Note: This guideline has been updated. The National Guideline Clearinghouse (NGC) is working to update this summary. The recommendations that follow are based on the previous version of the guideline.
Definitions for the grades of recommendation (A-B) are provided at the end of the "Major Recommendations" field.
Diagnosis and Staging of Testicular Cancer
Table: Recommended Tests for Staging at Diagnosis
Test |
Recommendation Grade B |
Recommendation Grade C |
Serum tumour markers |
Alpha-fetoprotein
hCG
LDH (for advanced tumours)
|
|
Abdominopelvic CT scan |
All patients |
Slim adolescent |
Chest X-ray |
Seminomaa |
|
Chest CT scan |
NSGCT |
|
Testis ultrasound |
Clinical suspicion and normal scrotum at palpation |
|
MRI |
When abdominal CT is inconclusive |
All cases |
PET scanb |
Follow-up residual masses in seminoma |
|
Fertility investigations (should be offered) |
Total testosterone, LH, FSH, semen analysis, sperm banking |
|
Other |
If clinical suspicion |
|
hCG = human chorionic gonadotrophin; LDH = lactate dehydrogenase; CT = computed tomography; NSGCT = non-seminomatous germ cell tumour; MRI = magnetic resonance imaging; PET = positron emission tomography; FSH = follicle stimulating hormone
a If negative, abdominopelvic computed tomography (CT) scan.
b There is currently no indication for PET scan at diagnosis.
Guidelines on Diagnosis and Staging of Testicular Cancer
- Testicular ultrasound is mandatory. (Grade of recommendation: B).
- Orchidectomy and pathological examination of the testis is necessary to confirm the diagnosis and to define the local extension (pathologic tumour [pT] category) (Grade B recommendation). In a life-threatening situation due to extensive metastasis chemotherapy has to be started before orchidectomy.
- Serum determination of tumour markers (alpha-fetoprotein [AFP], human chorionic gonadotropin [hCG], and lactate dehydrogenase [LDH] in metastatic disease) must be performed before and after orchidectomy for staging and prognostic reasons (Grade of recommendation: B).
- Retroperitoneal, mediastinal and supraclavicular nodes and visceral state have to be assessed in testicular cancer. In seminoma, a chest computed tomography (CT) scan is not necessary if abdominal nodes are negative (Grade of recommendation: B).
Treatment of Seminoma Stage I
- Surveillance (if available facilities and patient compliance) (Grade of recommendation: B).
- Carboplatin based chemotherapy (one course at area under the curve [AUC] 7) can be recommended as an alternative to radiotherapy and surveillance (Grade of recommendation: A).
- Adjuvant radiotherapy to a para-aortic or a hockey stick field, to a total dose of 20 Gy (Grade of recommendation: A).
Treatment of Non-Seminomatous Germ Cell Tumor (NSGCT) Stage I
Clinical Stage (CS) 1
Risk-adapted treatments based on vascular invasion or surveillance are recommended treatment options (Grade of recommendation: B)
CS1A (pT1, No Vascular Invasion): Low Risk
- If the patient is willing and able to comply with a surveillance policy and long-term (at least 5 years) close follow-up should be recommended (Grade of recommendation: B).
- Adjuvant chemotherapy or nerve-sparing retroperitoneal lymph node dissection (RPLND) in low-risk patients remain options for those not willing to undergo surveillance. If RPLND reveals PN+ (nodal involvement) disease, chemotherapy with two courses of cisplatin/etoposide/bleomycin (PEB) should be considered (Grade of recommendation: A).
CS1B (pT2-pT4); High Risk
- Primary chemotherapy with two courses of PEB should be recommended (Grade of recommendation: B).
Surveillance or nerve-sparing RPLND in high-risk patients remain options for those not willing to undergo adjuvant chemotherapy. If pathological stage II is revealed at RPLND, further chemotherapy should be considered (Grade of recommendation: A).
Treatment of Metastatic Germ Cell Tumours
- Low volume NSGCT stage IIA/B with elevated markers should be treated like 'good or intermediate prognosis' advanced NSGCT with 3 or 4 cycles of PEB. Stage II A/B without marker elevation can be treated either by RPLND or close surveillance.
- In metastatic NSGCT (stage IIA [with positive markers]) with a good prognosis, three courses of PEB is the primary treatment of choice (Grade of recommendation: A).
- In metastatic NSGCT with an intermediate or poor prognosis, the primary treatment of choice is four courses of standard PEB (Grade of recommendation: A).
