eMedicine Specialties > Urology > Cancer, Testicle

Testicular Seminoma

Michael B Williams, MD, MS, Fellow, Department of Urologic Oncology, MD Anderson Cancer Center
Paul Schellhammer, MD, Chairman, Program Director, Professor, Department of Urology, Eastern Virginia Medical School; John W Davis, MD, Assistant Professor, Department of Urology, University of Texas MD Anderson Cancer Center

Updated: May 21, 2009

Introduction

Background

The study of testicular germ cell tumors (GCTs) is a unique area of urologic oncology, as treatment algorithms have benefited from numerous randomized prospective clinical trials (unlike prostate cancer) and because metastatic disease is highly responsive to multimodal treatment (unlike renal cell carcinoma). Seminoma is a histologic subtype of GCTs, which are discussed separately as nonseminomas in Germ Cell Tumors.

The interest in GCTs is disproportional to its incidence because of its fascinating pathologic subtypes, success of multimodal therapy (even for metastatic disease), and almost universal incidence in otherwise healthy males aged 15-35 years. Testicular GCTs have various pathologic subtypes, including seminoma, embryonal, yolk sac, teratoma, and choriocarcinoma. The most important clinical distinction is between seminoma and nonseminoma, two broad categories with different treatment algorithms: (1) Seminoma as a classification refers to pure seminoma upon histopathologic review, and (2) any nonseminomatous elements (even if seminoma is prevalent) change the classification to nonseminoma.

Pathophysiology

Testicular seminoma is a pathologic diagnosis in which only seminomatous elements are observed upon histopathologic review after a radical orchiectomy and in which serum alpha-fetoprotein (AFP) is within the reference range. Any elevation of AFP levels or nonseminomatous elements in the testis specimen mandates diagnosis of nonseminomatous GCT (NSGCT) and an appropriate treatment change.

GCTs have the following subtypes and frequencies: seminoma (40%), embryonal (25%), teratocarcinoma (25%), teratoma (5%), and choriocarcinoma (pure; 1%). Seminomas can be further subdivided into one of three categories based on histology: classic, anaplastic, and spermatocytic (see Histologic Findings).¹

Germ cell carcinoma in situ (CIS) is a premalignant condition with a natural history of progression to seminoma or embryonal cancer. Patients with infertility, intersex disorders, cryptorchidism, prior contralateral GCTs, or atrophic testes more commonly have CIS. Histologically, it demonstrates intratubular atypical germ cells within seminiferous tubules. Most patients with seminomas (except spermatocytic seminoma) and NSGCTs have CIS or severe atypia associated with the primary tumor.² In patients with GCTs, 5% of those with contralateral testes harbor CIS.³

Testicular microcalcifications observed on scrotal sonograms were long held to be implicated in the development of testicular carcinoma. However, a recent analysis of 83 patients with asymptomatic microcalcifications observed for 5 years demonstrated only one with testicular carcinoma development over the interim. This represented an odds ratio for the study population of 317 (95% CI, 36-2756), with over 98% of men with asymptomatic microcalcifications having a benign course. A recommendation of continued monthly self-examination without further intervention was given for management of this indolent finding.⁴

Frequency

United States

Testicular GCTs are rare, representing only 1%-2% of all male malignancies and occurring in 1 of 250 men by age 65 years; however, GCT is the most common malignancy in men aged 15-35 years. Incidence rates are 3.7 and 0.9 cases per 100,000 persons per year for whites and blacks, respectively.⁵

International

The incidence of testis cancer has increased from the early 1960s to the mid 1980s. Nonwhite populations have a lower incidence than white populations. The highest rates of testis cancer are in Denmark (11.5 cases per 100,000 persons per year), Norway (9 cases per 100,000 persons per year), and Switzerland (11 cases per 100,000 persons per year). Rates vary across Europe.⁶

A review by Bray and colleagues (2006) of 41 cancer registries in 14 countries found the seminoma rates to be highest in Denmark and Switzerland (9 cases per 100,000 persons per year) and the lowest rates in Japan, Israel, and Finland (1-3 cases per 100,000 persons per year).⁷

Race

Established data sets have consistently demonstrated a higher incidence of GCTs in whites than in African Americans—as high as a 5:1 ratio. McGlynn et al (2005) published an analysis of 9 registries of the Surveillance, Epidemiology, and End Results (SEER) database from 1973-2001. They found an increasing incidence among African Americans starting in the 1990s. The increased incidence was 100% for GCTs overall—124% for seminoma and 64% for nonseminoma. The reasons for this increase are unclear, and the author's review of the data suggests environmental or nonperinatal factors (occupation, physical activity, diet) rather than early screening as the predominant cause.⁸

Age

Testicular GCTs represent the most common malignancy in men aged 15-35 years. Seminoma accounts for one third of these diagnoses.⁹

