Testicular Cancer

Archetype B 19 regimens (Main Regimens) testicular

Seminoma and non-seminomatous germ cell tumours

DefinitionClick to collapse

The provided source text is the NCCN Clinical Practice Guidelines in Oncology for Testicular Cancer, Version 2.2026. This document does not contain a definition for Soft Tissue Sarcoma. The source exclusively covers testicular germ cell tumors, including seminoma and nonseminoma subtypes, their diagnosis, staging, and treatment.

EpidemiologyClick to collapse

The source provides epidemiological data for testicular cancer, not Soft Tissue Sarcoma. Testicular cancer accounts for <1% of new cancer cases, with a majority diagnosed between ages 20 and 34. The global incidence has been rising, with an estimated 9,810 new cases and 630 deaths projected in the United States in 2026. The 5-year relative survival rate is approximately 94%.

SubtypesClick to collapse

Molecular PathogenesisClick to collapse

The source does not describe the molecular pathogenesis of Soft Tissue Sarcoma. It provides limited information on the genetic basis of testicular germ cell tumors, noting that the 2016 WHO classification introduced germ cell neoplasia in situ (GCNIS) as a precursor lesion and distinguished between GCNIS-derived (postpubertal) and unrelated (prepubertal) tumors. Specific driver mutations or pathways for testicular germ cell tumors are not detailed in the provided text.

Risk FactorsClick to collapse

Clinical FeaturesClick to collapse

Typical Presentation

Testicular cancer most often presents as a painless or painful testicular nodule, mass, enlargement, or induration (hardening). Many patients present with testicular discomfort or swelling suggestive of epididymitis or orchitis. Germ cell tumors (GCTs) comprise 95% of malignant tumors arising in the testes and are broadly categorized into two main histologic subtypes: seminoma and nonseminoma. Seminomas and nonseminomas typically occur at about the same rate, but nonseminomas tend to be more aggressive and often include multiple cell types. The four types of nonseminomas are embryonal carcinoma, choriocarcinoma, yolk sac tumor, and teratoma. Most nonseminomas are mixed tumors of these four subtypes. Testicular cancer accounts for <1% of new cancer cases with a majority of patients being diagnosed between the ages of 20 and 34 years. The global incidence has been steadily rising over the past several decades, with an estimated 9,810 new cases projected in the United States in 2026 [MS-2]. Several risk factors have been identified, including personal or family history of testicular cancer and cryptorchidism [MS-2]. An estimated 630 deaths will occur from testicular cancer in the United States in 2026, reflecting the excellent 5-year relative survival rate (~94%) [MS-2].

Symptoms

Most frequent presenting symptom
Painless testicular nodule or mass

Most common presentation; a firm, hard mass within the testis that may be painless or painful.

Common
Testicular discomfort or swelling

Often mistaken for or suggestive of epididymitis or orchitis; patients may have received a trial of antibiotics which is never warranted in a suspicious mass but can be considered in pain without a mass.

Common
Testicular induration (hardening)

Hardening of the testicular tissue detected on physical examination.

Common
Testicular enlargement

Diffuse or focal enlargement of the testis.

Less common
Gynecomastia

Breast enlargement may occur due to hormonal effects of hCG-producing tumors.

Less common; more typical of advanced disease
Low back or flank pain

May indicate retroperitoneal lymphadenopathy from metastatic disease.

Uncommon; indicates advanced disease
Supraclavicular lymphadenopathy

Enlarged lymph nodes of the lower neck or upper chest, indicating lymphatic spread.

Uncommon; indicates advanced disease
Retroperitoneal mass symptoms

Abdominal fullness, nausea, or early satiety from large retroperitoneal nodal masses.

Rare
Neurologic symptoms

Headache, seizures, focal deficits, or altered mental status may indicate brain metastases.

Uncommon; indicates advanced disease
Symptoms of disseminated disease

Weight loss, fatigue, dyspnea from pulmonary metastases, bone pain from skeletal metastases.

Signs

Most common sign
Palpable testicular mass

Firm, often painless mass on physical examination; the most characteristic sign.

Common
Testicular induration or enlargement

Hardening or enlargement of the testis on palpation.

Less common
Gynecomastia

Bilateral breast enlargement on physical examination.

Uncommon; indicates metastatic disease
Supraclavicular lymphadenopathy

Palpable lymphadenopathy in the supraclavicular fossa.

Uncommon; indicates advanced disease
Abdominal or retroperitoneal mass

Palpable abdominal mass on examination.

Red FlagsClick to collapse

InvestigationsClick to collapse

Diagnostic

History and physical examination

Initial evaluation to identify testicular mass, lymphadenopathy, gynecomastia, and symptoms of disseminated disease.

Testicular ultrasound with Doppler

Confirm presence of a testicular mass, determine if intra- or extratesticular, and evaluate the contralateral testis. Should be performed if testicular cancer is considered. Transscrotal biopsies should NOT be performed as scrotal violation increases risk of local recurrence.

Serum alpha-fetoprotein (AFP)

Mandatory serum tumor marker. AFP is associated with yolk sac tumors but can also be elevated in embryonal carcinoma or teratoma. Seminomas do NOT produce AFP; elevated AFP in histologic pure seminoma indicates nonseminomatous elements. Expected half-life is 5-7 days. Mildly elevated non-rising levels <20 ng/mL may not indicate GCT. Used for staging, prognosis, and monitoring treatment response.

