Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

suspicious testicular mass

1st line – inguinal (radical) orchiectomy

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INITIAL
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suspicious testicular mass
1st line – 

inguinal (radical) orchiectomy

A biopsy is generally not advised in the evaluation of a testicular mass; diagnosis is established by removing and examining the involved testicle.

Patients with a testicular lesion suspicious for malignant neoplasm and a normal contralateral testis should undergo a radical inguinal orchiectomy.[2]​ Testis-sparing surgery is not recommended with a normal contralateral testis.​[2][49]

Should be performed early in evaluation. In early-stage disease, an orchiectomy is often curative.

Complications include reduced fertility or complete infertility depending on the function of the remaining testicle and any future treatments.

Procedural risks of an orchiectomy are generally considered to be low and largely limited to postoperative haemorrhage.[102]

Nadir serum tumour markers should be repeated after orchiectomy at the approximate T-half-life intervals per marker for staging and risk stratification.​[2]

Patients with a history of germ cell tumour or germ cell neoplasia in situ should be informed of increased risk of cancer in the contralateral testis.​[2]

1st line – testis sparing surgery

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INITIAL
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suspicious testicular mass
1st line – 

testis sparing surgery

Testis sparing surgery (TSS) through an inguinal incision may be offered as an alternative to radical orchiectomy in highly selected patients if the following criteria are met: 1) patients wishing to preserve gonadal function with masses <2 cm; 2) equivocal ultrasound/physical examination findings and negative tumour markers (human chorionic gonadotrophin and alpha-fetoprotein); 3) congenital, acquired, or functionally solitary testis; 4) bilateral synchronous tumours.​[2]

In TSS, multiple biopsies of the ipsilateral testicle normal parenchyma are obtained in addition to the suspicious mass for evaluation simultaneously.​[2]

Patients considering TSS should be informed of the higher risk of local recurrence and the importance of surveillance with physical examination and ultrasound following TSS. The role of adjuvant radiation to reduce local recurrence, the impact of radiotherapy on testosterone and sperm production, and the risk of testicular atrophy, hypogonadism, and subfertility/infertility should be explained.[2][49]

Patients with a history of germ cell tumour or germ cell neoplasia in situ should be informed of increased risk of cancer in the contralateral testis.​[2]

ACUTE

early-stage seminoma

1st line – surveillance post-orchiectomy

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ACUTE
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early-stage seminoma
|
stage I disease (A/B)
1st line – 

surveillance post-orchiectomy

Stage I seminoma includes stage IA (tumour confined to testis) and stage IB (locally invasive tumour with spread beyond tunica albuginea, but no nodal or metastatic disease).

Surveillance is the preferred first-line strategy for patients with stage I seminoma in whom follow-up is ensured, minimising the potential adverse effects of radiation or chemotherapy.[2][69][71]

Surveillance is favoured in all patients and especially those at increased risk for radiation toxicity, including those with a history of prior radiation, horseshoe/pelvic kidney, or inflammatory bowel disease.

Approximately 15% to 20% of stage I seminoma patients who are observed after orchiectomy and do not receive adjuvant therapy will relapse, but prognosis following chemotherapy for relapsed disease is excellent.[72]​ ​Similar survival outcomes are observed in early-stage seminoma, regardless of post-orchiectomy treatment (including careful surveillance and appropriately treated relapse).[73][74]​ 

Information on short-term and long-term adjuvant treatment-related toxicity, such as infertility, major cardiac events, and second malignancy, should be provided to patients to inform shared decision-making.[69]

1st line – carboplatin chemotherapy post-orchiectomy

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ACUTE
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early-stage seminoma
|
stage I disease (A/B)
1st line – 

carboplatin chemotherapy post-orchiectomy

Stage I seminoma includes stage IA (tumour confined to testis) and stage IB (locally invasive tumour with spread beyond tunica albuginea, but no nodal or metastatic disease).