- Surgical resection of residual masses after chemotherapy in NSGCT is indicated in the case of visible residual masses and when serum levels of tumour markers are normal or normalizing (Grade of recommendation: B).
- Clinical stage (CS) IIA/B can initially be treated with radiotherapy. When necessary, chemotherapy can be used as a salvage treatment with the same schedule as for the corresponding prognostic groups of NSGCT (Grade of recommendation: A). In stage IIB chemotherapy with three cycles of standard-dose bleomycin, etoposide, and cisplatin (BEP), or four cycles of etoposide (EP), represents a treatment alternative to radiotherapy, but may be associated with a higher risk of acute toxicity as compared to radiotherapy.
- Seminoma, stage IIC and higher should be treated with primary chemotherapy according to the same principles used for NSGCT (Grade of recommendation: A).
Follow-up after Curative Therapy
General Considerations
The selection of the test to be performed in follow-up should adhere to the following principles:
- The interval between examinations and duration of testing should be consistent with the time of maximal risk of recurrence and the natural history of the tumour.
- The tests should be directed at the most likely sites of recurrence and should have a high predictive value, both positive and negative.
- Therapy should be available that will result in cure of the recurrence, significant prolongation of life or palliation of symptoms. The initiation of earlier therapy should improve the outcome compared with therapy given when the patient becomes symptomatic from the tumour recurrence.
- The increased risk of second malignancy, both in the primary site and in other tissues that may have been exposed to the same carcinogens, or in which there is epidemiological evidence of increased risk, should also guide the ordering tests. Malignant and non-malignant complications of therapy must also be considered. Such testing should also be performed with a frequency and duration consistent with the nature of the risk and include only tests with high positive- and negative-predictive values.
The following considerations apply in a general manner for the selection of an appropriate schedule and testing in the follow-up of all stages of testis tumour:
- Most recurrences after curative therapy will occur in the first 2 years; consequently surveillance should be most frequent and intensive during this time.
- Late relapses can occur beyond 5 years and therefore yearly follow-up for life may be advocated.
- After RPLND, relapse in the retroperitoneum is rare; the most likely site of recurrence being the chest.
- The value of chest X-ray has been recently questioned in the follow-up of patients with disseminated disease after complete remission.
- CT of the chest has a higher predictive value than chest X-ray.
- The results of therapy are dependent on the bulk of disease; thus an intensive strategy to detect asymptomatic disease may be justifiable.
- After chemotherapy or radiotherapy, a long-term risk for secondary malignancies development exists.
Table: Recommended Minimum Follow-Up Schedule in a Surveillance Policy: Stage I Non-Seminoma
Procedure |
Year |
|
1 |
2 |
3–5 |
6–10 |
Physical examination |
3-monthly |
3-monthly |
Twice/year |
Once/year |
Tumour markers |
3-monthly |
3-monthly |
Twice/year |
Once/year |
Chest X-ray |
Twice/year |
Twice/year |
|
|
Abdominopelvic computed tomography (CT) scan |
Twice/year (at 3 and 12 months) |
|
|
|
Table: Recommended Minimum Follow-Up Schedule after Retroperitoneal Lymphadenectomy or Adjuvant Chemotherapy: Stage I Non-Seminoma
Procedure |
Year |
|
1 |
2 |
3–5 |
6–10 |
Physical examination |
3-monthly |
3-monthly |
Twice/year |
Once/year |
Tumour markers |
3-monthly |
3-monthly |
Twice/year |
Once/year |
Chest X-ray |
Twice/year |
Twice/year |
|
|
Abdominopelvic CT scan |
Once/year |
Once/year |
|
|
Table: Recommended Minimum Follow-Up Schedule for Post-Orchidectomy Surveillance, Radiotherapy or Chemotherapy: Stage I Seminoma
Procedure |
Year |
|
1 |
2 |
3 |
4–5 |
Physical examination |
3-monthly |
3-monthly |
Twice/year |
Once/year |
Tumour markers |
3-monthly |
3-monthly |
Twice/year |
Once/year |
Chest X-ray |
Twice/year |
Twice/year |
Once/year |
Once/year |
Abdominopelvic CT scan |
Twice/year |
Twice/year |
Once/year |
Once/year |
Table: Recommended Minimum Follow-Up Schedule in Advanced NSGCT and Seminoma
Procedure |
Year |
|
1 |
2 |
3–5 |
Thereafter |
Physical examination |
3-monthly |
3-monthly |
Twice/year |
Once/year |
Tumour markers |
3-monthly |
3-monthly |
Twice/year |
Once/year |
Chest X-ray |
3-monthly |
3-monthly |
Twice/year |
Once/year |
Abdominopelvica, b CT scan |
Twice/year |
Twice/year |
Once/year |
Once/year |
Chest CTb, c |
As indicated |
As indicated |
As indicated |
As indicated |
Brain CTd |
As indicated |
As indicated |
As indicated |
As indicated |
a Abdominal CT scanning has to be performed at least annually if teratoma is found in the retroperitoneum.