Serum beta-human chorionic gonadotropin (beta-hCG)

Mandatory serum tumor marker. Most commonly elevated marker in testicular cancer. Can be elevated in both seminomatous and nonseminomatous tumors. Expected half-life is ≤3 days. Used for staging, prognosis, and monitoring treatment response. Further workup needed before treatment for mildly elevated beta-hCG (generally <20 IU/L) as hypogonadism, hyperthyroidism, cannabis use, and heterophile antibodies can cause false-positive results.

Serum lactate dehydrogenase (LDH)

Mandatory serum tumor marker for risk stratification when starting first-line chemotherapy. Less specific than AFP and beta-hCG. Not generally used to monitor for relapse due to false-positive elevations. Important for IGCCCG risk classification. Should not be used alone to make treatment decisions when mildly elevated (<2.5 x ULN).

Chemistry profile

Baseline assessment including renal function (GFR) which is relevant for bleomycin and cisplatin dosing, and liver function. Consider measuring baseline levels of gonadal function.

Radical inguinal orchiectomy

Gold standard for diagnosis and initial management of suspected testicular cancer. Provides histopathologic diagnosis and pathologic staging (pT). Trans-scrotal orchiectomy is discouraged due to higher rates of local recurrence. May consider testis-sparing surgery (partial orchiectomy) in select patients (bilateral tumors, solitary testicle with adequate function).

Testis-sparing surgery (TSS) / partial orchiectomy

Can be considered in select patients: equivocal mass in bilateral otherwise normal testes, synchronous bilateral tumors, solitary testicle with adequate gonadal function. Frozen section of tumor and surrounding parenchyma by experienced genitourinary pathologist should be performed. Higher risk of local recurrence; continued surveillance needed.

Staging

Abdomen/pelvis CT scan with contrast

Essential for assessing retroperitoneal lymph nodes, which are the primary site of metastatic spread. Should be performed unless done prior to orchiectomy. Recommended within 4 weeks prior to initiation of chemotherapy, RPLND, or RT to confirm staging, even if scan was performed previously. For stage I seminoma, pelvis should be included in imaging for patients with discontinuous spermatic cord invasion (pT3) due to higher risk of pelvic relapse.

Abdomen/pelvis MRI with and without contrast

Alternative to CT for staging assessment. Can be considered for surveillance instead of CT (TRISST trial demonstrated noninferiority of MRI to CT for stage I seminoma surveillance). MRI protocol should include visualization of retroperitoneal and pelvic nodes. Use same imaging modality throughout surveillance.

Chest x-ray

Part of standard staging workup. May be used for routine follow-up. In stage I seminoma and nonseminoma, routine chest x-ray may have limited value for detecting relapse — studies show relapses detected by rising markers and/or CT rather than chest x-ray alone. Chest CT with contrast is preferred in presence of thoracic symptoms.

Chest CT with contrast

Recommended if abdomen/pelvis CT/MRI or chest x-ray shows evidence of metastatic disease. Should be performed at baseline if supradiaphragmatic disease present. Preferred over chest x-ray in presence of thoracic symptoms.

Brain MRI with and without contrast

Indicated if clinically indicated based on: beta-hCG >5,000 IU/L, non-pulmonary visceral metastases, extensive lung metastases, neurologic symptoms, AFP >10,000 ng/mL, predominance of choriocarcinoma. Patients with post-orchiectomy serum beta-hCG >5,000 IU/L are at increased risk of brain metastases.

FDG-PET/CT (skull base to mid-thigh)

NOT indicated for initial staging of testicular GCTs. Should NOT be used for staging nonseminoma. In seminoma, may be considered for evaluating residual masses >3 cm after primary chemotherapy (at least 6 weeks post-chemotherapy). Negative FDG-PET/CT is very reassuring. Positive results should lead to resection or biopsy consideration. Not indicated for residual masses ≤3 cm. Has no role in assessing treatment response in nonseminoma post-chemotherapy.

Scrotal ultrasound (repeat)

Should be repeated to rule out contralateral testis mass if not conducted in the last 3 months, particularly for stage IS workup and in patients with bilateral testicular abnormalities, cryptorchidism, or marked atrophy.

Biomarkers

Serum alpha-fetoprotein (AFP)

Essential for staging, prognosis, and treatment monitoring. Seminomas do NOT produce AFP; elevated AFP indicates nonseminomatous elements. Expected half-life is 5-7 days. Decisions to treat should not be based solely on AFP values <20 ng/mL. AFP is most associated with yolk sac tumors but can also be elevated in embryonal carcinoma or teratoma.

Serum beta-human chorionic gonadotropin (beta-hCG)

Essential for staging, prognosis, and treatment monitoring. Most commonly elevated marker. Quantitative analysis of beta subunit. Expected half-life is ≤3 days. Mildly elevated beta-hCG (generally <20 IU/L) requires further workup as hypogonadism, hyperthyroidism, cannabis use, and heterophile antibodies can cause false positives.

Serum lactate dehydrogenase (LDH)

Used for IGCCCG risk classification at initiation of first-line chemotherapy. Not generally used to monitor for relapse due to false-positive elevations. LDH is a less specific marker compared to AFP and beta-hCG. For good-risk seminoma, LDH >2.5 x ULN is associated with worse prognosis.

Molecular testing (NGS and IHC)

Recommended for third-line therapy to assess eligibility for pan-cancer, tumor-agnostic, biomarker-directed therapies for patients with actionable mutations. Should include both next-generation sequencing (NGS) and immunohistochemistry (IHC) testing.

