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This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER.
Incidence and Mortality
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%.[2,3,4,5,6]
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.
Types of testicular germ cell tumors: Seminomas versus nonseminomas
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.
Prognosis and Staging
Serum tumor markers and testis cancer: AFP, beta-hCG, and LDH
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.[11,12,13] 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.[10,16]
Staging and risk stratification
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.[21,22] 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.[23,24,25] 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.[26,27,28] 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.)
Follow-up and Survivorship
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.[30,31] 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 patients.
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.[45,46] 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.
Other risk factors
Cardiovascular disease in testicular cancer survivors
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.[47,48,49] Other studies have reported that chemotherapy for testis cancer is associated with an increased risk of developing metabolic syndrome and hypogonadism.[50,51] 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.
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.[1,2,3]
Definitions of TNM
The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification to define testicular cancer.
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.[1,2,3] 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.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with testicular cancer. 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.
Stage I Seminoma
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.[2,3,4,5,6,7,8,9] 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.[13,18] 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.[14,18][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.[18,21] 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.[3,4,22,23,24,25,26] 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
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.[27,28,29] 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.[31,32] 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.[34,35,36] 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%.[38,39] 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.[40,41,42] 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.[40,41]
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.[44,45]
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.[12,31,40,41,47] 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 testicular cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
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 (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,[1,2,3,4] 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.[6,7]
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
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:
This 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.[13,15] 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.[16,17,18] 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.[17,18] 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 rate.
This 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.[14,21]
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.[20,28]
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.[29,30] 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 testicular cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
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.
Clinical Trials of Chemotherapy for Disseminated Testis and Extragonadal Germ Cell Tumors
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.[4,5,6][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.[7,8,9]
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.[13,14,15] These results have led to some controversy as to whether three cycles of BEP is superior to four cycles of EP.
Special Considerations During Chemotherapy
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.[19,20,21] 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 Masses After Chemotherapy in Men with Seminomas
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.[25,26,27] 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.[24,25,26] 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 After Chemotherapy in Men with Nonseminomas
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.[24,32]
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,[28,33] 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 thoracotomy.
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:
Chemotherapy combinations include:
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 testicular cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
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.[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.[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.[4,5,6,7,8,9,10,11] 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.[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.
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 testicular cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
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.
Stage Information for Testicular Cancer
Added Stage 0 as a new subsection.
Stage 0 Testicular Cancer
Added this new section.
Stage I Testicular Cancer
Added Warde et al. as reference 1.
Added text to state that 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. Also added that 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 second cancers compared with the general population (cited Beard et al. as reference 19). Added that 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 (cited Travis et al. as reference 20).
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of testicular cancer. It 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.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Testicular Cancer Treatment are:
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Some of the reference citations in this 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 in developing its level-of-evidence designations.
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National Cancer Institute: PDQ® Testicular Cancer Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/treatment/testicular/HealthProfessional. Accessed <MM/DD/YYYY>.
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Last Revised: 2014-07-11
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