10.1245/ASO.2005.01.013
Annals of Surgical Oncology 12:871-880 (2005)
© 2005 Society of Surgical Oncology
Germ Cell Tumors of the Testis
Brett S. Carver, MD and
Joel Sheinfeld, MD
Department of Urology, Memorial Sloan-Kettering Cancer Center, 353 East 68th Street, New York, New York 10021
Correspondence: Address correspondence and reprint requests to: Joel Sheinfeld, MD; E-mail: sheinfej{at}mskcc.org.
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ABSTRACT
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Testicular cancer is the most common malignancy in men aged 20 to 35 years and accounts for approximately 1% of all male malignancies. Through the appropriate utilization of clinical trials, effective treatment paradigms have been developed for the management of all stages of testicular cancer. The multidisciplinary approach to the management of germ cell tumors of the testis has resulted in survival rates of > 90% overall. This review summarizes the principal management of germ cell tumors of the testis, highlighting the indications for surgery, controversies surrounding the integration of surgery, and alternative management strategies.
Key Words: Testicular cancer • Primary retroperitoneal lymph node dissection • Chemotherapy • Germ cell tumors
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INTRODUCTION
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Testicular cancer is the most common malignancy in men aged 20 to 35 years and accounts for approximately 1% of all malignancies in men. It was projected that in the United States, approximately 8010 new cases of testicular cancer would be diagnosed and 390 men would die of this disease in 2005.1 Although there is considerable geographical variation in the incidence of testicular cancer, with Scandinavia and Switzerland having the highest rates, there has been a recent worldwide increase in the incidence of testicular cancer.2,3 Germ cell tumors (GCTs) of the testis occur predominantly in Caucasians and are rarely seen in African Americans. Previous reports have found at least a 5-fold greater incidence of testicular cancer in Caucasians compared with African-Americans.4
GCTs of the testis can be divided into two major subgroups based on histological findings: seminoma and nonseminoma. Seminoma accounts for approximately 50% of all GCTs and most frequently appears in the fourth decade of life. The remainder of GCTs are composed of nonseminomatous histology (embryonal cell carcinoma, yolk sac tumor, choriocarcinoma, and teratoma) and frequently present in the third decade of life. Most nonseminomatous tumors are mixed (composed of two or more cell types of which seminoma may be a component); however, the definition of a pure seminoma excludes the presence of any nonseminomatous elements or an increased serum alfa fetoprotein (AFP) level.
Although the treatment paradigms differ for seminomatous and nonseminomatous tumors, the successful multidisciplinary approach for the management of GCT has resulted in survival rates of >90% overall. Although testicular cancer is highly curable, it requires appropriate management at all stages.5 Inappropriate management increases the morbidity, mortality, and therapy burden. This review summarizes the principal management of GCTs of the testis, highlighting the indications for surgery, associated complications, controversies surrounding the integration of surgery, and alternative management strategies.
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PRESENTATION AND MANAGEMENT OF THE PRIMARY TUMOR
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The most common symptom at the time of diagnosis is painless swelling or enlargement of the testis. Acute testicular pain is reported to occur in approximately 10% of patients with testicular cancer and often represents infarction or hemorrhage within the tumor. At initial presentation, symptoms manifesting secondary to metastatic disease occur in approximately 20% of patients and include a mass in the left neck, pulmonary complaints such as hemoptysis or dyspnea, abdominal mass, or back pain that can often be disabling. In approximately 5% of patients, gynecomastia or tenderness of the breast is reported. A delay in diagnosis ranging from 2.5 to 4.4 months has been reported in the literature and is associated with a more advanced clinical stage at the time of diagnosis. Reasons for the delay in diagnosis are multifactorial but may include both a physician and patient component. Previous reports have shown that approximately 18% to 33% of patients with testicular cancer were initially treated for epididymitis.6,7 Patients have also been initially mis-diagnosed, undergoing unnecessary mastectomy or exploratory laparotomy; this ultimately delays and increases the burden of therapy.8,9
Testicular ultrasonography is the initial imaging modality of choice, with a >95% sensitivity and specificity in identifying intratesticular lesions. The serum tumor markers (STMs) AFP, human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH) have a clear role in both the diagnosis and clinical management of testicular GCTs. Elevation of one or more markers occurs in 80% of metastatic GCTs of the testis.