StagingClick to collapse

AJCC 8th Edition TNM Staging Classification (2017) with serum marker (S) component unique to testicular cancer

T Categories

StageDescription
cTXPrimary tumor cannot be assessed
cT0No evidence of primary tumor
cTisGerm cell neoplasia in situ
cT4Tumor invades scrotum with or without vascular/lymphatic invasion
pTXPrimary tumor cannot be assessed
pT0No evidence of primary tumor
pTisGerm cell neoplasia in situ
pT1Tumor limited to testis (including rete testis invasion) without lymphovascular invasion. Substage pT1a: tumor smaller than 3 cm. Substage pT1b: tumor 3 cm or larger.
pT2Tumor limited to testis (including rete testis invasion) with lymphovascular invasion OR tumor invading hilar soft tissue or epididymis or penetrating visceral mesothelial layer covering the external surface of tunica albuginea with or without lymphovascular invasion
pT3Tumor directly invades spermatic cord soft tissue with or without lymphovascular invasion. NOTE: The Panel recommends staging tumors with discontinuous invasion of the spermatic cord as pT3 (high-risk stage I) and NOT as M1 (stage III) as recommended by the 8th edition AJCC [ST-1, MS-5, MS-17].
pT4Tumor invades scrotum with or without lymphovascular invasion

N Categories

StageDescription
cNXRegional lymph nodes cannot be assessed
cN0No regional lymph node metastasis
cN1Metastasis with a lymph node mass 2 cm or smaller in greatest dimension OR multiple lymph nodes, none larger than 2 cm in greatest dimension
cN2Metastasis with a lymph node mass larger than 2 cm but not larger than 5 cm in greatest dimension OR multiple lymph nodes, any one mass larger than 2 cm but not larger than 5 cm in greatest dimension
cN3Metastasis with a lymph node mass larger than 5 cm in greatest dimension
pNXRegional lymph nodes cannot be assessed
pN0No regional lymph node metastasis
pN1Metastasis with a lymph node mass 2 cm or smaller in greatest dimension and less than or equal to five nodes positive, none larger than 2 cm in greatest dimension
pN2Metastasis with a lymph node mass larger than 2 cm but not larger than 5 cm in greatest dimension; or more than five nodes positive, none larger than 5 cm; or evidence of extranodal extension of tumor
pN3Metastasis with a lymph node mass larger than 5 cm in greatest dimension

M Categories

StageDescription
M0No distant metastases
M1Distant metastases
M1aNon-retroperitoneal nodal or pulmonary metastases
M1bNon-pulmonary visceral metastases

Stage Groupings

GroupCriteriaClinical MeaningFive Yr SurvivalTreatment Intent
Stage 0pTis N0 M0 S0Germ cell neoplasia in situ (GCNIS) — precursor lesionNonecurative
Stage IpT1-T4 N0 M0 SXDisease limited to the testis with normal post-orchiectomy markers. Overall survival for stage I approaches 100% regardless of management strategy.~100% overall survival for stage Icurative
Stage IApT1 N0 M0 S0Tumor limited to testis without lymphovascular invasion; normal post-orchiectomy markers~100%curative
Stage IBpT2, pT3, or pT4 N0 M0 S0Tumor with lymphovascular invasion, spermatic cord invasion, or scrotal invasion; normal post-orchiectomy markers~100%curative
Stage ISAny pT/TX N0 M0 S1-3Normal imaging but persistently elevated post-orchiectomy serum tumor markers indicating occult metastatic disease. Elevated tumor markers increase risk of disease outside retroperitoneum.Nonecurative
Stage IIAny pT/TX N1-3 M0 SXMetastatic disease to retroperitoneal lymph nodes without distant metastasesNonecurative
Stage IIAAny pT/TX N1 M0 S0 or S1Metastasis with lymph node mass 2 cm or smaller; low-volume nodal diseaseNonecurative
Stage IIBAny pT/TX N2 M0 S0 or S1Metastasis with lymph node mass 2-5 cm; moderate-volume nodal diseaseNonecurative
Stage IICAny pT/TX N3 M0 S0 or S1Metastasis with lymph node mass >5 cm; bulky nodal diseaseNonecurative
Stage IIIAny pT/TX Any N M1 SXDistant metastatic diseaseNonecurative
Stage IIIAAny pT/TX Any N M1a S0 or S1Non-retroperitoneal nodal or pulmonary metastases with low-to-normal tumor markersNonecurative
Stage IIIBAny pT/TX N1-3 M0 S2 OR Any pT/TX Any N M1a S2Moderate tumor marker elevation (LDH 1.5-10 x N, hCG 5,000-50,000, or AFP 1,000-10,000) with nodal or pulmonary metastasesNonecurative
Stage IIICAny pT/TX N1-3 M0 S3 OR Any pT/TX Any N M1a S3 OR Any pT/TX Any N M1b Any SHigh tumor marker elevation (LDH >10 x N, hCG >50,000, or AFP >10,000) or non-pulmonary visceral metastasesNonecurative

