Chapter 93: Testicular Cancer¶

Oncology and Hematology · Part 4 – Oncology: Solid Tumors

Detailed clinical reference synthesised from Harrison's Principles of Internal Medicine, 22nd Edition

🔑 Key Clinical Points¶

Testicular germ cell tumors (GCTs) represent 95% of all testicular neoplasms and are the most common malignancy in adolescent and young adult males (age 15–39 years).
Radical inguinal orchiectomy is the gold standard initial treatment; transscrotal biopsy or aspiration is contraindicated due to risk of tumor seeding.
Seminomas are exquisitely sensitive to chemotherapy and radiation; nonseminomatous GCTs are chemotherapy sensitive but teratomas are chemoresistant.
Serum tumor markers (AFP, hCG, LDH) are essential for diagnosis and staging; AFP is never elevated in seminoma.
Active surveillance is the preferred management for Stage I seminoma, while Stage I nonseminomatous GCTs may be managed with surveillance or adjuvant therapy depending on risk features.
Cisplatin-based chemotherapy (BEP or EP) is the standard for metastatic disease; fertility preservation via sperm banking is recommended prior to treatment.
Postchemotherapy residual masses often represent necrosis or teratoma; resection is indicated for viable nonteratomatous GCT or masses >3 cm.
Relapse occurs in 20–30% of patients with metastatic GCT; prognosis is determined by the International Germ Cell Consensus Classification System.
Extragonadal GCTs occur in ~5% of cases, commonly in the mediastinum, retroperitoneum, or pineal gland.
Risk factors include cryptorchidism, history of testicular GCT, and germ cell neoplasia in situ (GCNIS).

📑 Table of Contents¶

1. DEFINITION & OVERVIEW
1.1 Classification
2. EPIDEMIOLOGY
2.1 Risk Factors
3. ETIOLOGY & PATHOPHYSIOLOGY
3.1 Serum Tumor Markers
3.2 Pathology
4. CLINICAL FEATURES
4.1 Physical Examination
5. DIFFERENTIAL DIAGNOSIS
5.1 Diagnostic Clues
6. INVESTIGATIONS & DIAGNOSIS
6.1 Diagnostic Algorithm
7. MANAGEMENT & TREATMENT
7.1 Stage-Based Management
8. PROGNOSIS & COMPLICATIONS
8.1 Relapsed Disease
8.2 Fertility
9. SPECIAL CONSIDERATIONS
9.1 Postchemotherapy Surgery
10. KEY PEARLS & CLINICAL TRAPS
10.1 Diagnostic Clues
Flowcharts & Algorithms
Figures & Illustrations

📋 Figures in This Chapter¶

#	Type	Description
1	🔀 Flowchart	Stage-based management of testicular germ cell tumor
1	🖼 Figure	(Continued)

1. DEFINITION & OVERVIEW¶

Testicular germ cell tumors (GCTs) represent 95% of all testicular neoplasms.
Non-GCTs of the testis are much less common.
Approximately 5% of GCTs arise in extragonadal locations including the mediastinum, retroperitoneum, and pineal gland.
Treatment for testicular GCTs is determined by pathology and stage.
The development of effective chemotherapy for this disease represents a landmark achievement in oncology.
About 95% of newly diagnosed patients with testicular GCTs will be cured.
Testicular cancer has been called 'a model for a curable neoplasm.'
Harrison's defines this as: 'Testicular germ cell tumors (GCTs) represent 95% of all testicular neoplasms. Non-GCTs of the testis are much less common. Approximately 5% of GCTs arise in extragonadal locations including the mediastinum, retroperitoneum, and pineal gland. Treatment for testicular GCTs is determined by pathology and stage. The development of effective chemotherapy for this disease represents a landmark achievement in oncology. About 95% of newly diagnosed patients with testicular GCTs will be cured. For this reason, testicular cancer has been called a model for a curable neoplasm.'

1.1 Classification¶

GCTs are either seminomas or nonseminomas.
For a tumor to be considered a seminoma, it must be 100% seminoma.
Any mixed GCT should be approached as a nonseminomatous GCT.
Seminomas represent ~50% of cases.
Nonseminomatous GCTs are most commonly diagnosed in the third decade of life.
Histologic subtypes of nonseminomatous GCTs include embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma.
Teratoma is composed of somatic cell types derived from two or more germinal layers (endoderm, mesoderm, and ectoderm).
Teratomas are classified as mature, immature, or malignant.

