Testicular Cancer Follow-up

Updated: Jul 05, 2017
  • Author: Kush Sachdeva, MD; Chief Editor: E Jason Abel, MD  more...
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Follow-up

Further Outpatient Care

 Surveillance for seminoma

In patients with clinical stage I seminoma, the National Comprehensive Cancer Network (NCCN) recommends surveillance with history and physical examination (H&P) and abdominal and pelvic computed tomography (CT). The NCCN guidelines advise that follow-up for seminoma should be modified for the individual patient and may be extended beyond 5 years. [14]

Serum tumor marker assays are optional. Testicular ultrasound should be performed in patients with an equivocal exam. Chest x-rays should be performed as clinically indicated, with chest CT considered in symptomatic patients.

The NCCN surveillance schedule for clinical stage I seminoma patients treated with orchiectomy only is as follows:

  • Year 1 - H&P every 3-6 mo; abdominal/pelvic CT at 3, 6, and 12 mo
  • Years 2-3 - H&P and abdominal/pelvic CT every 6-12 mo
  • Years 4-5 - H&P annually; abdominal/pelvic CT every 12-24 mo

The NCCN surveillance schedule for clinical stage I seminoma patients treated with adjuvant chemotherapy or radiation therapy is as follows:

  • Years 1-2 - H&P every 6-12 mo; abdominal/pelvic CT annually
  • Year 3 - H&P and abdominal/pelvic CT annually
  • Years 4-5 - H&P annually

In patients with clinical stage IIA and non-bulky stage IIB seminomas, the NCCN recommendations for surveillance are as follows:

  • H&P
  • Abdominal and pelvic CT
  • Chest x-ray, with chest CT preferred in patients with thoracic symptoms
  • Serum tumor marker assays are optional
  • Testicular ultrasound should be performed in patients with an equivocal exam

In clinical stage IIA and non-bulky stage IIB seminoma, the NCCN surveillance schedule after radiotherapy or chemotherapy is as follows:

  • Year 1 - H&P every 3 mo; abdominal/pelvic CT at mo and then 6-12 mo; chest x-ray every 6 mo
  • Year 2 - H&P every 6 mo, abdominal/pelvic CT annually, chest x-ray every 6 mo
  • Year 3 - H&P every 6 mo, abdominal/pelvic CT annually
  • Years 4-5 - H&P every 6 mo, abdominal/pelvic CT as clinically indicated

In patients with bulky clinical stage IIB, IIC and stage III seminomas, the NCCN surveillance post-chemotherapy with no residual mass or residual mass <3 cm and normal tumor marker recommend abdominal and pelvic CT scan with contrast at 3-6 months, then as clinically indicated. PET/CT scan as clinically indicated. The surveillance schedule is as follows:

  • Year 1 - H&P, tumor markers, and chest x-ray every 2 mo
  • Year 2 - H&P, tumor markers, and chest x-ray every 3 mo
  • Years 3-4 - H&P and tumor markers every 6 mo and chest x-ray annually
  • Year 5 - H&P, tumor markers, and chest x-ray annually

Surveillance for nonseminoma

In patients with clinical stage I-III nonseminomas, the NCCN recommends surveillance with H&P, serum tumor markers, abdominal/pelvic CT, and chest x-ray, with chest CT preferred in patients with thoracic symptoms. Testicular ultrasound should be performed in patients with an equivocal exam.

In clinical stage IA nonseminoma, the NCCN active surveillance schedule is as follows:

  • Year 1 - H&P and tumor markers every 2 mo; abdominal/pelvic CT every 4-6 mo; chest x-ray at 4 and 12 mo
  • Year 2 - H&P and tumor markers every 3 mo; abdominal/pelvic CT every 6-12 mo; chest x-ray annually
  • Year 3 - H&P and tumor markers every 4-6 mo; abdominal/pelvic CT annually; chest x-ray annually
  • Year 4 - H&P and tumor markers every 6 mo; chest x-ray annually
  • Year 5 - H&P, tumor markers, and chest x-ray annually

In clinical stage IB nonseminoma, the NCCN active surveillance schedule is as follows:

  • Year 1 - H&P and tumor markers every 2 mo; abdominal/pelvic CT every 4 mo; chest x-ray every 2 mo
  • Year 2 - H&P and tumor markers every 3 mo; abdominal/pelvic CT every 4-6 mo; chest x-ray every 3 mo
  • Year 3 - H&P and tumor markers every 4-6 mo; abdominal/pelvic CT every 6 mo chest x-ray every 4-6 mo
  • Year 4 - H&P and tumor markers every 6 mo; abdominal/pelvic CT annually; chest x-ray every 6 mo
  • Year 5 - H&P, tumor markers, and chest x-ray annually

In clinical stage IB nonseminoma treated with 1-2 cycles of adjuvant BEP chemotherapy, the NCCN surveillance schedule is as follows:

  • Year 1 - H&P and tumor markers every 3 mo; abdominal/pelvic CT annually; chest x-ray every 6-12 mo
  • Year 2 - H&P and tumor markers every 3 mo; abdominal/pelvic CT annually; chest x-ray annually
  • Years 3-4 - H&P and tumor markers every 6 mo
  • Year 5 - H&P and tumor markers annually

