum hCG and some experts recommend querying patients about drug use and retesting hCG levels after a period of abstinence from marijuana use. Similarly, AFP is chronically mildly elevated in some individuals for unclear reasons and can be substantially elevated by liver disease.
LDH: Seminomas and nonseminomas alike may result in elevated lactate dehydrogenase (LDH) but such values are of less clear prognostic significance because LDH may be elevated in many different conditions unrelated to cancer. A study of the utility of LDH in 499 patients with testicular germ cell tumor undergoing surveillance after orchiectomy or after treatment of stage II or III disease reported that 7.7% of patient visits had elevations in LDH unrelated to cancer, whereas only 1.4% of visits had cancer-related increases in LDH. Of 15 relapses, LDH was elevated in six and was the first sign of relapse in one. Over 9% of the men had a persistent false-positive increase in LDH. The positive predictive value for an elevated LDH was 12.8%.
A second study reported that among 494 patients with stage I germ cell tumors who subsequently relapsed, 125 had an elevated LDH at the time of relapse. Of these 125, all had other evidence of relapse: 112 had a concurrent rise in AFP and/or hCG, one had CT evidence of relapse prior to the elevation in LDH, one had palpable disease on examination and one complained of back pain that led to imaging that revealed retroperitoneal relapse. Measuring LDH thus appears to have little value during surveillance of germ cell tumors for relapse. On the other hand, for patients with metastatic NSGCT, large studies of prognostic models have found the LDH level to be a significant independent predictor of survival on multivariate analysis.
There are two major prognostication models for testicular cancer: staging, and for risk-stratification of men with distant and/or bulky retroperitoneal metastases, the International Germ Cell Cancer Consensus Group classification. The prognosis of testicular germ cell tumors is determined by the following factors:
Thus, for men with disseminated seminomas, the main adverse prognostic variable is the presence of metastases to organs other than the lungs (e.g., bone, liver, or brain). For men with disseminated nonseminomas, the following variables are independently associated with poor prognosis:
Nonetheless, even patients with widespread metastases at
presentation, including those with brain metastases, may have curable disease and
should be treated with this intent.
Radical inguinal orchiectomy with initial high ligation of the spermatic cord
is the procedure of choice in diagnosing and treating a malignant testicular mass.
As noted above, serum AFP, LDH, and hCG should be measured prior to orchiectomy. Transscrotal biopsy is not considered appropriate because of the risk of local
dissemination of tumor into the scrotum or its spread to inguinal lymph nodes. A
retrospective analysis of reported series in which transscrotal approaches had
been used showed a small but statistically significant increase in local
recurrence rates compared with the recurrence rates when the inguinal approach was used (2.9% vs. 0.4%).[Level of evidence: 3iiiDii] Distant recurrence and survival rates, however, were
indistinguishable in the two approaches.
Evaluation of the retroperitoneal lymph nodes, usually by CT scanning, is an important aspect of
staging and treatment planning in adults with testicular cancer. Patients with a negative result have
a substantial chance of having microscopic involvement of the lymph nodes. Nearly 20% of seminoma patients and 30% of nonseminoma patients with normal CT scans and serum tumor markers will subsequently relapse if not given additional treatment after orchiectomy. For nonseminoma patients, retroperitoneal lymph node dissection (RPLND) increases the accuracy of staging but as many as 10% of men with normal imaging, normal tumor markers, and benign pathology at RPLND will still go on to relapse. About 25% of patients with clinical stage I
nonseminomatous testicular cancer will be upstaged to pathologic stage II with
RPLND, and about 25% of clinical
stage II patients will be downstaged to pathologic stage I with RPLND. In
prepubertal children, the use of serial measurements of AFP has proven sufficient for
monitoring response after initial orchiectomy. Lymphangiography and
para-aortic lymph node dissection do not appear to be useful or necessary in
the proper staging and management of testicular cancer in prepubertal boys. (Refer to the Genital/Urinary Tumors section in the PDQ summary on Unusual Cancers of Childhood for more information.)
Patients who have been cured of testicular cancer have approximately a 2% cumulative risk of developing a cancer in the opposite testicle during the 15
years after initial diagnosis. Within this range, men with nonseminomatous primary tumors appear to have a lower risk of subsequent contralateral testis tumors than men with seminomas.
HIV-infected men are reported to be at increased risk for developing testicular
seminomas. Depending on comorbid conditions such as active
infection, these men are generally managed similarly to non-HIV-infected
Because the majority of testis cancer patients who receive adjuvant chemotherapy or radiation therapy are
curable, it is necessary to be aware of possible long-term effects of
the various treatment modalities, such as the following:
Radiation therapy, used to treat pure seminomatous testicular cancers, can
cause fertility problems because of radiation scatter to the remaining testicle
during radiation therapy to retroperitoneal lymph nodes (as evidenced in the SWOG-8711 trial, for example). (Refer to the PDQ summary on Sexuality and Reproductive Issues for more information on fertility.) Depending on scatter
dose, sperm counts fall after radiation therapy but may recover over the course of 1
to 2 years. Shielding techniques can be used to decrease the radiation scatter
to the remaining normal testicle. Because chemotherapy, retroperitoneal lymph node dissection, and radiation therapy can each result in infertility, men should be offered the opportunity to bank sperm before undergoing any treatment for testis cancer other than orchiectomy.
Although acute bleomycin pulmonary toxic effects may occur, they are rarely fatal at
total cumulative doses of less than 400 units. Because life-threatening
pulmonary toxic effects can occur, the drug should be discontinued if early
signs of pulmonary toxic effects develop. Although decreases in pulmonary
function are frequent, they are rarely symptomatic and are reversible after the
completion of chemotherapy. Survivors of testis cancer who were treated with chemotherapy have been reported to be at increased risk of death from respiratory diseases, but it is unknown whether this finding is related to bleomycin exposure.
Radiation therapy, often used in the management of pure seminomatous germ cell
cancers, has been linked to the development of secondary cancers, especially
solid tumors in the radiation portal, usually after a latency period of a
decade or more. These include melanoma and cancers of the stomach, bladder, colon,
rectum, pancreas, lung, pleura, prostate, kidney, connective tissue, and thyroid.
Chemotherapy has also been associated with an elevated risk of secondary cancers.
More recently, men with testis cancer who have been treated with radiation therapy and/or chemotherapy have been reported to be at increased risk of cardiovascular events. Other studies have reported that chemotherapy for testis cancer is associated with an increased risk of developing metabolic syndrome and hypogonadism. Moreover, an international population-based study reported that men treated with either radiation or chemotherapy were at increased risk of death from circulatory diseases.
In a retrospective series of 992 patients treated for testicular cancer at the Royal Marsden Hospital between 1982 and 1992, cardiac events were increased approximately 2.5-fold in patients treated with radiation therapy and/or chemotherapy compared with those who underwent surveillance after a median of 10.2 years. The actuarial risks of cardiac events were 7.2% for patients who received radiation therapy (92% of whom did not receive mediastinal radiation therapy), 3.4% for patients who received chemotherapy (primarily platinum-based), 4.1% for patients who received combined therapy, and 1.4% for patients who underwent surveillance management after 10 years of follow-up.
A population-based, retrospective study of 2,339 testicular cancer survivors in the Netherlands, treated between 1965 and 1995 and followed for a median of 18.4 years, found that the overall incidence of coronary heart disease (i.e., myocardial infarction and/or angina pectoris) was increased 1.17 times (95% confidence interval [CI], 1.04–1.31) compared with the general population. Patients who received radiation therapy to the mediastinum had a 2.5-fold (95% CI, 1.8–3.4) increased risk of coronary heart disease, and those who also received chemotherapy had an almost 3-fold (95% CI, 1.7–4.8) increased risk. Patients who were treated with infradiaphragmatic radiation therapy alone had no significantly increased risk of coronary heart disease. In multivariate Cox regression analyses, the older chemotherapy regimen of cisplatin, vinblastine, and bleomycin (PVB), used until the mid-1980s, was associated with a significant 1.9-fold (95% CI, 1.2–2.9) increased risk of cardiovascular disease (i.e., myocardial infarction, angina pectoris, and heart failure combined). The newer regimen of bleomycin, etoposide, and cisplatin (BEP) was associated with a borderline significant 1.5-fold (95% CI, 1.0–2.2) increased risk of cardiovascular disease. Similarly, an international pooled analysis of population-based databases reported that the risk of death from circulatory disease was increased in men treated with chemotherapy (standardized mortality ratio 1.58) or radiation therapy (SMR = 1.70).[Level of evidence: 3iiiDii]
Although testicular cancer is highly curable, all newly diagnosed patients are
appropriately considered candidates for clinical trials designed to decrease
morbidity of treatment while further improving cure rates.
