# 22 - 93 Testicular Cancer

### 93 Testicular Cancer

following patients as they are treated with various forms of therapy. 
Asymptomatic patients do not require treatment regardless of the size 
of the gland, while those with an inability to urinate, gross hematuria, 
recurrent infection, or bladder stones require evaluation and treat­
ment. In patients with symptoms, uroflowmetry can identify those 
with normal flow rates who are unlikely to benefit from treatment, and 
bladder ultrasound can identify those with high postvoid residuals who 
may need intervention. Pressure-flow (urodynamic) studies detect pri­
mary bladder dysfunction. Cystoscopy is recommended if hematuria 
is documented and to assess the urinary outflow tract before surgery. 
Imaging of the upper tracts is advised for patients with hematuria, a 
history of calculi, or prior urinary tract problems.

Symptomatic relief is the most common reason patients seek treat­
ment for BPH, and therefore, symptomatic relief is usually the goal of 
therapy for BPH. α-Adrenergic receptor antagonists are thought to treat 
the dynamic aspect of BPH by reducing sympathetic tone of the blad­
der outlet, thereby decreasing resistance and improving urinary flow. 
5ARIs are thought to treat the static aspect of BPH by reducing prostate 
volume and having a similar, albeit delayed effect. 5ARIs have also 
proven beneficial in the prevention of BPH progression, as measured 
by prostate volume, the risk of developing acute urinary retention, and 
the risk of having BPH-related surgery. The use of an alpha-adrenergic 
receptor antagonist and a 5ARI as combination therapy seeks to provide 
symptomatic relief while preventing progression of BPH.
PART 4
Oncology and Hematology
Another class of medications that has shown improvement in 
LUTS secondary to BPH is phosphodiesterase-5 (PDE5) inhibitors, 
used currently in the treatment of erectile dysfunction. All four of the 
PDE5 inhibitors available in the United States—sildenafil, vardenafil, 
tadalafil, and avanafil—appear to be effective in the treatment of LUTS 
secondary to BPH. The use of PDE5 inhibitors is not without con­
troversy, however, given the fact that short-acting phosphodiesterase 
inhibitors such as sildenafil need to be dosed separately from alpha 
blockers such as tamsulosin because of potential hypotensive effects.
Symptoms due to BPH often coexist with symptoms due to overac­
tive bladder, and the most common pharmacologic agents for the treat­
ment of overactive bladder symptoms are anticholinergics. This has led 
to multiple studies evaluating the efficacy of anticholinergics for the 
treatment of LUTS secondary to BPH.
Surgical therapy is now considered second-line therapy and is usu­
ally reserved for patients after a trial of medical therapy. The goal of 
surgical therapy is to reduce the size of the prostate, effectively reduc­
ing resistance to urine flow. Surgical approaches include TURP, trans­
urethral incision, or removal of the gland via a retropubic, suprapubic, 
or perineal approach. Also used are transurethral ultrasound–guided 
laser-induced prostatectomy (TULIP), stents, and hyperthermia.
■
■FURTHER READING
Bergengren O et al: 2022 Update on prostate cancer epidemiology 
and risk factors: A systematic review. Eur Urol 84:191, 2023.
Deek MP et al: Multi-institutional analysis of metastasis-directed ther­
apy with or without androgen deprivation therapy in oligometastatic 
castration-sensitive prostate cancer. Eur Urol Oncol 7:1403, 2024. 
Donovan JL et al: Patient-reported outcomes 12 years after localized 
prostate cancer treatment. NEJM Evid 2:EVIDoa2300018, 2023. Erra­
tum in: NEJM Evid 2:EVIDx2300122, 2023.
Eastham JA et al: Clinically localized prostate cancer: AUA/ASTRO 
Guideline. J Urol 208:505, 2022.
Fendler WP et al: Assessment of 68Ga-PSMA-11 PET accuracy in 
localizing recurrent prostate cancer: A prospective single-arm clinical 
trial. JAMA Oncol 5:856, 2019.
Haile ES et al: Medical management of benign prostatic hyperplasia. 
Cleve Clin J Med 91:163, 2024.
Hamdy FC et al: Fifteen-year outcomes after monitoring, surgery, or 
radiotherapy for prostate cancer. N Engl J Med 388:1547, 2023.
Hugosson J et al: Prostate cancer screening with PSA and MRI fol­
lowed by targeted biopsy only. N Engl J Med 387:2126, 2022.
Hussain M et al: Survival with olaparib in metastatic castration-

resistant prostate cancer. N Engl J Med 383:2345, 2020.