Staging Pearls

  • The AJCC TNM staging system incorporates serum tumor marker elevation as a distinct category (S), which is unique to this organ site [MS-5]
  • Stage I staging is pathologic (p) staging assigned after orchiectomy; clinical staging uses 'c' prefix [MS-5]
  • The 8th edition AJCC introduced invasion of epididymis and hilar soft tissue as pathologic criteria for T classification of stage I GCTs, but the Panel discourages using these for clinical decision-making as they have not been validated for relapse prediction — instead, the Panel recommends using lymphovascular invasion, spermatic cord invasion, and scrotal invasion as risk factors [MS-5]
  • The Panel recommends staging tumors with discontinuous spermatic cord invasion as pT3 (high-risk stage I) rather than pM1 (stage III) as recommended by the 8th edition AJCC, due to concern about overtreatment and lack of outcome difference data [ST-1, MS-5, MS-17]
  • If surveillance is elected for patients with discontinuous spermatic cord invasion, pelvis should be included in imaging due to higher risk of pelvic relapses [SEM-1, NSEM-1]
  • Mediastinal primary seminoma should be treated by risk status used for gonadal seminomas with etoposide/cisplatin for 4 cycles or bleomycin/etoposide/cisplatin for 3 cycles [SEM-1]
  • Mediastinal primary nonseminoma is poor-risk disease and should be treated with either VIP or BEP with careful pulmonary functioning monitoring [NSEM-1, MS-17]
  • Stage IIIB does not apply to pure seminomas — patients with elevated AFP have nonseminomas; in patients with serum beta-hCG >1,000 IU/L, consider possibility of nonseminoma, re-review surgical specimen with pathology, and consider discussion with a high-volume center [SEM-4, MS-7]
  • Beta-hCG alone should not be used to stage or risk stratify patients with pure seminoma; use of LDH to risk stratify metastatic seminoma is controversial [SEM-4, MS-7]
  • For select cases of clinical stage IIA disease with borderline retroperitoneal lymph nodes, waiting 4-8 weeks and repeating imaging (CT or MRI) to confirm staging before initiating treatment can be considered [SEM-3, NSEM-3]
  • Germ cell tumors are not graded [ST-3]
  • In 2016, the WHO tumor classification was modified: germ cell neoplasia in situ (GCNIS) is the recommended term for precursor lesions; spermatocytic seminoma was renamed spermatocytic tumor; reporting of anaplasia or distinguishing mature from immature teratoma is not required [MS-6]
  • Histologic grade (G) is not used for germ cell tumors [ST-3]
  • The 5-year overall survival for all testicular cancer is approximately 94% [MS-2]
  • The IGCCCG Update Model (2021) identified LDH >2.5 x ULN, increasing age, and presence of lung metastases as additional adverse prognostic factors [MS-7]

Management PrinciplesClick to collapse

Testicular germ cell tumors (GCTs) are highly curable malignancies requiring a multidisciplinary approach integrating surgery, systemic therapy, and radiation therapy based on histologic subtype (seminoma vs nonseminoma), stage, and risk classification. The NCCN Guidelines provide evidence-based recommendations for all stages of testicular GCTs with the goal of maximizing cure rates while minimizing unnecessary side effects, complications, and late toxicities. Testicular GCTs are broadly categorized into seminoma and nonseminoma subtypes, which have different natural histories and treatment approaches. When both seminoma and nonseminoma elements are present, management follows nonseminoma guidelines. Together, these guidelines aim to maximize the potential for cure and to avoid unnecessary side effects, complications, and late toxicities [MS-2].

Curative

All stages of testicular GCTs

The primary goal is cure with treatment intensity adapted to disease stage and risk. Stage I disease has cure rates approaching 100% regardless of management strategy. Even metastatic disease is cured in the majority of patients, with 5-year overall survival rates of 96% for good-risk disease, 89% for intermediate-risk, and 67% for poor-risk nonseminoma per IGCCCG update data [MS-23].

Risk-adapted treatment

Stage I nonseminoma

Risk factors for recurrence include lymphovascular invasion (LVI), invasion of spermatic cord, or invasion of scrotum. Some centers consider predominance of embryonal carcinoma as an additional risk factor. Surveillance is preferred for low-risk patients while all three options (surveillance, RPLND, or adjuvant BEP x1) should be carefully considered for high-risk patients [MS-18].

Risk-adapted treatment

Metastatic disease

IGCCCG risk classification guides first-line chemotherapy intensity: good-risk disease (3 cycles BEP or 4 cycles EP), intermediate-risk (4 cycles BEP preferred), and poor-risk (4 cycles BEP preferred or 4 cycles VIP for patients at risk for bleomycin toxicity) [TEST-D, TEST-E].

Multidisciplinary team involvement is essential. The guidelines recommend referral to high-volume centers for: patients with poor-risk disease [MS-23], residual masses with abnormal AFP and/or beta-hCG levels [NSEM-7], retroperitoneal lymph node dissection (RPLND) [TEST-H], post-chemotherapy RPLND in complex cases [TEST-H], brain metastases treatment planning [MS-28], and extragonadal germ cell tumors [TEST-D]. Shared decision-making with patients is recommended for stage IIA/IIB seminoma treatment options [SEM-3]. Social work referral is recommended considering social determinants of health that may affect treatment follow-through [SEM-1].

Performance status assessment guides treatment intensity. Poor-risk patients with mediastinal primary nonseminoma require VIP or BEP with careful pulmonary functioning monitoring [MS-17]. Bleomycin-free regimens should be considered in patients at increased risk for bleomycin toxicity including those with reduced GFR, older age, or lung disease [TEST-E]. G-CSFs should be used with high-risk febrile neutropenia regimens including TIP, VeIP, and VIP [TEST-F]. The guidelines do not provide specific performance status cutoffs but emphasize individualized treatment decisions.