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van den Belt-Dusebout AW, Nuver J, de Wit R, et al.: Long-term risk of cardiovascular disease in 5-year survivors of testicular cancer. J Clin Oncol 24 (3): 467-75, 2006.
Haugnes HS, Aass N, Fosså SD, et al.: Components of the metabolic syndrome in long-term survivors of testicular cancer. Ann Oncol 18 (2): 241-8, 2007.
Nuver J, Smit AJ, Wolffenbuttel BH, et al.: The metabolic syndrome and disturbances in hormone levels in long-term survivors of disseminated testicular cancer. J Clin Oncol 23 (16): 3718-25, 2005.
The following histologic classification of malignant testicular germ cell tumors (testicular cancer) reflects the classification used by the World Health Organization (WHO). Less than 50% of malignant testicular germ cell tumors have a single cell type, of which roughly 50% are seminomas. The rest have more than one cell type, and the relative proportions of each cell type should be specified. The cell type of these tumors is important for estimating the risk of metastases and the response to chemotherapy. Polyembryoma presents an unusual growth pattern and is sometimes listed as a single histologic type, though it might better be regarded as a mixed tumor.
Woodward PJ, Heidenreich A, Looijenga LHJ, et al.: Germ cell tumours. In: Eble JN, Sauter G, Epstein JI, et al.: Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Lyon, France: IARC Press, 2004, pp 221-49.
Ulbright TM, Berney DM: Testicular and paratesticular tumors. In: Mills SE, Carter D, Greenson JK, et al., eds.: Sternberg's Diagnostic Surgical Pathology. Philadelphia, Pa: Lippincott Williams & Wilkins, 2010, pp 1944-2004.
Bosi GJ, Feldman DR, Bajorin DE, et al.: Cancer of the testis. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1280-1301.
The American Joint Committee on Cancer (AJCC) has designated staging by TNM
classification to define testicular cancer.
Primary tumor cannot be assessed.
No evidence of primary tumor (e.g., histologic scar in testis).
Intratubular germ cell neoplasia (carcinoma in situ).
Tumor limited to the testis and epididymis without vascular/lymphatic invasion; tumor may invade into the tunica albuginea but not the tunica vaginalis.
Tumor limited to the testis and epididymis with vascular/lymphatic invasion, or tumor extending through the tunica albuginea with involvement of the tunica vaginalis.
Tumor invades the spermatic cord with or without vascular/lymphatic invasion.
Tumor invades the scrotum with or without vascular/lymphatic invasion.
aReprinted with permission from AJCC: Testis. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 469-78.
bThe extent of primary tumor is usually classified after radical orchiectomy, and for this reason, a pathologic stage is assigned.
cExcept for pTis and pT4, extent of primary tumor is classified by radical orchiectomy. TX may be used for other categories in the absence of radical orchiectomy.
Regional lymph nodes cannot be assessed.
No regional lymph node metastasis.
Metastasis with a lymph node mass ≤2 cm in greatest dimension; or multiple lymph nodes, none >2 cm in greatest dimension.
Metastasis with a lymph node mass >2 cm but not >5 cm in greatest dimension; or multiple lymph nodes, any one mass >2 cm but not >5 cm in greatest dimension.
Metastasis with a lymph node mass >5 cm in greatest dimension.
Metastasis with a lymph node mass ≤2 cm in greatest dimension and ≤5 nodes positive, none >2 cm in greatest dimension.
Metastasis with a lymph node mass >2 cm but not >5 cm in greatest dimension; or >5 nodes positive, none >5 cm; or evidence of extranodal extension of tumor.
No distant metastasis.
Nonregional nodal or pulmonary metastasis.
Distant metastasis other than to nonregional lymph nodes and lung.
S (Serum Tumor Markers)
Serum Tumor Markers (S) Required for Staging
Marker studies not available or not performed.
Marker study levels within normal limits.
LDH <1.5 × Nband hCG (mIu/ml) <5,000 and AFP (ng/ml) <1,000.
LDH 1.5–10 × N or hCG (mIu/ml) 5,000–50,000 or AFP (ng/ml) 1,000–10,000.
LDH >10 × N or hCG (mIu/ml) >50,000 or AFP (ng/ml) >10,000.
AFP = alpha-fetoprotein; hCG = human chorionic gonadotropin; LDH = lactase dehydrogenase; N indicates the upper limit of normal for the LDH assay.
In addition to the clinical stage definitions, surgical stage may be designated
based on the results of surgical removal and microscopic examination of tissue.
Stage 0 testicular cancer is testicular intraepithelial neoplasia (TIN), which is also referred to as intratubular germ cell neoplasia (ITGCN). TIN is analogous to carcinoma in situ. In most cases, TIN is diagnosed as a result of an orchiectomy that was performed to remove an invasive germ cell tumor (pT1–T4); generally, TIN has already been removed from the body at the time of diagnosis and requires no treatment. A more challenging situation arises if a biopsy is performed of the contralateral testis and TIN is discovered. Because of the low incidence and low mortality rates associated with contralateral germ cell tumors, such biopsies are performed rarely in the United States; therefore, TIN is almost never diagnosed in testicles that do not also have an invasive tumor. Consequently, a treatment decision about TIN in stage 0 testicular cancer is rarely faced in the United States. Treatment options for ITGCN include radiation therapy, surveillance, and orchiectomy.
Stage I testicular cancer is limited to the testis. Invasion of the scrotal
wall by tumor or interruption of the scrotal wall by previous surgery does not
change the stage but does increase the risk of spread to the inguinal lymph
nodes, and this must be considered in treatment and follow-up. Invasion of the
epididymis tunica albuginea and/or the rete testis does not change the
stage. Invasion of the tunica vaginalis or lymphovascular invasion signifies a T2 tumor, while invasion of the spermatic cord signifies a T3 tumor, and invasion of the scrotum signifies a T4. Increases in T stage are associated with increased risk of occult metastatic disease and recurrence. Men with stage I disease who have persistently elevated serum tumor markers after orchiectomy are staged as IS, but stage IS nonseminomas are treated as stage III. Elevated serum tumor markers in stage I or II seminoma are of unclear significance except that a persistently elevated or rising hCG usually indicates metastatic disease.
Stage II testicular cancer involves the testis and the retroperitoneal or
peri-aortic lymph nodes usually in the region of the kidney. Retroperitoneal
involvement should be further characterized by the number of nodes involved and
the size of involved nodes. The risk of recurrence is increased if more than five
nodes are involved or if the size of one or more involved nodes is more than 2
cm. Bulky stage II disease
(stage IIC) describes patients with extensive retroperitoneal nodes (>5 cm), which portends a less favorable prognosis.
Stage III implies spread beyond the retroperitoneal nodes based on physical
examination, imaging studies, and/or blood tests (i.e., patients with retroperitoneal adenopathy and highly elevated serum tumor markers are stage III). Stage III can be further stratified based on the location of metastasis and the degree of elevation of serum tumor markers. In the favorable group (IIIA), metastases are
limited to lymph nodes and lung, and serum tumor markers are no more than mildly elevated. Stage IIIB patients have moderately elevated tumor markers, while stage IIIC patients have highly elevated markers and/or metastases to liver, bone, brain or some organ other than the lungs. These subclassifications of stage III correspond to the International Germ Cell Consensus Classification system for disseminated germ cell tumors.