b If the post-chemotherapy evaluation shows any mass >3 cm, the appropriate CT scan should be repeated 2 and 4 months later to ensure that the mass is continuing to regress. If available, fluorodeoxyglucose-positron-emission tomography (FDG-PET) scanning can be performed.
c A chest CT is indicated if abnormality is detected on chest X-ray and after pulmonary resection.
d In patients with headaches, focal neurological findings or any central nervous system symptom.
Testicular Stromal Tumours
Leydig Cell Tumours
Diagnosis
Diagnostic work-up must include markers, hormones (at least testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH); if not conclusive, additionally, oestrogen, oestradiol, progesterone and cortisol), ultrasound of both testes and CT scan of chest and abdomen. On ultrasound, it may be possible to observe well-defined, small, hypoechoic lesions with hypervascularization, but the appearance is variable and is indistinguishable from germ cell tumours.
Treatment
Asymptomatic testicular tumours of small volume are often misinterpreted as germ cell tumours and inguinal orchidectomy is performed. It is highly recommended to perform an organ-sparing procedure in every small intraparenchymal lesion to gain the histological diagnosis. Especially in patients with symptoms of gynaecomastia or hormonal disorders, a non germ-cell tumour should be considered and immediate orchidectomy should be avoided. In cases of germ cell tumour in either frozen section or paraffin histology, orchidectomy is recommended as long as a contralateral normal testicle is present.
In stromal tumours with histological signs of malignancy, especially in patients of older age, orchidectomy and retroperitoneal lymphadenectomy is recommended to prevent metastases. Without histological signs of malignancy, an individualized surveillance strategy after orchidectomy is recommended (CT follow-up may be most appropriate since specific tumour markers are not available).
Tumours that have metastasized to lymph nodes, lung, liver or bone respond poorly to chemotherapy or radiation and survival is poor.
Follow-up
Recommendations for appropriate follow-up cannot be given because of the lack of follow-up data in most reported cases and the lethal outcome of metastatic tumours, irrespective of the therapy chosen.
Sertoli Cell Tumour
Diagnosis
Diagnostic work-up has to include tumour markers, hormones (at least testosterone, LH and FSH; if not conclusive, additionally, oestrogen, oestradiol, progesterone and cortisol), ultrasound of both testes and CT scan of chest and abdomen.
Treatment
Testicular tumours of small volume, otherwise asymptomatic, are often misinterpreted as germ cell tumours and inguinal orchidectomy is performed. It is highly recommended to proceed with an organ-sparing approach in small intraparenchymal testicular lesions until final histology is available. Especially, in patients with symptoms of gynaecomastia or hormonal disorders or typical imaging on ultrasound (calcifications, small circumscribed tumours), organ-sparing surgery should be considered. Secondary orchidectomy can be performed if final pathology reveals a non-stromal (e.g., germ cell) tumour. Organ-sparing surgical approaches are justified as long as the remaining testicular parenchyma is sufficient for endocrine (and in stromal tumours also exocrine) function.
In tumours with histological signs of malignancy, especially in patients of older age, orchidectomy and retroperitoneal lymphadenectomy are recommended to prevent metastases. Without signs of malignancy, an individualized surveillance strategy after orchidectomy is recommended (CT scans may be most appropriate since specific tumour-markers are not available). Tumours metastasizing to lymph nodes, lung or bone respond poorly to chemotherapy or radiation and survival is poor.
Follow-up
Recommendations for appropriate follow-up cannot be given because of the lack of follow-up data in most reported cases and the lethal outcome of metastatic tumours, irrespective of the therapy chosen.
Definitions:
Grades of Recommendation
- Based on clinical studies of good quality and consistency addressing the specific recommendations and including at least one randomized trial
- Based on well-conducted clinical studies, but without randomized clinical trials
- Made despite the absence of directly applicable clinical studies of good quality