Management PathwaysClick to collapse

Pure Seminoma Stage IA/IB: Primary Treatment After Orchiectomy

Branching: Pathologic stage (IA vs IB), Patient preference and ability to comply with surveillance, Risk factors including tumor size and rete testis invasion, Contraindications to specific treatments

Stage IA or IB pT1-pT3 seminoma after radical inguinal orchiectomy
Active Surveillance (strongly preferred) (preferred); Single-agent Carboplatin (AUC 7 x1 or x2 cycles) (other_recommended); Radiation Therapy (20 Gy preferred) (other_recommended)
For patients not choosing surveillance, adjuvant therapy options include single-agent carboplatin or radiation therapy. Both reduce relapse risk but carry potential late effects. Carboplatin has limited long-term follow-up data. RT associated with increased risk of secondary malignancies and non-cancer-related mortality [MS-10].
Pure Seminoma Stage IS: Evaluation and Treatment

Branching: Persistent elevation of serum tumor markers post-orchiectomy, Radiographic evidence of metastatic disease, Marker trajectory

Stage IS: persistent elevation of serum tumor markers post-orchiectomy with no radiographic evidence of metastatic disease
Repeat measurements and imaging (preferred); First-line Chemotherapy (preferred)
Pure Seminoma Stage IIA/IIB: Primary Treatment

Branching: Lymph node mass size (<3 cm vs 3-5 cm), Bulky vs non-bulky disease, Patient preference and shared decision-making, Borderline lymph nodes

Stage IIA/IIB non-bulky (largest node <3 cm transaxial long axis)
RT (para-aortic and ipsilateral iliac nodes, 30-36 Gy) (other_recommended); BEP x3 or EP x4 (preferred); Nerve-sparing RPLND (other_recommended); Carboplatin + RT (category 2B) (other_recommended)
For RPLND: pN0 surveillance; pN1 surveillance (preferred) or adjuvant chemotherapy; pN2 surveillance or adjuvant chemotherapy; pN3 surveillance (category 2B) or adjuvant chemotherapy (preferred) [SEM-3].
Stage IIA/IIB bulky (3-5 cm)
BEP x3 or EP x4 (preferred) (preferred)
Pure Seminoma Stage IIC/III: Primary Treatment Based on Risk

Branching: IGCCCG risk classification, Presence of non-pulmonary visceral metastases, LDH levels >2.5x ULN in good-risk patients

Good risk: Stage IIC or III without non-pulmonary visceral metastases
BEP x3 (category 1) or EP x4 (category 1) (preferred); VIP x4 (for bleomycin contraindication) (other_recommended)
Intermediate risk: Stage III with non-pulmonary visceral metastases (bone, liver, brain)
BEP x4 (category 1, preferred) or VIP x4 (category 1) (preferred)
Pure Seminoma Stage IIA/III Post First-Line Chemotherapy Management

Branching: Residual mass size (>3 cm vs ≤3 cm), Serum AFP and beta-hCG levels, FDG-PET/CT results

No residual mass or residual mass ≤3 cm with normal AFP and beta-hCG
Surveillance (preferred)
Residual mass >3 cm with normal serum AFP and beta-hCG
Consider FDG-PET/CT (skull base to mid-thigh, ≥6 weeks post-chemotherapy) (other_recommended)
FDG-PET/CT positive for viable seminoma
Resection or biopsy (preferred); Repeat imaging in 6-12 weeks (other_recommended)
If complete resection shows viable seminoma, consider 2 cycles adjuvant chemotherapy (EP or TIP or VIP or VeIP). If incomplete resection or positive biopsy, second-line chemotherapy [SEM-5].
Nonseminoma Stage I: Primary Treatment Based on Risk Factors

Branching: Presence of risk factors (LVI, spermatic cord invasion, scrotal invasion), Patient preference, Ability to comply with surveillance

Stage I without risk factors
Surveillance (preferred) (preferred); Nerve-sparing RPLND (other_recommended); Adjuvant BEP x1 cycle (other_recommended)
Stage I with risk factors (LVI, spermatic cord/scrotal invasion)
Surveillance (other_recommended); Adjuvant BEP x1 cycle (other_recommended); Nerve-sparing RPLND (other_recommended)
With risk factors, all three management options should be carefully considered. Surveillance or RPLND also recommended for pure teratoma with normal markers. RPLND preferred for somatic type malignancy [NSEM-2, MS-18].
Nonseminoma Stage IIA/IIB: Primary Treatment Based on Markers and Disease Distribution

Branching: Serum tumor marker levels, Lymph node size and distribution, Disease confined to landing zones vs aberrant drainage, Presence of somatic type malignancy

Stage IIA with normal markers
Nerve-sparing RPLND (preferred); BEP x3 or EP x4 (preferred)
Following RPLND: pN0 surveillance; pN1 surveillance preferred or EP x2; pN2 EP x2 preferred or surveillance; pN3 chemotherapy preferred or surveillance (2B). Surveillance preferred for pure teratoma [NSEM-5, MS-21].
Stage IIB with normal markers, disease confined to landing zone
BEP x3 or EP x4 (preferred); Nerve-sparing RPLND in highly selected cases (useful_in_certain_circumstances)
Stage IIA/IIB with persistent marker elevation or aberrant disease distribution
BEP x3 or EP x4 (preferred)
Nonseminoma Stage IS, IIC, IIIA-C, Brain Metastases: Risk-Stratified Primary Treatment

Branching: IGCCCG risk classification, Primary tumor site, Serum marker levels, Brain metastases presence

Good risk: Stages IS, IIA (S1), IIB (S1), IIC, IIIA
BEP x3 (category 1) or EP x4 (category 1) (preferred)
Intermediate risk: Stage IIIB
BEP x4 (category 1, preferred) or VIP x4 (category 1) (preferred)
Poor risk: Stage IIIC
BEP x4 (category 1, preferred) or VIP x4 (category 1) (preferred)
Brain metastases
First-line chemotherapy as for poor-risk disease +/- RT +/- surgery (preferred)
Nonseminoma Post-Chemotherapy Management of Partial Response

Branching: Residual mass size, Serum AFP and beta-hCG levels, Pathology of resected tissue, Marker kinetics