Clinical

History

• Common presentation
  • Typically, a male aged 15-35 years presents with a painless testicular lump that has been noticeable for several days to months.
  • Delay in diagnosis is common because of (1) a patient's failure to perform self-examinations, (2) a patient's failure to alert the physician about the mass, or (3) a physician's delay while treating the patient for presumed epididymoorchitis or testicular trauma.
  • Patients commonly have abnormal findings on semen analysis at presentation, and they may be subfertile.¹⁰
  • Patients may present with a hydrocele, and scrotal ultrasonography may identify a nonpalpable testis tumor. The presence of a hydrocele complicates manual examination and identification of a testicular lump, nodule, or mass.
  • Overall, in approximately 75% of patients, the seminomas are localized (stage I) at diagnosis. However, 15% have metastatic disease to the regional lymph nodes, and 5-10% have involvement of juxtaregional nodes or visceral metastases.
• Uncommon presentation
  • Testicular pain, possibly with an acute onset, especially when associated with a hydrocele, prevents adequate physical examination.
  • A testis tumor may become metastatic and may manifest as large retroperitoneal and/or chest lesions, while the primary tumor is nonpalpable. Scrotal ultrasonography may locate the primary tumor. Histopathology of the primary testis often shows a focus of tumor surrounded by fibrous scar, termed burned-out testis cancer.
  • In 1996, Miller and associates reported on a series of patients with previously nonpalpable testes that were explored and incorrectly diagnosed as vanished testes. A subsequent seminoma was diagnosed intra-abdominally.¹¹

Causes

• Patients with history of cryptorchidism have a 10- to 40-times increased risk of testis cancer; 10% of patients with GCTs have a history of cryptorchidism (see Image 1).¹¹
  • 
    

    

    Testicular seminoma. A 57-year-old man presents with abdominal pain of slow onset. CT scanning shows a large 25-cm retroperitoneal lesion encompassing the aorta and renal vasculature and displacing the right kidney laterally. The patient had a history of cryptorchidism repaired at age 8 years. Testes were normal and descended; however, ultrasonography showed a small 5-mm lesion on the right testis, which proved to be pure seminoma at orchiectomy. The beta-human chorionic gonadotropin level was 70 mIU/mL (reference range, <5 mIU/mL), and the alpha-fetoprotein level was within the reference range; no metastatic lesions were observed above the diaphragm, indicating stage IIb (bulky), T1N3M0. The patient was referred for 4 cycles of cisplatin-based chemotherapy.

    
    
  • Risk is greater for the abdominal versus inguinal location of undescended testis.
  • An abdominal testis is more likely to be seminoma, while a testis surgically brought to the scrotum by orchiopexy is more likely to be NSGCT.
• Orchiopexy allows for earlier detection by physical examination but does not alter the risk of GCT.
• Genetic changes in the form of amplifications and deletions are observed mainly in the 12p11.2-p12.1 chromosomal regions.¹²
  • A gain of 12p sequences is associated with invasive growth of both seminomas and NSGCTs.
  • In contrast, spermatocytic seminoma shows a gain of chromosome 9, while most infantile yolk sac tumors and teratomas show no chromosomal changes.
• Somatic mutations of the KIT gene occur in approximately 5% of all testicular GCTs. Of these, Coffey and colleagues (2008) demonstrated that only seminomas contain activating mutations of the KIT gene.¹³
• Other risks include trauma, mumps, and maternal estrogen exposure.
• Hemminki and colleagues (2004) demonstrated a familial risk for testicular cancer, with a 4-fold increased risk in a male with a father who had a GCT and a 9-fold increased risk if a brother was affected.¹⁴

Differential Diagnoses

Epididymitis
Hydrocele
Testicular Choriocarcinoma
Testicular Trauma
Testicular Tumors: Nonseminomatous

Other Problems to Be Considered

Testicular teratocarcinoma

Workup

Laboratory Studies

• Yolk sac elements secrete AFP; an elevated AFP level rules out pure seminoma, despite possible contrary histopathologic orchiectomy findings.
• Lactate dehydrogenase (LDH) is a less-specific marker for GCTs, but levels can correlate with overall tumor burden.
• Measure beta-human chorionic gonadotropin (bhCG).
  • bHCG is a glycoprotein with the same alpha unit as thyroid-stimulating hormone, follicle-stimulating hormone, and luteinizing hormone.
  • It has a 24- to 36-hour half-life and is secreted by syncytiotrophoblast cells within GCTs.
  • In 5%-10% of patients with seminomas, bHCG levels are elevated. Its elevation may correlate with metastatic disease but not with overall survival.
  • If bHCG levels do not normalize after orchiectomy, Richie (1998) suggests the treatment approach should be that for NSGCT, citing a study in which one third of patients who died of metastatic seminoma were found to have nonseminomatous elements at autopsy.¹² With the 10% incidence of pure seminomas producing bHCG, NSGCT chemotherapy regimens may better serve these patients.
• Placentalike alkaline phosphatase levels can be elevated in patients with seminoma, especially as the tumor burden increases; it may also increase with smoking.