If a surveillance strategy is not acceptable to the patient (due to anxiety or other reasons) or the patient is unable to adhere to a surveillance schedule, adjuvant carboplatin chemotherapy may be used for one or two cycles in stage I seminoma.[67][75]

Carboplatin chemotherapy is favoured (if surveillance is declined) in patients at increased risk for radiation toxicity, including those with a history of prior radiation, horseshoe/pelvic kidney, or inflammatory bowel disease.[49]

Information on short-term and long-term adjuvant treatment-related toxicity, such as infertility, major cardiac events, and second malignancy, should be provided to patients to inform shared decision-making.[69]

See local specialist protocol for dosing guidelines.

Primary options

carboplatin

1st line – external beam radiation post-orchiectomy

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ACUTE
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early-stage seminoma
|
stage I disease (A/B)
1st line – 

external beam radiation post-orchiectomy

Stage I seminoma includes stage IA (tumour confined to testis) and stage IB (locally invasive tumour with spread beyond tunica albuginea, but no nodal or metastatic disease).

Radiotherapy can be considered in stage I patients if the patient declines or is not eligible for active surveillance and where adjuvant carboplatin chemotherapy is contraindicated or declined by the patient.[47][76]

If offered, radiotherapy is given to the para-aortic lymph nodes in all patients and the ipsilateral iliac nodes in patients with more advanced disease.[77][78]

Radiotherapy is not recommended in patients at increased risk for radiation toxicity, including those with a history of prior radiation, horseshoe/pelvic kidney, or inflammatory bowel disease.[49]

Information on short-term and long-term adjuvant treatment-related toxicity, such as infertility, major cardiac events, and second malignancy, should be provided to patients to inform shared decision-making.[69]

1st line – external beam radiation post-orchiectomy

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ACUTE
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early-stage seminoma
|
stage II disease (A/B)
1st line – 

external beam radiation post-orchiectomy

Stage II A/B seminomas include any tumour size; regional nodes <5 cm; with or without slightly elevated tumour markers. Lymph nodes may measure up to 2 cm in stage IIA and more than 2 cm and up to 5 cm in stage IIB.

Patients with stage IIA or stage IIB seminoma with retroperitoneal lymph node involvement <3 cm in greatest dimension, may be offered radiotherapy, multi-agent cisplatin-based chemotherapy, or retroperitoneal lymph node dissection.[2]​​[49][69]

For patients with IIB seminoma with a lymph node mass ≥3 cm, chemotherapy is the preferred first-line treatment.​[2][49]

International guidance differs in that lymph node size limits are not always defined.[46][47][79]

In a meta-analysis, radiotherapy and chemotherapy appear to be equally effective in stage IIA, whereas chemotherapy tends to be more effective in stage IIB seminoma.[70]

If offered, radiation therapy is given to the para-aortic lymph nodes and the ipsilateral iliac nodes in patients with stage II disease.[49] Radiation therapy is not recommended in patients at increased risk for radiation toxicity, including those with a history of prior radiation, horseshoe/pelvic kidney, or inflammatory bowel disease.[49]​​​​

Information on short-term and long-term adjuvant treatment-related toxicity, such as infertility, major cardiac events, and second malignancy, should be provided to patients to inform shared decision-making.[69][70]

1st line – chemotherapy post-orchiectomy

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ACUTE
|
early-stage seminoma
|
stage II disease (A/B)
1st line – 

chemotherapy post-orchiectomy

Stage II A/B seminomas include any tumour size; regional nodes <5 cm; with or without slightly raised tumour markers. Lymph nodes may measure up to 2 cm in stage IIA and between 2 cm to 5 cm in stage IIB.

Patients with stage IIA or stage IIB seminoma with retroperitoneal lymph node involvement <3 cm in greatest dimension, may be offered radiotherapy, multi-agent cisplatin-based chemotherapy, or retroperitoneal lymph node dissection.[2][49][69]

For patients with IIB seminoma with a lymph node mass ≥3 cm, chemotherapy is the preferred first-line treatment.​[2][49]

​International guidance differs in that lymph node size limits are not always defined.[46][47][79]

In a meta-analysis, radiotherapy and chemotherapy appear to be equally effective in stage IIA, whereas chemotherapy tends to be more effective in stage IIB seminoma.[70]

Information on short-term and long-term adjuvant treatment-related toxicity, such as infertility, major cardiac events, and second malignancy, should be provided to patients to inform shared decision-making.[69][70]

A multi-agent cisplatin-based chemotherapy is used, such as bleomycin, etoposide, and cisplatin (BEP [also known as PEB]), or etoposide and cisplatin (EP).​[2]

See local specialist protocol for dosing guidelines.