Negative markers with residual mass ≥1 cm
Nerve-sparing bilateral RPLND (preferred)
If teratoma or necrosis: surveillance. If embryonal/yolk sac/choriocarcinoma/seminoma: chemotherapy x2 cycles (EP or TIP or VIP or VeIP) preferred, or surveillance for select patients with <10% viable cancer [NSEM-7, MS-22].
Elevated and rising AFP and/or beta-hCG levels
Second-line therapy (preferred); Surgery in highly select cases (useful_in_certain_circumstances)
Elevated but stable AFP and/or beta-hCG levels
Close surveillance (other_recommended); Surgery in highly select cases (useful_in_certain_circumstances)
Mildly elevated and normalizing AFP and/or beta-hCG levels
Consider surgical resection of residual masses (preferred); Surveillance (for selected patients) (other_recommended)
If embryonal/yolk sac/choriocarcinoma/seminoma element: chemotherapy x2 cycles preferred. If teratoma/necrosis: surveillance [NSEM-7].
Recurrent Seminoma: Second-Line and Third-Line Therapy

Branching: Prior treatment history, Timing of relapse, Response to prior therapy

Prior first-line chemotherapy, recurrent seminoma
Clinical trial (other_recommended); Conventional-dose: VeIP x4 or TIP x4 (other_recommended); High-dose chemotherapy (other_recommended)
Prior first- and second-line conventional-dose chemotherapy
High-dose chemotherapy (preferred) (preferred); Clinical trial (other_recommended); Molecular testing for biomarker-driven therapy (other_recommended); Surgical treatment if resectable solitary site (useful_in_certain_circumstances)
Prior high-dose chemotherapy
Clinical trial (preferred) (preferred); Conventional-dose third-line chemotherapy (other_recommended); Molecular testing for biomarker-driven therapy (other_recommended)
Recurrent Nonseminoma: Second-Line and Third-Line Therapy

Branching: Prior treatment history, Timing of relapse (≤2 years vs >2 years), Resectability, Marker levels

Prior first-line chemotherapy, early relapse (≤2 years)
Clinical trial (other_recommended); Conventional-dose: VeIP x4 or TIP x4 (other_recommended); High-dose chemotherapy (other_recommended); Surgical treatment if resectable with normal/mildly elevated markers (useful_in_certain_circumstances)
Prior first-line chemotherapy, late relapse (>2 years)
Surgical treatment if resectable (preferred) (preferred); Clinical trial if unresectable (other_recommended); Chemotherapy: VeIP/TIP or high-dose (other_recommended)
Prior high-dose chemotherapy, recurrent disease
Clinical trial (preferred) (preferred); Conventional-dose third-line chemotherapy (other_recommended); Molecular testing for biomarker-driven therapy (other_recommended); Surgical treatment if solitary site (useful_in_certain_circumstances)

Pretreatment EvaluationClick to collapse

Initial evaluation
History and physical examination (H&P)
Essential initial evaluation for all patients with suspected testicular cancer [TEST-1].
Testicular ultrasound with Doppler
Should be performed when testicular cancer is being considered. Confirms presence of mass, determines intra- vs extratesticular location, explores contralateral testis. GCTs are typically heterogeneous, hypoechoic, and vascular [TEST-1, MS-3].
Serum tumor markers: AFP, beta-hCG, LDH
Must be assessed both before and after orchiectomy for prognosis and staging. For risk stratification in metastatic disease, levels should be measured on Day 1 of cycle one of first-line chemotherapy [TEST-1, MS-4].
Chemistry profile
Baseline assessment including consideration of baseline gonadal function levels [TEST-1].
Scrotal ultrasound to rule out contralateral testis mass
Repeat if not conducted in last 3 months [SEM-2, NSEM-2].
Staging imaging
Abdomen/pelvis CT with contrast or MRI with and without contrast
Should be performed within 4 weeks prior to initiation of chemotherapy, RPLND, or RT to confirm staging, even if previously performed [TEST-1, TEST-I].
Chest x-ray
Recommended as part of staging. Chest CT should be performed if abdomen/pelvis CT or chest x-ray is abnormal [TEST-1, TEST-I].
Brain MRI (with and without contrast)
If clinically indicated: beta-hCG >5000 IU/L, non-pulmonary visceral metastases, extensive lung metastasis, neurologic symptoms [TEST-1, SEM-1].
Pathologic diagnosis
Radical inguinal orchiectomy
Gold standard for diagnosis and initial management. Trans-scrotal orchiectomy is discouraged due to higher rates of local recurrence and altered pathways of metastatic dissemination [TEST-H, MS-5].
Testis-sparing surgery (partial orchiectomy) in select patients
May be considered for equivocal mass <2 cm with normal markers, synchronous bilateral tumors, solitary testicle with adequate gonadal function [TEST-H, MS-5].
Inguinal exploration of contralateral testis
Consider for bilateral testicular abnormalities or if testis is cryptorchid or shows marked atrophy [TEST-1].
Fertility and psychosocial
Sperm banking discussion
Recommended prior to chemotherapy, radiation therapy, or RPLND if fertility preservation desired. For single testicle and bilateral orchiectomy patients, recommend prior to orchiectomy [TEST-1, MS-5].
Testicular prosthesis discussion
Should be discussed prior to radical inguinal orchiectomy [TEST-1].
Social work referral
Consider referral to social work. Refer to NCCN Distress Thermometer and Problem List, which includes social determinants of health [SEM-1, NSEM-1].
Gonadal function baseline assessment
Consider measuring baseline levels of gonadal function given higher rates of hypogonadism in testicular cancer population [TEST-1, MS-4].

SurgeryClick to collapse

Radical inguinal orchiectomy is the gold standard for diagnosis and initial management of suspected testicular cancer. Retroperitoneal lymph node dissection (RPLND) serves both diagnostic and therapeutic roles for staging and treatment of retroperitoneal disease.