In clinical stage II-III nonseminoma that has shown a complete response to chemotherapy, with or without post-chemotherapy RPLND, the NCCN surveillance schedule is as follows:

  • Year 1 - H&P and tumor markers every 2 mo; abdominal/pelvic CT every 6 mo; chest x-ray every 6 mo
  • Year 2 - H&P and tumor markers every 3 mo; abdominal/pelvic CT annually; chest x-ray every 6 mo
  • Year 3 - H&P and tumor markers every 6 mo; chest x-ray annually (optional at month 36 and 48)
  • Year 4 - H&P and tumor markers every 6 mo; chest x-ray annually (optional at month 36 and 48)
  • Year 5 - H&P and tumor markers every 6 mo

In pathologic stage IIA-B nonseminoma, after primary RPLND and treatment with adjuvant chemotherapy, the NCCN surveillance schedule is as follows:

  • Year 1 - H&P and tumor markers every 6 mo; abdominal/pelvic CT after RPLND; chest x-ray every 6 mo
  • Year 2 - H&P and tumor markers every 6 mo; abdominal/pelvic CT as clinically indicated; chest x-ray annually
  • Years 3-5 - H&P and tumor markers annually; abdominal/pelvic CT as clinically indicated; chest x-ray annually

In pathologic stage IIA-B nonseminoma, after primary RPLND and NOT treated with adjuvant chemotherapy, the NCCN surveillance schedule is as follows:

  • Year 1 - H&P and tumor markers every 2 mo; abdominal/pelvic CT at 3-4 mo (assuming complete resection has taken place); chest x-ray every 2-4 mo
  • Year 2 - H&P and tumor markers every 3 mo; chest x-ray every 3-6 mo
  • Year 3 - H&P and tumor markers every 4 mo; abdominal/pelvic CT as clinically indicated; chest x-ray annually
  • Year 4 - H&P and tumor markers every 6 mo; abdominal/pelvic CT as clinically indicated; chest x-ray annually
  • Year 3 - H&P and tumor markers annually; abdominal/pelvic CT as clinically indicated; chest x-ray annually
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Complications

Treatment-related toxicity

Pulmonary complications: Bleomycin can cause pneumonitis and pulmonary fibrosis; therefore, pulmonary function tests are done before starting chemotherapy that includes this agent. Bleomycin-induced lung toxicity is cumulative and although it can be fatal, it is rarely fatal if the total cumulative dose is less than 400 units.

Patients with bleomycin-induced pneumonitis present with nonproductive cough, dyspnea on exertion, and bibasilar rales. Chest x-ray may show pulmonary nodules. A decline in carbon monoxide diffusing capacity (DLCO) is the earliest sign of lung toxicity; bleomycin should be discontinued if it occurs. Smokers should be counseled regarding smoking cessation.

An increase in the incidence of restrictive lung disease has also been reported in patients who receive cisplatin-based chemotherapy for testicular cancer. The effect was dose dependent, with no increase in risk for men who received up to 850 mg of cisplatin but a three-fold increase in men who received over 850 mg of cisplatin. In absolute terms, the incidence of restrictive lung disease in men receiving over 850 mg of cisplatin was nearly 18%. [28]

Renal toxicity: 20-30% of patients who receive cisplatin have a reduction in glomerular filtration rate. Cisplatin can also cause hypomagnesemia, hypophosphatemia, and hypokalemia.

Cardiovascular toxicity: Cardiovascular disorders are late complications of radiation therapy and/or chemotherapy (particularly platinum based). They include hypertension, dyslipidemia, coronary artery disease, thromboembolic events, and Raynaud phenomenon. However, the risk of cardiovascular disease appears to be of only borderline significance with the newer regimen of bleomycin, etoposide, and cisplatin (BEP), compared with the older regimen of cisplatin, vinblastine, and bleomycin (PVB), which was used until the mid-1980s. [1]

Infertility: Many patients have oligospermia or sperm abnormalities before treatment, but semen analysis results generally become more normal after treatment. Data on the effect of chemotherapy on fertility remain uncertain; most men can father children after treatment, and the risk of congenital malformations does not seem to be increased, but waiting for at least 3 months after completion of chemotherapy before attempting to conceive a child has been recommended. [1]

Hematologica toxicity: Anemia, leukopenia/neutropenia, and thrombocytopenia may occur. Prophylactic treatment with hematopoietic growth factors is recommended to avoid the need for dose attenuation or treatment delays.

Bone loss: In patients who had metastatic germ cell tumors, Willemse et al reported a significant decrease in bone mineral density (BMD) in the first year after curative chemotherapy, with no recovery of BMD in the 5 years afterward. These researchers note that whether this bone loss is associated with increased fracture risk and whether it could be prevented by bone-modifying treatment remains uncertain. [29]

Other compications include the following:

  • Gastrointestinal toxicity: Nausea and vomiting
  • Neurological toxicity: Cisplatin and oxaliplatin can cause neuropathy
  • Ototoxicity: Tinnitus and high-frequency sensorineural loss may occur

Secondary malignancy

Secondary malignancies are the most common cause of death in testicular cancer survivors. A second testicular cancer develops in 1% to 2% of testicular cancer survivors.

