Key points
- Testicular cancer is fairly rare, but it is the most common cancer in young men (roughly 15 to 40 years old) [2, 4].
- The most common sign is a painless lump or swelling in one testicle. If you notice one, see a doctor soon [3, 8].
- Diagnosis is by examination, ultrasound and blood tests, and treatment starts with removing the testicle through the groin; a biopsy through the scrotum is not done [3, 5].
- Testicular cancer is one of the most curable cancers: at the first stage almost all patients are cured, and even when it has spread most patients are cured [5, 6, 7].
- At stage 1, most patients need only regular follow-up (surveillance) after surgery; sometimes a single dose or one short course of chemotherapy is offered [3].
- Before any treatment, even before surgery, ask about sperm banking. Most men can father children after treatment [3, 5].
What is testicular cancer?
The testicles are two oval glands inside the scrotum that make sperm and the male hormone (testosterone). Most testicular cancers start in the cells that make sperm and are called “germ cell tumours” [5]. These tumours fall into two main groups: seminoma and non-seminoma; their treatment and follow-up differ somewhat [5].
Testicular cancer is rare: about 1 in every 100 cancers in men is testicular cancer [2]. In 2024, about 71,000 men worldwide were diagnosed with it and about 9,000 died of it [1]. Unlike most cancers, it is a disease of young men, and it is most common between the ages of 25 and 34 [2]; most patients are 18 to 40 years old at diagnosis [3]. The number of men diagnosed has risen in recent decades, but deaths have fallen sharply thanks to effective treatment [2, 3].
The good news is that in the long term almost all patients survive (about 97 in every 100) [3]. About two-thirds of patients are diagnosed while the cancer is still only in the testicle [2].
Seminoma and non-seminoma
Seminoma is very sensitive to radiotherapy and chemotherapy and spreads to distant organs less often than non-seminoma [5]. Non-seminoma is usually a mixture of several cell types and may contain a part called “teratoma”, which does not respond to chemotherapy and has to be removed by surgery [5]. If a tumour contains even a small non-seminoma part, it is treated as a non-seminoma [5]. The pathologist determines the tumour type after the testicle has been removed.
For physicians
| Marker | Pure seminoma | Non-seminoma | Clinical note |
|---|---|---|---|
| AFP | Not produced | Raised in 40% to 60% | A raised AFP with seminoma histology means a non-seminoma component; treat as non-seminoma unless there is a more convincing explanation such as liver disease |
| Beta-hCG | Raised in about 14% at stage I and in about half with metastatic disease | Raised in 40% to 60% | False positives from cross-reactivity with LH (normalises after an intramuscular testosterone injection) and reports with cannabis use |
| LDH | May be raised | May be raised | Not specific and of little value during surveillance, but an independent prognostic factor in metastatic non-seminoma |
Markers are measured before orchidectomy and repeated afterwards taking their half-lives into account; normal markers do not rule out cancer [3]. Teratoma is resistant to chemotherapy and usually needs surgery [5].
Symptoms of testicular cancer
Testicular cancer usually shows up as a painless lump or swelling in one testicle; sometimes it is found by chance on an ultrasound done for another problem [3]. Most often the man finds it himself [2].
Other signs [8]:
- A change in how the testicle feels
- A dull ache in the lower abdomen or the groin
- A sudden build-up of fluid in the scrotum
- Pain or discomfort in a testicle or in the scrotum
Pain in the scrotum, abdomen or back can also occur and sometimes delays the diagnosis [9]. In a small number of patients the breasts become enlarged, which is why the doctor also checks the chest during the examination [9, 3].
These signs can have causes other than cancer [8], but only an examination and an ultrasound can find the cause. More detail is given in What are the symptoms of testicular cancer?
When should I contact my doctor?
If you have any of these, see a GP or a urologist within the next few days, and do not wait for it to go away on its own [8, 3]:
- Any lump, hardness or swelling in a testicle, even if it is not painful
- A change in the size or feel of one testicle
- A dull ache or discomfort in the scrotum, lower abdomen or groin
- A sudden build-up of fluid in the scrotum
If you are having chemotherapy, tell your treatment team straight away about fever, chills, new shortness of breath or a cough [11, 10]. Details are given in the guide to low blood counts and infection.
Risk factors, testicular self-examination and screening
The exact cause of testicular cancer is not known, and it can also develop in men who have no risk factors [12]. The most important risk factors are:
- An undescended testicle: a testicle that did not come down into the scrotum in childhood raises the risk about threefold [13]. Surgery to bring the testicle down before puberty probably lowers the risk, but this is not certain [5].
- Family history: especially an affected father or brother [5, 12]; in first-degree relatives of a patient, the risk is several times higher [4].
- A previous testicular cancer: someone who has had testicular cancer once is at risk of cancer in the other testicle; this risk is small, affecting about 2 in every 100 men over the following 15 years [14, 5].
- A small or abnormal testicle, precancerous changes in the testicle (“germ cell neoplasia in situ”) and Klinefelter syndrome [12].
- Testicular cancer is more common in white men [12].
Testicular self-examination and screening
For men with no symptoms, regular examination by a doctor or a screening test is not recommended; no study has shown that it lowers deaths, and this cancer can usually be cured at any stage [15, 2]. Even so, most testicular cancers are found by men themselves [2]. The European guideline advises young men to know about the importance of testicular examination; men with a history of an undescended testicle or a personal or family history of testicular cancer in particular should examine their testicles [9].
How do I examine my testicles?
- 1
The right time
After a warm bath or shower, when the skin of the scrotum is soft and relaxed.
- 2
Check each testicle separately
Gently roll the testicle between your thumb and fingers and feel its surface.
