Table of Contents Purpose of This PDQ Summary General Information Cellular Classification Stage Information
Treatment Option Overview Stage I Testicular Cancer Stage II Testicular Cancer Stage III Testicular Cancer Recurrent Testicular Cancer Get More Information From NCI Changes to This Summary (01/15/2009) More Information
Purpose of This PDQ Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of testicular cancer. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board 1.
Information about the following is included in this summary:
- Prognostic factors.
- Cellular classification.
- Staging.
- Treatment options by cancer stage.
This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system 2 in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.
This summary is available in a patient version 3, written in less technical language, and in Spanish 4. General Information
Note: A separate PDQ summary on Testicular Cancer Screening 5 is also
available.
Note: Estimated new cases and deaths from testicular cancer in the United States in 2008:[1]
- New cases: 8,090.
- Deaths: 380.
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence 2 for more
information.)
Testicular cancer is a highly treatable, often curable, cancer that usually
develops in young and middle-aged men. Testicular cancer is broadly divided
into seminoma and nonseminoma types for treatment planning because seminomas
are more sensitive to radiation therapy. For patients with seminoma (all
stages combined), the cure rate exceeds 90%. For patients with low-stage
disease, the cure rate approaches 100%.[2,3]
Tumors that have a mixture of seminoma and nonseminoma components should be
managed as nonseminomas. Nonseminomas include embryonal carcinomas, teratomas,
yolk sac carcinomas, choriocarcinomas, and various combinations of these cell
types. Tumors that appear to have a seminoma histology but that have elevated
serum levels of alpha-fetoprotein (AFP) should be treated as nonseminomas.
Elevation of the beta subunit of human chorionic gonadotropin (hCG) alone is
found in approximately 10% of the patients with pure seminoma.
Risk of metastases is lowest for teratoma and highest for choriocarcinoma, with
the other cell types having intermediate risk.
A number of prognostic classification schema are in use for metastatic
nonseminomatous testicular cancer and for primary extragonadal nonseminomatous
germ cell cancers treated with chemotherapy.[4-6] Most incorporate some or all
of the following factors, which may independently predict worse prognosis:
- Presence of liver, bone, or brain metastases.
- Very high serum markers.
- Primary mediastinal nonseminoma.
- Large number of lung metastases.
Even patients with widespread metastases at
presentation, including those with brain metastases, may be curable and
should be treated with this intent.[7]
Radical inguinal orchiectomy with initial high ligation of the spermatic cord
is the procedure of choice in treating a malignant testicular mass.[8]
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%).[9][Level of evidence: 3iiiDii] Distant recurrence and survival rates, however, were
indistinguishable in the two approaches. Local recurrence was similar in
patients who did not have scrotal violation, regardless of whether or not
additional treatments, such as hemiscrotal radiation therapy, hemiscrotal resection, or
inguinal lymph node dissection, were used.
An important aspect of the diagnosis and follow-up of testicular cancer is the
use of serum markers. Serum markers include AFP, hCG (measurement of the beta
subunit reduces luteinizing hormone cross-reactivity), and lactate
dehydrogenase. The serum markers may detect a tumor that is too small to be discovered
on physical examination or x-rays. In patients younger than 15 years, approximately 90% of
testicular germ cell cancers are yolk sac tumors. In these
types of patients, the AFP is elevated at diagnosis and is an excellent indicator of
response to therapy and disease status.[10] Serum markers plus chest x-rays are
important parts of the monthly checkups for patients after definitive therapy
of testicular cancer as well as periodic abdominal computed tomographic (CT)
scans for 2 to 3 years. The absence of markers does not mean the absence of
tumor. After diagnosis and treatment, patients typically receive follow-up monthly for the first year and
every other month for the second year. While the
majority of tumor recurrences appear within 2 years, late relapse has been
reported, and lifelong marker, radiologic, and physical examination is
recommended.[11]
Evaluation of the retroperitoneal lymph nodes, usually by CT scanning, is an important aspect of
treatment planning in adults with testicular cancer.[12,13] Patients with a negative result however, have
a 25% to 30% chance of having microscopic involvement of the lymph nodes. For
seminoma, some physicians think that knowing the results of both the
lymphangiogram and the CT scan is important for treatment planning. For nonseminoma, the inaccuracy of both is a problem, and frequently surgical
staging is required. About 25% of patients with clinical stage I
nonseminomatous testicular cancer will be upstaged to pathologic stage II with
retroperitoneal lymph node dissection (RPLND), and about 25% of clinical
stage II patients will be downstaged to pathologic stage I with RPLND.[14] In
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 these patients.[10]
Patients who have been cured of testicular cancer have approximately a 2% to 5%
cumulative risk of developing a cancer in the opposite testicle during the 25
years after initial diagnosis.[15-17] Within this range, men with nonseminomatous primary tumors appear to have a lower risk of subsequent contralateral testis tumors than men with seminomas.[17,18]
HIV-infected men are reported to be at increased risk for developing testicular
germ cell cancer.[19] Depending on comorbid conditions such as active
infection, these men are generally managed similarly to non-HIV-infected
patients.
Because the majority of testis cancer patients who receive chemotherapy are
curable, it is necessary to be aware of possible long-term effects of
platinum-based treatment, such as the following:
- Fertility: Many patients have oligospermia or sperm abnormalities prior to
therapy. Virtually all become oligospermic during chemotherapy. Many
recover sperm production, however, and can father children, often without the use of cryopreserved semen. In a population-based study, 70% of patients actually fathered children.[20] The likelihood of recovering fertility is related to the type of treatment received. The children do not appear
to have an increased risk of congenital malformations.[21-24]
- Secondary leukemias: Several reports of elevated risk of secondary acute
leukemia, primarily nonlymphocytic, have appeared.[25] In some cases, the
risks were associated with the prolonged use of alkylating agents or with the use of
radiation.[26,27] Etoposide-containing regimens are also associated with a
risk of secondary acute leukemias, usually in the myeloid lineage, and with a
characteristic 11q23 translocation.[25,28-30] Etoposide-associated leukemias
typically occur sooner after therapy than alkylating agent-associated
leukemias and often show balanced chromosomal translocations on the long arm of
chromosome 11.[25] Standard etoposide dosages (<2 g/m2 cumulative dose) are associated with a relative risk of 15 to 25, but this
translates into a cumulative incidence of leukemia of less than 0.5% at 5
years. Preliminary data suggest that cumulative doses of more than 2 g/m2 of etoposide may confer higher risk.
- Renal function: Minor decreases in creatinine clearance occur (about a 15%
decrease, on average) during platinum-based therapy, but these appear to remain
stable in the long term and without significant deterioration.[31]
- Hearing: Bilateral hearing deficits occur with cisplatin-based
chemotherapy, but the deficits generally occur at sound frequencies of 4 kHz to 8
kHz, which is outside the range of conversational tones;[31] therefore, hearing
aids are rarely required if standard doses of cisplatin are administered.
Although bleomycin pulmonary toxic effects may occur, it is rarely fatal at
total cumulative doses of less than 400U. 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. Reportedly, men treated
curatively for germ cell tumors with cisplatin-based regimens have had
elevations in total serum cholesterol.[32] This could not be
confirmed, however, in another study.[33]
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.[25,34] 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.[25]
Oligospermia or sperm abnormalities prior to therapy are common.
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 6 trial, for example.[35] (For more information on fertility, refer to the Sexuality and Reproductive Issues 7 summary.) 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. As with treatment with chemotherapy, some
men have been reported to father children after radiation treatment of
seminoma, and the children do not appear to have a high risk of congenital
malformations.[20,35][Level of evidence: 3iiiDiv]
Radiation therapy and/or chemotherapy for patients with testicular cancer may be associated with an increase in cardiovascular morbidity. 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.[36] 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.[37] 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.[25,37][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.