Imaging Studies

• Scrotal ultrasonography¹⁵
  • Consider this study in any male with a suspicious or questionable testicular mass that is palpable upon physical examination (see Image 2).
    
    

    

    Testicular seminoma. This scrotal ultrasound of a 37-year-old man with a painless mass in his right testis shows a right testis with hypoechoic solid masses compared to the homogeneous, more hyperechoic, healthy left testis. Levels of serum beta-human chorionic gonadotropin and alpha-fetoprotein were within the reference range, and the metastatic workup findings were negative. Histopathology showed a pure seminoma. Metastatic workup showed no nodal or distant spread, T1N0M0 stage I. After orchiectomy, the patient underwent adjuvant external beam radiotherapy to the para-aortic nodes. At a 3-year follow-up study, the patient is disease free and has a greater than 95% chance of remaining disease free.

    
    
  • Other indications may include acute scrotal pain (especially when associated with a hydrocele), nonspecific scrotal pain, swelling, or the presence of a mass.
  • If an asymptomatic hydrocele obscures physical examination of the testicle, this study may be appropriate prior to surgical intervention. It may also be appropriate for males who are at the peak age range for testicular cancer (ie, 15-35 y).
  • Scrotal ultrasonography commonly shows a homogeneous hypoechoic intratesticular mass. Larger lesions may be more inhomogeneous.
  • Calcifications and cystic areas are less common in seminomas than in nonseminomatous tumors.
• Abdominal and pelvic CT scanning: This study, along with intravenous and oral contrast, can be used to identify metastatic disease to the retroperitoneal lymph nodes; however, CT scanning results in understaging in approximately 15%-20% of patients thought to be at stage I.¹⁶
• Chest CT scanning: This is indicated only when abnormal findings are observed on a chest radiograph.
• Fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET): This technique has been evaluated for its utility in staging and restaging of seminomatous and nonseminomatous tumors.^17,18,19 In primary staging, FDG-PET has been found to have no benefit over CT scanning alone. However, in restaging assessments of residual masses, FDG-PET was noted to improve the ability to detect a fibrotic residual mass compared to that of residual teratoma postchemotherapy. Hinz et al (2008) prospectively evaluated 20 patients with a residual mass following chemotherapy for seminoma greater than stage IIa prior to surgical resection. Although all patients with viable tumor were identified, FDG-PET findings were falsely positive in 9 of the 20 patients. They concluded that FDG-PET should be as an adjunctive tool for patient counseling.²⁰

Histologic Findings

Seminomas can have 3 histologic variants.¹

The first is classic seminoma, and it has a uniform population of large cells that form sheets and nests separated by delicate connective tissue (see Images 3-4). Leukocytic infiltration (20%), multinucleated cells, syncytiotrophoblasts (7%-35%), and microcalcifications (60%) may be present. Upon gross examination, the tumor has a uniform yellow color and bulges from the cut surface. Classic seminoma is the most common histologic type.

Testicular seminoma. This is a classic seminoma at low power. Uniform tumor cells are observed with mild inflammatory response (lymphocytes). Other seminoma findings not seen could include a fibrovascular stroma, syncytiotrophoblastic cells, and multinucleated histiocytes.

This is a classic testicular seminoma, high-power view, from a 37-year-old man with a painless mass in his right testis. Levels of serum beta-human chorionic gonadotropin and alpha-fetoprotein were within the reference range, and the metastatic workup findings were negative. Histopathology showed a pure seminoma. Metastatic workup showed no nodal or distant spread, T1N0M0 stage I. After orchiectomy, the patient underwent adjuvant external beam radiotherapy to the para-aortic nodes. At a 3-year follow-up study, the patient is disease free and has a greater than 95% chance of remaining disease free. See Image 2 for a scrotal sonogram of this patient. Note here that tumor cells are uniform, have abundant clear cytoplasm, a large centrally located nucleus, and a variable mitotic pattern.

The second is anaplastic seminoma, and it is observed in 5%-15% of patients with seminomas. Histopathology is as described for classic seminoma but with increased mitotic figures. Patients tend to present at more advanced stages than those with classic seminoma, but stage prognosis is similar.

The third is spermatocytic seminoma, and it is a rare variant that occurs in older adults. Histopathology shows tumor cells arranged in solid sheets, containing poorly developed inconspicuous septae without leukocytic infiltrate. No glycogen is present. Small, medium, and large cell types are observed. Orchiectomy alone is sufficient treatment; metastases are rare.