Testicular cancer is broadly divided into seminoma and nonseminoma for
treatment planning because seminomatous types of testicular cancer are more
sensitive to radiation therapy and chemotherapy and are less prone to distant metastases. Moreover, nonseminomas may include teratomatous elements, which tend to be resistant to chemotherapy and often require surgery for cure. By definition, pure seminomas do not contain elements of teratoma. Therefore, surgery plays a larger role in the management of nonseminomas than in the management of seminomas. Nonseminomatous testicular tumors include:
An international germ cell tumor prognostic classification has been developed
based on a retrospective analysis of 5,202 patients with metastatic
nonseminomatous and 660 patients with metastatic seminomatous germ cell
tumors. All patients received treatment with cisplatin- or carboplatin-containing therapy as their first chemotherapy course. The prognostic
classification, shown below, was agreed on in 1997 by all major clinical
trial groups worldwide. It should be used for reporting clinical trial
results of patients with germ cell tumors.
A meta-analysis of treatment outcomes for patients with advanced nonseminoma suggested that 5-year survival rates have improved for those patients with a poor prognosis during the period of 1989 to 2004. In addition to improved therapy, the improvement seen in these survival rates could be the result of publication bias, changes in patient selection in reported clinical trials, or more sensitive staging methods that could migrate less-advanced stages to more-advanced stage categories (i.e., stage migration).
56%–61% of nonseminomas
5-year progression-free survival (PFS) is 89%; 5-year survival is 92%–94%
90% of seminomas
5-year PFS is 82%;
5-year survival is 86%
13%–28% of nonseminomas
5-year PFS is 75%; 5-year survival is 80%–83%
10% of seminomas
5-year PFS is 67%; 5-year survival is 72%
16%–26% of nonseminomas
5-year PFS is 41%; 5-year survival is 71%
Among men diagnosed with an invasive testicular germ cell tumor (stages 1–3), 0.5% to 1.0% will present with tumors in both testes, and another 1% to 2% will develop a subsequent invasive germ cell tumor in the contralateral testis. Death from metachronous contralateral germ cell tumors is rare. One study of 29,515 U.S. men with testicular germ cell tumors who were diagnosed between 1973 and 2001 reported that 287 men developed a metachronous contralateral testis cancer, one of whom died. As a result, there is limited rationale for performing biopsies to search for testicular intraepithelial neoplasia (TIN) in men diagnosed with invasive testis cancer.
If biopsies of the contralateral testis are performed in men with testis cancer, 4% to 8% of men will be found to have TIN in the contralateral testis. When it is diagnosed, the treatment is typically radiation therapy (18 Gy–20 Gy), surveillance, or orchiectomy. Men undergoing radiation therapy or orchiectomy will subsequently be sterile. Men undergoing orchiectomy will also be hypogonadal as will many men undergoing radiation therapy.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with malignant testicular germ cell tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Schaapveld M, van den Belt-Dusebout AW, Gietema JA, et al.: Risk and prognostic significance of metachronous contralateral testicular germ cell tumours. Br J Cancer 107 (9): 1637-43, 2012.
Tabernero J, Paz-Ares L, Salazar R, et al.: Incidence of contralateral germ cell testicular tumors in South Europe: report of the experience at 2 Spanish university hospitals and review of the literature. J Urol 171 (1): 164-7, 2004.
Dieckmann KP, Wilken S, Loy V, et al.: Treatment of testicular intraepithelial neoplasia (intratubular germ cell neoplasia unspecified) with local radiotherapy or with platinum-based chemotherapy: a survey of the German Testicular Cancer Study Group. Ann Oncol 24 (5): 1332-7, 2013.
Kleinschmidt K, Dieckmann KP, Georgiew A, et al.: Chemotherapy is of limited efficacy in the control of contralateral testicular intraepithelial neoplasia in patients with testicular germ cell cancer. Oncology 77 (1): 33-9, 2009.
Stage I seminoma has a cure rate that approaches 100% regardless of whether postorchiectomy adjuvant therapy is given.
Standard treatment options:
Results of multiple clinical series, including more than 1,200
patients with stage I seminoma managed by postorchiectomy surveillance, have
been reported. The overall 10-year tumor recurrence rate is 15% to 20%, and nearly
all patients whose disease recurred were cured by radiation therapy or
chemotherapy. Thus, the overall cure rate is indistinguishable from that
achieved with adjuvant radiation therapy or carboplatin chemotherapy. Relapses after 5 years are unusual but can occur in as many as 4% of patients. Independent risk factors for relapse include tumor size greater than 4 cm and invasion of the rete testis. The 5-year risk of relapse is about 10% without either risk factor, 16% with one risk factor, and 32% with both risk factors.
Treatment options when surveillance is not chosen:
The surveillance-after-orchiectomy treatment option is associated with a cure rate that approaches 100%. Relapses requiring additional therapy occur in about 15% of patients who are treated with the surveillance treatment option. The surveillance strategy avoids the need for radiation or chemotherapy in most patients. However, some patients are uncomfortable with surveillance only and wish to minimize the risk of relapse. For such patients, one of the following options may be used; however, there is controversy about which strategy is preferred:
One of the following two treatment fields is typically used: a para-aortic strip covering the retroperitoneal nodes or a dog-leg field that includes the ipsilateral iliac lymph nodes as well as the retroperitoneum. The dose ranges from 20 Gy to 26 Gy. Relapse rates and toxic effects were studied in a randomized
comparison (MRC-TE10) of para-aortic radiation therapy alone versus para-aortic radiation
therapy with an added ipsilateral iliac lymph node field. Five-year
RFS rates were virtually identical (96.1% for patients who were treated with the para-aortic strip vs. 96.2% for patients who were treated by a dog-leg field) as
were overall survival (OS) rates (one death from seminoma occurred in the para-aortic radiation therapy arm). Pelvic RFS
rates were 98.2% versus 100%; the 95% confidence interval (CI) for the difference in
pelvic RFS rates was 0% to 3.7%. A statistically
significant increase was observed in leukopenia and diarrhea associated with the ipsilateral
iliac radiation therapy.
In a randomized trial (MRC-TE18), a radiation dose of 20 Gy over 10 daily fractions was clinically equivalent to 30 Gy over 15 fractions after a median follow-up of 7 years in both RFS and OS. Patients reported that lethargy and their ability to perform normal work were better in the lower-dose regimen.[Level of evidence: 1iiA]
Radiation therapy for clinical stage I testicular seminoma is no longer favored because of evidence that this treatment is associated with an increased risk of secondary malignancies and an increased risk of death from secondary malignancies. An analysis of data from the population-based Surveillance, Epidemiology, and End Results (SEER) registries in the United States between the years 1973 and 2001 indicated that among 7,179 men receiving radiation therapy for stage I seminoma, 246 had an increased risk of death from secondary cancers compared with the general population (standardized mortality ratio, 1.89; 95% CI, 1.67–2.14). An international study of more than 40,000 testis cancer survivors reported that among the 7,885 survivors who had been followed for 20 to 29 years, radiation therapy was associated with a doubling of the risk of secondary cancers (relative risk, 2.0; 95% CI, 1.8–2.3).
In a large, randomized, controlled, noninferiority trial (MRC-TE19 [NCT00003014]), 1,477 men with stage I seminoma were randomly assigned to undergo para-aortic (or dog-leg field, if clinically indicated) radiation therapy or to receive a single dose of carboplatin (concentration-versus-time or area-under-the-curve [AUC] × 7) after radical inguinal orchiectomy study participants were followed up for a median of 6.5 years. The RFS rate at 5 years was 94.7% in the carboplatin arm and 96.0% in the radiation therapy arm (1.3% difference; 90% CI, 0.7%–3.5%; hazard ratio [HR], 1.25 [nonsignificant trend in favor of radiation therapy]; 90% CI, 0.83–1.89). The one death from seminoma occurred in the radiation therapy arm. There was a reduced number of contralateral testicular germ cell tumors in the carboplatin arm: 2 versus 15 (HR, 0.22; 95% CI, 0.05–0.95; P = .03).[Level of evidence: 1iiA] In this trial, AUC dosing was based on radioisotope measurement of glomerular filtration rate; dosing based on calculations of creatinine clearance is not equivalent, has not been validated in this setting, and is discouraged.
Phase II studies, including several with more than 4 years median follow-up, have consistently reported lower relapse rates (0%–3.3%) when two doses of carboplatin were administered either 3 or 4 weeks apart and dosed either at 400 mg/m2 or at an AUC of 7. Administration of two doses of carboplatin has never been compared with a single dose nor with radiation therapy in a randomized trial.