2. EPIDEMIOLOGY¶

In 2023, ~9200 cases of testicular GCTs will be diagnosed in the United States, with 470 deaths.
The incidence of testicular GCTs appears to be increasing worldwide.
The disease has the highest incidence in Scandinavia, Western Europe, and Australia/New Zealand.
Africa and Asia have the lowest incidence.
The incidence in the United States and the United Kingdom is intermediate.
While a distinct biology related to geography is not apparent, several countries have reported a migration to earlier stage disease in part related to public awareness and earlier diagnosis.
Testicular GCT is the most common malignancy diagnosed in adolescent and young adult males (defined as age 15–39 years).
The incidence in patients over 50 is increasing.
Testicular GCT is most commonly diagnosed in Caucasians.
The disease is much less commonly seen in African Americans.
Testicular GCTs have an estimated heritability of almost 50%.
The risk of GCT is higher in male siblings than in offspring of the patient.

2.1 Risk Factors¶

The strongest risk factors for testicular GCT include a prior history of the disease, cryptorchidism, and a history of testicular germ cell neoplasia in situ.
Patients with a prior history of testicular GCT have a 1–2% risk of developing a contralateral GCT.
These are more commonly metachronous than synchronous.
Men with cryptorchidism have approximately a four- to sixfold increased risk of developing testicular GCT.
Orchidopexy before puberty decreases but does not eliminate this risk.
The contralateral descended testis is also at risk for this disease.
Men undergoing infertility evaluation in which a testicular biopsy demonstrates germ cell neoplasia in situ have a significant risk of developing GCT.
Although epidemiologic studies have been performed attempting to identify a relationship with environmental exposures, no conclusive causal links have been established.

3. ETIOLOGY & PATHOPHYSIOLOGY¶

The primordial germ cell is the cell of origin for GCTs.
Most malignant GCTs arise from in situ neoplasia.
The molecular events that result in the development of germ cell neoplasia in situ and subsequent malignant GCT have not been fully determined.
Genetic analysis of GCTs has demonstrated an excess copy number of isochromosome 12p (i[12p]) in most cases.
Several genome-wide association studies have identified multiple independent loci associated with testicular GCT risk.
The strongest of these is the KITLG (KIT ligand) locus on chromosome 12.
These loci contribute significantly to the heritable risk of this disease.

3.1 Serum Tumor Markers¶

AFP, hCG, and lactate dehydrogenase (LDH) should be measured in patients suspected of testicular GCT.
AFP is elevated in ~60–70% of patients who present with nonseminomatous GCTs.
Seminomas never secrete AFP.
A patient with a seminoma with elevation of AFP should be approached as having a nonseminomatous GCT.
The half-life of AFP is 5–7 days.
A falsely elevated AFP may be seen in patients with hepatic disease or a condition called hereditary persistence of AFP, in which patients may have baseline AFP levels that are mildly elevated.
hCG may be elevated in both nonseminomatous GCTs as well as seminomas.
Patients with choriocarcinoma may have markedly elevated levels of hCG.
The half-life for hCG is 24–36 h.
False-positive elevation of hCG may be seen secondary to hypogonadism, marijuana use, or because of interfering substances measured by the assay.
LDH is a nonspecific marker for GCT.
Its principal use is to help in the assessment of the risk classification of a patient with metastatic disease.
Although elevation of serum tumor markers supports the diagnosis of a testicular GCT, most patients with seminoma and up to a third of patients with nonseminomatous GCTs do not have elevated levels.
Serum microRNA (miR)-371a-3 has been identified as a promising biomarker for GCT, and validation studies are ongoing.

3.2 Pathology¶

Seminomas arise most commonly in patients in the fourth decade of life.
Seminomas may contain syncytiotrophoblastic cells, which may secrete β-human chorionic gonadotropin (hCG).
Seminomas do not secrete α-fetoprotein (AFP).
Seminomas are exquisitely sensitive to both chemotherapy and radiation therapy.
Nonseminomatous GCT subtypes are all considered chemotherapy sensitive.
Embryonal carcinoma is the most undifferentiated nonseminomatous GCT subtype with the potential to differentiate into the other subtypes.
Embryonal carcinoma may secrete AFP, hCG, both, or neither.
Yolk sac tumor often secretes AFP.
Choriocarcinoma is an aggressive subtype, often secreting hCG at very high levels.
Teratoma is chemotherapy resistant and must be treated surgically.

