Nonseminoma Testicular Cancer Treatment Protocols 

Updated: Jan 17, 2014
  • Author: Kush Sachdeva, MD; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
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Treatment Protocols

Treatment protocols for nonseminoma testicular cancer are provided below, including recommendations for treatment of stage I-III disease, second-line recommendations for metastatic disease, and recommendations for persistent or recurrent disease.

Treatment recommendations for stage I nonseminoma testicular cancer

Stage IA:

  • Recommendations after orchiectomy include surveillance in compliant patients or use of nerve-sparing retroperitoneal lymph node dissection (RPLND)
  • If the dissected lymph nodes are not involved with a tumor (pN0), there is no need for adjuvant chemotherapy after RPLND
  • If resected lymph nodes do involve the tumor, a decision must be made as to whether to give adjuvant chemotherapy based on degree of nodal involvement; chemotherapy is preferred in patients with pN2 or pN3 disease [1]
  • Recommended chemotherapy includes 2 cycles of EP ( etoposide 100 mg/m 2 IV on days 1-5 plus  cisplatin 20 mg/m 2 IV on days 1-5; every 21d) or
  • BEP ( bleomycin 30 U IV on days 1, 8, and 15 plus  etoposide 100 mg/m 2 IV on days 1-5 plus  cisplatin 20 mg/m 2 IV on days 1-5; every 21d) [2]

Stage IB:

  • Treatment recommendations after orchidectomy include nerve-sparing RPLND or chemotherapy
  • Chemotherapy includes 2 cycles of BEP (bleomycin 30 U IV on days 1, 8, and 15 plus  etoposide 100 mg/m 2 IV on days 1-5 plus  cisplatin 20 mg/m 2 IV on days 1-5; every 21d) or
  • One cycle of BEP (bleomycin 30 U IV on days 1, 8, and 15 plus  etoposide 100 mg/m 2 IV on days 1-5 plus  cisplatin 20 mg/m 2 IV on days 1-5 or
  • Surveillance for compliant patients with T2 disease
  • Adjuvant therapy after a nerve-sparing RPLND is the same as in stage IA

Stage IS:

  • There is a persistent marker elevation in patients in this stage; patients are treated with 4 cycles of EP [3] (etoposide 100 mg/m 2 IV on days 1-5 plus  cisplatin 20 mg/m 2 IV on days 1-5; every 12d [3] ) or
  • 3 cycles of BEP (bleomycin 30 U IV on days 1, 8, and 15 plus  etoposide 100 mg/m 2 IV on days 1-5 plus  cisplatin 20 mg/m 2 IV on days 1-5; every 21d)

Treatment recommendations for stage II nonseminoma testicular cancer

Stage IIA:

  • Treatment recommendations are based on serum tumor marker results after orchiectomy
  • Markers that are normal should be treated with nerve-sparing RPLND or chemotherapy with 4 cycles of EP [3] (etoposide 100 mg/m 2 IV on days 1-5 plus  cisplatin 20 mg/m 2 IV on days 1-5; every 12d [3] ) or
  • 3 cycles of BEP (bleomycin 30 U IV on days 1, 8, and 15 plus  etoposide 100 mg/m 2 IV on days 1-5 plus  cisplatin 20 mg/m 2 IV on days 1-5; every 21d)
  • In patients who underwent RPLND and were found to have pN1 or pN2 disease, adjuvant chemotherapy with 2 cycles of EP or  2 cycles of BEP is preferred [3, 1]
  • Those with pN3 disease should receive 3 cycles of BEP or 4 cycles of EP

Stage IIB:

  • As with stage IIA, treatment recommendations are based on serum tumor markers
  • Treatment for negative tumor markers in the presence of lymph node metastases within lymphatic drainage sites is nerve-sparing RPLND plus adjuvant therapy (as in stage IIA) or chemotherapy
  • Chemotherapy includes 4 cycles of EP [3] (etoposide 100 mg/m 2 IV on days 1-5 plus  cisplatin 20 mg/m 2 IV on days 1-5; every 21d) or
  • 3 cycles of BEP (bleomycin 30 U IV on days 1, 8, and 15 plus  etoposide 100 mg/m 2 IV on days 1-5 plus  cisplatin 20 mg/m 2 IV on days 1-5; every 21d)
  • For patients with multifocal, symptomatic, or lymph node metastases with lymphatic drainage treatment, include chemotherapy with 4 cycles of EP and 3 cycles of BEP; nerve-sparing RPLND is not recommended