- 3
What to look for
A hard lump, swelling, or a change in the size or firmness of the testicle. The soft tube you can feel at the back of the testicle (the epididymis) is a normal part of the body.
- 4
If you notice a change
See a doctor soon [8]. Not every change is cancer, but it needs to be checked with an examination and an ultrasound.
Diagnosis and staging
How testicular cancer is diagnosed
- 1
Examination
The doctor examines both testicles, the abdomen, the area above the collarbones and the chest [3].
- 2
Ultrasound of both testicles
Ultrasound is simple and uses no radiation. It shows whether the lump is inside or outside the testicle, how big it is and whether the other testicle is healthy [3].
- 3
Blood tests before surgery
Three “tumour markers” called AFP, beta-hCG and LDH are measured. They help with the diagnosis and with working out the tumour type, but normal results do not rule out cancer [3, 16]. Read more: What is a tumour marker?
- 4
Sperm banking
If possible, freeze sperm before the testicle is removed [3].
- 5
- 6
A biopsy or operation through the scrotum may carry cancer cells into the scrotum or the lymph nodes of the groin and makes it more likely that the cancer comes back in that area [5, 3]. That is why, when testicular cancer is likely, the whole testicle is removed through the groin. If you have had previous surgery through the scrotum, be sure to tell your doctor, because it affects treatment and follow-up plans [5]. Read more: Does a biopsy spread cancer?
Stages of testicular cancer and prognostic groups
| Stage | What it means | Usual treatment |
|---|---|---|
| Stage 1 | The cancer is only in the testicle | Removal of the testicle; then usually just regular follow-up, sometimes a single dose or one short course of chemotherapy |
| Stage 2 | The cancer has reached the lymph nodes at the back of the abdomen | Chemotherapy; for seminoma sometimes radiotherapy, and for some non-seminomas surgery on the lymph nodes |
| Stage 3 | The cancer has reached more distant lymph nodes, the lungs or other organs, or the blood markers are very high | 3 or 4 courses of chemotherapy depending on the prognostic group, then sometimes surgery to remove remaining masses |
For physicians
| Category | LDH | Beta-hCG (mIU/mL) | AFP (ng/mL) |
|---|---|---|---|
| S0 | Within normal limits | Within normal limits | Within normal limits |
| S1 | Less than 1.5 × upper limit of normal, and | Less than 5,000, and | Less than 1,000 |
| S2 | 1.5 to 10 × upper limit of normal, or | 5,000 to 50,000, or | 1,000 to 10,000 |
| S3 | More than 10 × upper limit of normal, or | More than 50,000, or | More than 10,000 |
Stage I: confined to the testis (IA: pT1; IB: pT2 to pT4; IS: persistently raised markers after orchidectomy). Stage II: retroperitoneal nodes (IIA: up to 2 cm; IIB: 2 to 5 cm; IIC: more than 5 cm). Stage III: distant metastasis (M1a: non-regional nodes or lung; M1b: non-pulmonary visceral) or N+ with S2–S3. pT2 means lymphovascular invasion or invasion of hilar soft tissue, the epididymis or the mesothelial layer; pT3 invasion of the spermatic cord; pT4 invasion of the scrotum (AJCC 8th edition) [5]. Stage IS non-seminoma is treated as metastatic disease [5].
| Group | Criteria | Proportion of patients | 5-year progression-free survival (1997 → 2021) | 5-year overall survival (1997 → 2021) |
|---|---|---|---|---|
| Non-seminoma – good | Testis or retroperitoneal primary, no non-pulmonary visceral metastases, and all of: AFP less than 1,000 ng/mL, beta-hCG less than 5,000 IU/L, LDH less than 1.5 × upper limit of normal | 56% to 61% | 89% → 90% | 92% → 96% |
| Non-seminoma – intermediate | Testis or retroperitoneal primary, no non-pulmonary visceral metastases, and any of: AFP 1,000 to 10,000, beta-hCG 5,000 to 50,000 or LDH 1.5 to 10 × upper limit of normal | 13% to 28% | 75% → 78% | 80% → 89% |
| Non-seminoma – poor | Mediastinal primary, or non-pulmonary visceral metastases, or any of: AFP more than 10,000, beta-hCG more than 50,000 or LDH more than 10 × upper limit of normal | 16% to 26% | 41% → 54% | 48% → 67% |
| Seminoma – good | Any primary site, no non-pulmonary visceral metastases, normal AFP, any beta-hCG and LDH | 90% | 82% → 89% | 86% → 95% |
| Seminoma – intermediate | Any primary site, with non-pulmonary visceral metastases, normal AFP, any beta-hCG and LDH | 10% | 67% → 79% | 72% → 88% |
Seminoma has no poor-prognosis group. The proportions of patients are from the original data [5]. The 2021 update (9,728 non-seminoma and 2,451 seminoma patients treated with cisplatin- and etoposide-based regimens between 1990 and 2013) added LDH above 2.5 × the upper limit of normal as an adverse factor and, in non-seminoma, older age and lung metastases as well; the EORTC online calculator is based on this, but the original classification remains the reference for treatment decisions [6, 7]. Pre-chemotherapy markers should be measured on the day chemotherapy starts [3].
Testicular cancer survival rates and chances of cure
| Situation | Out of every 10 patients |
|---|---|
| Stage 1 (only in the testicle) | Almost all are cured, whether with regular follow-up or with a short treatment after surgery |
| Stage 2 (lymph nodes at the back of the abdomen) | More than 9 are cured |
| Spread, good prognosis group | More than 9 are alive after 5 years |
| Spread, intermediate prognosis group | About 9 are alive after 5 years |
| Spread, poor prognosis group (non-seminoma only) | About 7 (about 2 in every 3) are alive after 5 years |
These figures come from patients treated between 1990 and 2013 and cannot predict any one person’s future exactly; your doctor will explain what they mean for you.