Stage I nonseminoma is highly curable (>99%). Orchiectomy alone will cure about 70% of patients, but the remaining 30% will relapse and require additional treatment. The relapses are highly curable, and postorchiectomy surveillance is a standard treatment option, but some physicians and patients prefer to reduce the risk of relapse by having the patient undergo either a retroperitoneal lymph node dissection (RPLND) or one or two cycles of chemotherapy. Each of these three approaches has unique advantages and disadvantages, and none has been shown to result in longer survival or superior quality of life.
Typically, patients are seen monthly during the first year, every 2 months during the second year, every 3 months during the third year, every 4 months during the fourth year, every 6 months during the fifth year, and annually for the subsequent 5 years. At each visit, the history is reviewed, a physical examination is given, determination of serum markers are performed, and a chest x-ray is obtained (sometimes at alternating visits). An additional key aspect of surveillance involves abdominal or abdominopelvic CT scans, but the preferred frequency of such scans is controversial.
A randomized, controlled trial (MRC-TE08) compared a schedule that used only two scans at 3 months and 12 months with a schedule that used five scans at 3, 6, 9, 12, and 24 months. With over 400 randomly assigned patients and a median follow-up of 40 months, all relapsing patients had either good- or intermediate-risk disease, and there were no differences in the stage or extent of disease at relapse between the two arms. No deaths were reported. Nonetheless, some organizations recommend CT scans every 3 to 4 months during the first 3 years of follow-up and continuing but less-frequent CT scans thereafter. While this study would appear to indicate that scans at 3 and 12 months are adequate during the first year, longer follow-up will be needed to assess whether discontinuing scans after 12 months is safe.[Level of evidence: 1iiA] With regard to chest imaging, disease recurrence is rarely detected by chest x-ray alone, so chest x-ray may play little or no role in routine surveillance but is nonetheless included in the mainstream surveillance schedules.
The need for long-term follow-up has not been adequately investigated. Surveillance series with long follow-up times have reported that fewer than 1% of clinical stage I patients relapse after 5 years. Late relapses often occur in the retroperitoneum when they do occur. Therefore, some schedules discontinue CT scans after 12 months, while others recommend at least annual scans for 10 years.
The option of a radical inguinal orchiectomy followed by a regular and frequent surveillance schedule should be considered only if:
A nerve-sparing RPLND that preserves ejaculation in virtually every patient has
been described in clinical stage I patients and appears to be as effective as
the standard RPLND. Surgery should be followed by monthly
determination of serum markers and chest x-rays for the first year and every-other-month determinations for the second year.
Men undergoing RPLND, who are found to have pathological stage I disease, have a roughly 10% risk of relapsing subsequently, whereas men with pathological stage II disease (i.e., those who are found to have lymph node metastases at RPLND) have as much as a 50% risk of relapse without further treatment. Two cycles of post-RPLND chemotherapy using either bleomycin, etoposide, and cisplatin (BEP) or etoposide plus cisplatin (EP) lowers the risk of relapse in men with pathological stage II disease to about 1%. The vast majority of reported patients in studies of RPLND underwent the operation at a center of excellence with a urological surgeon who had performed hundreds of such operations. The ability of less-experienced urologists to achieve similar results is unknown.
In patients with pathologic stage
I disease after RPLND, the presence of lymphatic or venous invasion or a predominance of embryonal carcinoma in the
primary tumor appears to predict for relapse. In a large, Testicular Cancer
Intergroup Study, the relapse rate among men with pathological stage I disease was 19% in those with vascular invasion
versus 6% in those without vascular invasion. One study reported that the relapse rate for men with pathological stage I disease was 21.2% (18 of 85 men relapsed), if their tumors were predominantly embryonal carcinoma and 29% if there was a predominance of embryonal carcinoma plus lymphovascular invasion versus 3% (5 of 141 men relapsed), if there was not a predominance of embryonal carcinoma.
Among pathological stage II patients, the relapse rate was 32% among men with embryonal carcinoma-predominant tumors compared with15.6% in the other stage II patients. The risk of metastatic disease (i.e., either pathological stage II disease or relapsed pathological stage I disease) in men with tumors showing a predominance of embryonal carcinoma plus lymphovascular invasion was 62% compared with 16% in men with neither risk factor.
These data have shown that high-risk patients undergoing RPLND have a substantial risk of subsequently receiving chemotherapy. Data from one institution have shown that about half of men with stage I pure embryonal carcinoma undergoing RPLND will subsequently receive cisplatin-based chemotherapy.
Retroperitoneal dissection of
lymph nodes is not helpful in the management of children, and potential
morbidity of the surgery is not justified by the information obtained. In
men who have undergone RPLND, chemotherapy is employed immediately on first evidence of recurrence.
A randomized, controlled trial compared a single cycle of BEP chemotherapy to RPLND in 382 patients. The 2-year recurrence-free survival rates were 99.5% with chemotherapy versus 91.9% with RPLND (absolute difference = 7.6%; 95% CI, 3.1%–12.1%). There were no treatment-related or cancer-specific deaths in either arm of the study.
A Swedish and Norwegian study reported results of a risk-adapted therapy protocol in which patients with nonseminomas with lymphovascular invasion underwent postorchiectomy chemotherapy with one or two cycles of BEP chemotherapy, while those without lymphovascular invasion underwent either surveillance or a single cycle of BEP. The study included 745 patients and, with a median follow-up of 4.7 years and 2-year follow-up of 89% of patients, there were no deaths from testicular cancer, although one patient died of a stroke immediately after completing chemotherapy for relapsed disease. OS and cause-specific survival were 98.9% and 99.9%, respectively. Both of these studies were conducted at community-based hospitals and demonstrated that postorchiectomy chemotherapy could be delivered at a regional or national level without depending on centers of excellence.
Several phase II studies and case series reporting the results after two cycles of BEP in intermediate- or high-risk patients have identified relapse rates ranging from 0% to 4% (average = 2.4%). Fewer than 1% of patients in these series died of testicular cancer. While chemotherapy produces the lower relapse rate and a comparable disease-specific survival rate compared with RPLND or surveillance, it is unknown whether a brief course of chemotherapy results in late toxic effects or an increased risk of late relapse. Longer follow-up is awaited.
There is no consensus about the optimal management of men with stage I nonseminomas, but each of the three strategies above produces a disease-specific survival rate of about 99%. Some clinicians have advocated a risk-adapted approach such that low-risk patients undergo surveillance, while others undergo either RPLND or chemotherapy. The goal of this approach is to minimize the side effects of treatment, but risk-adapted therapy has never been demonstrated to result in better outcomes. Some experts prefer a surveillance strategy generally so as to minimize unnecessary treatment. Others prefer RPLND to obtain more accurate staging, to reduce the risk of needing chemotherapy (and, therefore, chemotherapy's side effects and toxicity) and to, theoretically, reduce the risk of late relapse. At the same time, many experts reject RPLND as insufficiently effective at lowering relapse rates and prefer chemotherapy. Surveillance and chemotherapy have been tested at the regional and national level with excellent results, however, the limited data concerning RPLND in the regional setting have shown higher than expected in-field relapse rates but no deaths.
With regard to risk stratification, data suggest that relapse rates are higher in patients with histologic evidence
of lymphatic or venous invasion or a predominance of embryonal carcinoma. Tumors that consist of mature teratoma appear to have a lower relapse rate.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I malignant testicular germ cell tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
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Williams SD, Stablein DM, Einhorn LH, et al.: Immediate adjuvant chemotherapy versus observation with treatment at relapse in pathological stage II testicular cancer. N Engl J Med 317 (23): 1433-8, 1987.
Behnia M, Foster R, Einhorn LH, et al.: Adjuvant bleomycin, etoposide and cisplatin in pathological stage II non-seminomatous testicular cancer. the Indiana University experience. Eur J Cancer 36 (4): 472-5, 2000.
Kondagunta GV, Sheinfeld J, Mazumdar M, et al.: Relapse-free and overall survival in patients with pathologic stage II nonseminomatous germ cell cancer treated with etoposide and cisplatin adjuvant chemotherapy. J Clin Oncol 22 (3): 464-7, 2004.