Treatment recommendations for advanced metastatic nonseminoma testicular cancer

The International Germ Cell Cancer Consensus Group (IGCCCG) developed a risk classification for advanced nonseminoma testicular cancer based on identifying clinically independent prognostic features, including extent of disease and levels of serum tumor markers. In testicular cancer post orchiectomy, markers are used to determine risk classification. [4, 1]

Stages IS, IIA-S1, IIB-S1, IIC, IIIA (good risk):

  • Good risk is classified as the presence of testicular or retroperitoneal primary tumors with no nonpulmonary visceral metastases and S1 markers; 5-y progression-free survival (PFS) is 89%; 5-y survival is 92-94%
  • Primary chemotherapy includes 4 cycles of EP [3] (etoposide 100 mg/m 2 IV on days 1-5 plus  cisplatin 20 mg/m 2 IV on days 1-5; every 21d) or
  • 3 cycles of BEP (bleomycin 30 U IV on days 1,8, and 15 plus  etoposide 100 mg/m 2 IV on days 1-5 plus  cisplatin 20 mg/m 2 IV on days 1-5; every 21d [5] [5-day schedule]; or  bleomycin 30 U IV on days 1, 8, and 15 plus  etoposide 165 mg/m 2 IV on days 1-3 plus  cisplatin 50 mg/m 2 IV on days 1-2; every 21d [5] [3-day schedule])

Stage IIIB (intermediate risk):

  • Intermediate risk is classified as presence of testicular or retroperitoneal primary tumors with no nonpulmonary visceral metastases and S2 markers; 5-y PFS is 75%; 5-y survival is 80-83%
  • Patients with stage IIIB intermediate risk should be treated with 4 cycles of BEP (bleomycin 30 U IV on days 1, 8, and 15 plus  etoposide 100 mg/m 2 IV on days 1-5 plus  cisplatin 20 mg/m 2 IV on days 1-5; every 21d [5] [5-d schedule]; or  bleomycin 30 U IV on days 1, 8, and 15 plus  etoposide 165 mg/m 2 IV on days 1-3 plus  cisplatin 50 mg/m 2 IV on days 1-2; every 21d [5] [3-d schedule])
  • Tumor markers should be measured immediately before each cycle of chemotherapy regimen and ongoing response should be measured via continued reduction in tumor markers
  • In patients with intermediate risk, chemotherapy can be followed by surveillance or RPLND for those with complete tumor response and negative markers
  • Residual masses with normal markers should be resected; depending on the pathology, further chemotherapy should be considered with regimens such as VIP (etoposide 75 mg/m 2 IV on days 1-5 plus  ifosfamide 1.2 g/m 2 IV on days 1-5 plus  cisplatin 20 mg/m 2 IV on days 1-5 plus  mesna 400 mg/m 2 IV infused over 30 min before ifosfamide, then 4h and 8h after the start of each ifosfamide dose (or 1200 mg/m 2/24h) on days 1-5; every 21d for 4 cycles [6, 7] )
  • If markers are persistently abnormal after the completion of initial chemotherapy, second-line therapy should be considered

Stage IIIC (poor risk):

  • Poor risk is classified as the presence of a mediastinal primary tumor, nonpulmonary visceral metastases, or S3 markers; 5-y PFS is 41%; 5-y survival is 71%
  • Patients with stage IIIC poor risk should be treated with 4 cycles of BEP (bleomycin 30 U IV on days 1, 8, and 15 plus  etoposide 100 mg/m 2 IV on days 1-5 plus  cisplatin 20 mg/m 2 IV on days 1-5; every 21d [5] [5-day schedule]; or  bleomycin 30 U IV on days 1, 8 and 15 plus  etoposide 165 mg/m 2 IV on days 1-3 plus  cisplatin 50 mg/m 2 IV on days 1-2; every 21d [5] [3-day schedule])
  • In the presence of brain metastases, cisplatin-based chemotherapy should be combined with surgery and radiation therapy as clinically indicated
  • Tumor markers should be measured immediately before each cycle of chemotherapy, and ongoing response should be measured via continued reduction in tumor markers
  • In patients with poor risk, chemotherapy can be followed by surveillance or RPLND for those with complete tumor response and negative markers
  • Residual masses with normal markers should be resected; depending on the pathology, further chemotherapy should be considered with regimens such as VIP (etoposide 75 mg/m 2 IV on days 1-5 plus  ifosfamide 1.2 g/m 2 IV on days 1-5 plus  cisplatin 20 mg/m 2 IV on days 1-5 plus  mesna 400 mg/m 2 IV infused over 30 min before ifosfamide, then 4h and 8h after the start of each ifosfamide dose (or 1200 mg/m 2/24h) on days 1-5; every 21d for 4 cycles [6, 7] )
  • If markers are persistently abnormal after the completion of initial chemotherapy, second-line/salvage therapy should be considered