A radical orchiectomy with high ligation of the spermatic cord at the level of the inguinal ring provides histopathologic diagnosis, primary tumor staging, and excellent local control of the tumor with minimal morbidity and no mortality. The most common complication after radical orchiectomy is postoperative bleeding, which may result in either a scrotal or retroperitoneal hematoma. Furthermore, significant retroperitoneal hematomas may be misinterpreted as metastatic disease on staging computed tomographic (CT) scan and result in unnecessary treatment.10
Suboptimal approaches to testicular neoplasms, including scrotal orchiectomy and transscrotal biopsy, can alter the normal lymphatic drainage of the testis and increase the burden of therapy for the patient.11 A meta-analysis of 206 cases of scrotal violation reported a local recurrence rate of 2.9%, compared with .4% for patients treated with inguinal orchiectomy, but no differences in systemic relapse or survival were appreciated.11
A small subset of carefully selected patients with a solitary testicle, bilateral testicular tumors, or a suspected benign lesion may be candidates for a testis-sparing procedure. Favorable selection criteria include organ-confined disease with a size <2 cm, negative margins, and the absence of intratubular germ cell neoplasia in the remaining testicle. The German Testicular Cancer Intergroup reported on 63 patients with a median follow-up of 74 months and found only 4 local recurrences, all of which occurred in patients with associated untreated intratubular germ cell neoplasia.12
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CLINICAL AND PATHOLOGIC STAGING
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Staging evaluation must include a thorough history and physical examination, with particular attention to possible sites of metastases and the contralateral testis. STMs (AFP, HCG, and LDH) should be obtained before and after radical orchiectomy. The STMs are necessary for diagnosis, staging, and risk classification. Although a normal postorchiectomy STM does not preclude the finding of metastatic disease, an increase of either AFP or HCG does signify the presence of metastasis.
AFP is a glycoprotein produced in the liver, gastrointestinal tract, and fetal yolk sac, and its secretion in GCT is restricted to nonseminomatous histology. Therefore, any patients with histological pure seminomas and an increased serum AFP are classified and treated like those with nonseminomatous GCTs (NSGCT). AFP is increased in approximately 60% of patients with metastatic NSGCT and 20% of patients with clinical stage I NSGCT. HCG is a glycoprotein produced by the synctiotrophoblasts and is increased in approximately 15% of pure seminomas and in 40% of advanced nonseminomas. The serum half-lives of AFP and HCG are approximately 5 days and 24 hours, respectively. LDH comprises multiple isoenzymes, but in clinical practice the total LDH value is used for decision making. Increases in serum LDH correlate with tumor burden, growth rate, and cellular proliferation. Elevation of LDH is present in approximately 60% of patients with advanced NSGCT and 80% of patients with metastatic seminoma.
The initial staging evaluation should include a CT scan of the chest, abdomen, and pelvis. CT is the most effective radiographical technique for identifying metastatic disease both above and below the diaphragm. Abdominal CT scan results are normal in approximately 70% of patients with seminoma and 30% of patients with NSGCT. Lymph nodes in the primary landing zone measuring 10 to 20 mm are positive for GCT approximately 70% of the time, and nodes measuring 5 to 10 mm are involved approximately 50% of the time.13,14
Magnetic resonance imaging, like CT, is capable of identifying lymphadenopathy with similar sensitivity and specificity. Magnetic resonance imaging may provide additional preoperative information regarding the vascular anatomy and patency of the great vessels in patients with bulky retroperitoneal disease, but overall, it contributes little to the management of most patients with GCT.
In 1997, the American Joint Committee on Cancer revised the tumor-node-metastasis staging system for testicular cancer, and for the first time STMs were incorporated into the staging criteria15 (Tables 1
–3). Broadly, stage I refers to disease confined to the testis, stage II refers to metastases restricted to the retroperitoneum, and stage III refers to metastases to nonretroperitoneal sites.
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TABLE 1. Testicular cancer staging system of the American Joint Committee of Cancer and the International Union Against Cancer: tumor-node-metastasis staging
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The International Germ Cell Cancer Collaborative Group (IGCCCG) evaluated independent prognostic factors for predicting progression-free survival in men with GCT and stratified these patients into three risk classifications: good-, intermediate-, and poor-risk disease (Table 4).16 This risk classification has been used for clinical decision making in patients with advanced GCT and for the design of clinical trials.