Treatment of testicular cancer by stage
Treatment options for testicular cancer
Regular follow-up (surveillance)
A single dose of carboplatin
In stage 1 seminoma, a single injection of the drug carboplatin, instead of follow-up alone, lowers the risk of the cancer coming back [21, 3].
Chemotherapy
Radiotherapy
Seminoma is very sensitive to radiation. Today it is used mostly at stage 2 as an alternative to chemotherapy, because after many years it raises the risk of a second cancer [3, 5]. Read more: What is radiotherapy?
Surgery on the lymph nodes at the back of the abdomen
High-dose chemotherapy with the patient’s own stem cells
For some patients whose cancer has come back after chemotherapy; even in this situation some patients are cured [24]. Read more: Stem cell transplant
Stage 1 seminoma
More than 8 in every 10 men are cured by removing the testicle alone and their cancer does not come back [3]. That is why the European guideline sees regular follow-up (surveillance) as the preferred option, as long as the patient attends every appointment [3]. If the cancer comes back during follow-up, it is almost always cured with chemotherapy or radiotherapy [5].
If you do not want follow-up alone, a single dose of carboplatin is another option. In a large study of about 1,500 men, its results were almost the same as radiotherapy, and new cancer in the other testicle was seen less often [20, 21]. Radiotherapy is now used only for a few selected patients [3].
Stage 1 non-seminoma
About 7 in every 10 men are cured by surgery alone [5]. The most important sign of a higher risk of the cancer coming back is “lymphovascular invasion”, meaning the pathologist sees cancer cells inside the small vessels of the testicle; in that case, without further treatment, up to half of patients relapse [3].
If this sign is absent, regular follow-up is usually advised. If it is present, one course of chemotherapy (BEP) is the preferred option and brings relapses down to about 3 in every 100 men; follow-up remains an option too [3, 22]. Surgery on the lymph nodes at the back of the abdomen is done only for a few selected patients and in experienced centres [3].
Stage 2: lymph nodes at the back of the abdomen
In stage 2 seminoma with nodes smaller than 5 cm, the European guideline’s preferred option is 3 courses of BEP chemotherapy (or 4 courses without bleomycin), with radiotherapy to the nodes at the back of the abdomen as an alternative [3]. Most patients are cured with either; short-term side effects are more common with chemotherapy and late effects (such as bowel problems and second cancers in the radiation area) with radiotherapy [3]. If the nodes are larger than 5 cm, chemotherapy is the main treatment [3, 5].
In stage 2 non-seminoma, chemotherapy is given if the blood markers are raised; if the markers are normal and the nodes small, surgery on the lymph nodes at the back of the abdomen is sometimes done first [3]. Lymph node surgery instead of chemotherapy or radiotherapy for seminoma is still experimental [23, 3].
Stage 3 and spread disease
When the cancer has reached more distant lymph nodes, the lungs or other organs, chemotherapy is the main treatment: 3 courses of BEP in the good prognosis group and 4 courses in the intermediate and poor groups [3]. If a patient cannot have bleomycin (for example because of lung disease), another combination is used instead [3]. Chemotherapy should be given on time and at full dose [3]. Read more: How many chemotherapy sessions are there?
Results are very good: in the good prognosis group almost all patients, and in the poor group about 2 in every 3, are alive after 5 years [6, 7]. If a mass larger than 1 cm remains after chemotherapy in non-seminoma, it is removed by surgery, because it may contain living cancer or teratoma [3, 5].
If the cancer comes back
Even if the cancer comes back after chemotherapy, a cure is still possible. With “salvage chemotherapy” (combinations based on cisplatin and ifosfamide, usually 4 courses), about half of patients achieve a long-lasting remission [3]. For some patients, high-dose chemotherapy followed by return of the patient’s own stem cells is used; at one large centre, more than half of these patients stayed free of disease [24]. A large international study is comparing these two approaches and its results have not yet been reported [25]. Relapse should be treated in specialist centres [3].
Fertility, male hormones and sex life
Many men with testicular cancer have lower sperm quality even before treatment, and surgery, chemotherapy and radiotherapy can also reduce fertility [3, 5]. That is why freezing sperm (sperm banking) should be offered before treatment and, if possible, before the testicle is removed [3, 26]. If a semen sample is not possible, sperm can be taken directly from the testicle [26].
The good news is that most men can father children after treatment; in two large studies about 7 in every 10 men had children after treatment, often without needing frozen sperm [5]. It is advised to wait at least 3 months after finishing chemotherapy before trying for a pregnancy, unless using sperm frozen before treatment [5]. Sperm counts fall after radiotherapy but may recover within 1 to 2 years [5]. Nerve-sparing surgery on the lymph nodes at the back of the abdomen preserves ejaculation in almost all patients [5].
In some survivors, especially after chemotherapy, testosterone (the male hormone) levels are low, which can raise the risk of metabolic and heart disease; so it should be measured during follow-up and treated if needed [3]. If you wish, an artificial testicle can be fitted [9].
Read more: guide to fertility and sex during cancer treatment. For doctors: fertility preservation before cancer treatment.
Life after treatment: follow-up and late effects
After treatment, a regular follow-up plan (examinations, blood tests and scans) is important, especially in the first 2 to 3 years, when most relapses happen [18, 3]. Examine your remaining testicle regularly too and tell your doctor about any change promptly [27].