Primary options

BEP

bleomycin

and

etoposide

and

cisplatin

OR

EP

etoposide

and

cisplatin

1st line – retroperitoneal lymph node dissection (RPLND) post-orchiectomy

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ACUTE
|
early-stage seminoma
|
stage II disease (A/B)
1st line – 

retroperitoneal lymph node dissection (RPLND) post-orchiectomy

Stage II A/B seminomas include any tumour size; regional nodes <5 cm; with or without slightly elevated tumour markers. Lymph nodes may measure up to 2 cm in stage IIA and more than 2 cm and up to 5 cm in stage IIB.

RPLND may be considered as an option for stage II seminoma patients who wish to avoid chemotherapy- or radiotherapy-related toxicities. It is recommended for patients with normal post-orchiectomy tumour markers, and performed within 2 weeks of tumour marker testing and 4 weeks of CT or MRI scan.[2][49]​ Low rates of recurrence and low long-term morbidity have been demonstrated with RPLND, with the potential to avoid the long-term toxicity and secondary neoplasm risk associated with chemotherapy or radiotherapy.[80][81]

​​RPLND should be performed by an experienced surgeon at a high-volume specialist centre, ideally as part of a clinical trial.[46][49]​​​

A template dissection or nerve-sparing approach should be considered to reduce the risk of ejaculatory dysfunction.[49]

Information on short-term and long-term adjuvant treatment-related toxicity, such as infertility, major cardiac events, and second malignancy, should be provided to patients to inform shared decision-making.

early stage non-seminoma

1st line – surveillance post-orchiectomy

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ACUTE
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early stage non-seminoma
|
stage I disease
1st line – 

surveillance post-orchiectomy

Surveillance is the preferred option for patients with stage I non-seminoma that has not yet invaded the local structures (no spermatic cord or scrotal involvement), although there is risk of relapse of up to 50% in those with high risk features (evidence of lymphovascular invasion, invasion of the spermatic cord or scrotum, or with a substantial component of embryonal carcinoma).[83] The relapse rate for all patients with surveillance is between 20% and 30%.[84] Lymphovascular invasion increases the risk of relapse, making surveillance less advisable but still an option for those where close follow-up can be ensured.[85]

Information on short-term and long-term adjuvant treatment-related toxicity, such as infertility, major cardiac events, and secondary malignancy, should be provided to patients to inform shared decision-making.

1st line – retroperitoneal lymph node dissection (RPLND) post-orchiectomy

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ACUTE
|
early stage non-seminoma
|
stage I disease
1st line – 

retroperitoneal lymph node dissection (RPLND) post-orchiectomy

RPLND is an alternative option for patients with stage I non-seminoma, with or without high-risk features (evidence of lymphovascular invasion, invasion of the spermatic cord or scrotum, or with a substantial component of embryonal carcinoma).[49] It can be considered if a surveillance strategy is not acceptable to the patient or the patient is unable to adhere to a surveillance schedule.

European guidelines favour adjuvant chemotherapy over RPLND for stage I non-seminoma when surveillance is unsuitable or declined.[46][47]

RPLND is performed in patients with normal post-orchiectomy tumour markers, within 2 weeks of tumour marker testing and 4 weeks of CT or MRI scan.[2][49] RPLND should be performed by an experienced surgeon at a high-volume specialist centre.[49]

A template dissection or nerve-sparing approach should be considered to reduce the risk of ejaculatory dysfunction.[49][103]

Information on short-term and long-term adjuvant treatment-related toxicity, such as infertility, major cardiac events, and secondary malignancy, should be provided to patients to inform shared decision-making.