Hermans BP, Sweeney CJ, Foster RS, et al.: Risk of systemic metastases in clinical stage I nonseminoma germ cell testis tumor managed by retroperitoneal lymph node dissection. J Urol 163 (6): 1721-4, 2000.
Sweeney CJ, Hermans BP, Heilman DK, et al.: Results and outcome of retroperitoneal lymph node dissection for clinical stage I embryonal carcinoma--predominant testis cancer. J Clin Oncol 18 (2): 358-62, 2000.
Sesterhenn IA, Weiss RB, Mostofi FK, et al.: Prognosis and other clinical correlates of pathologic review in stage I and II testicular carcinoma: a report from the Testicular Cancer Intergroup Study. J Clin Oncol 10 (1): 69-78, 1992.
Stephenson AJ, Bosl GJ, Bajorin DF, et al.: Retroperitoneal lymph node dissection in patients with low stage testicular cancer with embryonal carcinoma predominance and/or lymphovascular invasion. J Urol 174 (2): 557-60; discussion 560, 2005.
Albers P, Siener R, Krege S, et al.: Randomized phase III trial comparing retroperitoneal lymph node dissection with one course of bleomycin and etoposide plus cisplatin chemotherapy in the adjuvant treatment of clinical stage I Nonseminomatous testicular germ cell tumors: AUO trial AH 01/94 by the German Testicular Cancer Study Group. J Clin Oncol 26 (18): 2966-72, 2008.
Heidenreich A, Sesterhenn IA, Mostofi FK, et al.: Prognostic risk factors that identify patients with clinical stage I nonseminomatous germ cell tumors at low risk and high risk for metastasis. Cancer 83 (5): 1002-11, 1998.
Alexandre J, Fizazi K, Mahé C, et al.: Stage I non-seminomatous germ-cell tumours of the testis: identification of a subgroup of patients with a very low risk of relapse. Eur J Cancer 37 (5): 576-82, 2001.
Stage II seminoma is divided into bulky and nonbulky disease for treatment
planning and expression of prognosis. Bulky disease is generally defined as
tumors larger than 5 cm on a computed tomographic (CT) scan (i.e., stage IIC disease). Nonbulky disease can be further subdivided into stage IIA, meaning no lymph node mass larger than 2 cm, and stage IIB, meaning a lymph node mass between 2 cm and 5 cm.
Nonbulky stage II disease has a cure rate of about 90% to 95% with radiation
alone at doses of 30 Gy to 36 Gy, and most relapsing patients can be cured with chemotherapy. Cure rates are slightly higher for patients with stage IIA disease than for those with IIB disease, but the figures are within the range given above. Risk factors for relapse include multiple enlarged nodes.
Results for patients with stage IIC disease have been less favorable. For example, one institution reported that 9 of 16 (56%) stage IIC patients relapsed following radiation therapy, while relapse occurred in only 1 of 23 (4%) IIC patients treated with chemotherapy. A pooled analysis of earlier studies reported a 65% relapse-free survival (RFS) for men receiving radiation therapy for bulky stage II seminoma. Unfortunately, only sparse contemporary data are available on the use of radiation therapy to treat bulky stage II seminomas, and there are no randomized trials comparing radiation therapy with chemotherapy in this population. Combination
chemotherapy with cisplatin is effective therapy in patients with bulky
stage II seminomas and has become the most widely accepted treatment option.
Residual radiologic abnormalities are common at the
completion of chemotherapy. Many abnormalities gradually regress over a period
of months. Some clinicians advocate empiric attempts to resect residual masses 3 cm or larger, while others advocate close surveillance, with intervention only if the residual mass increases in size. Postchemotherapy radiation therapy is no longer favored, in part because of a retrospective
study of a consecutive series of 174 seminoma patients with postchemotherapy residual
disease seen at ten treatment centers that reported that empiric radiation was not associated with
any medically significant improvement in progression-free survival after
completion of platinum-based combination chemotherapy.[Level of evidence: 3iiDiii]
In some series, surgical resection of specific masses has yielded a
significant number of patients with residual seminoma who require additional therapy.
Nevertheless, other reports indicate that the size of the residual mass does not
correlate well with active residual disease, most residual masses do not grow,
and frequent marker and CT scan evaluation is a viable option even when the
residual mass is 3 cm or larger.
A more recent approach has been to obtain an 18-fluorodeoxyglucose-positron emission tomography (FDG-PET) scan following chemotherapy. A study of 56 patients reported that positron emission tomography (PET) scans correctly identified eight of ten patients with residual seminoma with no false positives among the 46 patients with benign masses. In this study, PET scans were 100% accurate in patients with residual masses greater than 3 cm in greatest diameter whereas residual malignant masses less than 3 cm were only detected in one of three men. This study provides support for observing men with residual FDG-PET-negative masses greater than 3 cm and for performing a biopsy or resection of any FDG-PET-positive mass.
Standard treatment options for patients with nonbulky tumors:
Standard treatment options for patients with bulky tumors:
Stage II nonseminoma is highly curable (>95%). Men with stage II disease and persistently elevated serum tumor markers are generally treated as having stage III disease and receive chemotherapy. For men with normal markers after orchiectomy, nonseminomas are divided into stages IIA, IIB, and IIC for treatment purposes. In general, stage IIA patients undergo RPLND to confirm the staging. As many as 40% of clinical stage IIA patients will have benign findings at RPLND and will be restaged as having pathological stage I disease. RPLND can thus prevent a significant number of clinical stage IIA patients from receiving unnecessary chemotherapy.
In contrast, stage IIB and IIC patients are usually treated with systemic chemotherapy for disseminated disease because these patients have a higher relapse rate after RPLND. One study reported that by limiting RPLND to patients with earlier stage II disease and normal serum tumor markers, 5-year RFS increased from 78% to 100% after RPLND, while RFS did not change significantly among stage II patients receiving chemotherapy (100% vs. 98%). However, the question of whether to treat patients with stage II nonseminomas germ cell tumors with RPLND or chemotherapy has never been subjected to a randomized trial.
Standard treatment options:
option of surgery and careful follow-up, reserving chemotherapy for relapse, is
particularly attractive for patients who have pathological stage I or IIA disease (fewer than six positive nodes at
RPLND, none of which are larger than 2
cm in diameter). Such
patients appear to have a relapse rate of about 10% if followed
without chemotherapy, and most are curable with standard chemotherapy if they
do relapse. Presence of lymphatic or venous invasion and the proportion of the primary tumor that is embryonal carcinoma also help to
predict which patients may relapse. In one study, the relapse rate in men with pathological stage I disease was 3% in men with nonembryonal carcinoma-predominant tumors, 21% in men with embryonal carcinoma-predominant tumors, and 31% in those with embryonal carcinoma-predominant tumors and lymphovascular invasion. In children, surgical resection of retroperitoneal nodes is generally not
performed. Patients with clinical stage II disease are given chemotherapy.
This option of RPLND plus adjuvant chemotherapy applies to patients who have pathologically confirmed lymph node metastases as a result of RPLND and is most attractive for patients with pathological stage IIB or IIC disease. The results of a
large study comparing the first treatment option with the second treatment option were published. Two courses of
cisplatin-based chemotherapy (either cisplatin, vinblastine, bleomycin [PVB] or
vinblastine, dactinomycin, bleomycin, cyclophosphamide, cisplatin [VAB VI])
prevented a relapse in more than 95% of patients. A 49% relapse
rate was seen in patients assigned to observation; however, the majority of these patients
could be effectively treated, and no significant differences were found in overall survival. The study concluded that adjuvant
therapy will most often prevent relapse in patients treated with optimal surgery, follow-up, and
chemotherapy; however, observation with chemotherapy only for relapse will lead to a similar cure
option is most attractive for patients with elevated serum tumor markers and/or clinical stage IIB or IIC disease. The combination of chemotherapy plus resection of residual masses in these patients results in cure in more than 95% of patients.
Chemotherapy regimens include:
A randomized study has shown that bleomycin is an essential component of the
BEP regimen when only three courses are administered.
Other regimens that appear to produce similar survival outcomes but are no longer considered standard include:
In a randomized comparison of PVB versus BEP, equivalent anticancer
activity was seen but with less toxic effects with the use of BEP.
