Testicular Cancer

Risk factors:

• History of cryptorchidism (undescended testis)

• Family history of testicular cancer

• Personal history of testicular cancer

Initial work up:

• Testicular ultrasound

• Tumor markers: AFP, hCG, LDH

• Do not biopsy testis.

• Radical inguinal orchiectomy (through inguinal incision, not scrotum)

• Brain MRI recommended if:

  • Neurologic symptoms

  • Post-orchiectomy beta-hCG > 5000

  • Extensive lung metastases

  • Non-pulmonary visceral metastases

  • AFP >10000 (non-seminoma)

  • Predominant choriocarcinoma component (non-seminoma)

• isochromosome 12p is a hallmark cytogenetic abnormality in testicular germ cell tumors

  • It is a somatic genetic abnormality/ Not considered a hereditary predisposition factor

Types:

• Seminoma:

  • More likely to present with localized disease, indolent growth, less likely to be metastatic beyond RP nodes

• Non seminoma:

  • Embryonal Carcinoma, Choriocarcinoma, Yolk Sac Tumor (endodermal sinus tumor), Teratoma

Tumor Markers:

• AFP:

  • NOT produced by seminomas (if high, assume non-seminoma)

  • Half life ~7 days

  • May be elevated due to liver disease/toxicity. 

  • Generally ignore if <20-25 ng/mL

• B-HCG:

  • Can be made by any germ cell tumor. 

  • Half life ~3 days. 

  • Can have false positives from hyperthyroidism, marijuana consumption or in hypogonadism from pituitary HCG production (can test this by administering testosterone. if coming down, then not from cancer).

• LDH:

  • Very non-specific. used for staging purposes, but not very important in response to treatment or relapse.

Risk Stratification:

Risk Status	Nonseminoma	Seminoma
Good Risk	Testicular or retroperitoneal primary tumor + No nonpulmonary visceral metastases + Post-orchiectomy markers (all): AFP <1000, hCG <5,000, LDH < 1.5 ×ULN	Any primary site + No nonpulmonary visceral metastases + Normal AFP, any hCG, any LDH
Intermediate Risk	Testicular or retroperitoneal primary tumor + No nonpulmonary visceral metastases + Post-orchiectomy markers (any): AFP 1,000–10,000, hCG 5,000–50,000, LDH 1.5–10 ×ULN	Any primary site + Nonpulmonary visceral metastases + Normal AFP, any hCG, any LDH
Poor Risk	Mediastinal primary tumor OR Nonpulmonary visceral metastases OR Post-orchiectomy markers (any): AFP >10,000, hCG >50,000, LDH >10 ×ULN	No patients classified as poor prognosis

Seminoma Testicular Cancer

AFP is normal in seminomas.

Treatment:

• Stage IA, IB (limited to testes):

  • Radical inguinal orchiectomy followed by:  

    • Surveillance - preferred approach

    • Adjuvant Carboplatin (AUC/Area Under Curve 7) x1-2 cycles

    • Adjuvant radiation to retroperitoneum (consider risk of secondary cancers in younger patients)

  • Consider adjuvant treatment if “high risk” features for recurrence, specifically rete testis invasion or tumor size > 4cm.

  • Monitor tumor markers to ensure downtrended

• Stage IS (limited to testis but have persistent elevation of tumor markers after orchiectomy)

  • Tumor marker elevation after orchiectomy generally indicates presence of metastatic disease despite radiographic evidence of disease, thus treat like stage III (see below)

  • Treat as good/intermediate risk based of how high tumor markers are

  • CAP CT with contrast

• Stage IIA Seminoma (spread to RP nodes, <3cm)

  • RT to para-aortic and ipsilateral LNs

  • BEP x 3, or EP x 4

    • BEP: Bleomycin + Etoposide + Cisplatin

  • Nerve sparing RPLND

• Stage IIB Seminoma (spread to RP nodes, >3 cm)

  • BEP x3, or EP x 4

• Stage IV:

  • Treatment is same for seminomas and nonseminomas

  • Chemo regimen based on risk stratification (Table above):

    • Good risk: BEP x3 cycles, or EP x4 cycles

    • Intermediate/Poor risk: BEP x4 cycles, or VIP x4 cycles (if contraindication to Bleomycin)

• Residual Masses >3 cm:

  • PET CT and resect if FDG avid

  • If residual mass is present after completion of treatment: perform PET/CT and likely surgery (if FDG avid). The mass may be teratoma vs fibrosis/necrosis.

    • About 10-15% of resected residual masses harbor viable germ cell tumor

• Late relapse (> 2 years after completion of chemo)

  • Consider surgery if resectable

  • Consider VeIP or TIP x 4

  • Consider high dose chemotherapy

Non-Seminoma Testicular Cancer

• Stage I:

  • Radical inguinal orchiectomy followed by:  

    • Surveillance (preferred)

    • BEP x 1

    • RPLND

  • RT is NOT an option for non-seminoma.

  • Consider adjuvant treatment if “high risk” features for recurrence, specifically lymphovascular invasion, predominant embryonal carcinoma >50%, histology, Invasion of spermatic cord or scrotum

  • Monitor tumor markers to ensure downtrended

• Stage II:

  • RPLND → if malignant nodes, consider adjuvant EP x2

  • BEP x3 or EP x4

• Stage IV:

  • Treatment is same for seminomas and nonseminomas

  • Chemo based on risk stratification (Table above):

    • Good risk: BEP x3 cycles, or EP x4 cycles

    • Intermediate/Poor risk: BEP x4 cycles, or VIP x4 cycles (if contraindication to Bleomycin)

  • Later Line therapies:

    • TIP: Paclitaxel, Ifosfamide, Cisplatin

    • VeIP: Vinblastine, Etoposide, Ifosfamide, Cisplatin

    • High-Dose chemo:

      • Carboplatin/Etoposide x2 cycles

      • Paclitaxel/Ifosfamide/Carboplatin/Etoposide x3 cycles

    • Pembrolizumab (MSI-high, dMMR, TMB high)

    • HSCT

• Residual Masses >3 cm:

  • Resect RPLND: all NSGCT residual masses MUST be resected.

    
    
  
  

  Clinical Pearls

• Check tumor markers immediately prior to initiation of treatment for risk stratification.

• It is unlikely to be a seminoma if AFP is elevated, regardless of what pathology says.

• Beta-hCG can be mildly elevated in hypogonadism, hyperthyroidism, marijuana use.

• Avoid bleomycin in patients with underlying lung disease, elderly, reduced GFR

  • If bleomycin toxicity develops: complete course with EP or change to VIP

  • Bleomycin does not cause neutropenia. Typically G-CSF is not needed and would treat through myelosuppression

• Testicular cancer is associated with cryptorchidism