Following RPLND, adjuvant chemotherapy may be considered if any significant non-teratomatous disease is discovered in the resected lymph nodes.[2][47][49]

1st line – chemotherapy post-orchiectomy

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ACUTE
|
early stage non-seminoma
|
stage I disease
1st line – 

chemotherapy post-orchiectomy

A single cycle of adjuvant bleomycin, etoposide, and cisplatin (BEP) can be considered as an alternative to RPLND for stage I patients, particularly for those with high-risk tumours (evidence of lymphovascular invasion, invasion of the spermatic cord or scrotum, or with substantial component of embryonal carcinoma) and those who decline surveillance.[2][47][87]​​​

European guidelines favour adjuvant chemotherapy over RPLND for stage I non-seminoma when surveillance is unsuitable or declined.[46][47]

See local specialist protocol for dosing guidelines.

Primary options

BEP

bleomycin

and

etoposide

and

cisplatin

1st line – retroperitoneal lymph node dissection (RPLND) post-orchiectomy

Back
ACUTE
|
early stage non-seminoma
|
stage II disease (A/B)
1st line – 

retroperitoneal lymph node dissection (RPLND) post-orchiectomy

Patients with stage II A/B non-seminoma should be managed initially with RPLND or chemotherapy.[2][47]

For stage IIA with normal post-orchiectomy marker levels, the prognosis is excellent with either treatment option, therefore shared decision-making should be used, incorporating the patient’s medical history, values, and goals. For stage IIB patients with normal post-orchiectomy marker levels, chemotherapy is generally preferred as the initial treatment, although RPLND can be considered in highly selected patients.

RPLND is performed in patients with normal post-orchiectomy tumour markers, within 2 weeks of tumour marker testing and 4 weeks of CT or MRI scan.[2][49] RPLND should be performed by an experienced surgeon at a high-volume specialist centre.[49]

A template dissection or nerve-sparing approach should be considered to reduce the risk of ejaculatory dysfunction.[49][86]

Following RPLND, adjuvant chemotherapy may be considered if any significant non-teratomatous disease is discovered in the resected lymph nodes.[2][47][49]

Information on short-term and long-term adjuvant treatment-related toxicity, such as infertility, major cardiac events, and secondary malignancy, should be provided to patients to inform shared decision-making.

1st line – chemotherapy post-orchiectomy

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ACUTE
|
early stage non-seminoma
|
stage II disease (A/B)
1st line – 

chemotherapy post-orchiectomy

Patients with stage II A/B non-seminoma should be managed initially with RPLND or chemotherapy.[2][47]

For stage IIA with normal post-orchiectomy marker levels, the prognosis is excellent with either treatment option, therefore shared decision-making should be used, incorporating the patient’s medical history, values, and goals. For stage IIB patients with normal post-orchiectomy marker levels, chemotherapy is generally preferred.

Chemotherapy for stage II A/B patients typically comprises either 3 cycles of bleomycin, etoposide, and cisplatin (BEP), or 4 cycles of etoposide and cisplatin (EP).[2][46][47][49]

For patients with stage II non-seminoma and persistently elevated post-orchiectomy marker levels, chemotherapy with 3 cycles of BEP or 4 cyclers of EP is recommended because of increased risk of relapse from micrometastatic disease.[2][46][49]

Information on short-term and long-term adjuvant treatment-related toxicity, such as infertility, major cardiac events, and secondary malignancy, should be provided to patients to inform shared decision-making.

See local specialist protocol for dosing guidelines.

Primary options

BEP

bleomycin

and

etoposide

and

cisplatin

OR

EP

etoposide

and

cisplatin

ONGOING

seminoma or non-seminoma: stage IIC or stage III disease

1st line – combination chemotherapy post-orchiectomy

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ONGOING
|
seminoma or non-seminoma: stage IIC or stage III disease
1st line – 

combination chemotherapy post-orchiectomy

Combination chemotherapy is the mainstay of treatment for advanced disease (stage IIC [any tumour size; regional nodes ≥5 cm; with or without slightly raised tumour markers] or stage III [metastatic or spread to regional nodes with high tumour marker levels]), both seminoma and non-seminoma.

Chemotherapy regimens and number of cycles are determined by risk stratification (using the International Germ Cell Cancer Collaborative Group classification criteria) based on post-orchiectomy tumour marker levels and extent of disease from imaging and tumour histology.[2][49][61][62]​ Patients are categorised as: good risk (seminoma stage IIC and IIIA/B; non-seminoma stage II and IIIA); intermediate risk (seminoma stage IIIC; non-seminoma stage IIIB); or poor risk (non-seminoma stage IIIC).

