Testicular Cancer

Page updated Winter 2021.
DisclaimerMedicine is an ever-changing science.  We have been witnessing changes in diagnostic and therapeutic modalities and guidelines during last several years. We have used sources believe to be reliable for purpose of this website including AUA guidelines, EAU guidelines, NCCN guidelines, Campbell-Walsh-Wein Urology, UpToDate, Merck Manual, Lexi-Comp, FDA website, and other reputable resources. However, due to possibility of human error or changes in medicine, readers are required to confirm the information provided in this website with other sources. Readers are specially required to read all parts of the product information sheet included in the package of each drug they plan to administer and follow those instructions. Readers are also needed to follow instructions of FDA and other regulatory bodies and their own department in this regard. Authors can cite information provided in our textbooks or they need to cite the original resources. This website serves as a general framework. We and other users would adjust the approach per departments policies and patients situation. Forms can be used by other health care professionals.

Epidemiology

Germ cell tumor is the most common solid malignancy among males age 20 to 40 years.

Diagnosis:

Solid testicular mass: 

Any solid mass in the testis identified by physical exam or imaging should be treated as a malignant tumor until proven otherwise.

Scrotal ultrasound with doppler

CT scan/ MRI of the abdomen and pelvis with IV contrast 

Chest imaging.

Serum tumor markers before rrchiectomy:

We check AFP, hCG, and LDH before any treatments.

Serum tumor markers after orchiectomy:

If elevated before orchiectomy, we measure them again after orchiectomy.

Sperm Banking

We discuss sperm banking before treatment.

Radical Orchiectomy 

Radical inguinal orchiectomy will be performed next.

Germ Cell Neoplasm In Situ

Germ cell neoplasm in situ is a precursor lesion for germ cell tumor and is associated with a 50% risk of developing an invasive germ cell tumor within 5 years.

Radical orchiectomy or low-dose (≥ 20 Gy) RT is an effective treatment  for germ cell neoplasm in situ.

Stage Grouping

IA: pT1

IB: pT2-4

IS: S1-3

IIA: N1

IIB: N2

IIC:N3

IIIA: M1a

IIIB: M1a S2, or N1-3 S2

IIIC: M1a S3, or N1-3 S3, M1b

Risk classification non-seminoma 

Good prognosis

Testicular/retroperitoneal primary

No nonpulmonary visceral metastases

AFP <1000 ng/mL
HCG <5000 IU/L 
LDH <1.5 × upper limit of normal (N)

Intermediate prognosis

Testicular/retroperitoneal primary

No nonpulmonary visceral metastases

AFP ≥1000–10,000 ng/mL 
HCG ≥5000–50,000 IU/L 
LDH ≥1.5 × N and ≤10 × N

Poor  prognosis

Mediastinal primary or Nonpulmonary visceral metastases or

AFP >10,000 ng/mL or
HCG >50,000 IU/L (10,000 ng/mL) or
LDH >10 × upper limit of normal

Risk classification seminoma: 

Normal AFP

Good prognosis

No nonpulmonary visceral metastases

Intermediate prognosis

Nonpulmonary visceral metastases

Seminoma

Serum HCG is elevated in about 15% of patients with
metastatic seminoma. Unlike non-seminoma, serum tumor marker levels are not used to guide treatment decisions.

Stage I: Treatment options after orchiectomy are:

Surveillance (preferred), carboplatin x 1, RT (20 Gy)

Stage IS: Perform CT chest/abdomen/pelvis & manage accordingly

Stage IIA: RT (30 Gy) or Chemotherapy (BEP X 3 or EP X 4)

Stage IIB with a lymph node ≤3cm: 

Chemotherapy (BEP X 3 or EP X 4) or  RT (36 Gy)

Stage IIB seminoma with a lymph node >3 cm: 

Chemotherapy (BEP X 3 or EP X 4)

Stage IIC and III good risk: BEP X 3 or EP X 4

III intermediate risk (nonpulmonary visceral
metastases)BEP X 4 or VIP X 4

Residual masses > 3 cm after first-line chemotherapy: 

FDG-PET will be done. Patients with PET positive
residual masses should undergo surgical resection. 
Residual masses that are PET-negative or less than 3 cm can be safely observed after chemotherapy.