4. CLINICAL FEATURES¶

Although a painless testicular mass is the primary landing zone of left paraaortic lymph nodes inferior to the left renal vessels, most patients present with testicular swelling, firmness, discomfort, or a combination of these.
The differential diagnosis may include epididymitis or orchitis, and a trial of antibiotics may be considered.
Patients with retroperitoneal metastases may complain of back or flank pain.
Patients may have cough, shortness of breath, or hemoptysis because of lung metastases.
In patients with elevation of serum hCG, gynecomastia may be present.
Careful examination of the affected testis should be performed.
The contralateral normal testis should be performed.
Many tumors will have a hard consistency to palpation.
Some patients may show testicular atrophy.
Evaluation for supraclavicular lymphadenopathy, gynecomastia, and abdominal mass should be performed.

4.1 Physical Examination¶

Careful examination of the affected testis should be performed.
The contralateral normal testis should be performed.
Many tumors will have a hard consistency to palpation.
Some patients may show testicular atrophy.
Evaluation for supraclavicular lymphadenopathy, gynecomastia, and abdominal mass should be performed.

5. DIFFERENTIAL DIAGNOSIS¶

Epididymitis or orchitis.
A trial of antibiotics may be considered.

5.1 Diagnostic Clues¶

A painless testicular mass is the primary landing zone of left paraaortic lymph nodes inferior to the left renal vessels.
A solid mass identified on ultrasound should be considered malignant until otherwise proven.
On ultrasound, a testicular GCT is hypoechoic and may be multifocal.
Transscrotal aspiration or biopsy of a testicular mass should never be performed.
Such scrotal violation may result in tumor seeding of the scrotum or inguinal lymph nodes.

6. INVESTIGATIONS & DIAGNOSIS¶

If a firm testicular mass is identified, a scrotal ultrasound should be performed.
Patients with suspected epididymitis or orchitis who do not respond to antibiotics should also undergo scrotal ultrasound.
Scrotal ultrasound should include both testicles.
On ultrasound, a testicular GCT is hypoechoic and may be multifocal.
A solid mass identified on ultrasound should be considered malignant until otherwise proven.
Transscrotal aspiration or biopsy of a testicular mass should never be performed.
Such scrotal violation may result in tumor seeding of the scrotum or inguinal lymph nodes.
Patients with newly diagnosed testicular GCTs should undergo computed tomography (CT) scan of the abdomen and pelvis.
Chest x-ray is performed if retroperitoneal metastases are present or if lung nodules are identified on chest x-ray.
CT scan of the chest is performed if retroperitoneal metastases are present or if lung nodules are identified on chest x-ray.
Bone scan and magnetic resonance imaging (MRI) of the brain are not routinely performed unless clinically indicated.
Positron emission tomography (PET) has little role in the initial staging of testicular GCTs.

6.1 Diagnostic Algorithm¶

Step 1: If a firm testicular mass is identified, a scrotal ultrasound should be performed.
Step 2: If ultrasound shows a solid mass, consider malignant until otherwise proven.
Step 3: Serum tumor markers (AFP, hCG, LDH) should be measured.
Step 4: Prompt referral to urology should be performed if a testicular GCT is suspected.
Step 5: The initial treatment for most patients suspected of having a testicular GCT is radical inguinal orchiectomy with removal of the testicle and spermatic cord to the level of the internal inguinal ring.
Step 6: In patients who present with metastatic disease and the diagnosis of GCT is certain, orchiectomy may be deferred until completion of chemotherapy.
Step 7: Serum tumor markers should be obtained before and after orchiectomy.