References
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American Cancer Society.: Cancer Facts and Figures 2008. Atlanta, Ga: American Cancer Society, 2008. Also available online. 8 Last accessed October 1, 2008.
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Bosl GJ, Bajorin DF, Sheinfeld J, et al.: Cancer of the testis. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 1269-90.
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Krege S, Beyer J, Souchon R, et al.: European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 53 (3): 478-96, 2008.
[PUBMED Abstract]
-
Bajorin DF, Bosl GJ: The use of serum tumor markers in the prognosis and treatment of germ cell tumors. Cancer: Principles and Practice of Oncology Updates 6(1): 1-11, 1992.
-
Mead GM, Stenning SP, Parkinson MC, et al.: The Second Medical Research Council study of prognostic factors in nonseminomatous germ cell tumors. Medical Research Council Testicular Tumour Working Party. J Clin Oncol 10 (1): 85-94, 1992.
[PUBMED Abstract]
-
International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group. J Clin Oncol 15 (2): 594-603, 1997.
[PUBMED Abstract]
-
Krege S, Beyer J, Souchon R, et al.: European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): part II. Eur Urol 53 (3): 497-513, 2008.
[PUBMED Abstract]
-
Leibovitch I, Baniel J, Foster RS, et al.: The clinical implications of procedural deviations during orchiectomy for nonseminomatous testis cancer. J Urol 154 (3): 935-9, 1995.
[PUBMED Abstract]
-
Capelouto CC, Clark PE, Ransil BJ, et al.: A review of scrotal violation in testicular cancer: is adjuvant local therapy necessary? J Urol 153 (3 Pt 2): 981-5, 1995.
[PUBMED Abstract]
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Huddart SN, Mann JR, Gornall P, et al.: The UK Children's Cancer Study Group: testicular malignant germ cell tumours 1979-1988. J Pediatr Surg 25 (4): 406-10, 1990.
[PUBMED Abstract]
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Gerl A, Clemm C, Schmeller N, et al.: Late relapse of germ cell tumors after cisplatin-based chemotherapy. Ann Oncol 8 (1): 41-7, 1997.
[PUBMED Abstract]
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Socinski MA, Stomper PC: Radiologic evaluation of nonseminomatous germ cell tumor of the testis. Semin Urol 6 (3): 203-15, 1988.
[PUBMED Abstract]
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Consensus conference. Magnetic resonance imaging. JAMA 259 (14): 2132-8, 1988.
[PUBMED Abstract]
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Donohue JP, Thornhill JA, Foster RS, et al.: The role of retroperitoneal lymphadenectomy in clinical stage B testis cancer: the Indiana University experience (1965 to 1989). J Urol 153 (1): 85-9, 1995.
[PUBMED Abstract]
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Osterlind A, Berthelsen JG, Abildgaard N, et al.: Risk of bilateral testicular germ cell cancer in Denmark: 1960-1984. J Natl Cancer Inst 83 (19): 1391-5, 1991.
[PUBMED Abstract]
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Colls BM, Harvey VJ, Skelton L, et al.: Bilateral germ cell testicular tumors in New Zealand: experience in Auckland and Christchurch 1978-1994. J Clin Oncol 14 (7): 2061-5, 1996.
[PUBMED Abstract]
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Fosså SD, Chen J, Schonfeld SJ, et al.: Risk of contralateral testicular cancer: a population-based study of 29,515 U.S. men. J Natl Cancer Inst 97 (14): 1056-66, 2005.
[PUBMED Abstract]
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van Leeuwen FE, Stiggelbout AM, van den Belt-Dusebout AW, et al.: Second cancer risk following testicular cancer: a follow-up study of 1,909 patients. J Clin Oncol 11 (3): 415-24, 1993.
[PUBMED Abstract]
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Foster RS, Donohue JP: Surgical treatment of clinical stage A nonseminomatous testis cancer. Semin Oncol 19 (2): 166-70, 1992.
[PUBMED Abstract]
-
Brydøy M, Fosså SD, Klepp O, et al.: Paternity following treatment for testicular cancer. J Natl Cancer Inst 97 (21): 1580-8, 2005.
[PUBMED Abstract]
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Drasga RE, Einhorn LH, Williams SD, et al.: Fertility after chemotherapy for testicular cancer. J Clin Oncol 1 (3): 179-83, 1983.
[PUBMED Abstract]
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Nijman JM, Schraffordt Koops H, Kremer J, et al.: Gonadal function after surgery and chemotherapy in men with stage II and III nonseminomatous testicular tumors. J Clin Oncol 5 (4): 651-6, 1987.
[PUBMED Abstract]
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Hansen PV, Trykker H, Helkjoer PE, et al.: Testicular function in patients with testicular cancer treated with orchiectomy alone or orchiectomy plus cisplatin-based chemotherapy. J Natl Cancer Inst 81 (16): 1246-50, 1989.
[PUBMED Abstract]
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Stephenson WT, Poirier SM, Rubin L, et al.: Evaluation of reproductive capacity in germ cell tumor patients following treatment with cisplatin, etoposide, and bleomycin. J Clin Oncol 13 (9): 2278-80, 1995.
[PUBMED Abstract]
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van den Belt-Dusebout AW, de Wit R, Gietema JA, et al.: Treatment-specific risks of second malignancies and cardiovascular disease in 5-year survivors of testicular cancer. J Clin Oncol 25 (28): 4370-8, 2007.
[PUBMED Abstract]
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Redman JR, Vugrin D, Arlin ZA, et al.: Leukemia following treatment of germ cell tumors in men. J Clin Oncol 2 (10): 1080-7, 1984.
[PUBMED Abstract]
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Travis LB, Andersson M, Gospodarowicz M, et al.: Treatment-associated leukemia following testicular cancer. J Natl Cancer Inst 92 (14): 1165-71, 2000.
[PUBMED Abstract]
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Pedersen-Bjergaard J, Daugaard G, Hansen SW, et al.: Increased risk of myelodysplasia and leukaemia after etoposide, cisplatin, and bleomycin for germ-cell tumours. Lancet 338 (8763): 359-63, 1991.
[PUBMED Abstract]
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Nichols CR, Breeden ES, Loehrer PJ, et al.: Secondary leukemia associated with a conventional dose of etoposide: review of serial germ cell tumor protocols. J Natl Cancer Inst 85 (1): 36-40, 1993.
[PUBMED Abstract]
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Bajorin DF, Motzer RJ, Rodriguez E, et al.: Acute nonlymphocytic leukemia in germ cell tumor patients treated with etoposide-containing chemotherapy. J Natl Cancer Inst 85 (1): 60-2, 1993.
[PUBMED Abstract]
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Osanto S, Bukman A, Van Hoek F, et al.: Long-term effects of chemotherapy in patients with testicular cancer. J Clin Oncol 10 (4): 574-9, 1992.
[PUBMED Abstract]
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Raghavan D, Cox K, Childs A, et al.: Hypercholesterolemia after chemotherapy for testis cancer. J Clin Oncol 10 (9): 1386-9, 1992.
[PUBMED Abstract]
-
Ellis PA, Fitzharris BM, George PM, et al.: Fasting plasma lipid measurements following cisplatin chemotherapy in patients with germ cell tumors. J Clin Oncol 10 (10): 1609-14, 1992.