If these patients do not achieve a complete response on chemotherapy, surgical
removal of residual masses should be performed. The timing of such surgery
requires clinical judgment but would occur most often after three or four cycles of
combination chemotherapy and normalization or stabilization of serum markers. The presence of persistently elevated markers is not a contraindication to resection of residual masses, but patients with rising markers at the end of chemotherapy are generally treated with salvage chemotherapy. Despite numerous studies, no sufficiently accurate predictors of the histology of residual masses have been validated. Therefore, the standard of care is to resect all residual masses
apparent on scans in patients who have normal or stable markers after responding to
chemotherapy. The presence of persistent
nonseminomatous germ-cell malignant elements in the resected specimen is a poor prognostic sign and is often a trigger for additional chemotherapy. However, men with only microscopic residual cancer have a much more favorable prognosis than men with more substantial residual disease. Identifying the patients who benefit from additional chemotherapy is not possible from existing data.
In some cases, chemotherapy is
initiated prior to orchiectomy because of life-threatening metastatic disease.
When this is done, orchiectomy after initiation or completion of
chemotherapy is advisable to remove the primary tumor. There is a
higher incidence (approximately 50%) of residual cancer in the testicle than in
remaining radiographically detectable retroperitoneal masses after platinum-based chemotherapy.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II malignant testicular germ cell tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Bauman GS, Venkatesan VM, Ago CT, et al.: Postoperative radiotherapy for Stage I/II seminoma: results for 212 patients. Int J Radiat Oncol Biol Phys 42 (2): 313-7, 1998.
Chung PW, Gospodarowicz MK, Panzarella T, et al.: Stage II testicular seminoma: patterns of recurrence and outcome of treatment. Eur Urol 45 (6): 754-59; discussion 759-60, 2004.
Classen J, Schmidberger H, Meisner C, et al.: Radiotherapy for stages IIA/B testicular seminoma: final report of a prospective multicenter clinical trial. J Clin Oncol 21 (6): 1101-6, 2003.
Thomas GM: Over 20 Years of Progress in Radiation Oncology: Seminoma. Semin Radiat Oncol 7 (2): 135-145, 1997.
Warde P, Gospodarowicz M, Panzarella T, et al.: Management of stage II seminoma. J Clin Oncol 16 (1): 290-4, 1998.
De Santis M, Becherer A, Bokemeyer C, et al.: 2-18fluoro-deoxy-D-glucose positron emission tomography is a reliable predictor for viable tumor in postchemotherapy seminoma: an update of the prospective multicentric SEMPET trial. J Clin Oncol 22 (6): 1034-9, 2004.
Mencel PJ, Motzer RJ, Mazumdar M, et al.: Advanced seminoma: treatment results, survival, and prognostic factors in 142 patients. J Clin Oncol 12 (1): 120-6, 1994.
Culine S, Abs L, Terrier-Lacombe MJ, et al.: Cisplatin-based chemotherapy in advanced seminoma: the Institut Gustave Roussy experience. Eur J Cancer 34 (3): 353-8, 1998.
Zagars GK, Pollack A: Radiotherapy for stage II testicular seminoma. Int J Radiat Oncol Biol Phys 51 (3): 643-9, 2001.
Stephenson AJ, Bosl GJ, Motzer RJ, et al.: Nonrandomized comparison of primary chemotherapy and retroperitoneal lymph node dissection for clinical stage IIA and IIB nonseminomatous germ cell testicular cancer. J Clin Oncol 25 (35): 5597-602, 2007.
Richie JP, Kantoff PW: Is adjuvant chemotherapy necessary for patients with stage B1 testicular cancer? J Clin Oncol 9 (8): 1393-6, 1991.
Williams SD, Birch R, Einhorn LH, et al.: Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide. N Engl J Med 316 (23): 1435-40, 1987.
Horwich A, Norman A, Fisher C, et al.: Primary chemotherapy for stage II nonseminomatous germ cell tumors of the testis. J Urol 151 (1): 72-7; discussion 77-8, 1994.
de Wit R, Roberts JT, Wilkinson PM, et al.: Equivalence of three or four cycles of bleomycin, etoposide, and cisplatin chemotherapy and of a 3- or 5-day schedule in good-prognosis germ cell cancer: a randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council. J Clin Oncol 19 (6): 1629-40, 2001.
Einhorn LH, Williams SD, Loehrer PJ, et al.: Evaluation of optimal duration of chemotherapy in favorable-prognosis disseminated germ cell tumors: a Southeastern Cancer Study Group protocol. J Clin Oncol 7 (3): 387-91, 1989.
Xiao H, Mazumdar M, Bajorin DF, et al.: Long-term follow-up of patients with good-risk germ cell tumors treated with etoposide and cisplatin. J Clin Oncol 15 (7): 2553-8, 1997.
Loehrer PJ Sr, Johnson D, Elson P, et al.: Importance of bleomycin in favorable-prognosis disseminated germ cell tumors: an Eastern Cooperative Oncology Group trial. J Clin Oncol 13 (2): 470-6, 1995.
Bosl GJ, Gluckman R, Geller NL, et al.: VAB-6: an effective chemotherapy regimen for patients with germ-cell tumors. J Clin Oncol 4 (10): 1493-9, 1986.
Wozniak AJ, Samson MK, Shah NT, et al.: A randomized trial of cisplatin, vinblastine, and bleomycin versus vinblastine, cisplatin, and etoposide in the treatment of advanced germ cell tumors of the testis: a Southwest Oncology Group study. J Clin Oncol 9 (1): 70-6, 1991.
Stoter G, Koopman A, Vendrik CP, et al.: Ten-year survival and late sequelae in testicular cancer patients treated with cisplatin, vinblastine, and bleomycin. J Clin Oncol 7 (8): 1099-104, 1989.
Fizazi K, Oldenburg J, Dunant A, et al.: Assessing prognosis and optimizing treatment in patients with postchemotherapy viable nonseminomatous germ-cell tumors (NSGCT): results of the sCR2 international study. Ann Oncol 19 (2): 259-64, 2008.
Spiess PE, Tannir NM, Tu SM, et al.: Viable germ cell tumor at postchemotherapy retroperitoneal lymph node dissection: can we predict patients at risk of disease progression? Cancer 110 (12): 2700-8, 2007.
Leibovitch I, Little JS Jr, Foster RS, et al.: Delayed orchiectomy after chemotherapy for metastatic nonseminomatous germ cell tumors. J Urol 155 (3): 952-4, 1996.
Stage III seminoma and nonseminomas are usually curable but have different criteria for estimating prognosis.
Patients with disseminated seminomas can be divided into good-risk and intermediate-risk groups based on whether nonpulmonary visceral metastases are present. Good-risk patients (i.e., those with metastases only to lymph nodes and/or lungs) have a 5-year progression-free survival (PFS) and overall survival (OS) of 82% and 86%, respectively. Intermediate-risk seminoma patients have a 5-year PFS and OS rate of 67% and 72%, respectively.
Patients with disseminated nonseminomas can be divided into good-, intermediate-, and poor-risk groups based on whether nonpulmonary visceral metastases are present, the site of the primary tumor (i.e., mediastinal vs. either gonadal or retroperitoneal), and the level of serum tumor markers.
In the 1997 analysis that established these risk groups, 5-year OS was 92%, 80% and 48% in good-, intermediate-, and poor-risk groups while the figures for PFS were 89%, 75% and 41%. However, a 2006 pooled analysis of chemotherapy trials reported improved outcomes compared with the 1997 paper: survival in the good-, intermediate-, and poor-risk groups was 94%, 83%, and 71%, respectively.
Four cycles of bleomycin plus etoposide plus cisplatin (BEP) chemotherapy as a standard-of-care treatment option for patients with metastatic testicular germ cell tumors was established by a randomized trial showing that it produced similar outcomes with fewer toxic effects in comparison with cisplatin, vinblastine, and bleomycin (PVB). Two randomized trials comparing four courses of BEP with four courses of etoposide plus ifosfamide plus cisplatin (VIP) showed
similar OS and time-to-treatment failure for the two regimens in
patients with intermediate- and poor-risk advanced disseminated germ cell tumors who had not received prior
chemotherapy.[Level of evidence: 1iiA] Hematologic toxic effects were
substantially worse with the VIP regimen.