Teratoma at metastatic sites:
This is less common in seminoma compared to non-seminoma but should be considered in patients who fail to respond to chemotherapy.

Non Seminoma

Stage I: Surveillance (preferred) or RPLND or BEP X 1

RPLND: stage I non-seminoma who had teratoma with malignant transformation at orchiectomy.

We recommend active treatment (RPLND or chemotherapy) to those with lymphovascular invasion  and/or embryonal carcinoma predominance.

Stage IS: Chemotherapy: BEP X 3 or EP X 4

Stage IIA with normal post-orchiectomy AFP & HCG:  

RPLND or chemotherapy

Stage IIA S1: Chemotherapy: BEP X 3 or EP X 4

Stage: IIB: chemotherapy (BEP X 3 or EP X 4) for these patients. RPLND may be done in highly selected patients.

Stage IIB S1: Chemotherapy: BEP X 3 or EP X 4

IIC, and IIIA: Chemotherapy: BEP X 3 or EP X 4

IIIB and IIIC: BEP X 4 or VIP X 4

Post RPLND management:

pN0: surveillance

pN1: surveillance (preferred) or BEP X 2 or EP X 2

pN2: BEP X 2 or EP X 2

pN2: BEP X 3 or EP X 4

pN1-3 pure teratoma: surveillance is preferred.

Post-chemo residual masses with normal tumor markers:

Resect if ≥ 1 cm and tumor markers are negative.

Next step is going to be per resected pathology:

Teratoma or necrosis: surveillance

Other germ cells: 2 cycles of EP or TIP or VIP or VeIP 

Post-chemo residual masses with elevated tumor markers:

Mildly elevated and normalizing: manage like masses with normal tumor markers.

Elevated but stable: Close surveillance. Manage accordingly

Elevated and rising: Second line therapy

Second line therapy:

If relapse occurs <2 years, consider chemo. Surgery is an option for a single mass.

Conventional chemotherapy regimen: TIP or VeIP

High dose chemotherapy regimen:

Carboplatin/ etoposide or P-ICE

Relapse occurs > 2 years, consider surgery, if respectable.




RPLND

Cephalad extent of the dissection: 

Level of the renal arteries.

Caudad extent of the dissection: 

The crossing of the ureter over the ipsilateral common iliac artery.

Right modified template: 

We omit the para-aortic lymph nodes below the inferior mesenteric artery

Left modified template: 

We omit paracaval, precaval, and retrocaval lymph nodes.

Full bilateral template dissection: 

We recommend this if there is suspicious lymph nodes on CT, or during the surgery or when the primary tumor is teratoma.

Nerve-sparing: 

Is appropriate for selected patients who want to preserve their ejaculation.

Gonadal vessels: 

Ipsilateral ones should be removed.

Retrocrural Dissection

May be considered at the time of RPLND.

Nephrectomy

It is the most common auxiliary procedure.

Major Vascular Reconstruction

In some series, 15% of patients needed vascular procedures. This included aortic resection, cavotomy/caval resection, iliac resection, and renovascular resection with repair.

Primary reconstruction of the IVC is preferred if possible.

Small vessel wall injuries may be repaired via patch
venoplasty or with bovine/porcine pericardial grafts.

PTFE or Dacron grafts may be used.

Liver Resection

RPLND in patients with liver involvement is usually done after first, second or  third-line chemotherapy. All lesions including residual liver masses should be resected at this time.

Thoracic Masses

These masses should be addressed after RPLND is done.

All masses > 1 cm should be considered for resection unless the retroperitoneum only had fibrosis.


Brain metastases

Primary chemo ± RT ± Surgery
Brain metastases are associated with choriocarcinoma and
should be suspected in any patient with a very high serum
HCG level. Patients with choriocarcinoma of the brain are at risk of bleeding and should be monitored for this when chemotherapy is started.

Chemotherapy Regimens

BEP

Bleomycin + etoposide + cisplatin

EP

Etoposide + cisplatin

VIP 

Etoposide + Ifosfamide + Cisplatin

TIP 

Paclitaxel + ifosfamide + cisplatin

VeIP

Vinblastine + ifosfamide +cisplatin (Platinol).

Carboplatin + etoposide

P-ICE

Paclitaxel + ifosfamide + carboplatin + etoposide