7. MANAGEMENT & TREATMENT¶

Treatment of testicular GCT is based on two factors: (1) whether the tumor is seminoma or nonseminomatous GCT and (2) the stage of the patient.
This is summarized in Figure 93-1.
Stage I • SEMINOMA: About 70% of newly diagnosed patients with seminoma present with stage I disease. This is defined as no evidence of metastatic disease on imaging of the chest, abdomen, and pelvis.
Approximately 15% of patients with stage I seminoma have metastatic disease at the microscopic level, usually in the retroperitoneum.
Historically, patients with stage I seminoma were treated with a course of adjuvant radiation therapy to the paraaortic lymph nodes.
While still an option, this is not usually performed because of concerns for late radiation-induced secondary malignancies.
Active surveillance is the most common approach elected by these patients following orchiectomy.
With active surveillance, interval physical examination and CT scan of the abdomen are performed.
For the 15% of patients who develop metastatic disease during active surveillance, treatment is curative in nearly all.
A third option for clinical stage I seminoma is adjuvant chemotherapy with carboplatin monotherapy for one or two cycles.
While effective in decreasing the risk of recurrence, most patients are cured by orchiectomy alone, and therefore, the additional treatment is unnecessary.
In addition, long-term data on toxicity are not available.
Stage I • NONSEMINOMATOUS GCTS: About 40% of newly diagnosed patients with nonseminomatous GCTs present with stage I disease.
Because nonseminomatous GCTs have an increased potential for invasion and metastasis, spread to the retroperitoneum and beyond is more common than with seminoma.
If pre-orchiectomy serum tumor markers are elevated, these must normalize after orchiectomy to be considered stage I.
Patients with persistently elevated or rising serum tumor markers after orchiectomy have stage IS disease and should be treated with cisplatin-based chemotherapy.
If the tumor is limited to testis without lymphovascular invasion, the risk of recurrence is approximately 20%.
However, if the tumor has high-risk features including lymphovascular invasion, invasion of the spermatic cord, or invasion of the scrotum, the risk of recurrence is ~50% or higher.
Historically, a prophylactic retroperitoneal lymph node dissection (RPLND) was performed.
This surgery is not only diagnostic but also therapeutic.
In fact, most patients who undergo prophylactic RPLND will never require chemotherapy.
While still an option, this approach subjects many patients to unnecessary major abdominal surgery.
RPLND is also associated with sterility.
Approximately 30% of newly diagnosed testicular GCT patients have severe oligospermia or azoospermia.
For the remainder with normal baseline spermatogenesis who receive cisplatin-based chemotherapy, all will be azoospermic at the completion of therapy.
Approximately 80% of these patients will recover spermatogenesis over a period of several years.
For this reason, prechemotherapy sperm banking should be offered to all patients treated with chemotherapy.
Active surveillance is frequently performed especially for patients without lymphovascular invasion.
Most patients who relapse will be treated with cisplatin-based chemotherapy and achieve cure rates approaching 100%.
Active surveillance can also be employed for patients with higher risk features, although the risk of progression is significantly higher.
For this reason, some advocate adjuvant cisplatin-based chemotherapy with BEP (bleomycin, etoposide, cisplatin) for one cycle for these patients.
Other centers favor a prophylactic RPLND.
Almost all patients who present with stage I nonseminomatous GCTs will achieve cure.
Stage II • SEMINOMA: Approximately 15–20% of newly diagnosed patients with seminoma present with stage II disease.
Patients are subgrouped into IIA, IIB, or IIC based on the size of the retroperitoneal nodes (≤2 cm, >2 to 5 cm, or >5 cm, respectively).
Patients with stage IIA disease are usually treated with 'dogleg' radiation therapy, which includes the paraaortic and ipsilateral iliac nodes.
Cisplatin-based chemotherapy may also be considered.
Stage IIB disease is treated with cisplatin-based chemotherapy or, in select patients, radiation therapy.
Most patients with stage IIB and IIC disease are best initially managed with cisplatin-based chemotherapy.
Stage II • NONSEMINOMATOUS GCTS: Approximately 15% of newly diagnosed patients with nonseminomatous GCTs present with clinical stage II disease.