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NATURAL HISTORY AND PATTERNS OF METASTASIS
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The natural history of testicular cancer provides the basis for its evaluation and management and, in turn, is favorably influenced by effective therapy. Lymphatic spread is common to all forms of GCT, although in the case of choriocarcinoma, vascular dissemination is a common clinical feature. Early anatomical studies found that the primary drainage of the testis was to the area of its embryological origin: the retroperitoneum.17,18 Surgical mapping studies demonstrated that the primary landing zone for right-sided testicular tumors was the interaortocaval lymph nodes, followed by the precaval and preaortic nodes.19,20 For left-sided testicular tumors, the primary landing zone is the para-aortic and pre-aortic lymph nodes, followed by the interaortocaval nodes. Contralateral spread is more common with right-sided tumors and is usually associated with large-volume retroperitoneal disease.21 These detailed mapping studies have increased our understanding of the lymphatic spread of testicular cancer and have sharpened the focus of clinical staging and treatment by identifying the early and most common sites of metastasis.
The rationale for treatment of the retroperitoneum in patients with testicular cancer is based on several factors. First, the retroperitoneal lymph nodes are usually the first—and often the only—site of meta-static disease. Second, although clinical staging has improved over recent years, clinical understaging of the retroperitoneum occurs in approximately 20% to 30% of patients classified as having clinical stage I GCT. Third, untreated retroperitoneal nodal metastases are usually fatal; autopsy studies indicate that distant visceral metastases were often late occurrences in men with bulky retroperitoneal disease. Finally, the most common site of a late recurrence of both viable GCT and teratoma is the retroperitoneum, and recurrences are often chemorefractory and associated with poor survival.
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THE MANAGEMENT OF LOW-VOLUME SEMINOMA (STAGE cI AND cIIA)
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In the United States, radiotherapy remains the treatment of choice for patients with clinical stage I and IIa seminoma. For patients with clinical stage I seminoma, a randomized trial demonstrated equivalent 3-year relapse-free rates for simple para-aortic portal irradiation compared with the traditional dog-leg portal (96.0% vs. 96.6%, respectively).22 Although four (1.7%) patients in the para-aortic group experienced a pelvic relapse, acute toxicity and leukopenia were less, and recovery of spermatogenesis was improved compared with the dog-leg portal group. The para-aortic portal with 30 Gy of total radiation may be considered the standard of care for clinical stage I seminoma.
Although the data for adjuvant radiotherapy for clinical stage I seminoma suggest that almost 100% of patients are cured (Table 5)23–26 the concern for long-term clinical effects from irradiation has resulted in the emergence of surveillance protocols for compliant patients with clinical stage I seminoma. Surveillance protocols mandate careful, long-term follow-up, and seminoma patients are disadvantaged in that STMs are frequently not increased until late in the disease progression. Published series report that approximately 15% to 20% of patients will relapse on surveillance, with a median time to relapse of 15 months, although relapses have occurred beyond 5 years.26,27 Risk factors for relapse while on surveillance include testicular tumors >6 cm, rete testis invasion, and vascular invasion.27 Overall survival in this group is approximately 98% after salvage with cisplatin-based chemotherapy.
Radiotherapy administered by a dog-leg portal (30 Gy with a boost of 5–7.5 Gy) is the treatment of choice for clinical stage IIa seminoma. Prophylactic mediastinal radiotherapy is contraindicated because relapses solely in the mediastinum are infrequent and because supradiaphragmatic radiotherapy has been shown to result in a higher rate of treatment-related mortality due to chemotherapy.28 Relapse after therapy occurs in approximately 5% to 15% of men, and most receive salvage treatment with cisplatin-based chemotherapy.24,25
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THE MANAGEMENT OF LOW-VOLUME NSGCT (STAGE cI AND cIIA)
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After radical orchiectomy, many patients with clinical stage I NSGCT are cured; however, approximately 20% to 30% of patients are under-staged by CT scan and will relapse either systemically or in the retroperitoneum. Treatment options for patients with clinical stage I NSGCT include surveillance, primary retroperitoneal lymph node dissection (RPLND), or chemotherapy.