Kasivisvanathan V et al: MRI-targeted or standard biopsy for 

prostate-cancer diagnosis. N Engl J Med 378:1767, 2018.
Merseburger AS et al: Genomic testing in patients with metastatic 
castration-resistant prostate vancer: A pragmatic guide for clinicians. 
Eur Urol 79:519, 2021.
Morgan TM et al: Salvage therapy for prostate cancer: AUA/ASTRO/
SUO guideline part I: Introduction and treatment decision-making at 
the time of suspected biochemical recurrence after radical prostatec­
tomy. J Urol 211:509, 2024.
Pinsky PF, Parnes H: Screening for prostate cancer. N Engl J Med 
388:1405, 2023.
Roach M 3rd et al: Prostate cancer, race, and health disparity: What we 
know. Cancer J 29:328, 2023.
Sartor O et al: Lutetium-177-PSMA-617 for metastatic castrationresistant prostate cancer. N Engl J Med 385:1091, 2021.
Virgo KS et al: Initial management of noncastrate advanced, recurrent, 
or metastatic prostate cancer: ASCO guideline update. J Clin Oncol 
39:1274, 2021.
David J. Vaughn

Testicular Cancer
Testicular germ cell tumors (GCTs) represent 95% of all testicular neo­
plasms. 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.”
INCIDENCE AND GLOBAL 
CONSIDERATIONS
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.
■
■EPIDEMIOLOGY
Testicular GCT is the most common malignancy diagnosed in adoles­
cent 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%. Interestingly, the risk of GCT is higher in male siblings 
than in offspring of the patient. Although epidemiologic studies have 
been performed attempting to identify a relationship with environmental 
exposures, no conclusive causal links have been established.
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 crypt­
orchidism have approximately a four- to sixfold increased risk of 
developing testicular GCT. Orchidopexy before puberty decreases but 
does not eliminate this risk. Interestingly, the contralateral descended 
testis is also at risk for this disease. Men undergoing infertility evalu­
ation in which a testicular biopsy demonstrates germ cell neoplasia 
in situ have a significant risk of developing GCT. Although scrotal 
ultrasound of patients with testicular GCT may demonstrate testicular 
microcalcifications that may be related to germ cell neoplasia in situ, 
the significance of testicular microcalcifications in the general popula­
tion is unclear.
■
■BIOLOGY
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 malig­
nant GCT have not been fully determined. However, 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.
■
■PATHOLOGY
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 repre­
sent ∼50% of cases. 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 exqui­
sitely sensitive to both chemotherapy and radiation therapy. Nonsemi­
nomatous GCTs are most commonly diagnosed in the third decade of 
life. The histologic subtypes include embryonal carcinoma, yolk sac 
tumor, choriocarcinoma, and teratoma. Embryonal carcinoma is the 
most undifferentiated nonseminomatous GCT subtype with the poten­
tial 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. These nonseminomatous GCT subtypes are all considered 
chemotherapy sensitive. Teratoma is composed of somatic cell types 
that are derived from two or more germinal layers (endoderm, meso­
derm, and ectoderm). Teratomas are classified as mature, in which 
cell types resemble normal adult somatic tissue; immature, in which cell 
types resemble fetal somatic tissue; and malignant, in which the cell 
types have undergone malignant transformation into the malignant 
counterpart of the somatic tissue. Teratomas are chemotherapy resis­
tant and must be treated surgically.
■
■INITIAL PRESENTATION
Signs and Symptoms 
Although a painless testicular mass is 
pathognomonic of a GCT, most patients present with testicular swell­
ing, firmness, discomfort, or a combination of these. The differential 
diagnosis may include epididymitis or orchitis, and a trial of antibacte­
rials 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. Diagnostic 
delay is not uncommon and may be associated with a more advanced 
stage at diagnosis.
Physical Examination 
Careful examination of the affected testis 
and 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. Inguinal 

lymphadenopathy is rare. Most patients with lung metastases will have 
normal auscultation of the lungs.