Because patients are young and have decades of life ahead, late effects matter [3]:
- Heart and blood vessels: chemotherapy and radiotherapy raise the risk of high blood pressure, high cholesterol and heart disease in later years [3, 28].
- Hearing: cisplatin may reduce hearing of high-pitched sounds or cause ringing in the ears (tinnitus); the higher the total dose, the more likely this is [29, 5].
- Nerves: tingling and numbness in the hands and feet [11]; see the guide to peripheral neuropathy.
- Second cancers: after many years the risk of other cancers is slightly higher, especially after radiotherapy [5, 3].
- Low testosterone in some patients [3].
Things you can do: do not smoke, exercise, keep your blood pressure and cholesterol under control and avoid loud noise [3, 29].
What should I do after diagnosis?
Frequently asked questions
Can you have children with one testicle?
Yes, most men can. In two large studies, about 7 in every 10 men became fathers after treatment for testicular cancer, often without needing frozen sperm [5]. Because chemotherapy and radiotherapy can reduce fertility, it is best to freeze sperm before treatment [3, 26]. After chemotherapy, wait at least 3 months before trying for a pregnancy [5].
Is testicular cancer curable?
Is testicular cancer painful?
What happens to male hormones and sexual function after a testicle is removed?
Why did the doctor remove the testicle straight away instead of taking a biopsy?
If my cancer is stage 1, do I definitely need chemotherapy?
No. Most stage 1 patients need only regular follow-up, and if the cancer comes back it is almost always cured [3, 18]. A single dose of carboplatin (for seminoma) or one course of chemotherapy (for high-risk non-seminoma) is an option to lower the chance of relapse [3].
How many courses of chemotherapy are used for testicular cancer?
Is testicular cancer hereditary?
Evidence and recent advances (for physicians)
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First-line chemotherapy for metastatic disease
BEP replaced PVB: in the randomised trial by Williams and colleagues (261 patients; 244 evaluable), 83% with the etoposide regimen vs 74% with the vinblastine regimen became disease-free (not significant); in 157 patients with high tumour volume, 77% vs 61% (P less than 0.05), survival was better with BEP (P = 0.048), and paraesthesia, abdominal cramps and myalgia were less frequent [30].
Good prognosis: 3 cycles are enough, but do not omit bleomycin. In the SECSG trial (184 patients), 92% of patients in both the 3-cycle and 4-cycle PVP16B arms remained continuously disease-free [31]. In the EORTC/MRC factorial trial (812 patients), 2-year progression-free survival was 90.4% with 3 cycles vs 89.4% with 4 cycles, and the 3-day schedule was equivalent to the 5-day schedule (89.7% vs 88.8%); quality of life was better preserved with 3 cycles [19]. In the Australian and New Zealand trial, the Indiana regimen (3 cycles of 5-day BEP with bleomycin on days 1, 8 and 15) had fewer deaths than 4 cycles with a lower dose and dose intensity of bleomycin and etoposide (3 vs 13; HR 0.22; 95% CI 0.06–0.77) [32]. Omitting bleomycin from a 3-cycle regimen lowered failure-free survival (86% vs 69%) and overall survival (95% vs 86%) [33]. Four cycles of EP vs 3 cycles of BEP did not differ in favourable response, but the trend favoured BEP (4-year event-free survival 91% vs 86%; 5 vs 12 deaths; neither significant, and the trial was underpowered for survival) [34]. For good prognosis, the EAU recommends 5-day BEP×3 as standard and EP×4 only when bleomycin is contraindicated [3].
Intermediate and poor prognosis: 4 cycles of BEP are standard [3]. VIP had similar efficacy but more toxicity in two randomised trials: in the Intergroup trial (304 patients), 2-year overall survival was 74% vs 71%, with more grade 3 or higher toxicity (especially haematological and genitourinary) [35], and in the EORTC trial in intermediate prognosis (84 patients), 5-year progression-free survival was 85% vs 83%, with leucocytes below 2,000 in 89% vs 37% [36]. In poor prognosis, the GETUG 13 trial measured markers on days 18–21 after one cycle of BEP: 20% had a favourable decline, and 203 patients with an unfavourable decline were randomised to continued BEP or a dose-dense regimen; 3-year progression-free survival was 59% vs 48% (HR 0.66; 95% CI 0.44–1.00; P = 0.05) [37]. In the updated report (median follow-up 7.1 years), 5-year progression-free survival was 58.9% vs 46.7% (HR 0.65; 0.44–0.97) and 5-year overall survival 70.9% vs 61.3% (HR 0.74; 0.46–1.20; P = 0.22) [38]. Upfront high-dose chemotherapy has not shown an overall survival benefit in randomised trials [3].
Stage I: surveillance, carboplatin and one cycle of BEP
Active surveillance: in 2,483 patients with clinical stage I disease (1,139 non-seminoma and 1,344 seminoma), relapse occurred in 19% of non-seminoma and 13% of seminoma patients; median time to relapse was 4 months (non-seminoma with lymphovascular invasion), 8 months (non-seminoma without it) and 14 months (seminoma); 90% of non-seminoma relapses occurred within 2 years and 92% of seminoma relapses within the first 3 years, 99% of seminoma relapses had IGCCCG good-prognosis features, and 5-year disease-specific survival was 99.7% [18]. In seminoma, tumour size greater than 4 cm and invasion of the rete testis are associated with relapse: the 5-year relapse risk is about 10% with neither factor, 16% with one and 32% with both [5]. The EAU regards surveillance as the preferred option and does not recommend adjuvant treatment in patients without risk factors [3].