Solid tumors

A followup study of more than 40,000 testicular cancer survivors in Europe and North America showed that the relative risk of developing a secondary tumor was 1.9 (95% confidence index, 1.8 to 2.1) for 10 years and 1.7 for 35 years. [11] Cancers of the lung, colon, bladder, pancreas, stomach, mesothelioma, and esophagus were found. Testicular cancer patients who were treated with radiation alone were at higher risk of having bladder, stomach, pancreas, and kidney cancers.

Leukemia

Patients treated with regimens that contain etoposide have an increased risk of developing leukemia, mainly of the myeloid lineage. In such cases, the Hallmark chromosomal translocation involving the long arm of chromosome 11 (11q23) occurs 2 to 3 years following treatment. Leukemia develops in 16 per 10,000 patients treated with standard-dose chemotherapy.

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Prognosis

The International Germ Cell Consensus Classification (IGCCC), [17] an easily applicable, clinically based prognostic instrument, is used in clinical practice for risk classification and is the current standard for all practice guidelines, including that of the National Comprehensive Cancer Network.

The IGCCC is based on a retrospective analysis of 5,202 patients with metastatic nonseminomatous germ cell tumor (NSGCT) and 660 patients with metastatic seminomatous germ cell tumors from 10 countries, who were treated between 1975 and 1990. All patients received treatment with cisplatin- or carboplatin-containing therapy as their first chemotherapy course. Median followup was 5 years.

For NSGCT, the following independent adverse factors were identified:

  • Mediastinal primary site
  • Degree of elevation of alpha-fetoprotein, human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH)
  • Presence of nonpulmonary visceral metastates (NPVM), such as liver, bone, and brain

For patients with NSGCT, prognostic categories and reported survival rates were as follows:

  • Good - 5-year survival 92%; 5-year progression-free survival (PFS) 89%
  • Intermediate - 5-year survival 80%; 5-year PFS 75%
  • Poor - 5-year survival 48%; 5-year PFS 41%

A subsequent meta-analysis of survival of patients with NSGCT, treated after 1989 and classified according to the IGCC classification, reported a small increase in survival for good-prognosis and intermediate-prognosis patients, and a large increase in survival for patients with a poor prognosis. Pooled 5-year survival estimates were 94% with good prognosis (n = 1087), 83% with intermediate prognosis (n = 232), and 71% with poor prognosis (n = 456). The researchers suggested that the improved survival most likely reflected both more effective treatment strategies and more experience in treating NSGCT patients. [30]

For seminoma, the predominant adverse feature was the presence of NPVM. IGCCC prognostic categories and reported survival rates in patients with seminoma were as follows:

  • Good - 5-year survival 86%; 5-year PFS 82%
  • Intermediate - 5-year survival 72%; 5-year PFS 67%
  • No seminoma patients are classified as poor prognosis

IGCCC prognostic criteria for nonseminoma

Criteria for good-prognosis nonseminoma (56% to 61% of nonseminomas) consist of all of the following:

  • Testis/retroperitoneal primary
  • No nonpulmonary visceral metastases
  • Good serum tumor marker levels

Good tumor marker levels are defined as all of the following:

  • Alpha-fetoprotein (AFP) less than 1,000 ng/mL
  • Human chorionic gonadotropin (hCG) less than 5,000 IU/mL (1,000 ng/mL)
  • Lactate dehydrogenase (LDH) less than 1.5 times the upper limit of normal

Criteria for intermediate-prognosis nonseminoma (13-28% of nonseminomas) consist of all of the following:

  • Testis/retroperitoneal primary
  • No nonpulmonary visceral metastases
  • Intermediate elevation of serum tumor markers

Intermediate tumor marker levels are defined as any of the following:

  • AFP 1,000 to 10,000 ng/mL
  • hCG 5,000 IU/L to 50,000 IU/L
  • LDH 1.5 to 10 times normal

Criteria for poor-prognosis nonseminoma (16%–26% of nonseminomas) are any of the following:

  • Mediastinal primary
  • Nonpulmonary visceral metastases
  • Poor serum tumor markers

Poor tumor marker levels are defined as any of the following:

  • AFP more than 10,000 ng/mL
  • hCG more than 50,000 IU/mL (10,000 ng/mL)
  • LDH more than 10 times the upper limit of normal

IGCCC prognostic criteria for seminoma

Criteria for good-prognosis seminoma (90% of seminomas) are all of the following:

  • Any primary site
  • No nonpulmonary visceral metastases
  • Normal AFP, any hCG, any LDH

Criteria for intermediate-prognosis seminoma (10% of seminomas) are all of the following:

  • Any primary site
  • Nonpulmonary visceral metastases
  • Normal AFP, any hCG, any LDH
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Patient Education

For patient education information, see Testicular Cancer. For information from the National Cancer Institute, see Testicular Cancer–Patient Version.

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