Staging

American Joint Committee on Cancer and the International Union Against Cancer: Testicular Cancer Staging System²¹

Table 1. Primary Tumor (T)

Table 2A. Regional Lymph Nodes (N): Clinical

Table 2B. Regional Lymph Nodes (N): Pathologic

Table 3. Distant Metastases (M)

Table 4. Serum Tumor Markers (S)

N = upper limit of normal for the LDH assay

†HCG = human chorionic gonadotropin

Table 5. Stage Grouping

Additional staging systems are well discussed by Prow (1998).²²

Treatment

Medical Care

• External beam radiotherapy for stage I and nonbulky stage II disease
  • Refer patients with stage I and nonbulky stage II seminomas for external beam radiotherapy. Over a 3-week period, administer 2500 cGy in a hockey-stick field, including the para-aortic, paracaval, bilateral common iliac, and external iliac nodal regions. Recent protocols are reducing the radiation field to the para-aortic area only.
  • A 2005 randomized trial from the Medical Research Council compared adjuvant radiotherapy at 30 Gy versus 20 Gy for stage I seminoma. The lower dose resulted in equivalent associated relapse rates and reduced morbidity, especially regarding fatigue. Further follow-up was recommended to determine if associated long-term secondary malignancies develop.²³
  • Mediastinal radiation was commonly administered but is currently avoided because chemotherapy is more effective. Mediastinal radiation may also diminish the ability to provide salvage chemotherapy later, if needed.
  • Only 3% of patients relapse after radiation therapy. Relapses are usually located outside the radiation field.
  • Short-term adverse effects include fatigue, nausea, vomiting, and GI upset.
  • Long-term adverse effects have become of more concern over the last several years. Zagars and colleagues (2004) published a review of all patients who underwent radiotherapy postorchiectomy for seminoma between 1951 and 1999. They then computed standardized mortality ratios based on the person-years method. They found an increased risk after 15 years for cardiovascular and secondary cancer mortalities and recommended investigating new therapies that do not confer these long-term effects.²⁴
  • As an alternative to radiotherapy, single-agent carboplatin protocols are being studied. The Medical Research Council compared adjuvant carboplatin with radiotherapy and found equivalent relapse rates after a median follow-up period of 4 years. Long-term success of carboplatin therapy is unknown so should be considered experimental at this time.²⁵
• Chemotherapy for stage II bulky or stage III disease
  • After radical orchiectomy (see Surgical Care) and metastatic workup, administer 4 cycles of chemotherapy without radiotherapy in patients with advanced seminoma (stage IIB bulky or stage III).²⁶
  • Clinical trials have evaluated numerous chemotherapeutic regimens. While the optimal regimen is debatable, 4 cycles of bleomycin, etoposide, and cisplatin (BEP) is standard.
  • Ongoing clinical trials are evaluating the omission of the fourth cycle, or bleomycin, in low-risk patients.
  • For poor-risk and salvage cases, physicians may use alternative regimens using ifosfamide and vinblastine with dose escalation.

Surgical Care

• Relevant anatomy¹²
  • Seminoma arises from abnormal germ cells in the seminiferous tubules. The TNM staging system (see Staging) stages the tumor based on its local, regional, and distant invasion.
  • Testicular lymphatics relate to the embryonic origin of the testis. The male gonad initially forms near the kidney and descends through the inguinal canal to the scrotal sac. The right gonadal vein derives from the inferior cava, while the left gonadal vein derives from the left renal vein. Additional blood supply derives from the artery of the vas and the cremasteric arteries. Testicular lymphatics follow the vessels of the spermatic cord through the inguinal canal and into the retroperitoneum. Testicular cancer spreads predominantly and initially through lymphatic routes. On the right, the cancer landing zone is between the aorta and the inferior vena cava; on the left, it is on top of and lateral to the aorta. Within the retroperitoneum, there can be a crossover from the lymphatics draining the right toward those of the left.
  • Scrotal skin lymphatics are different from testicular lymphatics and drain into the inguinal nodes. Perform all orchiectomies for solid masses through an inguinal route to avoid tumor spillage into the inguinal drainage basin. If a patient undergoes scrotal exploration, subsequent therapy may necessitate hemiscrotectomy and radiation treatment of the inguinal nodes.
  • In patients who have undergone prior herniorrhaphy, orchiopexy, or other alteration in lymphatic drainage, extend their radiation field to include the contralateral inguinal region with contralateral testis shielding.
• Radical inguinal orchiectomy
  • Preoperative details
    • Draw serum tumor markers preoperatively because values fall rapidly after orchiectomy. Other staging tests can be performed preoperatively or postoperatively.
    • Because of the rapid doubling time of a potential choriocarcinoma, schedule surgery for testis tumors rapidly to avoid upstaging.
    • Most patients with seminoma are young and healthy and require only routine preoperative preparation.
    • Discuss semen donation for subsequent fertility if the contralateral testis function is in question; however, many patients have poor semen quality that improves after orchiectomy.
    • Cosmetic testicular prostheses are currently available from Coloplast (formerly Mentor). The saline-filled testicular prosthesis has been FDA-approved since 2002 and can be implanted in an outpatient setting if desired by the patient.
    • If a patient presents with symptomatic metastatic lesions from a testis tumor, proceed with platinum-based chemotherapy and delay radical orchiectomy. Radical orchiectomy is not a morbid procedure, but it may delay initiation of chemotherapy.
    • Differentiation of seminoma versus NSGCT for advanced disease is not important at the outset of treatment because both groups receive the same regimen.
    • Although chemotherapy may result in disappearance of the testicular mass, orchiectomy is always indicated.
  • Intraoperative details
    • Patients may be administered spinal, general, or (uncommonly) local anesthesia. Shave the inguinal area, and prep in a standard fashion.
    • Create an inguinal incision to allow exposure of the external and internal iliac canal.
    • Open the external iliac fascia, exposing the spermatic cord and internal iliac canal. Control the spermatic cord with a Penrose drain in a tourniquet fashion to stop retroperitoneal lymphatic and venous drainage of tumor cells.
    • Then, deliver the testis from the scrotum and ligate separately the vas deferens and spermatic arteries.
    • Leave a long nonabsorbable tie on the patient side of the spermatic cord. This is to facilitate identification if retroperitoneal lymph node dissection (RPLND) becomes necessary and the patient requires dissection of the remaining spermatic cord structures from the abdominal exposure.
    • Reapproximate the external oblique fascia and close the skin in standard fashion.
  • Postoperative details
    • Radical orchiectomy is usually performed on an outpatient or 23-hour admission basis, often accompanied by the staging workup.
    • Conduct a follow-up study by staging and referring the patient for appropriate adjuvant therapies.
  • Complications are rare but may include wound infection, inguinal skin numbness due to injury to the genitofemoral nerve, hematoma, and standard anesthetic risks.