Carboplatin vs radiotherapy (MRC TE19/EORTC 30982): 1,477 patients with stage I seminoma were randomised to radiotherapy (para-aortic or dog-leg) or one injection of carboplatin dosed at 7 × (GFR + 25) mg; at a median follow-up of 4 years, 2-year relapse-free survival was 96.7% vs 97.7% (HR 1.28; 90% CI 0.85–1.93), and new contralateral germ cell tumours occurred in 10 patients in the radiotherapy arm vs 2 in the carboplatin arm [20]. In the mature results (median 6.5 years), the 5-year relapse-free rate was 94.7% with carboplatin and 96.0% with radiotherapy (HR 1.25; 90% CI 0.83–1.89), contralateral tumours were 2 vs 15 (HR 0.22; P = 0.03), and patients who received at least 99% of the dose had a 5-year relapse-free rate of 96.1% vs 92.6% with a lower dose [21]. In TE18, 20 Gy in 10 fractions vs 30 Gy in 15 fractions had similar relapse rates (11 vs 10 relapses) and less moderate to severe lethargy at week 4 (5% vs 20%) [39]; however, radiotherapy increases the risk of second non-germ cell cancers, and the EAU does not recommend it routinely [3, 5].
Stage I non-seminoma: on surveillance, about 30% relapse (5-year conditional risk 42% in high-risk and 17% in low-risk disease) [3]. In SWENOTECA, 517 patients received one cycle of adjuvant BEP; at a median follow-up of 7.9 years, 5-year relapse was 3.2% with lymphovascular invasion and 1.6% without it, and 5-year cause-specific survival was 100% [22]. In the 111 trial (246 patients with vascular invasion), one cycle of 3-day BE500P gave a 2-year malignant recurrence rate of 1.3% (95% CI 0.3–3.7%), with grade 3–4 febrile neutropenia in 6.8% [41]. For patients with lymphovascular invasion, the EAU regards one cycle of BEP as the preferred adjuvant option and primary RPLND as an option only for highly selected patients [3].
Stage II and salvage treatment
Seminoma IIA/IIB: in the German trial, radiotherapy with 30 Gy (IIA) and 36 Gy (IIB) to the para-aortic and high ipsilateral iliac nodes gave 6-year relapse-free survival of 95.3% and 88.9% [40]. The EAU reports relapse rates of 9–24% and 5-year relapse-free survival of 92% (IIA) and 90% (IIB) with radiotherapy and regards chemotherapy (BEP×3 or EP×4) as the preferred option in both [3]. Primary RPLND in PRIMETEST (33 patients) missed its primary endpoint (30% recurrence at a median follow-up of 32 months) and is not recommended outside trials [23, 3].
Salvage treatment: cisplatin-based salvage chemotherapy gives long-term remission in about 50% of relapsed patients, and the regimens of choice are 4 cycles of VIP, TIP or GIP [3]. TIP in 46 patients with favourable prognostic factors (testis primary and prior complete response) gave a complete response rate of 70%, a durable complete response rate of 63% and 2-year progression-free survival of 65% [42]. In the Indiana experience (184 patients), two consecutive courses of carboplatin 700 mg/m² and etoposide 750 mg/m² (each for 3 days) with autologous peripheral-blood stem-cell rescue kept 116 patients free of relapse at a median follow-up of 48 months: 94 of 135 treated in the second line, 22 of 49 in the third line or later and 18 of 40 with platinum-refractory disease; there were 3 treatment-related deaths and 3 cases of acute leukaemia [24]. In the randomised IT-94 trial (280 patients), one high-dose course (CarboPEC) after 3 conventional cycles did not improve 3-year event-free survival (42% vs 35%; P = 0.16) or overall survival, and toxic deaths were 7% vs 3% [43]; a secondary analysis of the IPFSG cohort (1,600 patients) showed a 10–15% improvement in overall survival with high-dose therapy [3]. The phase 3 TIGER trial (420 patients) compares TIP with TI-CE (paclitaxel and ifosfamide for stem-cell mobilisation, then 3 cycles of high-dose carboplatin and etoposide) as first salvage treatment, with overall survival as the primary endpoint; accrual is complete and results have not yet been reported (estimated primary completion: 2031) [25].
Survivorship follow-up and late effects
The EAU recommends screening for and treating hypertension, dyslipidaemia and testosterone deficiency during follow-up; a 35-year cumulative incidence of second malignancies of 20% (95% CI 18.9–21.5%) has been reported, and cardiovascular mortality is higher than in the general population [3]. In a median 19-year follow-up of 990 Norwegian survivors, BEP alone increased the risk of coronary artery disease 5.7-fold compared with surgery alone (95% CI 1.9–17.1) and the risk of myocardial infarction 3.1-fold compared with population controls [28]. In 488 survivors, every 100 mg/m² of cumulative cisplatin worsened the hearing threshold (4–12 kHz) by 3.2 dB; 18% had severe to profound hearing loss and 40% tinnitus, and routine inquiry about hearing, audiology referral and blood pressure control were recommended [29]. Cumulative cisplatin above 850 mg was associated with a threefold risk of restrictive lung disease; etoposide at standard cumulative doses (less than 2 g/m²) carries a relative risk of 15 to 25 for secondary leukaemia, which translates into a cumulative incidence of less than 0.5% at 5 years [5]. Cardiovascular monitoring: cardiac monitoring during cancer treatment.
- The role of high-dose chemotherapy as first salvage remains uncertain until TIGER reports; use TI-CE only in a trial or in specialist centres [25, 3].
- Primary RPLND in stage II seminoma and de-escalation strategies only in trials or high-volume centres [23, 3].
- miR-371a-3p is an emerging marker with higher accuracy than conventional markers, but it is not yet standardised for routine use [3].