[PUBMED Abstract]
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Travis LB, Fosså SD, Schonfeld SJ, et al.: Second cancers among 40,576 testicular cancer patients: focus on long-term survivors. J Natl Cancer Inst 97 (18): 1354-65, 2005.
[PUBMED Abstract]
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Gordon W Jr, Siegmund K, Stanisic TH, et al.: A study of reproductive function in patients with seminoma treated with radiotherapy and orchidectomy: (SWOG-8711). Southwest Oncology Group. Int J Radiat Oncol Biol Phys 38 (1): 83-94, 1997.
[PUBMED Abstract]
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Huddart RA, Norman A, Shahidi M, et al.: Cardiovascular disease as a long-term complication of treatment for testicular cancer. J Clin Oncol 21 (8): 1513-23, 2003.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
Cellular Classification
The following histologic classification of malignant testicular germ cell tumors (testicular cancer) reflects the classification used by the World Health Organization.[1] 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.[1-3]
- Intratubular germ cell neoplasia, unclassified.
- Malignant pure germ cell tumor (showing a single cell type):
- Seminoma.
- Embryonal carcinoma.
- Teratoma.
- Choriocarcinoma.
- Yolk sac tumor.
- Malignant mixed germ cell tumor (showing more than one histologic pattern):
- Embryonal carcinoma and teratoma with or without seminoma.
- Embryonal carcinoma and yolk sac tumor with or without seminoma.
- Embryonal carcinoma and seminoma.
- Yolk sac tumor and teratoma with or without seminoma.
- Choriocarcinoma and any other element.
- Polyembryoma.
References
-
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: Testicular and paratesticular tumors. In: Mills SE, ed.: Sternberg’s Diagnostic Surgical Pathology. 4th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2004, pp 2167-2232.
-
Bosl GJ, Bajorin DF, Sheinfeld J, et al.: Cancer of the testis. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 1269-90.
Stage Information
The American Joint Committee on Cancer (AJCC) has designated staging by TNM
classification.[1]
TNM Definitions
Primary tumor (T)
The extent of primary tumor is classified after radical orchiectomy, and for this reason a pathologic stage is assigned.
- pTX: Primary tumor cannot be assessed*
- pT0: No evidence of primary tumor (e.g., histologic scar in testis)
- pTis: Intratubular germ cell neoplasia (carcinoma)
- pT1: Tumor limited to the testis and epididymis without lymphatic/vascular
invasion; tumor may invade into the tunica albuginea but not the tunica vaginalis
- pT2: Tumor limited to the testis and epididymis with vascular/lymphatic
invasion, or tumor extending through the tunica albuginea with
involvement of the tunica vaginalis
- pT3: Tumor invades the spermatic cord with or without vascular/lymphatic
invasion
- pT4: Tumor invades the scrotum with or without vascular/lymphatic invasion
* [Note: Except for pTis and pT4, the 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 (N)
- NX: Regional lymph nodes cannot be assessed
- N0: No regional lymph node metastasis
- N1: Metastasis with a single lymph node mass 2 cm or less in greatest dimension; or multiple lymph nodes, 2 cm or less in greatest dimension
- N2: Metastasis with a single lymph node mass larger than 2 cm but no more than 5
cm in greatest dimension; or multiple lymph nodes, no more than 5 cm
in greatest dimension
- N3: Metastasis with a lymph node mass 5 cm or more in greatest dimension
Distant metastasis (M)
- MX: Presence of distant metastasis cannot be assessed
- M0: No distant metastasis
- M1: Distant metastasis
- M1a: Nonregional nodal or pulmonary metastasis
- M1b: Distant metastasis other than to nonregional lymph nodes and lungs
Serum tumor markers (S)
- SX: Marker studies not available or not performed
- S0: Marker study levels within normal limits
- S1: Lactate dehydrogenase (LDH) less than 1.5 × N*, and
- Human chorionic gonadotropin (hCG) less than 5,000 (mIU/mL), and
- Alpha-fetoprotein (AFP) less than 1,000
(ng/mL)
- S2: LDH 1.5–10 × N* or
- hCG 5,000–50,000 (mIU/mL), or
- AFP 1,000–10,000
(ng/mL)
- S3: LDH more than 10 × N*, or
- hCG more than 50,000 (mIU/mL), or
- AFP more than 10,000 (ng/mL)
* [Note: N indicates the upper limit of normal for the LDH assay.]
AJCC Stage Groupings
Stage 0
Stage I
Stage IA
Stage IB
- pT2, N0, M0, S0
- pT3, N0, M0, S0
- pT4, N0, M0, S0
Stage IS
Stage II
Stage IIA
- Any pT/Tx, N1, M0, S0
- Any pT/Tx, N1, M0, S1
Stage IIB
- Any pT/Tx, N2, M0, S0
- Any pT/Tx, N2, M0, S1
Stage IIC
- Any pT/Tx, N3, M0, S0
- Any pT/Tx, N3, M0, S1
Stage III
Stage IIIA
- Any pT/Tx, any N, M1a, S0
- Any pT/Tx, any N, M1a, S1
Stage IIIB
- Any pT/Tx, N1–3, M0, S2
- Any pT/Tx, any N, M1a, S2
Stage IIIC
- Any pT/Tx, N1–3, M0, S3
- Any pT/Tx, any N, M1a, S3
- Any pT/Tx, any N, M1b, any S
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 I
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 spermatic cord also does not change the
stage but does increase the risk of retroperitoneal nodal involvement and the
risk of recurrence. This stage corresponds to AJCC stage I and stage II.
Stage II
Stage II testicular cancer involves the testis and the retroperitoneal or
para-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, if the size of one or more involved nodes is more than 2
cm, or if there is extranodal fat involvement. Bulky stage II disease
describes patients with extensive retroperitoneal nodes (>5 cm) who
require primary chemotherapy and who have a less favorable prognosis. This
stage corresponds to AJCC stage III and stage IV (no distant metastasis).
Stage III
Stage III implies spread beyond the retroperitoneal nodes based on physical
examination, x-rays, and/or blood tests. Stage III is subdivided into nonbulky
stage III versus bulky stage III. In nonbulky stage III, metastases are
limited to lymph nodes and lung with no mass more than 2 cm in
diameter. Bulky stage III includes extensive retroperitoneal nodal
involvement, plus lung nodules or spread to other organs such as the liver or
brain. This stage corresponds to AJCC stage IV (distant metastasis).
References
-
Testis. In: American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp 317-322.
Treatment Option Overview
Testicular cancer is broadly divided into seminoma and nonseminoma for
treatment planning because seminomatous types of testicular cancer are more
sensitive to radiation therapy. Nonseminomatous testicular tumors include yolk
sac tumors.
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.[1] 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.[2] In addition to improved therapy, the improvement seen in these survival rates could be due to 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).
Good Prognosis
Nonseminoma:
Seminoma:
Intermediate Prognosis
Nonseminoma:
Seminoma:
Poor Prognosis
Nonseminoma:
Seminoma:
- No patients are classified as poor prognosis.
References
-
International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group. J Clin Oncol 15 (2): 594-603, 1997.
[PUBMED Abstract]
-
van Dijk MR, Steyerberg EW, Habbema JD: Survival of non-seminomatous germ cell cancer patients according to the IGCC classification: An update based on meta-analysis. Eur J Cancer 42 (7): 820-6, 2006.
[PUBMED Abstract]
Stage I Testicular Cancer
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence 2 for more
information.)
Stage I Seminoma
Stage I seminoma has a cure rate of greater than 95% regardless of whether or not postorchiectomy adjuvant therapy is given.