Combination chemotherapy with bleomycin, etoposide, and cisplatin (BEP) is considered a standard first-line treatment for those with advanced disease.[88][89]​ Due to the potential for serious pulmonary toxicity with bleomycin, particularly in older patients, those with reduced kidney function or lung disease, and those who smoke, alternate regimens (such as etoposide and cisplatin [EP], or etoposide, ifosfamide, and cisplatin [VIP]) are used in these patients.

For patients with good-risk disease, 3 cycles of BEP or 4 cycles of EP are recommended.[2][49][90]​ Combination chemotherapy with EP appears to have similar efficacy to BEP in patients with good risk, although a longer course is required.[61][66][90] Choice of regimen should take into account risk of complications and patient preferences.

For patients with intermediate- or poor-risk disease, the standard regimen is 4 cycles of BEP. If bleomycin is contraindicated, patients may be offered VIP as an alternate option, given in 4 cycles.[2][49][89][90]​ For prevention of hemorrhagic cystitis due to ifosfamide, mesna is administered with VIP.[91]

See local specialist protocol for dosing guidelines.

Primary options

BEP

bleomycin

and

etoposide

and

cisplatin

OR

EP

etoposide

and

cisplatin

Secondary options

VIP

etoposide

and

ifosfamide

and

cisplatin

Consider – resection of residual masses

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ONGOING
|
seminoma or non-seminoma: stage IIC or stage III disease
Consider – 

resection of residual masses

Additional treatment recommended for SOME patients in selected patient group

Residual masses are commonly seen on post-chemotherapy imaging studies in those with bulky lymph node or visceral disease at baseline. Surgical resection, rather than further chemotherapy, is the appropriate first-consideration for patients with non-seminoma and residual mass with normal tumour markers (or mildly elevated and not rising).[49][92] If tumour markers are elevated and rising, additional chemotherapy may be considered.

For patients with seminoma, a post-chemotherapy positron emission tomographyy/CT (PET/CT) scan may be used to assess the activity of residual masses greater than 3 cm.[93]​ If PET scan is positive, repeat imaging in 6-8 weeks may be considered, or resection, or biopsy performed to assess for residual seminoma and need for additional therapy.[49] Careful surveillance can be used to follow PET-negative masses, or masses less than 3 cm.

Patients with rising markers or a growing mass should be evaluated for additional chemotherapy or surgery.

seminoma or non-seminoma: relapse disease

1st line – salvage chemotherapy or surgery

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ONGOING
|
seminoma or non-seminoma: relapse disease
1st line – 

salvage chemotherapy or surgery

Patients with relapsed testicular cancer are often cured with second-line salvage chemotherapy regimens.

Conventional salvage chemotherapy options for relapse after primary chemotherapy include ifosfamide-containing combination chemotherapy regimens such as vinblastine, ifosfamide, and cisplatin (VeIP), or paclitaxel, ifosfamide, and cisplatin (TIP).[49][94][95]​ Alternatively, high-dose sequential carboplatin plus etoposide (CE) with autologous stem cell transplant support can be used.[96][97][98][99][100]​ Paclitaxel and ifosfamide may be incorporated into the high-dose CE regimen (paclitaxel, ifosfamide, carboplatin, and etoposide [TI-CE]).[99] Conventional-dose chemotherapy may also be selectively used to reduce tumour bulk or prevent progression prior to high-dose carboplatin and etoposide.[100]

Surgical salvage may be considered as an option for non-seminoma patients with a solitary, resectable recurrent mass, and for those with late relapse (>2 years after primary treatment) if the mass is resectable.[49]

Referral to a high volume centre with experience in treatment of testicular cancer is recommended.

See local specialist protocol for dosing guidelines.

Primary options

VeIP

vinblastine

and

ifosfamide

and

cisplatin

OR

TIP

paclitaxel

and

ifosfamide

and

cisplatin

OR

High-dose CE + autologous stem cell transplant support

carboplatin

and

etoposide

OR

TI-CE + autologous stem cell transplant support

paclitaxel

and

ifosfamide

and

carboplatin

and

etoposide

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Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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