Radical inguinal orchiectomy is the gold standard; trans-scrotal orchiectomy is discouraged due to scrotal violation associated with higher local recurrence rates and altered metastatic dissemination pathways [TEST-H].

When patient presents with rapidly increasing beta-hCG or AFP, metastatic disease on imaging, and symptoms of disseminated disease, chemotherapy can be initiated immediately without waiting for orchiectomy. However, radical inguinal orchiectomy should be performed at completion of chemotherapy [TEST-H].

Testis-sparing surgery (TSS) can be considered in select patients through inguinal approach with frozen section analysis [TEST-H].

Sperm banking should be discussed with reproductive age patients prior to any therapeutic intervention that may compromise fertility [TEST-H].

For equivocal mass <2 cm with normal AFP and beta-hCG, short-interval imaging can be considered prior to partial orchiectomy [TEST-H].

Use of testicular prosthesis should be discussed prior to radical inguinal orchiectomy [TEST-H].

Procedures

Radical inguinal orchiectomy

Primary treatment for most patients with suspicious testicular mass on ultrasound [TEST-H, MS-5].

Nerve-sparing retroperitoneal lymph node dissection (RPLND)

Primary RPLND for stage I nonseminoma and select stage II; post-chemotherapy RPLND for residual retroperitoneal masses in nonseminoma [TEST-H, MS-18].

Testis-sparing surgery (partial orchiectomy)

Select patients: equivocal mass <2 cm with normal markers, synchronous bilateral tumors, solitary testicle with adequate gonadal function [TEST-H].

Post-chemotherapy RPLND

Residual retroperitoneal mass (>1 cm on axial imaging) following systemic chemotherapy with normalized serum tumor markers in nonseminoma [TEST-H, MS-22].

Surgical resection of residual masses

Residual masses after second-line chemotherapy with normal markers [NSEM-9].

Radiation TherapyClick to collapse

RT is used in the management of pure seminoma for adjuvant treatment of stage I disease and primary treatment of stage IIA/IIB non-bulky disease. It is not used for nonseminoma management.

Principles

  • Modern radiotherapy involves smaller fields and lower doses than historically used [TEST-C].
  • CT-based AP-PA 3D-CRT has lower Dmean and D50% for kidneys, liver, and bowel compared to IMRT. IMRT is not necessary. Proton therapy can be considered [TEST-C].
  • RT should start once orchiectomy wound has fully healed. Patients treated 5 days per week [TEST-C].
  • Antiemetic prophylaxis encouraged at least 2 hours prior to each treatment [TEST-C].
  • Discussion of semen analysis and sperm banking prior to treatment if clinically indicated [TEST-C].
  • Non-contrast CT simulation with patient supine, arms at sides, in treatment position [TEST-C].
  • All patients except those with bilateral orchiectomy should be treated with scrotal shield [TEST-C].
  • Linear accelerators with >6 MV photons should be used when possible [TEST-C].

Dose Frameworks

NameTotal DoseDose Per FractionFractionsScheduleIndications
Stage I Seminoma Adjuvant RT20 Gy (preferred), 25.5 Gy, 19.8 Gy, or 21.6 Gy2.0 Gy, 1.5 Gy, 1.8 Gy, or 1.8 Gy respectively10, 17, 11, or 12 respectivelyDaily fractions over 2-3.5 weeksAdjuvant treatment for stage I seminoma after orchiectomy [TEST-C].
Stage IIA Seminoma RT30 Gy (1-2 cm disease)1.8-2.0 GyApproximately 16-17 fractionsTwo consecutive phases: modified dog-leg fields to 20-25.5 Gy then cone downClinical stage IIA seminoma with non-bulky disease [TEST-C].
Stage IIB Seminoma RT36 Gy (2-3 cm disease)1.8-2.0 GyApproximately 20 fractionsTwo consecutive phases: modified dog-leg fields to 20-25.5 Gy then cone downClinical stage IIB seminoma with non-bulky disease [TEST-C].

Approaches

NameDose FractionationConcurrent ChemotherapyIndicationKey TrialToxicities
Para-aortic Strip Fields RT (Stage I)20 Gy in 10 fractions of 2.0 Gy each (preferred) or alternative schedulesNoneStage I seminoma adjuvant treatmentMRC TE18/EORTC 30942 trial comparing 20 Gy vs 30 Gy showing no difference in relapse rates [MS-10]Late toxicities including secondary malignancies, potential cardiovascular effects. Long-term follow-up studies indicate increased late toxicities with RT [MS-10].
Modified Dog-Leg Fields + Cone Down (Stage IIA/B)Initial phase: 20-25.5 Gy; Cone down to 30 Gy (IIA) or 36 Gy (IIB)None (separate approach from chemotherapy)Clinical stage IIA/IIB seminomaClassen et al trial establishing standard field arrangements [MS-14]Acute: nausea, fatigue, diarrhea. Late: secondary malignancies, potential cardiovascular effects [MS-14]
Carboplatin + Involved-Node RT (SAKK 01/10)Single-dose carboplatin followed by involved-node RTSequential, not concurrentStage IIA/IIB seminoma (category 2B)SAKK 01/10: 3-year PFS 93.7% [SEM-3, MS-14]Grade 3-4: neutropenia 4%, thrombocytopenia 3%, vomiting 1%. No treatment-related deaths or late toxic effects reported [MS-14]

Systemic TherapyClick to collapse

Systemic therapy is the primary treatment for metastatic germ cell tumors and is based on cisplatin combination chemotherapy. The IGCCCG risk classification system guides treatment intensity. For stage I nonseminoma, adjuvant chemotherapy with one cycle of BEP reduces relapse risk. Testicular GCTs are highly chemosensitive with cure rates of approximately 90% for good-risk disease [MS-23].