Standard treatment options:
- Radical inguinal orchiectomy with no retroperitoneal node radiation therapy followed
by frequent determination of serum markers, chest x-rays, and computed tomographic (CT) scans
(surveillance). Results of multiple clinical series, with more than 900
patients with stage I seminoma managed by postorchiectomy surveillance, have
been reported.[1-3] The overall 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. Relapses after 5 years are unusual but can occur.[3]
- Radical inguinal orchiectomy followed by single-dose carboplatin adjuvant therapy. In a large randomized controlled equivalency trial comparing para-aortic (or dog-leg field, if clinically indicated) radiation to a single dose of carboplatin (concentration-versus-time curve [AUC] × 7) after radical inguinal orchiectomy, relapse-free survival (RFS) and overall survival (OS) rates were equivalent after a median follow-up of 4 years.[4][Level of evidence: 1iiA]
- Removal of the testicle via radical inguinal orchiectomy followed by radiation
therapy. Many radiation therapists recommend prophylactic radiation of the
retroperitoneal nodes even with a negative lymphangiogram and/or CT scan because approximately 15% of the patients will have occult nodal spread
that can be cured with radiation therapy.[5,6] Relapse rates and toxic effects were studied in a randomized
comparison in the MRC-TE08 9 trial, for example, of para-aortic radiation therapy alone versus para-aortic radiation
therapy with an added ipsilateral iliac lymph node field.[7] Three-year
RFS rates were virtually identical (96% vs. 96.6%) as
were OS rates (99.3% vs. 100%). 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. Patients with tumors with vascular invasion seem at
higher risk for nodal metastases.[8] In a randomized trial (EORTC-30942), radiation to 20 Gy over 10 daily fractions was clinically equivalent to 30 Gy over 15 fractions after a median follow-up of 61 months in both RFS and OS. Patient-reported lethargy and ability to perform normal work were better in the lower-dose regimen.[9][Level of evidence: 1iiA]
Stage I Nonseminoma
Stage I nonseminoma is highly curable (>95%). If preservation of fertility is
an important consideration, a surgical technique for sparing sympathetic
ganglia and chains should be used. This technique is associated with
postoperative fertility in most patients and appears to be as effective as
non-nerve-sparing procedures in preventing retroperitoneal relapse.[10]
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.[11]
Standard treatment options:
- Removal of the testicle through the groin followed (in adults) by
retroperitoneal lymph node dissection (RPLND) . 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 dissection.[10,12] Surgery should be followed by monthly
determination of serum markers and chest x-rays for the first year and 1- to 2-month determinations for the second year.[13,14] In patients with pathologic stage
I disease after RPLND, the presence of lymphatic or venous invasion in the
primary tumor appears to predict for relapse.[15] In a large Testicular Cancer
Intergroup Study, the relapse rate was 19% in those with vascular invasion
versus 6% in those without vascular invasion. 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.[11] In
a large study, 27% of clinical stage I tumors had metastatic involvement of
removed lymph nodes and were upstaged to pathological stage II.[16]
Chemotherapy is employed immediately on first evidence of recurrence. In a
large study, 15% of patients with a negative lymph node dissection experienced
recurrence, which was usually pulmonary and usually within 18 months.[16]
- Radical inguinal orchiectomy with no RPLND
followed by regular history (e.g., every 1–2 months), physical examination,
determination of serum markers, and, during the first year, abdominal CT scan
(surveillance).[2] Intervals for abdominal CT scans have varied from every 2
months to scans at 3 months and 12 months postorchiectomy with apparently similar
outcomes .[2,17][Level of evidence: 1iiA] Disease recurrence is rarely detected
by chest x-ray alone, so chest x-ray may play little or no role in routine
surveillance.[18] Long-term follow-up is important since relapses have been
reported more than 5 years after the orchiectomy in patients who did not
undergo a retroperitoneal dissection.[19-21]
This option should be considered only if:
- CT scan and serum markers are negative. Lymphangiography, when CT scan and
serum markers are negative, does not appear to significantly add to patient
management.[22]
- The patient and physician accept the need for repeat CT scans as necessary
to continue the periodic monitoring of the retroperitoneal lymph nodes.
Children are adequately followed by serum markers alpha-fetoprotein (AFP),
chest x-rays, and clinical examination.[11]
- The patient will diligently follow a program of regular checkups for 2 years,
which includes history, physical examination, x-ray of abdominal lymph nodes,
and determination of serum markers.
- The physician accepts responsibility for seeing that a follow-up schedule is
maintained as noted for 2 years and then periodically beyond 2 years.
- Adjuvant
therapy consisting of two courses of cisplatin, bleomycin, and etoposide in patients with clinical stage I disease who are considered at high
risk of relapse (about 50% predicted relapse rate based on presence of vascular
invasion and histologic type).[23] In 114 such patients, the RFS at 2 years was 98% (lower bound of 95% CI, 95%).
Another study of high-risk clinical stage I patients treated with two adjuvant
courses of cisplatin, etoposide, and bleomycin has been reported.[24]
Relapse rates after chemotherapy are less than 5% compared with about 50% in
historical series of high-risk patients followed without adjuvant chemotherapy.
In the historical series, however, cure rates have been 95% or more after
chemotherapy for relapse. It is unclear which approach is superior in outcome.
The adjuvant chemotherapy series is too small to draw conclusions about the
risk of chemotherapy-induced secondary malignancies, impact on fertility, or
risk of late relapse.
Data suggest that relapse rates are higher in patients with histologic evidence
of lymphatic or venous invasion and lower when the primary tumor contains
mature teratoma.[25] Some investigators have reported higher relapse rates in
patients with embryonal cell histology and recommend RPLND for such
patients.[16,26] Other investigators have not found a higher relapse rate for
this subgroup.[25,27] Additionally, some investigators recommend RPLND in
patients with a normal preorchiectomy AFP [16,26] because they feel the marker
cannot be used as an indicator of relapse during follow-up. Since
marker-negative patients may be marker-positive at relapse, and marker-positive
patients may be marker-negative at relapse, some investigators do not view a
negative AFP as a contraindication to a surveillance policy.[27]
A single course of cisplatin, bleomycin, and etoposide has also been given to clinical stage I patients with good results.[28] In a multicenter trial, 382 patients were randomly assigned to chemotherapy versus RPLND. The 2-year recurrence-free rates were 99.5% versus 91.9% (absolute difference 7.6%; 95% confidence interval 3.1% to 12.1%). There were no treatment-related or cancer-specific deaths in either arm of the study.[28][Level of evidence 1iiD]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage I malignant testicular germ cell tumor 10. 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 11.
References
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Gospodarwicz MK, Sturgeon JF, Jewett MA: Early stage and advanced seminoma: role of radiation therapy, surgery, and chemotherapy. Semin Oncol 25 (2): 160-73, 1998.
[PUBMED Abstract]
-
Francis R, Bower M, Brunström G, et al.: Surveillance for stage I testicular germ cell tumours: results and cost benefit analysis of management options. Eur J Cancer 36 (15): 1925-32, 2000.
[PUBMED Abstract]
-
Choo R, Thomas G, Woo T, et al.: Long-term outcome of postorchiectomy surveillance for Stage I testicular seminoma. Int J Radiat Oncol Biol Phys 61 (3): 736-40, 2005.
[PUBMED Abstract]
-
Oliver RT, Mason MD, Mead GM, et al.: Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial. Lancet 366 (9482): 293-300, 2005 Jul 23-29.
[PUBMED Abstract]
-
Stutzman RE, McLeod DG: Radiation therapy: a primary treatment modality for seminoma. Urol Clin North Am 7 (3): 757-64, 1980.