Because approximately 70% of patients with clinical stage I NSGCT are cured by orchiectomy alone, several investigators, in an effort to minimize treatment morbidity, have evaluated the role of surveillance. The rationale for surveillance protocols rests in the ability of cisplatin-based chemotherapy regimens to cure early relapses. Studies have demonstrated that even in properly selected patients (stage cIa), approximately 25% of patients will relapse during surveillance.29 The retroperitoneum is the most common site of relapse, followed by the lungs or increased STM alone. Survival rates after therapy for surveillance range from 96% to 100% and are comparable to those with primary RPLND.29,30 Several factors predictive of retroperitoneal or systemic failure have been identified, such as a primary tumor stage of T2 (cIb) or greater, lymphovascular invasion, or the histological finding of embryonal cell carcinoma predominance.30,31 Patient compliance is the most important selection criterion for entry into a surveillance program because strict adherence to frequent follow-up evaluations is critical. Long-term follow-up is required because relapses beyond 5 years have been reported.
Primary RPLND is both a diagnostic and therapeutic procedure. Patients at high risk for relapse in the retroperitoneum, i.e., predominant embryonal carcinoma, lymphovascular invasion, or extension into the tunica or scrotum, should undergo primary RPLND if STMs have normalized.30,31 A nerve-sparing RPLND should be performed: this results in successful preservation of ejaculatory function in approximately 95% of men.32,33 If suspicious or positive nodes are encountered, a full bilateral RPLND should be performed. Approximately 30% of patients with clinical stage I NSGCT and 60% of patients with clinical stage IIa NSGCT will be found to have retroperitoneal metastases at the time of RPLND, and embryonal cell carcinoma represents the most common histological subtype. After primary RPLND, 5% to 10% of men with negative nodes (pN0) will experience a systemic relapse, and overall survival exceeds 98%.34–37
Recent data from Memorial Sloan- Kettering Cancer Center demonstrate that in recent years, the incidence of pathologic N1 disease is increasing and relapse rates are declining. This seems to be secondary to improved patient selection (by excluding patients with increased STM) and widespread use of the chest CT scan. Compliant patients with low-volume disease (pN1) can be observed after primary RPLND, because these patients have a low risk of systemic relapse (Table 6).34–37 Patients with pathologic stage N2 and N3 disease have at least a 50% probability of relapse and usually receive two cycles of adjuvant cisplatin-based chemotherapy to prevent systemic recurrence.38,39 With this approach, approximately 98% of patients will remain free of disease.
In an attempt to minimize the perioperative morbidity associated with primary RPLND, several investigators have evaluated the role of laparoscopic RPLND (L-RPLND) in the management of clinical stage I and IIA NSGCT.40–43 L-RPLND has been proven to be technically feasible in the hands of dedicated experts after a steep learning curve. In addition to a quicker convalescence and more favorable cosmetic results, postoperative morbidity, operative blood loss, and the length of hospital stay are reduced compared with those of open surgery.40–43
However, the therapeutic efficacy of L-RPLND has remained difficult to assess for several important reasons. First, with rare exceptions, all patients with a diagnosis of pathologic stage II disease after L-RPLND have been routinely treated after surgery with adjuvant chemotherapy, regardless of the stage of nodal disease at the time of RPLND (Table 7).44–47 Second, it is not clear in the literature whether primary L-RPLND has been performed with therapeutic intent. Rassweiler et al.48 reported on 34 patients undergoing L-RPLND, and in 3 of these cases, the procedure was abandoned because intraoperative frozen-section analysis demonstrated metastatic disease. In the Johns Hopkins series, L-RPLND was limited if grossly positive lymph nodes were encountered and patients were subsequently treated with chemotherapy.45 Primary L-RPLND seems to be feasible in the hands of dedicated experts; however, its therapeutic efficacy remains unproven, and future institutional review board–approved trials need to be developed to evaluate this.