Diagnostic Testing 
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.
Serum Tumor Markers 
Serum AFP, hCG, and lactate dehydro­
genase (LDH) should be measured in patients suspected of testicular 
GCT. AFP is elevated in ∼60–70% of patients who present with non­
seminomatous 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 condi­
tion 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 cho­
riocarcinoma may have markedly elevated levels of hCG. The half-life 
for hCG is 24–36 h. False-positive elevation of hCG may be seen sec­
ondary to hypogonadism, marijuana use, or because of interfering sub­
stances 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.
CHAPTER 93
Testicular Cancer
■
■INITIAL MANAGEMENT
Inguinal Orchiectomy 
Prompt referral to urology should be 
performed if a testicular GCT is suspected. The initial treatment for 
most patients suspected of having a testicular GCT is radical ingui­
nal orchiectomy with removal of the testicle and spermatic cord to 
the level of the internal inguinal ring. In patients who present with 
metastatic disease and the diagnosis of GCT is certain, orchiectomy 
may be deferred until completion of chemotherapy. Although some 
institutions perform testis-sparing surgery in select patients, the gold 
standard remains radical inguinal orchiectomy. Pathologic examina­
tion of the entire testicle is important, since testicular GCTs may be 
multifocal. Given the rarity of this cancer, review by an experienced 
pathologist is essential for accurate tumor classification. Serum tumor 
markers should be obtained before and after orchiectomy.
Staging 
The staging of testicular GCT is based on an understanding 
of the pattern of spread. The initial spread is by the lymphatic route to the 
retroperitoneal lymph nodes. A left-sided testicular GCT spreads first to 
the primary landing zone of left paraaortic lymph nodes inferior to the 
left renal vessels. A right-sided testicular GCT spreads first to the primary 
landing zone of the aortocaval nodes inferior to the right renal vessels. 
Nodal metastases may extend into the iliac regions. If scrotal violation 
occurred, inguinal lymph node metastases may be seen. Subsequent 
lymphatic spread is to the retrocrural, mediastinal, and supraclavicular 
lymph nodes. Hematogenous spread to the lung is the next most com­
mon site of metastasis. Metastases to the liver, bone, and brain are less 
common. Patients with newly diagnosed testicular GCTs should undergo 
computed tomography (CT) scan of the abdomen and pelvis. Chest x-ray 
should be performed. 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.

The American Joint Committee on Cancer tumor-node-metastasis 
(TNM) staging classification is used. There are three main stages of 
testicular GCT. Stage I is limited to the testis; stage II involves the ret­
roperitoneal lymph nodes; and stage III includes lymph node involve­
ment beyond the retroperitoneum and/or distant metastatic disease.

■
■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 Fig. 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 retroperito­
neum. 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.
PART 4
Oncology and Hematology
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 com­
mon 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 mark­
ers 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 chemo­
therapy. While still an option, this approach subjects many patients 
to unnecessary major abdominal surgery. RPLND is also associated 
with a small risk of retrograde ejaculation due to nerve injury, and 
nerve-sparing techniques have been developed. 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 sur­
veillance can also be employed for patients with higher risk features, 
although the risk of progression is significantly higher. For this rea­
son, 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 diag­
nosed patients with seminoma present with stage II disease. Patients 
are subgrouped into IIA, IIB, or IIC based on the size of the retroperi­
toneal nodes (≤2 cm, >2 to 5 cm, or >5 cm, respectively). Patients with 
stage IIA disease are usually treated with “dogleg” radiation therapy 
(referring to the shape of the radiation field), which includes the para­
aortic 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 

treated with radiation therapy who relapse will subsequently be cured 
with cisplatin-based chemotherapy. RPLND has been considered in 
select patients with stage IIA and nonbulky stage IIB seminoma in an 
effort to avoid chemotherapy and radiation therapy. For patients with 
stage IIC disease, cisplatin-based chemotherapy should be used.
NSGCTS  Approximately 15% of newly diagnosed patients with non­
seminomatous 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 chemother­
apy. 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). Maintain­
ing 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 bleomycininduced 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 differen­
tiate 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.