[PUBMED Abstract]
-
Duchesne GM, Horwich A, Dearnaley DP, et al.: Orchidectomy alone for stage I seminoma of the testis. Cancer 65 (5): 1115-8, 1990.
[PUBMED Abstract]
-
Fosså SD, Horwich A, Russell JM, et al.: Optimal planning target volume for stage I testicular seminoma: A Medical Research Council randomized trial. Medical Research Council Testicular Tumor Working Group. J Clin Oncol 17 (4): 1146, 1999.
[PUBMED Abstract]
-
Marks LB, Rutgers JL, Shipley WU, et al.: Testicular seminoma: clinical and pathological features that may predict para-aortic lymph node metastases. J Urol 143 (3): 524-7, 1990.
[PUBMED Abstract]
-
Jones WG, Fossa SD, Mead GM, et al.: Randomized trial of 30 versus 20 Gy in the adjuvant treatment of stage I Testicular Seminoma: a report on Medical Research Council Trial TE18, European Organisation for the Research and Treatment of Cancer Trial 30942 (ISRCTN18525328). J Clin Oncol 23 (6): 1200-8, 2005.
[PUBMED Abstract]
-
Foster RS, McNulty A, Rubin LR, et al.: The fertility of patients with clinical stage I testis cancer managed by nerve sparing retroperitoneal lymph node dissection. J Urol 152 (4): 1139-42; discussion 1142-3, 1994.
[PUBMED Abstract]
-
Huddart SN, Mann JR, Gornall P, et al.: The UK Children's Cancer Study Group: testicular malignant germ cell tumours 1979-1988. J Pediatr Surg 25 (4): 406-10, 1990.
[PUBMED Abstract]
-
Foster RS, Donohue JP: Surgical treatment of clinical stage A nonseminomatous testis cancer. Semin Oncol 19 (2): 166-70, 1992.
[PUBMED Abstract]
-
Lange PH, Narayan P, Fraley EE: Fertility issues following therapy for testicular cancer. Semin Urol 2 (4): 264-74, 1984.
[PUBMED Abstract]
-
Williams SD, Einhorn LH: Clinical stage I testis tumors: the medical oncologist's view. Cancer Treat Rep 66 (1): 15-8, 1982.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
Klepp O, Olsson AM, Henrikson H, et al.: Prognostic factors in clinical stage I nonseminomatous germ cell tumors of the testis: multivariate analysis of a prospective multicenter study. Swedish-Norwegian Testicular Cancer Group. J Clin Oncol 8 (3): 509-18, 1990.
[PUBMED Abstract]
-
Rustin GJ, Mead GM, Stenning SP, et al.: Randomized trial of two or five computed tomography scans in the surveillance of patients with stage I nonseminomatous germ cell tumors of the testis: Medical Research Council Trial TE08, ISRCTN56475197--the National Cancer Research Institute Testis Cancer Clinical Studies Group. J Clin Oncol 25 (11): 1310-5, 2007.
[PUBMED Abstract]
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Sharir S, Jewett MA, Sturgeon JF, et al.: Progression detection of stage I nonseminomatous testis cancer on surveillance: implications for the followup protocol. J Urol 161 (2): 472-5; discussion 475-6, 1999.
[PUBMED Abstract]
-
Rørth M, Jacobsen GK, von der Maase H, et al.: Surveillance alone versus radiotherapy after orchiectomy for clinical stage I nonseminomatous testicular cancer. Danish Testicular Cancer Study Group. J Clin Oncol 9 (9): 1543-8, 1991.
[PUBMED Abstract]
-
Sujka SK, Huben RP: Clinical stage I nonseminomatous germ cell tumors of testis. Observation vs retroperitoneal lymph node dissection. Urology 38 (1): 29-31, 1991.
[PUBMED Abstract]
-
Sturgeon JF, Jewett MA, Alison RE, et al.: Surveillance after orchidectomy for patients with clinical stage I nonseminomatous testis tumors. J Clin Oncol 10 (4): 564-8, 1992.
[PUBMED Abstract]
-
Wishnow KI, Johnson DE, Tenney D: Are lymphangiograms necessary before placing patients with nonseminomatous testicular tumors on surveillance? J Urol 141 (5): 1133-5, 1989.
[PUBMED Abstract]
-
Cullen MH, Stenning SP, Parkinson MC, et al.: Short-course adjuvant chemotherapy in high-risk stage I nonseminomatous germ cell tumors of the testis: a Medical Research Council report. J Clin Oncol 14 (4): 1106-13, 1996.
[PUBMED Abstract]
-
Pont J, Albrecht W, Postner G, et al.: Adjuvant chemotherapy for high-risk clinical stage I nonseminomatous testicular germ cell cancer: long-term results of a prospective trial. J Clin Oncol 14 (2): 441-8, 1996.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
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Read G, Stenning SP, Cullen MH, et al.: Medical Research Council prospective study of surveillance for stage I testicular teratoma. Medical Research Council Testicular Tumors Working Party. J Clin Oncol 10 (11): 1762-8, 1992.
[PUBMED Abstract]
-
Colls BM, Harvey VJ, Skelton L, et al.: Results of the surveillance policy of stage I non-seminomatous germ cell testicular tumours. Br J Urol 70 (4): 423-8, 1992.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
Stage II Testicular Cancer
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence 2 for more
information.)
Stage II Seminoma
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.
Nonbulky stage II disease has a cure rate of more than 90% with radiation
alone at doses of 30 Gy to 36 Gy.[1] While earlier studies reported that bulky stage II seminoma had a cure
rate of 70% with radiation alone, studies using improved treatment planning and
equipment as well as careful selection of patients (including the use of tumor
markers) have reported an improvement in the results of radiation therapy in the
treatment of patients with bulky stage II seminoma.[2,3] Combination
chemotherapy with cisplatin is also effective therapy in patients with bulky
stage II seminomas. Residual radiologic abnormalities are common at the
completion of chemotherapy. Many abnormalities gradually regress over a period
of months. Some clinicians advocate empiric radiation of residual persistent
abnormalities or attempts to resect residual masses 3 cm or larger. Either approach is controversial. In a combined retrospective
consecutive series of 174 seminoma patients with postchemotherapy residual
disease seen at 10 treatment centers, empiric radiation was not associated with
any medically significant improvement in progression-free survival after
completion of platinum-based combination chemotherapy.[4][Level of evidence: 3iiDiii] In some series, surgical resection of specific masses has yielded a
significant number with residual seminoma that require additional therapy.[5]
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.[6]
Standard treatment options:
For patients with nonbulky tumors
- Radical inguinal orchiectomy followed by
radiation therapy to the retroperitoneal and ipsilateral pelvic lymph nodes. Evidence
favors the omission of prophylactic radiation therapy to the mediastinum and
neck.[7,8] Radiation therapy to inguinal nodes is not standard unless there has been
some damage to the scrotum to put inguinal lymph nodes at risk.