Consultations

• Low-stage disease - Radiation oncologist for external beam radiotherapy
• Advanced disease - Medical oncologist for platinum-based chemotherapy

Medication

BEP is the most common chemotherapy regimen administered for GCTs. It is usually administered in 4 cycles. Additional agents involved in primary, high-risk, and salvage protocols may include ifosfamide and vinblastine.

Antineoplastic agents

These agents inhibit deregulated growth of cells.

Bleomycin (Blenoxane)

Composed of cytotoxic glycopeptide antibiotics, which appear to inhibit DNA synthesis with some evidence of RNA and protein synthesis inhibition to a lesser degree; used in the management of several neoplasms as a palliative measure.

Dosing

Adult

30 U (0.25-0.5 U/kg) IV on days 1, 9, and 16

Pediatric

Not established

Interactions

May decrease plasma levels of digoxin and phenytoin; cisplatin may increase toxicity

Contraindications

Documented hypersensitivity; significant renal function impairment; compromised pulmonary function

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal impairment; possibly secreted in breast milk; may cause mutagenesis and pulmonary toxicity (10%); idiosyncratic reactions similar to anaphylaxis (1%) may occur; monitor for adverse effects during and after treatment

Etoposide (VP-16)

Arrests cells in the G2 portion of the cell cycle and induces DNA strand breaks by interacting with DNA topoisomerase II and forming free radicals.

Dosing

Adult

100 mg/m² IV on days 1-5

Pediatric

Not established

Interactions

May prolong effects of warfarin and increase clearance of methotrexate; cyclosporine and etoposide have additive effects in cytotoxicity of tumor cells

Contraindications

Documented hypersensitivity; IT administration, may cause death

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Bleeding and severe myelosuppression may occur

Cisplatin (Platinol, Platinol-AQ)

Inorganic metal complex thought to act analogously to alkylating agents; inhibits DNA synthesis and thus cell proliferation by causing DNA crosslinks and denaturation of double helix.

Dosing

Adult

20 mg/m² IV on days 1-5 and repeat q3-4wk

Pediatric

Not established

Interactions

Increases toxicity of bleomycin and ethacrynic acid

Contraindications

Documented hypersensitivity; preexisting renal insufficiency; myelosuppression; hearing impairment

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Administer adequate hydration before and 24 h after dosing to reduce risk of nephrotoxicity; myelosuppression, ototoxicity, nausea, and vomiting may occur

Ifosfamide (Ifex)

Related to nitrogen mustards and is a synthetic analog of cyclophosphamide; inhibits DNA and protein synthesis and thus cell proliferation by causing DNA cross-linking and denaturation of double helix.

Dosing

Adult

1.2 g/m²/d IV on days 1-5

Pediatric

Not established

Interactions

Phenobarbital, phenytoin, chloral hydrate, and other drugs that interfere with cytochrome P450 activity may alter effects

Contraindications

Documented hypersensitivity; depressed bone marrow function

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May cause hemorrhagic cystitis and severe myelosuppression; caution in renal function impairment or compromised bone marrow reserve

Vinblastine (Alkaban-AQ, Velban)

Inhibits microtubule formation, which in turn, disrupts the formation of mitotic spindle, causing cell proliferation to arrest at metaphase.