Second-line treatment recommendations for metastatic disease

Favorable prognosis:

  • Patients with a favorable prognosis [1] —defined as those with low markers, low volume, and complete response on first-line therapy—should be treated with conventional doses of VeIP [8] ( vinblastine 0.11 mg/kg IV push on days 1-2 plus  ifosfamide 1200 mg/m 2 IV on days 1-5 plus  mesna 400 mg/m 2 IV infused over 30 min before ifosfamide, then 4h and 8h after the start of each ifosfamide dose (or 1200 mg/m 2/24h) on days 1-5 plus  cisplatin 20 mg/m 2 IV on days 1-5; every 21d for 4 cycles) or
  • TIP [9] ( paclitaxel 250 mg/m 2 IV continuous infusion over 24h on day 1 plus  ifosfamide 1500 mg/m 2 IV on days 2-5 plus  cisplatin 25 mg/m 2 IV on days 2-5 plus  mesna 500 mg/m 2 IV infused over 30 min before ifosfamide and then 4h and 8h after each dose of ifosfamide on days 2-5; every 21d for 4 cycles) or
  • High-dose chemotherapy [10] with carboplatin 700 mg/m 2 IV plus  etoposide 750 mg/m 2 IV; administer 5, 4, and 3 days before peripheral blood stem infusion for 2 cycles; or
  • Paclitaxel 200 mg/m 2 IV over 24h on day 1 plus  ifosfamide 2000 mg/m 2 over 4h with mesna protection on days 2-4; every 14d for 2 cycles; followed by carboplatin AUC 7-8 IV over 60min on days 1-3 plus  etoposide 400 mg/m 2 IV on days 1-3; administer with peripheral blood stem cell support every 14-21d for 3 cycles [11]

Unfavorable prognosis:

  • Unfavorable prognosis [1] is defined by incomplete response, high markers, high volume, an extratesticular primary tumor, and late relapse
  • Treat these patients with chemotherapy; clinical trials or conventional-dose VeIP or TIP regimens are preferred; consider high-dose chemotherapy (as above)
  • Surgical salvage therapy or best supportive care should be considered [1]

Treatment recommendations for persistent or recurrent disease

See the list below:

  • All patients should be considered for palliative chemotherapy or radiation therapy
  • Patients who have been pretreated or who are cisplatin-resistant or have refractory germ cell tumors may be given combination chemotherapy with GEMOX ( gemcitabine 1000 or 1250 mg/m 2 IV on days 1 and 8 plus  oxaliplatin 130 mg/m 2 IV on day 1; every 21d [12, 13] ) or
  • High-dose chemotherapy and stem-cell rescue [14, 15]

Special considerations

See the list below:

  • Pulmonary function studies to ensure adequate function should be confirmed before initiation of any regimen that includes bleomycin
  • Smokers should be counseled regarding smoking cessation
  • If significant thoracic surgery is anticipated (eg, for a mediastinal tumor), a VIP regimen can be considered as an alternative to a BEP regimen
  • Surgical resection of residual or recurrent disease should be considered (including RPLND or pulmonary masses) in patients whose markers have normalized or remain normal
  • Sperm banking should be discussed with patients before initiation of therapy
  • Secondary malignancies are the most common cause of death in testicular cancer survivors
  • A second testicular cancer develops in 1-2% of testicular cancer survivors; treatment with etoposide can increase the risk of secondary leukemia [16, 17]