For good-risk patients, two randomized trials compared three versus four cycles of BEP and reported no significant benefit from longer treatment in that population.
Numerous attempts have been made to develop a regimen superior to BEP for poor-prognosis germ cell tumors but none have been successful. Most recently, four cycles of BEP was compared with two cycles of BEP followed by two cycles of high-dose cyclophosphamide, etoposide, and carboplatin, but there was no difference in survival between the two arms. Earlier trials of higher dose cisplatin or long-term maintenance chemotherapy were similarly disappointing.
For good-risk patients, the goal of clinical trials has been to minimize the toxic effects of treatment without sacrificing the therapeutic effectiveness. As noted above, no difference in outcome was seen when comparing three versus four cycles of BEP chemotherapy. However, attempts to eliminate bleomycin produced more ambiguous and usually disappointing results. A randomized, controlled trial comparing three cycles of BEP with three cycles of EP reported lower OS (95% vs. 86%, P = .01) in the EP arm. Similarly, when three cycles of BEP was compared with four cycles of EP in a randomized trial in more than 260 patients, there were 6 relapses and 5 deaths in the bleomycin arm compared with 14 relapses and 12 deaths in the EP arm, but these differences were not statistically significant. Several other studies have compared bleomycin-containing regimens to etoposide and cisplatin and in every trial, the trend in survival has favored the bleomycin arm, but the differences have not usually been statistically significant. These results have led to some controversy as to whether three cycles of BEP is superior to four cycles of EP.
In most patients, an orchiectomy is performed before starting chemotherapy. If the diagnosis has been made by biopsy of a metastatic site (or on the basis of highly elevated serum tumor markers and radiological imaging consistent with an advanced-stage germ cell tumor) and chemotherapy has been initiated, subsequent orchiectomy is generally performed because chemotherapy may not eradicate the primary tumor. Case reports illustrate that viable tumor has been found on postchemotherapy orchiectomy despite complete response of metastatic lesions.
Some retrospective data suggest that the experience of the treating institution
may impact the outcome of patients with stage III nonseminoma. Data from 380 patients
treated from 1990 to 1994 on the same study protocol at 49 institutions in the
European Organization for Research and Treatment of Cancer and the Medical
Research Council were analyzed. Overall, the 2-year survival rate for the 55
patients treated at institutions that entered fewer than five patients onto the
protocol was 62% (95% confidence interval [CI], 48%–75%) versus 77% (95% CI, 72%–81%) in the
institutions that entered five or more patients onto the protocol.
Similarly, a population-based study of testis cancer in Japan in the 1990s reported a significant association between survival and the number of testis cancer patients treated. The relative 5-year survival rate was 98.8% at high-volume hospitals compared with 79.7% at low-volume hospitals. After adjusting for stage and age, the hazard ratio for death in a high-volume hospital was 0.11 (95% CI, 0.025–0.495). Several other studies have reported similar findings. As in any
nonrandomized study design, patient selection factors and factors leading
patients to choose treatment at one center versus another can make interpretation
of these results difficult.
Many patients with poor-risk, nonseminomatous testicular germ cell tumors who
have a serum beta human chorionic gonadotropin (beta-hCG) level higher than 50,000
IU/mL at the initiation of cisplatin-based therapy
(BEP or PVB) will still have an elevated beta-hCG level at the completion of
therapy, showing an initial rapid decrease in beta-hCG followed by a plateau.
In the absence of other signs of progressing disease, monthly evaluation with
initiation of salvage therapy, if and when there is serologic progression, may be
appropriate. Many patients, however, will remain disease free without further
therapy.[Level of evidence: 3iiDiv]
Residual radiologic abnormalities are common at the completion of chemotherapy.
Such masses are not treated unless they grow or are histopathologically shown to contain viable cancer. In a combined retrospective consecutive series of 174 seminoma
patients with postchemotherapy residual disease seen at ten treatment centers,
empiric radiation was not associated with any medically significant improvement
in progression-free survival after completion of platinum-based combination
chemotherapy.[Level of evidence: 3iiDiii] In some series, surgical
resection of specific masses has yielded a significant number of patients with residual
seminoma that require additional therapy. Larger masses are more likely to harbor viable cancer, but there is no size criteria with high sensitivity and specificity. 18 fluorodeoxyglucose-positron emission tomography (FDG-PET) scans have been shown to be helpful in identifying patients who harbor viable cancers, but the false-positive rate is substantial in some series. The strength of positron emission tomograph (PET) scans in residual seminoma masses is that they have a very high sensitivity and a low false-negative rate. Thus, for men with residual masses for whom resection is being planned, a negative PET scan provides evidence that surgery is not necessary.
Although larger residual masses are more likely to harbor viable seminoma, the size of the residual mass is of limited prognostic value. Most residual masses do not grow, and regular marker and computed tomographic (CT) scan evaluation is a viable
management option for large or small masses.
An alternative approach is to operate on larger masses, to resect them when possible, and to perform biopsies of unresectable masses. Postchemotherapy masses are often difficult or impossible to resect because of a dense desmoplastic reaction. Historically, such surgery has been characterized by a high rate of complications or additional procedures such as nephrectomy or arterial or venous grafting.
Residual masses following chemotherapy in men with nonseminomatous germ cell tumors often contain viable cancer or teratoma, and the standard of care is to resect all such masses when possible. However, there are no randomized, controlled trials evaluating this issue. Instead, the practice is based on the fact that viable neoplasm is often found at surgery in these patients, and the presumption is that such tumors would progress if not resected. If serum tumor markers are rising, salvage chemotherapy is usually given, but stable or slowly declining tumor markers are not a contraindication to resection of residual masses.
Case series of men undergoing postchemotherapy resections have reported that roughly 10% will have viable germ cell cancer, 45% will have teratoma, and 45% will have no viable tumor. Numerous attempts have been made to identify the patients who need surgery and the patients who can be safely observed. Variables predictive of finding only necrosis or fibrosis at surgery are:
However, only a very small proportion of men have favorable enough features to have less than a 10% chance of having viable neoplasm in their residual masses, and thus the utility of current models has been questioned.
When multiple sites of residual disease are present, all residual masses are generally resected. If it is not surgically feasible, resection is generally not performed. Some patients may have discordant pathologic findings (e.g., fibrosis/necrosis,
teratoma, or carcinoma) in residual masses in the abdomen versus the
chest. Some medical centers perform simultaneous retroperitoneal
and thoracic operations to remove residual masses, but most do not. Although
the agreement among the histologies of residual masses found after chemotherapy
above the diaphragm versus those found below the diaphragm is only moderate (kappa statistic = 0.42),
some evidence exists that if retroperitoneal resection is performed first,
results can be used to guide decisions about whether to perform a
In a multi-institutional case series of surgery to remove
postchemotherapy residual masses in 159 patients, necrosis only was found at
thoracotomy in about 90% of patients who had necrosis only in their
retroperitoneal masses. The figure was about 95% if the original testicular
primary tumor had contained no teratomatous elements. Conversely, the
histology of residual masses at thoracotomy did not predict nearly as well the histology of retroperitoneal masses. Nonetheless, some centers continue to support resection of all residual masses, even if necrosis is found in the retroperitoneum.
The presence of persistent malignant
elements in the resected specimen is considered by some clinicians to be an indication for additional
chemotherapy. However, there are no prospective trials investigating the benefit of such treatment. In some cases, chemotherapy is initiated before the
orchiectomy because of life-threatening metastatic disease. When this is done,
orchiectomy after initiation or completion of chemotherapy is advisable to remove the primary tumor. A
physiologic blood-testis barrier seems to appear, and there is a higher incidence (approximately
50%) of residual cancer in the testicle than in remaining radiographically
detectable retroperitoneal masses after platinum-based chemotherapy. Some
investigators have suggested that in children, 90% of whom have yolk sac
tumors, radiation therapy should be given to residual masses after chemotherapy
rather than surgery.