Dosing

Adult

4-20 mg/m² (0.1-0.5 mg/kg) IV q7-10d or 5 d continuous infusion of 1.4-1.8 mg/m²/d or 0.1-0.5 mg/kg/wk

Pediatric

Not established

Interactions

Phenytoin plasma levels may be reduced when coadministered; toxicity may significantly increase with mitomycin

Contraindications

Documented hypersensitivity; severe bone marrow suppression; granulocytopenia; bacterial infections

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in patients diagnosed with impaired liver function and neurotoxicity; when patient is receiving mitomycin C, monitor closely for shortness of breath and bronchospasm

Follow-up

Further Inpatient Care

Most radical orchiectomies are performed in an outpatient setting, including 23-hour observation. This surgery is comparable to an inguinal herniorrhaphy, and the patient can expect limited physical activity for a brief period after surgery.

Further Outpatient Care

The primary management for all testicular GCT depends on the pathology, as outline above. Following orchiectomy, patients can expect repeat studies of serum tumor markers and pathologic staging completed to formulate the treatment plan.

Inpatient & Outpatient Medications

Following orchiectomy, a short course of pain management medication may be indicated.

Deterrence/Prevention

Prior to diagnosis of testicular GCT, men should begin monthly testicular self-examinations starting at puberty. Any abnormalities should be reported to their physician.

After diagnosis of testicular GCT, the patient and treating physician should come to a mutual understanding regarding strict adherence to follow-up regimens to monitor for tumor recurrence.

Prognosis

• Mortality rates increased until the 1970s but have since declined greatly as a result of advances in treatment.
• All stages have at least a 90% cure rate.²²
  • Stage I is 98%-100%.
  • Stage II (B1/B2 nonbulky) is 98%-100%.
  • Stage II (B3 bulky) and stage III have a 90% complete response to chemotherapy and an 86% durable response rate to chemotherapy.
• Second cancers and cardiac disease among long-term survivors
  • Patients with testicular cancer are at an increased risk of secondary cancers because of their young age at diagnosis, high cure rate, and exposure to radiation, chemotherapy, or both. Travis et al (2005) reported on a cohort of 14 population-based tumor registries in Europe and North America totaling 40,576 patients. A plethora of statistics is provided. Their key findings were that survivors of testicular cancer are at a significantly increased risk of solid tumors for at least 35 years after treatment. Tumors included malignant mesothelioma and those of the lung, colon, bladder, pancreas, and stomach. The relative risk increases were the same for seminoma, nonseminoma, and treatment with radiation, chemotherapy, or both. For patients diagnosed with seminoma at age 35 years, the cumulative risk 40 years later was 36%, compared with 23% for the general population.²⁷
  • Zagars et al (2004) reported on long-term follow-up involving 477 men with low-stage seminoma treated with orchiectomy and adjuvant radiation at a single institution. They compared long-term cancer-specific survival with cardiac-specific survival and performed a risk analysis in relation to standard US data for males. No differences were seen in the first 15 years, but, after 15 years, the relative risks of cardiac and secondary cancer deaths were increased.²⁴
  • In summary, these two long-term follow-up studies demonstrate that, although many men with seminoma are cured, they require counseling and long-term follow-up to minimize the risk of excess mortality from secondary cancers and cardiac disease.

Patient Education

• For excellent patient education resources, visit eMedicine's Men's Health Center and Cancer and Tumors Center. Also, see eMedicine's patient education articles Cancer of the Testicle and Testicular Self-Exam.

Miscellaneous

Medicolegal Pitfalls

• Failure to select patients well and to ensure patient compliance with the protocol for follow-up CT scanning and tumor marker assessment in patients with low-stage disease who elect the observation protocol instead of adjuvant radiation therapy
• Losing patients during the follow-up period and undetected recurrent disease
• Failure to consider the issue of fertility in patients with advanced disease who need chemotherapy
• Failure to carefully discuss the effects of chemotherapy on future fertility and to discuss options for banking healthy sperm before chemotherapy