Patients with stage IIA disease may be treated with primary RPLND.
Alternatively, these patients may be treated with cisplatin-based chemotherapy.
Patients with stage IIB and IIC disease are best initially managed with cisplatin-based chemotherapy.
Stage III: Patients who present with stage III GCT (seminoma or nonseminomatous GCT) are treated with cisplatin-based chemotherapy.
These patients are classified into good-, intermediate-, or poor-risk categories using the International Germ Cell Consensus Classification system, which is based on clinical factors including histology, site of primary, the presence of nonpulmonary visceral metastatic disease, and the level of postorchiectomy serum tumor markers (Table 93-1).
Most patients with stage III GCT present with good-risk disease and >90% will be cured.
The remainder present with intermediate-risk or poor-risk disease associated with 5-year survival rates of ~80% and 50%, respectively.
Select patients with rapidly progressive metastatic disease and life-threatening symptoms such as hemoptysis in whom there is a high clinical suspicion of GCT should emergently initiate cisplatin-based chemotherapy, even without a tissue diagnosis.
Chemotherapy: The development of cisplatin-based chemotherapy represents an important advance in cancer medicine.
Through a series of carefully performed clinical trials with the aim of maximizing cure while minimizing the extent of treatment, the chemotherapy approach to the treatment of these patients has been standardized.
Patients with good-risk metastatic GCT are treated with either three cycles of BEP or four cycles of etoposide and cisplatin (EP).
Patients with intermediate- and poor-risk metastatic disease are treated with either four cycles of BEP or four cycles of etoposide, ifosfamide, and cisplatin (VIP).
Maintaining dose and schedule is important, as dose modifications and delays have been associated with inferior outcomes.
Serum tumor markers should be monitored throughout treatment and should normalize during or after treatment.
Cisplatin-based chemotherapy is associated with myelosuppression, nausea and vomiting, and alopecia.
Cisplatin may result in nephrotoxicity, ototoxicity, and peripheral neuropathy.
Bleomycin may result in pulmonary toxicity, and risk factors for this include age >40, renal failure, tobacco use, and the cumulative dose of bleomycin received.
For patients at increased risk of bleomycin-induced pneumonitis, non–bleomycin-containing regimens as noted above may be given.
Cisplatin-based chemotherapy is also associated with sterility.
Approximately 30% of newly diagnosed testicular GCT patients have severe oligospermia or azoospermia.
For the remainder with normal baseline spermatogenesis who receive cisplatin-based chemotherapy, all will be azoospermic at the completion of therapy.
Approximately 80% of these patients will recover spermatogenesis over a period of several years.
For this reason, prechemotherapy sperm banking should be offered to all patients treated with chemotherapy.
Postchemotherapy Surgery: Upon completion of cisplatin-based chemotherapy, many patients with normalized serum tumor markers will have radiographic evidence of residual masses.
In approximately half of patients with nonseminomatous GCT, the residual mass is composed of necrosis and/or fibrosis.
About 40% will have residual teratoma, and only 10% will have residual viable nonteratomatous GCT.
Unfortunately, radiographic imaging cannot accurately differentiate between these entities.
For this reason, nonseminomatous GCT patients with residual masses after chemotherapy undergo resection of all sites of disease.
This most commonly includes a postchemotherapy RPLND.
However, thoracotomy and neck dissection are required in some patients.
Given the complexity of this surgery, patients should be referred to highly experienced centers.
If the patients are found to have residual necrosis or teratoma, no additional therapy is required.
However, for patients with residual viable nonteratomatous GCT, two additional cycles of chemotherapy may be considered.
It should be noted that in most centers, patients with minimal residual tumors defined as retroperitoneal lymph nodes of ≤1 cm forego postchemotherapy RPLND.
Patients who experience normalization of serum tumor markers with first-line chemotherapy but have enlarging tumors, most often cystic masses in the retroperitoneum, may have growing teratoma syndrome.
These patients are best approached with surgery.