For patients with bulky tumors
- Radical inguinal orchiectomy followed by
combination chemotherapy (with a cisplatin-based regimen) or by radiation therapy to
the abdominal and pelvic lymph nodes.[2,3,9-11] Recurrence rate is higher after
radiation therapy for bulky stage II tumors than radiation therapy for nonbulky tumors,
leading some authors to recommend primary chemotherapy for patients with bulky
disease (≥5–10 cm).[12] Controversy exists over whether any
residual masses present at the completion of chemotherapy should be empirically
irradiated, or whether masses larger than 3 cm should be
resected.[5,6]
Stage II Nonseminoma
Stage II nonseminoma is highly curable (>95%). If preservation of fertility is
an important consideration, surgical techniques for sparing sympathetic ganglia
and chains without compromising the total removal of all involved nodes are
available, though this technique may not be feasible in many patients. This
technique is associated with postoperative preservation of ejaculation in a
large number of patients.[13-15] In most patients, an orchiectomy is performed
prior to starting chemotherapy. If the diagnosis has been made by
biopsy of a metastatic site and chemotherapy has been initiated, subsequent
orchiectomy is generally performed, since chemotherapy may not
eradicate the primary cancer. Case reports
illustrate that viable tumor was found on postchemotherapy orchiectomy despite the complete
response of metastatic lesions.[16]
Standard treatment options:
- Radical inguinal orchiectomy followed by removal of retroperitoneal lymph
nodes with or without fertility-preserving retroperitoneal lymph node dissection (RPLND) followed by monthly checkups,
which include physical examination, chest x-ray, and serum marker tests (e.g., alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase). This
option of surgery and careful follow-up, reserving chemotherapy for relapse, is
particularly attractive for patients who have fewer than six positive nodes at
retroperitoneal lymph node dissection, none of which are larger than 2
cm in diameter and with no extracapsular lymph node invasion. Such
patients appear to have a relapse rate of about 20% to 30% if followed
without chemotherapy, and most are curable with standard chemotherapy if they
do relapse.[17] Patients whose markers do not return to normal following the
removal of retroperitoneal lymph nodes should be treated with
chemotherapy.[13,18] Presence of lymphatic or venous invasion also helps to
predict which patients may relapse. In a large Testicular Cancer Intergroup
Study, the relapse rate after RPLND was 64% in those who had microscopic evidence
of vascular invasion in the primary tumor versus 24% in those who did not.[19]
In children, surgical resection of retroperitoneal nodes is generally not
performed. Patients with clinical stage II disease are given chemotherapy.[20]
- Radical inguinal orchiectomy followed by removal of retroperitoneal lymph
nodes followed by chemotherapy and then monthly checkups. 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. 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 an equivalent cure
rate.[21,22]
- Radical inguinal orchiectomy followed by chemotherapy with delayed surgery
for removal of residual masses (if present) followed by monthly checkups. This
option is considered for patients in whom clinical examination,
lymphangiogram, or CT scan show retroperitoneal masses that are large enough to cause concern about resectability.
Chemotherapy regimens include: - BEP: bleomycin plus etoposide plus cisplatin for three courses.[23] A modified
regimen has been used in children.[20]
- EP: etoposide plus cisplatin for four courses in good-prognosis patients.[11]
A randomized study has shown that bleomycin is an essential component of the
BEP regimen when only three courses are administered.[24]
Other regimens that appear to produce similar survival outcomes but are in less
common use include:
- PVB: cisplatin plus vinblastine plus bleomycin.
- VAB VI: vinblastine plus dactinomycin plus bleomycin plus cyclophosphamide plus
cisplatin.[21]
- VPV: vinblastine plus cisplatin plus etoposide.[25]
In a randomized comparison of PVB versus BEP, equivalent anticancer
activity was seen but with less toxic effects with the use of BEP.[23,26]
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 of serum markers. The probability
of finding residual teratoma or carcinoma after chemotherapy may be dependent
on the histology of the primary tumor. Patients whose primary tumor contained
teratomatous elements have a higher probability of having residual teratoma or
carcinoma in the retroperitoneal nodes than do patients whose primary tumor
contains only embryonal cancer. One study has reported that irrespective of
initial histology, there is a significant risk of residual teratoma or
carcinoma in residual masses after chemotherapy. Some investigators think that
neither size of the initial tumor nor the degree of shrinkage during therapy
appears to accurately identify patients with residual teratoma or carcinoma.
This has led some to recommend surgery with resection of all residual masses
apparent on scans in patients who have normal markers after responding to
chemotherapy. Some investigators recommend surgery for patients who have
initial masses of 3 cm or larger [27] on a CT scan and after chemotherapy
have a normal CT scan. This approach remains controversial, and no
evidence is available that such an approach improves survival. The presence of persistent
nonseminomatous germ cell malignant elements in the resected specimen is an
indication for additional chemotherapy.[28] 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.[29]
Treatment options under clinical evaluation:
- In some clinical trials, primary chemotherapy has been administered to patients
with small volume retroperitoneal disease in an effort to avoid retroperitoneal
node dissections. Although a randomized comparison has not been performed, it
appears that primary chemotherapy, when compared with primary retroperitoneal
node dissection, may produce similar survival in clinical stage II testicular
cancer patients.[30,31]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage II malignant testicular germ cell tumor 12. 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 11.
References
-
Classen J, Souchon R, Hehr T, et al.: Radiotherapy for early stages testicular seminoma: patterns of care study in Germany. Radiother Oncol 63 (2): 179-86, 2002.
[PUBMED Abstract]
-
Smalley SR, Evans RG, Richardson RL, et al.: Radiotherapy as initial treatment for bulky stage II testicular seminomas. J Clin Oncol 3 (10): 1333-8, 1985.
[PUBMED Abstract]
-
Friedman EL, Garnick MB, Stomper PC, et al.: Therapeutic guidelines and results in advanced seminoma. J Clin Oncol 3 (10): 1325-32, 1985.
[PUBMED Abstract]
-
Duchesne GM, Stenning SP, Aass N, et al.: Radiotherapy after chemotherapy for metastatic seminoma--a diminishing role. MRC Testicular Tumour Working Party. Eur J Cancer 33 (6): 829-35, 1997.
[PUBMED Abstract]
-
Herr HW, Sheinfeld J, Puc HS, et al.: Surgery for a post-chemotherapy residual mass in seminoma. J Urol 157 (3): 860-2, 1997.
[PUBMED Abstract]
-
Schultz SM, Einhorn LH, Conces DJ Jr, et al.: Management of postchemotherapy residual mass in patients with advanced seminoma: Indiana University experience. J Clin Oncol 7 (10): 1497-503, 1989.
[PUBMED Abstract]
-
Stutzman RE, McLeod DG: Radiation therapy: a primary treatment modality for seminoma. Urol Clin North Am 7 (3): 757-64, 1980.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
Ball D, Barrett A, Peckham MJ: The management of metastatic seminoma testis. Cancer 50 (11): 2289-94, 1982.
[PUBMED Abstract]
-
Loehrer PJ Sr, Birch R, Williams SD, et al.: Chemotherapy of metastatic seminoma: the Southeastern Cancer Study Group experience. J Clin Oncol 5 (8): 1212-20, 1987.
[PUBMED Abstract]
-
Bajorin DF, Geller NL, Weisen SF, et al.: Two-drug therapy in patients with metastatic germ cell tumors. Cancer 67 (1): 28-32, 1991.
[PUBMED Abstract]
-
Mason BR, Kearsley JH: Radiotherapy for stage 2 testicular seminoma: the prognostic influence of tumor bulk. J Clin Oncol 6 (12): 1856-62, 1988.
[PUBMED Abstract]
-
Lange PH, Narayan P, Fraley EE: Fertility issues following therapy for testicular cancer. Semin Urol 2 (4): 264-74, 1984.
[PUBMED Abstract]
-
Jewett MA, Kong YS, Goldberg SD, et al.: Retroperitoneal lymphadenectomy for testis tumor with nerve sparing for ejaculation. J Urol 139 (6): 1220-4, 1988.
[PUBMED Abstract]
-
Donohue JP, Foster RS, Rowland RG, et al.: Nerve-sparing retroperitoneal lymphadenectomy with preservation of ejaculation. J Urol 144 (2 Pt 1): 287-91; discussion 291-2, 1990.