Stage I Nonseminoma Adjuvant
5-year relapse rate 3.2% with LVI, 1.6% without LVI. Survival exceeds 98%. One cycle preferred due to lower toxicity compared to 2 cycles [MS-18].
Preferred: BEP x1 cycle
Stage IS Nonseminoma
Elevated tumor markers indicate occult metastatic disease requiring systemic therapy [NSEM-2].
Preferred: BEP x3 or EP x4 (good-risk regimens)
Stage IIA/IIB Nonseminoma (normal markers)
Standard first-line chemotherapy for good-risk metastatic disease [NSEM-3].
Preferred: BEP x3 or EP x4
Good-Risk Metastatic (Stages IS, IIA-IIC, IIIA)
Both are category 1 preferred regimens with approximately 90% cure rate. No statistically significant difference in OS (96% vs 92%; P=.096) [MS-23].
Preferred: BEP x3 (category 1) or EP x4 (category 1)
Intermediate-Risk Metastatic (Stage IIIB)
Approximately 70% cure rate [MS-23].
Preferred: BEP x4 (category 1, preferred)
Poor-Risk Metastatic (Stage IIIC)
Less than 50% achieve durable complete response. Referral to high-volume center recommended [MS-23].
Preferred: BEP x4 (category 1, preferred)
Good-Risk Metastatic Seminoma
Standard treatment for good-risk seminoma. Consider intensification for LDH >2.5x ULN [MS-15].
Preferred: BEP x3 or EP x4
Intermediate-Risk Metastatic Seminoma
Stage IIIC with non-pulmonary visceral metastases [MS-15].
Preferred: BEP x4 (preferred) or VIP x4
Second-Line Chemotherapy (Relapsed GCTs)
Preferred conventional-dose regimens. High-dose chemotherapy based on retrospective data showing superiority over conventional-dose [MS-25].
Preferred: TIP x4 or VeIP x4 (conventional-dose) or high-dose chemotherapy
Third-Line Chemotherapy
Clinical trial preferred for patients who received prior high-dose chemotherapy [SEM-8, NSEM-10].
Preferred: High-dose chemotherapy (if not previously received) or clinical trial

Key Regimens

BEP
Etoposide 100 mg/m2 IV Days 1-5 + Cisplatin 20 mg/m2 IV Days 1-5 + Bleomycin 30 units IV Weekly on Days 1, 8, 15 or Days 2, 9, 16
EP
Etoposide 100 mg/m2 IV Days 1-5 + Cisplatin 20 mg/m2 IV Days 1-5
VIP
Etoposide 75 mg/m2 IV Days 1-5 + Ifosfamide 1200 mg/m2 IV Days 1-5 with mesna protection + Cisplatin 20 mg/m2 IV Days 1-5
TIP
Paclitaxel 250 mg/m2 IV Day 1 + Ifosfamide 1500 mg/m2 IV Days 2-5 with mesna protection + Cisplatin 25 mg/m2 IV Days 2-5
VeIP
Vinblastine 0.11 mg/kg IV Days 1-2 + Ifosfamide 1200 mg/m2 IV Days 1-5 with mesna protection + Cisplatin 20 mg/m2 IV Days 1-5
High-dose Carboplatin/Etoposide
Carboplatin 700 mg/m2/day IV Days -5, -4, -3 + Etoposide 750 mg/m2/day IV Days -5, -4, -3
TI-CE High-Dose
Paclitaxel 200 mg/m2 IV over 24 hours Day 1 + Ifosfamide 2000 mg/m2 IV over 4 hours with mesna Days 2-4
Gemcitabine/Oxaliplatin/Paclitaxel
Gemcitabine 800 mg/m2 IV over 30 min Days 1 and 8 + Paclitaxel 80 mg/m2 IV over 60 min Days 1 and 8 + Oxaliplatin 130 mg/m2 IV over 2 hours Day 1
Gemcitabine/Oxaliplatin
Gemcitabine 1000-1250 mg/m2 IV over 30 min Days 1 and 8 + Oxaliplatin 130 mg/m2 IV over 2 hours Day 1
Gemcitabine/Paclitaxel
Gemcitabine 1000 mg/m2 IV over 30 min Days 1, 8, 15 + Paclitaxel 100 mg/m2 IV over 60 min Days 1, 8, 15
Oral Etoposide
Etoposide 50-100 mg PO Daily Days 1-21

Treatment Response AssessmentClick to collapse

Title

Treatment Response Assessment for Testicular GCTs

Timing

Post-chemotherapy response assessment with CT scan with contrast or MRI with and without contrast of chest, abdomen, pelvis should be performed within 1 month of completing chemotherapy. FDG-PET/CT should be performed at least 6 weeks following completion of chemotherapy when indicated. For surveillance, imaging schedules vary by stage and treatment modality [TEST-I, TEST-A, TEST-B].

SurveillanceClick to collapse

ComplicationsClick to collapse

Supportive CareClick to collapse

PrognosisClick to collapse

Follow UpClick to collapse

Key TrialsClick to collapse

Clinical PearlsClick to collapse

Special SituationsClick to collapse

Guidelines ResourcesClick to collapse

Protective FactorsClick to collapse

The source does not mention any protective factors for Soft Tissue Sarcoma. The provided text focuses solely on the diagnosis and management of testicular germ cell tumors and does not discuss preventive measures or protective factors for any soft tissue malignancy.