7.1 Stage-Based Management¶

Treatment of testicular GCT is based on two factors: (1) whether the tumor is seminoma or nonseminomatous GCT and (2) the stage of the patient.
This is summarized in Figure 93-1.

Table 1 — Table 93-1 International Germ Cell Consensus Classification System¶

Risk Group	Seminoma Criteria	NSGCT Criteria
Good	Any primary site; and normal AFP, any hCG, any LDH; and nonpulmonary visceral metastases absent	Gonadal or retroperitoneal primary; and nonpulmonary visceral metastases absent; and AFP <1000 ng/mL; and hCG <5000 mIU/mL; and LDH <1.5 × ULN
Intermediate	Any primary site; and normal AFP, any hCG, any LDH; and nonpulmonary visceral metastases absent; and one of the following: HCG 5000–50,000 mIU/mL; or AFP 1000–10,000 ng/mL; or LDH 1.5–10 × ULN	Gonadal or retroperitoneal primary; and nonpulmonary visceral metastases absent; and one of the following: HCG 5000–50,000 mIU/mL; or AFP 1000–10,000 ng/mL; or LDH 1.5–10 × ULN
Poor	N/A	Mediastinal primary; or nonpulmonary visceral metastases present; or one of the following: AFP >10,000 ng/mL; or HCG >50,000 mIU/mL; or LDH >10 × ULN

Table 2 — Stage-Based Management of Testicular Germ Cell Tumor¶

Stage	Substage	Seminoma Treatment	NSGCT Treatment
Stage I	IA (Testis only, no lymphovascular invasion)	Active surveillance; or Adjuvant carboplatin × 1 or 2 cycles; or Adjuvant para-aortic RT	Active surveillance; or Nerve-sparing RPLND; or Adjuvant BEP × 1 cycle
Stage I	IB (Testis only, with lymphovascular invasion or invasion of spermatic cord or scrotum)	Active surveillance; or Adjuvant carboplatin × 1 or 2 cycles; or Adjuvant para-aortic RT	Active surveillance; or Adjuvant BEP × 1 cycle; or Nerve-sparing RPLND
Stage IS	Elevated serum tumor markers post-orchiectomy	BEP × 3 cycles; or EP × 4 cycles	BEP × 3 cycles; or EP × 4 cycles
Stage II	IIA (N1: nodes ≤ 2 cm)	Para-aortic and ipsilateral iliac RT; or BEP × 3 cycles or EP × 4 cycles; or Nerve-sparing RPLND in select patients	Nerve-sparing RPLND; or BEP × 3 cycles or EP × 4 cycles
Stage II	IIB (N2: nodes > 2 to 5 cm)	BEP × 3 cycles or EP × 4 cycles; or Para-aortic and ipsilateral iliac RT	BEP × 3 cycles or EP × 4 cycles +/– postchemotherapy RPLND
Stage II	IIC (N3: nodes > 5 cm)	BEP × 3 cycles or EP × 4 cycles	BEP × 3 cycles or EP × 4 cycles +/– postchemotherapy RPLND
Stage III	IIIA (good-risk)	BEP × 3 cycles; or EP × 4 cycles; +/– Postchemotherapy surgery	BEP × 3 cycles; or EP × 4 cycles; +/– Postchemotherapy surgery
Stage III	IIIB (intermediate-risk)	BEP × 4 cycles; or VIP × 4 cycles	BEP × 4 cycles; or VIP × 4 cycles
Stage III	IIIC (poor-risk)	N/A	BEP × 4 cycles; or VIP × 4 cycles

8. PROGNOSIS & COMPLICATIONS¶

Most patients with stage III GCT present with good-risk disease and >90% will be cured.
The remainder present with intermediate-risk or poor-risk disease associated with 5-year survival rates of ~80% and 50%, respectively.
Approximately 20–30% of patients with metastatic GCTs treated with cisplatin-based chemotherapy will not achieve durable disease control.
Most of these patients will experience disease progression within 2 years following completion of chemotherapy.
The International Prognostic Factors Study Group developed a risk stratification classification system for patients in first relapse.
Contributors to a worsened prognosis include NSGCT histology, extragonadal primary, incomplete response to first-line chemotherapy, time to relapse of 3 months or less, level of serum tumor markers at relapse, and the presence of nonpulmonary visceral metastatic disease.

8.1 Relapsed Disease¶

Approximately 20–30% of patients with metastatic GCTs treated with cisplatin-based chemotherapy will not achieve durable disease control.
Most of these patients will experience disease progression within 2 years following completion of chemotherapy.
The International Prognostic Factors Study Group developed a risk stratification classification system for patients in first relapse.
Contributors to a worsened prognosis include NSGCT histology, extragonadal primary, incomplete response to first-line chemotherapy, time to relapse of 3 months or less, level of serum tumor markers at relapse, and the presence of nonpulmonary visceral metastatic disease.