Treatment regimens and dosing (for physicians)
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Treatment regimens and doses: index12 regimens
- Bleomycin (BEP and other bleomycin-containing regimens): pulmonary toxicity occurs in 10% and death from pulmonary fibrosis in about 1% of patients; the risk is higher with older age and a total dose above 400 units, but it has been seen in young patients and at low doses, and in combination with other drugs it can occur at lower doses. The earliest symptom is dyspnoea and the earliest sign fine crackles; take chest X-rays every 1 to 2 weeks, and if DLCO is used for monitoring, measure it monthly; stop the drug if DLCO falls below 30% to 35% of the pre-treatment value or if pulmonary changes appear. Reduce the dose when CrCl is below 50 mL/min (40–50: 70%; 30–40: 60%; 20–30: 55%; 10–20: 45%; 5–10: 40% of the dose). During later surgery (for example RPLND), keep FiO2 close to room air (25%) and manage fluids carefully [10]. Pulmonary toxicity is rarely fatal at cumulative doses below 400 units [5].
- Cisplatin: adequate hydration before, during and after the infusion; monitor creatinine, BUN and electrolytes (including magnesium and potassium); give highly effective antiemetic premedication; consider audiometric assessment [11]. Antiemetic choice: antiemetic regimen.
- Ifosfamide (VIP, TIP and the GETUG 13 regimen): hydration of at least 2 litres per day and mesna to prevent haemorrhagic cystitis [45].
- Full dose, on time: give BEP at 21-day intervals without delay or dose reduction [3]. Measure pre-chemotherapy markers (for IGCCCG grouping) on the day chemotherapy starts [3]. Primary G-CSF prophylaxis: G-CSF decision tool and management of febrile neutropenia.
- Thromboembolism: patients with metastatic disease on chemotherapy are at high risk; weigh the benefits and risks of thromboprophylaxis individually and avoid central venous catheters whenever possible (weak EAU recommendations) [3]. Cancer-associated thrombosis.
- Sperm banking before any treatment, preferably before orchidectomy [3, 26].
Adjuvant treatment of stage I after orchidectomy
Single-dose carboplatin AUC 7 (stage I seminoma)
Clinical stage I seminoma after radical inguinal orchidectomy, when adjuvant treatment is chosen instead of active surveillance (surveillance is preferred; adjuvant treatment is not recommended in patients without risk factors)Cycle length: Single dose
Clinical stage I seminoma after radical inguinal orchidectomy, when adjuvant treatment is chosen instead of active surveillance (surveillance is preferred; adjuvant treatment is not recommended in patients without risk factors)
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Carboplatin | AUC 7; dose (mg) = 7 × (GFR + 25) | IV | Day 1, once |
Dosing as in the MRC TE19/EORTC 30982 trial [20, 21]: GFR was measured with a radioisotope (EDTA) method, and patients whose GFR was estimated from creatinine clearance received 90% of this dose [21]. Do not reduce the dose: patients who received at least 99% of the dose had a 5-year relapse-free rate of 96.1% vs 92.6% with a lower dose [21]. Dosing based on calculated creatinine clearance is not equivalent and has not been validated in this setting [5]. EAU recommendation: if adjuvant treatment is considered, one dose of carboplatin AUC 7 (strong) [3]. Calculation: carboplatin dose calculator.
Evidence: MRC TE19/EORTC 30982 (2011)
One cycle of adjuvant BEP (stage I non-seminoma)
Clinical stage I non-seminoma with lymphovascular invasion (the EAU’s preferred adjuvant option), or without it in patients who do not want or cannot undergo surveillanceCycle length: One 21-day cycle
Clinical stage I non-seminoma with lymphovascular invasion (the EAU’s preferred adjuvant option), or without it in patients who do not want or cannot undergo surveillance
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Bleomycin | 30 units (30 mg) | IV (or IM) | Days 1, 8 and 15 |
| Etoposide | 100 mg/m² | IV | Days 1 to 5 |
| Cisplatin | 20 mg/m² | IV | Days 1 to 5 |
The doses of each cycle are those of standard 5-day BEP [19]; SWENOTECA used one cycle of BEP [22]. In the 111 trial, one cycle of 3-day BE500P was given: bleomycin 30,000 IU on days 1, 8 and 15, etoposide 165 mg/m² on days 1 to 3 and cisplatin 50 mg/m² on days 1 and 2, with antibacterial and G-CSF prophylaxis [41]. EAU recommendation [3]. Stage I with persistently raised markers after orchidectomy (IS) is treated as metastatic disease [3, 5].