[PUBMED Abstract]
-
Leibovitch I, Baniel J, Rowland RG, et al.: Malignant testicular neoplasms in immunosuppressed patients. J Urol 155 (6): 1938-42, 1996.
[PUBMED Abstract]
-
Richie JP, Kantoff PW: Is adjuvant chemotherapy necessary for patients with stage B1 testicular cancer? J Clin Oncol 9 (8): 1393-6, 1991.
[PUBMED Abstract]
-
Donohue JP, Einhorn LH, Williams SD: Is adjuvant chemotherapy following retroperitoneal lymph node dissection for nonseminomatous testis cancer necessary? Urol Clin North Am 7 (3): 747-56, 1980.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
Huddart SN, Mann JR, Gornall P, et al.: The UK Children's Cancer Study Group: testicular malignant germ cell tumours 1979-1988. J Pediatr Surg 25 (4): 406-10, 1990.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
Toner GC, Panicek DM, Heelan RT, et al.: Adjunctive surgery after chemotherapy for nonseminomatous germ cell tumors: recommendations for patient selection. J Clin Oncol 8 (10): 1683-94, 1990.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
Logothetis CJ, Swanson DA, Dexeus F, et al.: Primary chemotherapy for clinical stage II nonseminomatous germ cell tumors of the testis: a follow-up of 50 patients. J Clin Oncol 5 (6): 906-11, 1987.
[PUBMED Abstract]
-
Socinski MA, Garnick MB, Stomper PC, et al.: Stage II nonseminomatous germ cell tumors of the testis: an analysis of treatment options in patients with low volume retroperitoneal disease. J Urol 140 (6): 1437-41, 1988.
[PUBMED Abstract]
Stage III Testicular Cancer
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence 2 for more
information.)
Stage III Seminoma
Stage III seminoma is usually curable.
Standard treatment options:
A randomized study comparing four courses of BEP to four courses of VIP showed
similar overall survival and time-to-treatment failure for the two regimens in
patients with advanced disseminated germ cell tumors who had not received prior
chemotherapy.[11][Level of evidence: 1iiA] Hematologic toxic effects were
substantially worse with the VIP regimen.
Residual radiologic abnormalities are common at the completion of chemotherapy.
Many abnormalities gradually regress over a period of months. Some clinicians
advocate empiric radiation of residual persistent abnormalities or attempts to
resect residual masses 3 cm or larger. Either approach is
controversial. 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.[12][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.[2] Nevertheless, other reports
indicate that 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.[3]
Treatment options under clinical evaluation:
- Patients are usually eligible for the same chemotherapy clinical trials as
those patients with nonseminomatous germ cell tumors.
Stage III Nonseminoma
Stage III nonseminoma is usually curable (70%) with standard chemotherapy. In
some patients fertility has returned following the use of chemotherapy. The
30% of patients who are not cured with standard chemotherapy usually have
widespread visceral metastases, high tumor markers, or mediastinal primary
tumors at presentation. In most patients, an orchiectomy is performed prior to
starting chemotherapy. If the diagnosis has been made by biopsy of a
metastatic site and chemotherapy has been initiated, subsequent orchiectomy is
generally performed because chemotherapy may not eradicate the
primary cancer. Case reports illustrate that viable tumor was
found on postchemotherapy orchiectomy despite complete response of metastatic
lesions.[13]
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.[14] Overall 2-year survival for the 55
patients treated at institutions that entered fewer than 5 patients onto the
protocol was 62% (95% confidence interval [CI], 48%–75%) versus 77% (95% CI, 72%–81%) in the
institutions that entered 5 or more patients onto the protocol. As in any
nonrandomized study design, patient selection factors and factors leading
patients to choose treatment at one center over another can make interpretation
of results difficult.
The results of a large cooperative group randomized study of PVB versus BEP
have been reported.[6] The BEP regimen produced less neuromuscular toxic
effects and was more effective in patients with advanced disease, which makes
it the preferable regimen of these two combinations. In addition, three courses of
BEP have been shown to be equivalent to four courses in patients with minimal or
moderate extent of disseminated germ cell tumors.[7] A randomized study has
shown that bleomycin is an essential component of the BEP regimen when only three
courses are administered.[15] Although another randomized study in
good-prognosis patients treated with four courses of cisplatin plus vinblastine
with or without bleomycin (PV with or without B) has shown better tumor-specific survival
with PVB, this was offset by more toxic deaths. OS rates were
not significantly different between four courses of PV versus PVB.[16]
In patients with poor-risk germ cell tumors, the standard-dose cisplatin
regimen has been shown to be the equivalent of high-dose cisplatin in terms of
complete response, cure rates, and survival; moreover, patients in the
high-dose cisplatin regimen experienced significantly more toxic effects.[17]
Many patients with poor-risk nonseminomatous testicular germ cell tumors who
have a serum beta human chorionic gonadotropin (βhCG) level higher than 50,000
IU/mL at the initiation of cisplatin-based therapy
(BEP or PVB) will still have an elevated βhCG level at the completion of
therapy, showing an initial rapid decrease in βhCG followed by a plateau.[18]
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.[18][Level of evidence: 3iiDiv]
Patients who present with brain metastases should be treated with chemotherapy
and simultaneous whole brain radiation therapy (50 Gy/25 fractions).[19]
Standard treatment options:
- Chemotherapy:
- BEP: bleomycin plus etoposide plus cisplatin.[6,7] A modified regimen has been
used in children.[8]
- EP: etoposide plus cisplatin for four courses in good-prognosis patients.[5]
Other regimens that appear to produce similar survival outcomes but have been
studied less extensively or are in less common use include:
- PVB: cisplatin plus vinblastine plus bleomycin.[20]
- POMB/ACE: platinum plus vincristine plus methotrexate plus bleomycin plus dactinomycin plus
cyclophosphamide plus etoposide.[21]
- VIP: etoposide plus ifosfamide plus cisplatin.
A randomized study comparing four courses of BEP to four courses of VIP showed
similar OS and time-to-treatment failure for the two regimens in
patients with advanced disseminated germ cell tumors who had not received prior
chemotherapy.[11][Level of evidence: 1iiA] Hematologic toxic effects
were substantially worse with the VIP regimen.
- In selected cases surgery should be used after chemotherapy to remove
residual masses to determine if viable tumor cells remain, since such a finding
is an indication for further chemotherapy. Surgical removal of residual masses
is also necessary to prevent regrowth of teratomas and growth of nongerm cell
elements present in some of these masses.[22,23]
A study has reported that regardless of initial histology, a
significant risk exists of teratoma or carcinoma in residual masses after
chemotherapy. Neither size of the initial tumor nor degree of shrinkage during therapy appears to accurately identify patients with residual teratoma or
carcinoma. This has led some to recommend surgery with resection of all
residual masses apparent on scans in patients who have normal markers after
responding to chemotherapy.[24]
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 [3,25] but most do not. Although
the agreement among the histologies of residual masses found after chemotherapy
above versus 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
thoracotomy.[26] 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.[26]
Even patients who have initial masses of 3 cm or larger on CT scan and
who, after chemotherapy have normal CT scan and markers, may have residual teratoma
or carcinoma. This approach remains controversial, and no evidence
exists that such an approach improves survival. The presence of persistent malignant
elements in the resected specimen is an indication for additional
chemotherapy.[27] 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. 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.[28] 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.[8]
Patients who relapse with brain metastases after a complete initial response to
chemotherapy require further chemotherapy, with simultaneous whole-brain
radiation therapy, and consideration of surgical excision of solitary lesions.[19]
Treatment options under clinical evaluation:
- Clinical trials.