8.2 Fertility¶

Cisplatin-based chemotherapy is associated with sterility.
Approximately 30% of newly diagnosed testicular GCT patients have severe oligospermia or azoospermia.
For the remainder with normal baseline spermatogenesis who receive cisplatin-based chemotherapy, all will be azoospermic at the completion of therapy.
Approximately 80% of these patients will recover spermatogenesis over a period of several years.
For this reason, prechemotherapy sperm banking should be offered to all patients treated with chemotherapy.

9. SPECIAL CONSIDERATIONS¶

For patients with residual viable nonteratomatous GCT, two additional cycles of chemotherapy may be considered.
It should be noted that in most centers, patients with minimal residual tumors defined as retroperitoneal lymph nodes of ≤1 cm forego postchemotherapy RPLND.
Patients who experience normalization of serum tumor markers with first-line chemotherapy but have enlarging tumors, most often cystic masses in the retroperitoneum, may have growing teratoma syndrome.
These patients are best approached with surgery.

9.1 Postchemotherapy Surgery¶

Upon completion of cisplatin-based chemotherapy, many patients with normalized serum tumor markers will have radiographic evidence of residual masses.
In approximately half of patients with nonseminomatous GCT, the residual mass is composed of necrosis and/or fibrosis.
About 40% will have residual teratoma, and only 10% will have residual viable nonteratomatous GCT.
Unfortunately, radiographic imaging cannot accurately differentiate between these entities.
For this reason, nonseminomatous GCT patients with residual masses after chemotherapy undergo resection of all sites of disease.
This most commonly includes a postchemotherapy RPLND.
However, thoracotomy and neck dissection are required in some patients.
Given the complexity of this surgery, patients should be referred to highly experienced centers.
If the patients are found to have residual necrosis or teratoma, no additional therapy is required.
However, for patients with residual viable nonteratomatous GCT, two additional cycles of chemotherapy may be considered.
It should be noted that in most centers, patients with minimal residual tumors defined as retroperitoneal lymph nodes of ≤1 cm forego postchemotherapy RPLND.
Patients who experience normalization of serum tumor markers with first-line chemotherapy but have enlarging tumors, most often cystic masses in the retroperitoneum, may have growing teratoma syndrome.
These patients are best approached with surgery.

10. KEY PEARLS & CLINICAL TRAPS¶

Transscrotal aspiration or biopsy of a testicular mass should never be performed.
Such scrotal violation may result in tumor seeding of the scrotum or inguinal lymph nodes.
A solid mass identified on ultrasound should be considered malignant until otherwise proven.
Seminomas never secrete AFP.
A patient with a seminoma with elevation of AFP should be approached as having a nonseminomatous GCT.
Approximately 95% of newly diagnosed patients with testicular GCTs will be cured.
Testicular cancer has been called a model for a curable neoplasm.

10.1 Diagnostic Clues¶

A painless testicular mass is the primary landing zone of left paraaortic lymph nodes inferior to the left renal vessels.
A solid mass identified on ultrasound should be considered malignant until otherwise proven.
On ultrasound, a testicular GCT is hypoechoic and may be multifocal.
Transscrotal aspiration or biopsy of a testicular mass should never be performed.
Such scrotal violation may result in tumor seeding of the scrotum or inguinal lymph nodes.

Flowcharts & Algorithms¶

Reproduced from Harrison's 22nd Edition.

Flowchart 1¶

Stage-based management of testicular germ cell tumor

Caption: FIGURE 93-1 Stage-based management of testicular germ cell tumor.

Figures & Illustrations¶

Reproduced from Harrison's 22nd Edition.

Figure 1¶

(Continued) *— Figure 93-1: Stage-based management of testicular germ cell...

Caption: FIGURE 93-1 (Continued) — Figure 93-1: Stage-based management of testicular germ cell tumor. The algorithm stratifies treatment options (Active Surveillance, Adjuvant Chemotherapy, Radiation Therapy, Retroperitoneal Lymph Node Dissection, or Cisplatin-based Chemotherapy) based on tumor type (Seminoma vs. Nonseminomatous GCT) and clinical stage (I, II, III).

Generated from Harrison's Principles of Internal Medicine, 22nd Edition.