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Radiotherapy for seminoma
Adjuvant radiotherapy 20 Gy (stage I seminoma)
Only highly selected patients who are unsuitable for surveillance and have a contraindication to chemotherapy (EAU: do not give adjuvant radiotherapy routinely)Cycle length: —
Only highly selected patients who are unsuitable for surveillance and have a contraindication to chemotherapy (EAU: do not give adjuvant radiotherapy routinely)
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| External-beam radiotherapy to the para-aortic nodes (strip field) or a dog-leg field | 20 Gy in 10 fractions | External-beam radiotherapy | 10 daily fractions over 2 weeks |
Radiotherapy 30 Gy (stage IIA seminoma)
Clinical stage IIA seminoma; an alternative to chemotherapy (BEP×3 or EP×4 is the EAU’s preferred option)Cycle length: —
Clinical stage IIA seminoma; an alternative to chemotherapy (BEP×3 or EP×4 is the EAU’s preferred option)
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| External-beam radiotherapy to the para-aortic and ipsilateral iliac nodes | 30 Gy (2 Gy × 15 fractions) | External-beam radiotherapy | 15 daily fractions |
Radiotherapy 36 Gy (stage IIB seminoma)
Clinical stage IIB seminoma (nodes 2 to 5 cm); an alternative to chemotherapy (BEP×3 or EP×4 is the EAU’s preferred option)Cycle length: —
Clinical stage IIB seminoma (nodes 2 to 5 cm); an alternative to chemotherapy (BEP×3 or EP×4 is the EAU’s preferred option)
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Base field | |||
| External-beam radiotherapy to the para-aortic and ipsilateral iliac nodes | 30 Gy (2 Gy × 15 fractions) | External-beam radiotherapy | 15 daily fractions |
| Boost | |||
| Boost to the enlarged lymph nodes | 6 Gy (2 Gy × 3 fractions) | External-beam radiotherapy | 3 fractions after the base field |
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
First-line chemotherapy for metastatic disease (by IGCCCG group)
BEP, 3 cycles (good prognosis)
Metastatic seminoma or non-seminoma with IGCCCG good prognosis; also stage IIA/IIB seminoma (the EAU’s preferred option) and stage IIA/IIB non-seminoma with raised markersCycle length: Every 21 days
Metastatic seminoma or non-seminoma with IGCCCG good prognosis; also stage IIA/IIB seminoma (the EAU’s preferred option) and stage IIA/IIB non-seminoma with raised markers
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Bleomycin | 30 units (30 mg) | IV (or IM) | Days 1, 8 and 15 |
| Etoposide | 100 mg/m² | IV | Days 1 to 5 |
| Cisplatin | 20 mg/m² | IV | Days 1 to 5 |
Doses as in the EORTC/MRC trial [19] and the Indiana regimen in the ANZ trial [32]; cisplatin and etoposide doses are within the FDA label ranges [11, 44]. EAU: 5-day schedule at 21-day intervals without delay or dose reduction [3]. A 3-day schedule (etoposide 165 mg/m² on days 1 to 3 and cisplatin 50 mg/m² on days 1 and 2) was equivalent in efficacy in the EORTC/MRC trial [19]. Full regimen page: BEP regimen.
EP, 4 cycles (good prognosis with a contraindication to bleomycin)
IGCCCG good prognosis (seminoma or non-seminoma) when bleomycin is contraindicated (for example lung disease); otherwise omitting bleomycin is not recommendedCycle length: Every 21 days
IGCCCG good prognosis (seminoma or non-seminoma) when bleomycin is contraindicated (for example lung disease); otherwise omitting bleomycin is not recommended
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Etoposide | 100 mg/m² | IV | Days 1 to 5 |
| Cisplatin | 20 mg/m² | IV | Days 1 to 5 |
BEP, 4 cycles (intermediate or poor prognosis)
Seminoma with intermediate prognosis and non-seminoma with IGCCCG intermediate or poor prognosis; in poor prognosis, continue BEP if the marker decline after cycle 1 is favourableCycle length: Every 21 days
Seminoma with intermediate prognosis and non-seminoma with IGCCCG intermediate or poor prognosis; in poor prognosis, continue BEP if the marker decline after cycle 1 is favourable
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Bleomycin | 30 units (30 mg) | IV (or IM) | Days 1, 8 and 15 |
| Etoposide | 100 mg/m² | IV | Days 1 to 5 |
| Cisplatin | 20 mg/m² | IV | Days 1 to 5 |
Doses of each cycle as for 3 cycles of BEP [19, 11, 44]; in the 4-cycle BEP arm of the EORTC trial, bleomycin 30 mg was given weekly for 12 weeks [36]. Place in therapy as in the EAU guideline [3]. In poor prognosis, measure AFP and beta-hCG on days 18–21 of cycle 1; with an unfavourable decline, consider intensification (GETUG 13 regimen) [37, 3]. With impaired lung function, VIP is the alternative [3].
VIP, 4 cycles (bleomycin contraindicated; intermediate or poor prognosis, or salvage)
IGCCCG intermediate or poor prognosis with a contraindication to bleomycin (for example impaired lung function); also one of the regimens of choice for salvage treatment
IGCCCG intermediate or poor prognosis with a contraindication to bleomycin (for example impaired lung function); also one of the regimens of choice for salvage treatment
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Etoposide | 75 mg/m² | IV | Days 1 to 5 |
| Ifosfamide | 1.2 g/m² | IV, infusion over at least 30 minutes | Days 1 to 5 |
| Cisplatin | 20 mg/m² | IV | Days 1 to 5 |
| Mesna | As per institutional protocol | IV | With each ifosfamide dose |
Doses as in the VIP regimen described in the FDA ifosfamide label (etoposide 75, ifosfamide 1.2 g and cisplatin 20 mg/m² on days 1 to 5); hydration of at least 2 litres per day and mesna to prevent haemorrhagic cystitis [45]. Efficacy similar to BEP in the first line, with more haematological and genitourinary toxicity [35, 36]; place in therapy as in the EAU guideline [3]. Myelosuppression is more severe: leucocytes below 2,000 in 89% vs 37% with BEP [36]; consider G-CSF prophylaxis.