- High-dose chemotherapy with autologous bone marrow transplantation in
selected patients with bulky disease such as in the MSKCC-94076 13 trial.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage III malignant testicular germ cell tumor 14. 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 11.
References
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Ball D, Barrett A, Peckham MJ: The management of metastatic seminoma testis. Cancer 50 (11): 2289-94, 1982.
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Herr HW, Sheinfeld J, Puc HS, et al.: Surgery for a post-chemotherapy residual mass in seminoma. J Urol 157 (3): 860-2, 1997.
[PUBMED Abstract]
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Schultz SM, Einhorn LH, Conces DJ Jr, et al.: Management of postchemotherapy residual mass in patients with advanced seminoma: Indiana University experience. J Clin Oncol 7 (10): 1497-503, 1989.
[PUBMED Abstract]
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Drasga RE, Einhorn LH, Williams SD, et al.: Fertility after chemotherapy for testicular cancer. J Clin Oncol 1 (3): 179-83, 1983.
[PUBMED Abstract]
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Bajorin DF, Geller NL, Weisen SF, et al.: Two-drug therapy in patients with metastatic germ cell tumors. Cancer 67 (1): 28-32, 1991.
[PUBMED Abstract]
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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.
[PUBMED Abstract]
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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.
[PUBMED Abstract]
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Huddart SN, Mann JR, Gornall P, et al.: The UK Children's Cancer Study Group: testicular malignant germ cell tumours 1979-1988. J Pediatr Surg 25 (4): 406-10, 1990.
[PUBMED Abstract]
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Einhorn LH, Williams SD: Chemotherapy of disseminated seminoma. Cancer Clin Trials 3 (4): 307-13, 1980.
[PUBMED Abstract]
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Loehrer PJ Sr, Birch R, Williams SD, et al.: Chemotherapy of metastatic seminoma: the Southeastern Cancer Study Group experience. J Clin Oncol 5 (8): 1212-20, 1987.
[PUBMED Abstract]
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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.
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Duchesne GM, Stenning SP, Aass N, et al.: Radiotherapy after chemotherapy for metastatic seminoma--a diminishing role. MRC Testicular Tumour Working Party. Eur J Cancer 33 (6): 829-35, 1997.
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Leibovitch I, Baniel J, Rowland RG, et al.: Malignant testicular neoplasms in immunosuppressed patients. J Urol 155 (6): 1938-42, 1996.
[PUBMED Abstract]
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Collette L, Sylvester RJ, Stenning SP, et al.: Impact of the treating institution on survival of patients with "poor-prognosis" metastatic nonseminoma. European Organization for Research and Treatment of Cancer Genito-Urinary Tract Cancer Collaborative Group and the Medical Research Council Testicular Cancer Working Party. J Natl Cancer Inst 91 (10): 839-46, 1999.
[PUBMED Abstract]
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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.
[PUBMED Abstract]
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Levi JA, Raghavan D, Harvey V, et al.: The importance of bleomycin in combination chemotherapy for good-prognosis germ cell carcinoma. Australasian Germ Cell Trial Group. J Clin Oncol 11 (7): 1300-5, 1993.
[PUBMED Abstract]
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Nichols CR, Williams SD, Loehrer PJ, et al.: Randomized study of cisplatin dose intensity in poor-risk germ cell tumors: a Southeastern Cancer Study Group and Southwest Oncology Group protocol. J Clin Oncol 9 (7): 1163-72, 1991.
[PUBMED Abstract]
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Zon RT, Nichols C, Einhorn LH: Management strategies and outcomes of germ cell tumor patients with very high human chorionic gonadotropin levels. J Clin Oncol 16 (4): 1294-7, 1998.
[PUBMED Abstract]
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Spears WT, Morphis JG 2nd, Lester SG, et al.: Brain metastases and testicular tumors: long-term survival. Int J Radiat Oncol Biol Phys 22 (1): 17-22, 1992.
[PUBMED Abstract]
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Einhorn LH, Williams SD: Chemotherapy of disseminated testicular cancer. A random prospective study. Cancer 46 (6): 1339-44, 1980.
[PUBMED Abstract]
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Newlands ES, Bagshawe KD, Begent RH, et al.: Current optimum management of anaplastic germ cell tumours of the testis and other sites. Br J Urol 58 (3): 307-14, 1986.
[PUBMED Abstract]
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Einhorn LH, Williams SD, Mandelbaum I, et al.: Surgical resection in disseminated testicular cancer following chemotherapeutic cytoreduction. Cancer 48 (4): 904-8, 1981.
[PUBMED Abstract]
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Loehrer PJ Sr, Hui S, Clark S, et al.: Teratoma following cisplatin-based combination chemotherapy for nonseminomatous germ cell tumors: a clinicopathological correlation. J Urol 135 (6): 1183-9, 1986.
[PUBMED Abstract]
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Toner GC, Panicek DM, Heelan RT, et al.: Adjunctive surgery after chemotherapy for nonseminomatous germ cell tumors: recommendations for patient selection. J Clin Oncol 8 (10): 1683-94, 1990.
[PUBMED Abstract]
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Brenner PC, Herr HW, Morse MJ, et al.: Simultaneous retroperitoneal, thoracic, and cervical resection of postchemotherapy residual masses in patients with metastatic nonseminomatous germ cell tumors of the testis. J Clin Oncol 14 (6): 1765-9, 1996.
[PUBMED Abstract]
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Steyerberg EW, Donohue JP, Gerl A, et al.: Residual masses after chemotherapy for metastatic testicular cancer: the clinical implications of the association between retroperitoneal and pulmonary histology. Re-analysis of Histology in Testicular Cancer (ReHiT) Study Group. J Urol 158 (2): 474-8, 1997.
[PUBMED Abstract]
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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.
[PUBMED Abstract]
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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.
[PUBMED Abstract]
Recurrent Testicular Cancer
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence 2 for more
information.)
Deciding on further treatment depends on many factors, including the specific
cancer, prior 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.[1,2] This regimen is now the standard
initial salvage regimen.[2,3] 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.[2][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.[4-11] 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.[12][Level of evidence: 1iiA] In some highly selected patients with chemorefractory
disease confined to a single site, surgical resection may yield long-term
DFS.[13,14] 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.[15]
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.[16] 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 who do not achieve a complete remission
following etoposide and cisplatin for their initial relapse, or for patients who
have a second relapse.[17]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent malignant testicular germ cell tumor 15. 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 11.
References
-
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.
[PUBMED Abstract]
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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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
Cullen MH: Dose-response relationships in testicular cancer. Eur J Cancer 27 (7): 817-8, 1991.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
Murphy BR, Breeden ES, Donohue JP, et al.: Surgical salvage of chemorefractory germ cell tumors. J Clin Oncol 11 (2): 324-9, 1993.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
-
Baniel J, Foster RS, Gonin R, et al.: Late relapse of testicular cancer. J Clin Oncol 13 (5): 1170-6, 1995.
[PUBMED Abstract]
-
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.
[PUBMED Abstract]
Get More Information From NCI
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The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator 18. These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237), TTY at 1-800-332-8615. Changes to This Summary (01/15/2009)
The PDQ cancer information summaries are reviewed regularly and updated as
new information becomes available. This section describes the latest
changes made to this summary as of the date above.
General Information 19
Added Krege et al. (part I) as reference 3 20.
Added Krege et al. (part II) as reference 7 21.
Stage I Testicular Cancer 22
Added text 23 about a multicenter trial and the results of a single course of cisplatin, bleomycin, and etoposide given to clinical stage I patients (cited Albers et al. as reference 28 and level of evidence 1iiD). More Information
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