Special Concerns

• Contralateral testis biopsy
  • In 1996, Daugaard and associates argued that a biopsy should be obtained from the contralateral testis at the time of orchiectomy. Because 5% of contralateral testes in men with GCT harbor CIS, nearly all of which eventually progress to invasive GCT, early diagnosis and treatment with surgery or radiation is recommended.²⁸
  • However, in 1997, Herr and Sheinfeld argued that biopsy is unnecessary because 95% of patients have a normal contralateral testis and the 5% who have an abnormal contralateral testis can be effectively treated at a later time. They recommend patient education and close follow-up studies, which is the common practice in the United States.²⁹
• Surveillance for stage I seminoma
  • Because cure rates are excellent for advanced disease and because only 25% of patients with stage I disease harbor occult metastatic disease, some interest lies in observing patients with stage I disease. Surveillance is appropriate only for well-motivated and compliant patients who adhere to strict follow-up imaging studies. Restricting surveillance to clinical trials may be reasonable until more outcome evidence is available.
  • Problems with surveillance in seminoma include (1) the fact that no chemical markers are available for monitoring (in contrast to NSGCT) and (2) the need for a longer follow-up time (compared to NSGCT); radiation treatment failures are observed 2-10 years later.
  • The following are prominent reports on outcomes of surveillance.
    • In 1997, Warde and associates reported on 201 patients with stage I seminoma placed on surveillance. The 5-year actuarial relapse-free survival rate was 85%, the actuarial survival rate was 97%, and the cause-specific survival rate was 99.5%.³⁰
    • In 1994, Miki and associates reported on a group of 27 patients who underwent radiation therapy, and one had failure in the lung. In a study of patients who did not receive radiation therapy, 5 of 41 had recurrence. However, all 5 patients with relapses were alive and had no disease following chemotherapy.³¹
• Extratesticular seminoma
  • In patients who present with a retroperitoneal mass, an elevated bhCG level, and normal findings on testis examination (physical examination and scrotal ultrasonography), the diagnosis of extratesticular seminoma must be considered.
  • It is possible that seminoma can be found only within the retroperitoneal lymph nodes and not within the primary tumor location of the testis, perhaps due to a primary lesion that undergoes degeneration, leaving the so called burned-out primary.
  • In this situation, diagnosis of the retroperitoneal mass is essential for diagnosis of the tumor type, with the subsequent therapeutic modality, if a GCT, being that of several cycles of tumor-specific chemotherapy.
• Recurrent mass after chemotherapy for seminoma
  • Chemotherapy for seminoma causes a fibrotic reaction in the retroperitoneum that is similar to retroperitoneal fibrosis; thus, postchemotherapy RPLND for seminoma is a difficult and potentially morbid procedure compared to the excellent results of postchemotherapy RPLND for NSGCT.
  • In 1987, Motzer and associates showed that residual masses larger than 3 cm had a 50% chance of harboring a tumor and recommended this cutoff for RPLND. Because this procedure is very difficult, they recommended referral to centers with experienced personnel.³² In a 1997 report on a series of patients with residual masses treated with radiation therapy, Duchesne and associates reported that only 2.3% benefited from treatment.³³
  • FDG-PET scanning has emerged as a diagnostic tool for evaluating recurrent retroperitoneal masses after chemotherapy. In a study by De Santis et al (1997), FDG-PET scans correctly predicted residual tumor in 19 of 19 cases residual masses larger than 3 cm. In cases of residual masses smaller than 3 cm, 35 of 37 were correctly predicted. Overall, FDG-PET scanning yielded a specificity of 100%, a sensitivity of 80%, a positive predictive value of 100%, and a negative predictive value of 96%. The results of this study support using PET rather than the 3-cm rule for deciding between subsequent salvage therapy and surveillance.³⁴
• Follow-up protocols are available on the National Comprehensive Cancer Network Web site. Surveillance is lifelong and includes the following:
  • Stage I
    • Orchiectomy plus adjuvant radiation
    • History and physical examination and serum tumor markers (bhCG, LDH, AFP) every 3-4 months the first year, every 6 months the second year, then annually thereafter
    • Imaging: Chest radiography each visit; CT scan of the pelvis annually for 3 years if status post para-aortic radiotherapy
  • Stage II
    • Orchiectomy plus surveillance
    • History and physical examination and serum tumor markers every 3-4 months years 1-3, every 6 months years 4-7, and then annually thereafter
    • Imaging: Radiotherapy at alternate visits for up to 10 years; CT scan of the abdomen and pelvis each visit
  • Stage IIa/b
    • Orchiectomy plus radiotherapy
    • History and physical examination and serum tumor markers every 3-4 months years 1-3, every 6 months year 4, and then annually thereafter
    • Imaging: radiotherapy each visit; CT scan of the abdomen and pelvis during month 4 of the first year
  • Stage IIc, III
    • Orchiectomy plus chemotherapy
    • History and physical examination and serum tumor markers every 2 months the first year, every 3 months the second year, every 4 months the third year, every 6 months the fourth year, and then annually thereafter
    • Imaging: Chest radiography each visit; CT scan of the abdomen and pelvis during month 4 of the first year status post surgery (otherwise, every 3 mo until stable); PET scan as clinically indicated

Multimedia

Media file 1: Testicular seminoma. A 57-year-old man presents with abdominal pain of slow onset. CT scanning shows a large 25-cm retroperitoneal lesion encompassing the aorta and renal vasculature and displacing the right kidney laterally. The patient had a history of cryptorchidism repaired at age 8 years. Testes were normal and descended; however, ultrasonography showed a small 5-mm lesion on the right testis, which proved to be pure seminoma at orchiectomy. The beta-human chorionic gonadotropin level was 70 mIU/mL (reference range, <5 mIU/mL), and the alpha-fetoprotein level was within the reference range; no metastatic lesions were observed above the diaphragm, indicating stage IIb (bulky), T1N3M0. The patient was referred for 4 cycles of cisplatin-based chemotherapy.