GETUG 13 dose-dense regimen (poor prognosis with an unfavourable marker decline)
Non-seminoma with IGCCCG poor prognosis and an unfavourable AFP or beta-hCG decline on days 18–21 after one cycle of BEP; experienced centres only
Non-seminoma with IGCCCG poor prognosis and an unfavourable AFP or beta-hCG decline on days 18–21 after one cycle of BEP; experienced centres only
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Phase 1: 2 cycles of T-BEP-oxaliplatin | |||
| Paclitaxel | 175 mg/m² | IV over 3 hours | Day 1, before BEP |
| Bleomycin, etoposide and cisplatin | Standard BEP doses | IV (bleomycin IV or IM) | As for BEP |
| Oxaliplatin | 130 mg/m² | IV over 3 hours | Day 10 |
| Phase 2: 2 cycles of cisplatin, ifosfamide and bleomycin | |||
| Cisplatin | 100 mg/m² | IV over 2 hours | Day 1 |
| Ifosfamide | 2 g/m² | IV over 3 hours | Days 10, 12 and 14 |
| Mesna | 500 mg/m² | IV | At hours 0, 3, 7 and 11 on ifosfamide days |
| Bleomycin | 25 units per day | Continuous 24-hour IV infusion | Days 10 to 14 |
Doses as in the GETUG 13 trial, with G-CSF (lenograstim) support [37]. It improved progression-free survival without a significant overall survival benefit [37, 38]. EAU: with an unfavourable marker decline after one cycle of BEP, switch to the dose-dense regimen (weak recommendation) [3]. In long-term follow-up, 3 patients in the dose-dense arm had grade 3 motor neurotoxicity in the first year [38].
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Salvage treatment: relapsed or refractory disease
TIP, 4 cycles (first salvage)
Relapse after cisplatin-based first-line chemotherapy; best results in patients with a testis primary and a prior complete responseCycle length: Every 21 days
Relapse after cisplatin-based first-line chemotherapy; best results in patients with a testis primary and a prior complete response
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Paclitaxel | 250 mg/m² | IV over 24 hours (with premedication) | Day 1 |
| Ifosfamide | 1,500 mg/m² | IV, with mesna | Days 2 to 5 |
| Cisplatin | 25 mg/m² | IV | Days 2 to 5 |
| Pegfilgrastim (or daily G-CSF) | 6 mg | Subcutaneous | Day 6 or 7 (daily G-CSF: days 6 to 18) |
Doses as in the TIP arm of the TIGER trial in the ClinicalTrials.gov registry, with premedication (for example dexamethasone, diphenhydramine and an H2 blocker) [25]. Durable complete response 63% in selected patients [42]. EAU: VIP, TIP or GIP, 4 cycles [3]. Hydration and mesna with ifosfamide [45].
High-dose carboplatin and etoposide with autologous stem-cell rescue (2 consecutive courses)
Metastatic germ cell tumour progressing after cisplatin-based chemotherapy (second line or later, including platinum-refractory disease); experienced transplant centres only
Metastatic germ cell tumour progressing after cisplatin-based chemotherapy (second line or later, including platinum-refractory disease); experienced transplant centres only
Before prescribing: Common safety considerations| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Carboplatin | 700 mg/m² | IV | Daily for 3 consecutive days |
| Etoposide | 750 mg/m² | IV | Daily for 3 consecutive days |
| Autologous peripheral-blood stem cells | — | IV infusion | After each course |
Doses as in the Indiana University experience; in 110 patients, 1 or 2 cycles of VeIP (vinblastine, ifosfamide and cisplatin) were given for cytoreduction before high-dose therapy [24]. A single high-dose course after 3 conventional cycles gave no benefit in a randomised trial [43]. A randomised comparison with TIP as first salvage (TIGER) is ongoing [25]. Transplant indications and conditioning.
Evidence: High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors (2007)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Scientific evidence
Show detailsHide
Key studies
6 itemsRandomized trial of carboplatin versus radiotherapy for stage I seminoma: mature results on relapse and contralateral testis cancer rates in MRC TE19/EORTC 30982 study (ISRCTN27163214)
Patterns of relapse in patients with clinical stage I testicular cancer managed with active surveillance
Equivalence of three or four cycles of bleomycin, etoposide, and cisplatin chemotherapy and of a 3- or 5-day schedule in good-prognosis germ cell cancer: a randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council
Treatment of Disseminated Germ-Cell Tumors with Cisplatin, Bleomycin, and either Vinblastine or Etoposide
Predicting Outcomes in Men With Metastatic Nonseminomatous Germ Cell Tumors (NSGCT): Results From the IGCCCG Update Consortium
High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors
Guidelines and further sources
3 itemsEuropean Association of Urology Guidelines on Testicular Cancer: 2023 Update
Fertility Preservation in People With Cancer: ASCO Guideline Update
National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Testicular, Prostate, Colorectal, Breast, and Ovarian Cancers
Common questions
Treatment regimens (physicians)
References
45 referencesShow all references, 9 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
- 1Testis fact sheet (GLOBOCAN 2024)
- 2
- 3European Association of Urology Guidelines on Testicular Cancer: 2023 UpdateStudy cardDOIPubMed Back to text: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107
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- 13A meta-analysis of the risk of boys with isolated cryptorchidism developing testicular cancer in later life
- 14Risk of contralateral testicular cancer: a population-based study of 29,515 U.S. men
- 15Testicular Cancer: Screening (reaffirmation recommendation statement)
- 16National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers
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- 19Equivalence of three or four cycles of bleomycin, etoposide, and cisplatin chemotherapy and of a 3- or 5-day schedule in good-prognosis germ cell cancer: a randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council
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- 25TIGER: Conventional-dose chemotherapy with paclitaxel, ifosfamide and cisplatin (TIP) versus high-dose chemotherapy with paclitaxel plus ifosfamide followed by high-dose carboplatin and etoposide (TI-CE) as first salvage treatment in relapsed or refractory germ cell tumors (NCT02375204)
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- 30Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide
- 31Evaluation of optimal duration of chemotherapy in favorable-prognosis disseminated germ cell tumors: a Southeastern Cancer Study Group protocol
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