Testis
Seminoma
NSGCT
Stage IA
Testis only, no lymphovascular
invasion
Active surveillance; or
Adjuvant carboplatin × 1 or 2
cycles; or Adjuvant para-aortic RT
Stage 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
Stage IS
Elevated serum tumor markers postorchiectomy
BEP × 3 cycles; or
EP × 4 cycles
BEP × 3 cycles; or
EP × 4 cycles
A
Lymph
nodes
Seminoma
NSGCT
Stage IIA
N1: nodes ≤ 2 cm
Para-aortic and ipsilateral iliac RT; or
BEP × 3 cycles or EP × 4 cycles; 
Nerve-sparing RPLND in select 
patients
Stage 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 IIC
N3: nodes > 5 cm
BEP × 3 cycles or EP × 4 cycles
BEP × 3 cycles or EP × 4 cycles +/–
postchemotherapy RPLND
B
FIGURE 93-1  Stage-based management of testicular germ cell tumor.

Stage 1
CHAPTER 93
Active surveillance; or
Nerve-sparing RPLND; or
Adjuvant BEP × 1 cycle
Active surveillance; or
Adjuvant BEP × 1 cycle; or
Nerve-sparing RPLND
Testicular Cancer
Stage 2
Testis
Nerve-sparing RPLND; or
BEP × 3 cycles or EP × 4 cycles

Stage 3
Lungs
Liver
Lymph
nodes
Testis
PART 4
Oncology and Hematology
Seminoma
NSGCT
Stage IIIA
(good-risk)
BEP × 3 cycles;
or EP × 4 cycles
BEP × 3 cycles;
or EP × 4 cycles;
+/– Postchemotherapy surgery
Stage IIIB
(intermediate-risk)
BEP × 4 cycles; or
VIP × 4 cycles
BEP × 4 cycles; or
VIP × 4 cycles
+/– Postchemotherapy surgery
Stage IIIC
(poor-risk)
N/A
BEP × 4 cycles; or
VIP × 4 cycles
+/– Postchemotherapy surgery
Abbreviations: BEP, bleomycin, etoposide, cisplatin; EP, etoposide, cisplatin; N/A,
not applicable; NSGCT, nonseminomatous germ cell tumor; RPLND, retroperitoneal
lymph node dissection; RT, radiation therapy; VIP, etoposide, ifosfamide, cisplatin.
C
FIGURE 93-1  (Continued)
TABLE 93-1  International Germ Cell Consensus Classification System
RISK GROUP
SEMINOMA
NSGCT
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 
present
Gonadal or retroperitoneal primary; 
and nonpulmonary visceral 
metastases absent; and one of the 
following:
AFP 1000–10,000 ng/mL
HCG 5000–50,000 mIU/mL
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
HCG >50,000 mIU/mL
LDH >10 × ULN
Abbreviations: AFP, α-fetoprotein; hCG, human chorionic gonadotropin; LDH, lactate 
dehydrogenase; N/A, not applicable; NSGCT, nonseminomatous germ cell tumor; 
ULN, upper limit normal. Nonpulmonary visceral metastases include liver, bone, and 
brain.
Source: Reproduced with permission from International Germ Cell Cancer 
Collaborative Group: International Germ-Cell Consensus Classification: A prognostic 
factor based staging system for metastatic germ cell tumors. J Clin Oncol 15:594, 1997.

Brain
Bone
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 postchemo­
therapy 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.
For patients with metastatic seminoma, most residual masses are 
necrotic and do not harbor viable tumor. Patients with residual masses 
of 3 cm or less may be observed without surgery. For patients with 
residual masses >3 cm, fluorodeoxyglucose (FDG)-PET may be used to 
distinguish necrosis from viable seminoma and identify patients who 
should be considered for postchemotherapy surgery or short interval 
imaging.
■
■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 sys­
tem 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.