Media file 2: Testicular seminoma. This scrotal ultrasound of a 37-year-old man with a painless mass in his right testis shows a right testis with hypoechoic solid masses compared to the homogeneous, more hyperechoic, healthy left testis. Levels of serum beta-human chorionic gonadotropin and alpha-fetoprotein were within the reference range, and the metastatic workup findings were negative. Histopathology showed a pure seminoma. Metastatic workup showed no nodal or distant spread, T1N0M0 stage I. After orchiectomy, the patient underwent adjuvant external beam radiotherapy to the para-aortic nodes. At a 3-year follow-up study, the patient is disease free and has a greater than 95% chance of remaining disease free.

Media file 3: Testicular seminoma. This is a classic seminoma at low power. Uniform tumor cells are observed with mild inflammatory response (lymphocytes). Other seminoma findings not seen could include a fibrovascular stroma, syncytiotrophoblastic cells, and multinucleated histiocytes.

Media file 4: This is a classic testicular seminoma, high-power view, from a 37-year-old man with a painless mass in his right testis. Levels of serum beta-human chorionic gonadotropin and alpha-fetoprotein were within the reference range, and the metastatic workup findings were negative. Histopathology showed a pure seminoma. Metastatic workup showed no nodal or distant spread, T1N0M0 stage I. After orchiectomy, the patient underwent adjuvant external beam radiotherapy to the para-aortic nodes. At a 3-year follow-up study, the patient is disease free and has a greater than 95% chance of remaining disease free. See Image 2 for a scrotal sonogram of this patient. Note here that tumor cells are uniform, have abundant clear cytoplasm, a large centrally located nucleus, and a variable mitotic pattern.

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Keywords

testicular seminoma, testis cancer, cancer of the testes, testis germ cell carcinoma, testicular cancer, seminoma, germ cell tumor, GCT, radical orchiectomy, germ cell carcinoma in situ, germ cell CIS, classic seminoma, anaplastic seminoma, spermatocytic seminoma

Contributor Information and Disclosures

Author

Michael B Williams, MD, MS, Fellow, Department of Urologic Oncology, MD Anderson Cancer Center
Disclosure: Nothing to disclose.

Coauthor(s)

Paul Schellhammer, MD, Chairman, Program Director, Professor, Department of Urology, Eastern Virginia Medical School
Paul Schellhammer, MD is a member of the following medical societies: American Urological Association
Disclosure: Nothing to disclose.

John W Davis, MD, Assistant Professor, Department of Urology, University of Texas MD Anderson Cancer Center
John W Davis, MD is a member of the following medical societies: American College of Surgeons and American Urological Association
Disclosure: Nothing to disclose.

Medical Editor

Gamal Mostafa Ghoniem, MD, FACS, Fellowship Program Director, Clinical Professor of Surgery, Head, Section of Voiding Dysfunction, Female Urology and Reconstruction, Cleveland Clinic Florida
Gamal Mostafa Ghoniem, MD, FACS is a member of the following medical societies: American College of Surgeons, American Urogynecologic Society, American Urological Association, Florida Medical Association, International Continence Society, and International Urogynaecology Association
Disclosure: Astellas Honoraria Speaking and teaching; Coloplasty Consulting fee Consulting; Uroplasty Consulting fee Consulting

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Dan Theodorescu, MD, PhD, Paul Mellon Professor of Urologic Oncology, Department of Urology, University of Virginia Health Sciences Center
Dan Theodorescu, MD, PhD is a member of the following medical societies: American Cancer Society, American College of Surgeons, American Urological Association, Medical Society of Virginia, Society for Basic Urologic Research, and Society of Urologic Oncology
Disclosure: Nothing to disclose.

CME Editor

J Stuart Wolf Jr, MD, FACS, David A Bloom Professor of Urology, Director of Division of Minimally Invasive Urology, Department of Urology, University of Michigan
J Stuart Wolf Jr, MD, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Catholic Medical Association, Endourological Society, Society for Urology and Engineering, Society of Laparoendoscopic Surgeons, Society of University Urologists, and Society of Urologic Oncology
Disclosure: Terumo Corporation Consulting fee Consulting; Gyrus-ACMI Honoraria Speaking and teaching

Chief Editor

Bradley Fields Schwartz, DO, FACS, Professor of Urology, Director, Center for Laparoscopy and Endourology, Department of Surgery, Southern Illinois University School of Medicine
Bradley Fields Schwartz, DO, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Association of Military Osteopathic Physicians and Surgeons, Endourological Society, Society of Laparoendoscopic Surgeons, and Society of University Urologists
Disclosure: Nothing to disclose.

Relevant guidelines

Guidelines on testicular cancer

Management of stage I nonseminomatous testicular cancer: guideline recommendations

Management of stage I seminoma: guideline recommendations

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