In an effort to avoid the potential morbidity of an RPLND, several European investigators have evaluated the role of two cycles of cisplatin-based adjuvant chemotherapy for patients with clinical stage I NSGCT. In three studies, relapse occurred in approximately 5% of patients, and approximately 1% died of recurrent disease.49–51 Despite an attempt to decrease the burden of therapy for patients with clinical stage I NSGCT by avoiding RPLND, approximately 70% of patients are treated with chemotherapy unnecessarily and are exposed to both short- and long-term complications, such as myelosuppression, neuropathy, Raynaud’s phenomenon, nephrotoxicity, and the risk of acute leukemia. The indiscriminate use of unnecessary chemotherapy may represent a potential increase rather than a decrease in long-term morbidity. Recent studies have demonstrated an increased incidence of coronary artery disease in men treated with platinum-based chemotherapy for testicular cancer compared with the general male population, and this risk was not due to increases in known cardiac risk factors, which suggests a direct or indirect treatment-related effect.52,53 Furthermore, given the paucity of long-term follow-up, the risk of late relapse secondary to unresected teratoma, which is chemoresistant, remains unknown. Recent data from Memorial Sloan-Kettering Cancer Center demonstrate that the incidence of teratoma in the retroperitoneum at the time of primary RPLND is approximately 20% and has remained stable over time.54
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THE MANAGEMENT OF ADVANCED GCTs (STAGE cIS, cIIB, cIIC, AND III)
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Regardless of histology, patients with advanced GCTs (cIIB to cIII) and those with persistently increased tumor markers after radical orchiectomy (cIS) are initially treated with platinum-based chemotherapy according to the IGCCCG risk stratification. Patients with good-risk disease are treated with three cycles of bleomycin, etoposide, and cisplatin (BEP) or four cycles of etoposide and cisplatin. Randomized clinical trials comparing three cycles of BEP with four cycles of etoposide and cisplatin have demonstrated equivalent response rates and survival in men with good-risk disease. Although patients with intermediate- or high-risk disease traditionally receive four cycles of BEP, approximately 30% to 40% of patients with poor-risk disease do not achieve a durable response to conventional chemotherapy.55–57
Postchemotherapy RPLND (PC-RPLND) is an integral component in the management of advanced NSGCT. After induction chemotherapy, approximately 40% of patients undergoing RPLND will have teratoma in their retroperitoneum, and an additional 10% to 15% will have viable GCTs (Table 8).58–61 Teratoma is chemorefractory and has an unpredictable biologic potential with the possibility of devastating late relapse if not completely resected. The systemic relapse rate for patients with fibrosis or teratoma after a complete RPLND ranges from 5% to 10%; therefore, additional chemotherapy is not required.62,63 For patients with completely resected viable GCT, the addition of two cycles of postoperative cisplatin-based chemotherapy has previously demonstrated a survival benefit, although several studies63–65 recently challenged this in patients with favorable risk factors (IGCCCG good-risk classification, complete resection, and <10% viable malignant cells). Overall, 5-year progression-free survival ranges from 50% to 70%.63–65
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TABLE 8. Histological findings at retroperitoneal lymph node dissection for nonseminomatous germ cell tumors (GCTs) after induction chemotherapy
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Because almost 50% of resected residual retroperitoneal specimens have only fibrosis, several investigators have attempted to reliably predict its presence before surgery and, thus, spare this subset of patients the associated morbidity of postchemotherapy surgery. Donohue and colleagues66 reported on 80 patients undergoing PC-RPLND, and, among 15 of these patients without teratoma in the primary tumor and at least a 90% reduction in retroperitoneal tumor volume, none had viable GCT or teratoma. However, in a subsequent analysis from the same institution, only 74% of patients with these same criteria were continuously free of disease.67 Several other investigators have reported that even with a normal postchemotherapy CT scan and no teratoma in the primary tumor, approximately 20% to 30% of patients will harbor either teratoma or viable malignancy.61,68 Currently there are no selection criteria to reliably predict the finding of fibrosis at the time of PC-RPLND.
Despite the histologically benign nature of teratoma, there are significant advantages to complete resection. First, teratoma may grow, obstruct, or invade adjacent structures and become unresectable. Second, there is the risk of malignant transformation to non–germ cell malignant elements such as sarcoma or carcinoma. The incidence of malignant transformation is approximately 3% to 6%, and complete surgical resection is the treatment of choice for this group of chemoresistant tumors.69 Finally, teratoma may result in devastating late relapses.
Late relapse beyond 2 years after primary treatment occurs in approximately 2% to 3% of patients with testicular cancer and has been shown to occur across all stages.70,71 The most common anatomical site of relapse is the retroperitoneum, followed by the lungs and mediastinum. The primary management for late relapse is complete surgical resection, and the histological distribution reveals viable GCT in 80% and teratomatous elements in 20%. Disease-free survival is poor in this cohort of patients: one study showed that only 26% of patients were continuously disease free, of whom 19 of 21 had a complete surgical resection.70
For patients who require second-line chemotherapy, the distribution of histological findings at PC-RPLND is markedly different. Viable GCT is noted in approximately 50% of cases, teratoma in 40% of cases, and fibrosis in only 10% of cases. Approximately 40% of patients remain disease free after a complete resection of viable GCT after second-line chemotherapy, and additional postoperative chemotherapy does not seem to offer any benefit.64 For patients with increased STMs despite appropriate chemotherapy, RPLND should be performed in carefully selected cases. With a complete resection, approximately 50% to 80% of patients will be rendered free of disease, and 20% to 30% of these will have long-term survival.72,73 Favorable criteria include a single site of nonvisceral disease and increased AFP versus HCG. Furthermore, a subset of patients with increased STM will have teratomatous elements that result in a "leak" of STM into the serum. In a series from Memorial Sloan-Kettering Cancer Center, fluid aspirated from the residual cystic mass contained increased STMs in all 11 patients.74 The retroperitoneal pathologic results revealed teratomatous elements in all 11 patients, and tumor markers declined to normal levels after surgery in 10 of 11 patients.