Standard treatment options for initial treatment for nonseminoma patients with good-risk disease:
Standard treatment options for initial treatment for nonseminoma patients with intermediate- and poor-risk disease:
Management of residual masses following chemotherapy for patients with seminoma
Management of residual masses following chemotherapy for patients with nonseminoma
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III malignant testicular germ cell tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Nichols CR, Catalano PJ, Crawford ED, et al.: Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study. J Clin Oncol 16 (4): 1287-93, 1998.
Hinton S, Catalano PJ, Einhorn LH, et al.: Cisplatin, etoposide and either bleomycin or ifosfamide in the treatment of disseminated germ cell tumors: final analysis of an intergroup trial. Cancer 97 (8): 1869-75, 2003.
de Wit R, Louwerens M, de Mulder PH, et al.: Management of intermediate-prognosis germ-cell cancer: results of a phase I/II study of Taxol-BEP. Int J Cancer 83 (6): 831-3, 1999.
Saxman SB, Finch D, Gonin R, et al.: Long-term follow-up of a phase III study of three versus four cycles of bleomycin, etoposide, and cisplatin in favorable-prognosis germ-cell tumors: the Indiana University experience. J Clin Oncol 16 (2): 702-6, 1998.
Motzer RJ, Nichols CJ, Margolin KA, et al.: Phase III randomized trial of conventional-dose chemotherapy with or without high-dose chemotherapy and autologous hematopoietic stem-cell rescue as first-line treatment for patients with poor-prognosis metastatic germ cell tumors. J Clin Oncol 25 (3): 247-56, 2007.
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Katz MH, McKiernan JM: Management of non-retroperitoneal residual germ cell tumor masses. Urol Clin North Am 34 (2): 235-43; abstract x, 2007.
Fox EP, Weathers TD, Williams SD, et al.: Outcome analysis for patients with persistent nonteratomatous germ cell tumor in postchemotherapy retroperitoneal lymph node dissections. J Clin Oncol 11 (7): 1294-9, 1993.
Bajorin DF, Geller NL, Weisen SF, et al.: Two-drug therapy in patients with metastatic germ cell tumors. Cancer 67 (1): 28-32, 1991.
de Wit R, Stoter G, Sleijfer DT, et al.: Four cycles of BEP vs four cycles of VIP in patients with intermediate-prognosis metastatic testicular non-seminoma: a randomized study of the EORTC Genitourinary Tract Cancer Cooperative Group. European Organization for Research and Treatment of Cancer. Br J Cancer 78 (6): 828-32, 1998.
Quek ML, Simma-Chiang V, Stein JP, et al.: Postchemotherapy residual masses in advanced seminoma: current management and outcomes. Expert Rev Anticancer Ther 5 (5): 869-74, 2005.
Herr HW, Sheinfeld J, Puc HS, et al.: Surgery for a post-chemotherapy residual mass in seminoma. J Urol 157 (3): 860-2, 1997.
Deciding on further treatment depends on many factors, including the specific
cancer, previous treatment, site of recurrence, and individual patient
considerations. Salvage regimens consisting of ifosfamide, cisplatin, and
either etoposide or vinblastine can induce long-term complete responses in
about 25% of patients with disease that has persisted or recurred
following other cisplatin-based regimens. Patients who have had an initial
complete response to first-line chemotherapy and those without extensive
disease have the most favorable outcomes. This regimen is now the standard
initial salvage regimen. Few, if any, patients with recurrent
nonseminomatous germ cell tumors of extragonadal origin, however, achieve long-term
disease-free survival (DFS) using vinblastine, ifosfamide, and cisplatin if their
disease recurred after they received an initial regimen containing etoposide
and cisplatin.[Level of evidence: 3iiDii]
High-dose chemotherapy with
autologous marrow transplantation has also been used in uncontrolled case series in the
setting of recurrent disease. However, a randomized, controlled trial comparing conventional doses of salvage chemotherapy with high-dose chemotherapy with autologous marrow rescue showed more toxic effects and treatment-related deaths in the high-dose arm without any improvement in response rate or overall survival.[Level of evidence: 1iiA] In some highly selected patients with chemorefractory
disease confined to a single site, surgical resection may yield long-term
DFS. One case series suggests that a maintenance regimen of daily oral
etoposide (taken 21 days out of 28 days) may benefit patients who achieve a complete
remission after salvage therapy.
A special case of late relapse may include patients who relapse more than 2 years
after achieving complete remission; this population represents less than 5% of
patients who are in complete remission after 2 years. Results with
chemotherapy are poor in this patient subset, and surgical treatment appears to
be superior, if technically feasible. Teratoma may be
amenable to surgery at relapse, and teratoma also has a better prognosis than carcinoma after late
relapse. Teratoma is a relatively resistant histologic subtype,
so chemotherapy may not be appropriate.
Clinical trials are appropriate and should be considered whenever possible,
including phase I and phase II studies for those patients who do not achieve a complete
remission with induction therapy, or for those who do not achieve a complete remission
following etoposide and cisplatin for their initial relapse, or for patients who
have a second relapse.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent malignant testicular germ cell tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Loehrer PJ Sr, Lauer R, Roth BJ, et al.: Salvage therapy in recurrent germ cell cancer: ifosfamide and cisplatin plus either vinblastine or etoposide. Ann Intern Med 109 (7): 540-6, 1988.
Loehrer PJ Sr, Gonin R, Nichols CR, et al.: Vinblastine plus ifosfamide plus cisplatin as initial salvage therapy in recurrent germ cell tumor. J Clin Oncol 16 (7): 2500-4, 1998.
Motzer RJ, Cooper K, Geller NL, et al.: The role of ifosfamide plus cisplatin-based chemotherapy as salvage therapy for patients with refractory germ cell tumors. Cancer 66 (12): 2476-81, 1990.
Broun ER, Nichols CR, Kneebone P, et al.: Long-term outcome of patients with relapsed and refractory germ cell tumors treated with high-dose chemotherapy and autologous bone marrow rescue. Ann Intern Med 117 (2): 124-8, 1992.
Droz JP, Pico JL, Ghosn M, et al.: Long-term survivors after salvage high dose chemotherapy with bone marrow rescue in refractory germ cell cancer. Eur J Cancer 27 (7): 831-5, 1991.
Cullen MH: Dose-response relationships in testicular cancer. Eur J Cancer 27 (7): 817-8, 1991.
Motzer RJ, Mazumdar M, Bosl GJ, et al.: High-dose carboplatin, etoposide, and cyclophosphamide for patients with refractory germ cell tumors: treatment results and prognostic factors for survival and toxicity. J Clin Oncol 14 (4): 1098-105, 1996.
Motzer RJ, Bosl GJ: High-dose chemotherapy for resistant germ cell tumors: recent advances and future directions. J Natl Cancer Inst 84 (22): 1703-9, 1992.
Bhatia S, Abonour R, Porcu P, et al.: High-dose chemotherapy as initial salvage chemotherapy in patients with relapsed testicular cancer. J Clin Oncol 18 (19): 3346-51, 2000.
Beyer J, Kramar A, Mandanas R, et al.: High-dose chemotherapy as salvage treatment in germ cell tumors: a multivariate analysis of prognostic variables. J Clin Oncol 14 (10): 2638-45, 1996.
Einhorn LH, Williams SD, Chamness A, et al.: High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors. N Engl J Med 357 (4): 340-8, 2007.
Pico JL, Rosti G, Kramar A, et al.: A randomised trial of high-dose chemotherapy in the salvage treatment of patients failing first-line platinum chemotherapy for advanced germ cell tumours. Ann Oncol 16 (7): 1152-9, 2005.
Murphy BR, Breeden ES, Donohue JP, et al.: Surgical salvage of chemorefractory germ cell tumors. J Clin Oncol 11 (2): 324-9, 1993.
Cooper MA, Einhorn LH: Maintenance chemotherapy with daily oral etoposide following salvage therapy in patients with germ cell tumors. J Clin Oncol 13 (5): 1167-9, 1995.
Baniel J, Foster RS, Gonin R, et al.: Late relapse of testicular cancer. J Clin Oncol 13 (5): 1170-6, 1995.
Motzer RJ, Geller NL, Tan CC, et al.: Salvage chemotherapy for patients with germ cell tumors. The Memorial Sloan-Kettering Cancer Center experience (1979-1989). Cancer 67 (5): 1305-10, 1991.
This information was last updated on July 11, 2014.