The approach to the patient with pure seminoma and a postchemotherapy residual mass is controversial.75 First, teratoma in the residual mass is very rare. Second, a complete RPLND is often not technically possible secondary to the severe desmoplastic reaction, and surgery is often limited to resection of the residual tumor or extensive biopsies. Although it is generally agreed that residual masses <3 cm should be observed, the management of the minority of patients with residual masses >3 cm is controversial. Investigators at Memorial Sloan-Kettering Cancer Center reported that 30% of patients with residual masses >3 cm had viable seminoma, and this directed immediate therapy.75 A recent study demonstrated the utility of positron emission tomography (PET) scanning in evaluating postchemotherapy residual masses in patients with pure seminoma. In this study, PET scan demonstrated a specificity of 100% and a sensitivity of 80% in patients with residual masses >3 cm.76 Therefore, current recommendations for performing postchemotherapy surgery in men with seminoma include a well-delineated residual mass >3 cm and a positive PET scan. The presence of a severe desmoplastic reaction often precludes complete surgical resection of the residual mass.
The complication rate of RPLND after chemotherapy is higher than that of primary RPLND.33,77 The postchemotherapy desmoplastic reaction, as well as a larger volume of residual disease, increases the technical demands of the operation. Chylous ascites occurs in approximately 2% to 3% of patients, and predisposing factors include resection of the vena cava, a suprahilar dissection, and simultaneous hepatic resection. Asymptomatic lymphoceles require no treatment; however, percutaneous drainage for infection, hydronephrosis, or bowel obstruction is necessary in approximately 1% to 2% of cases. Renovascular injury may be seen in 2% to 3% of cases and can result in renovascular hypertension or require nephrectomy. Small-bowel obstruction is seen in 2% to 3% of all patients and can be managed conservatively, with exploration reserved for select patients. Retrograde ejaculation occurs in approximately 90% of patients after non–nerve-sparing postchemotherapy RPLND and is dependent on the extent of the residual disease. In patients with low-volume residual disease, a nerve-sparing postchemotherapy RPLND may be safely performed that preserves ejaculation in >80% of men. Of men with antegrade ejaculation after postchemotherapy RPLND, approximately 50% are successful at fathering a child.
Patients undergoing postchemotherapy RPLND after therapy with bleomycin are at an increased risk for postoperative pulmonary complications. Judicious monitoring of perioperative fluid administration and avoiding unnecessary exposure to high concentrations of inspired oxygen are imperative. Nevertheless, the complications after postchemotherapy RPLND have significantly decreased over time. The Indiana group reported a significant decrease in overall morbidity, major complications, and length of hospital stay.77 Furthermore, for residual masses <2 cm, investigators at Memorial Sloan-Kettering Cancer Center report a 4% major complication rate.78
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RESECTION OF OTHER SITES
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A small percentage of patients will require resection of multiple nonretroperitoneal metastatic sites, usually the lung or neck.79 The size of the pretreatment and postchemotherapy residual mass does not correlate with the final histological results, and the histological findings at different sites are not predictable on the basis of those at one site. The incidence of pathologic discordance between different sites is approximately 35%.80,81 When the lung and retroperitoneum are simultaneously involved, multiple separate procedures may be required, but simultaneous thoracic and retroperitoneal resections are possible.82 Studies confirm that all sites of residual disease can generally be resected regardless of the histological findings at the initial procedure.
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CONCLUSIONS
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With the successful multidisciplinary approach to the management of GCTs, overall cure rates exceed 90%. Although testicular cancer is highly curable, it requires appropriate management at all stages to maximize survival and minimize the morbidity and burden of therapy.
Received for publication January 24, 2005.
Accepted for publication July 8, 2005.
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ABSTRACT
INTRODUCTION
