INTRODUCTION — Testicular cancers are among the most curable solid neoplasms; the five-year survival rate is over 95 percent. Initial therapy of early stage testicular germ cell tumors (GCTs) is based on histology and tumor extent.
An overview of therapy for males with testicular GCTs is presented here. The clinical manifestations, diagnosis, and staging are presented separately, as are more detailed discussions of specific clinical scenarios.
●(See "Clinical manifestations, diagnosis, and staging of testicular germ cell tumors".)
●(See "Treatment of stage I seminoma".)
●(See "Treatment of stage II seminoma".)
●(See "Management of stage I nonseminomatous germ cell tumors".)
●(See "Management of stage II nonseminomatous germ cell tumors".)
INITIAL DIAGNOSIS AND MANAGEMENT — The diagnosis of a testicular malignancy is generally established at radical orchiectomy, which also serves as the initial treatment for the primary tumor. Subsequent therapy depends on the presence or absence of more extensive disease, histology, or other risk factors (algorithm 1 and algorithm 2 and algorithm 3).
Whenever possible, a baseline sperm count and sperm banking should be performed prior to orchiectomy and further therapy. Semen cryopreservation should be made available to all males diagnosed with testicular cancer prior to instituting therapy if they wish to preserve fertility. (See "Clinical manifestations, diagnosis, and staging of testicular germ cell tumors", section on 'Cryopreservation of sperm'.)
For males who present with clinically advanced disease, we perform a radical orchiectomy prior to chemotherapy whenever possible. Despite this, there are some males who present with life-threatening advanced disease who undergo systemic chemotherapy prior to orchiectomy ("delayed orchiectomy"). In such patients, the diagnosis should be obtained by biopsy of a metastatic lesion prior to treatment. (See "Radical inguinal orchiectomy for testicular germ cell tumors".)
SEMINOMA VERSUS NONSEMINOMATOUS GERM CELL TUMORS — The final pathology analysis is used to stratify testicular germ cell tumors (GCTs) into seminomas and nonseminomatous germ cell tumors (NSGCTs). These differ in clinical and biologic behavior.
●Seminomas are more likely to present with localized disease. Approximately 80 percent of males with seminomas present with stage I disease (limited to the testicle), while 15 percent have stage II disease (limited to retroperitoneal nodes) (table 1 and table 2). Fewer than 5 percent of patients have spread beyond the retroperitoneal nodes at presentation.
●Seminomas display relatively indolent growth and a longer natural history, and they rarely spread via the bloodstream beyond the retroperitoneal lymph nodes to other areas (eg, liver, lung, bones, or brain). Stage III metastases occur more frequently in males with NSGCTs.
●Seminomas typically do not have marked elevation of serum beta-human chorionic gonadotropin (beta-hCG) and never have an elevated alpha-fetoprotein (AFP). Seminoma with an elevated serum AFP is considered a mixed GCT, and these cancers are treated as NSGCTs. In contrast, beta-hCG and AFP are elevated in the majority of males with NSGCTs. (See "Serum tumor markers in testicular germ cell tumors".)
●Seminomas are exquisitely sensitive to radiation therapy, while NSGCTs are more radioresistant
EARLY STAGE DISEASE — Stage I testicular germ cell tumors (GCTs) are limited to the testis, and stage II disease is limited to the testis and retroperitoneal lymph nodes, without evidence of more distant disease. For stages I and II, treatment differs based on histology.
For both seminoma and nonseminomatous germ cell tumors (NSGCTs), the initial treatment decisions are based on clinical staging following radical inguinal orchiectomy.
Seminoma
Stage I seminoma — For patients with stage I seminoma (table 1 and table 2), orchiectomy is usually curative. (See "Treatment of stage I seminoma".)
●For patients who are able to comply with follow-up, we suggest active surveillance rather than chemotherapy or adjuvant radiation therapy (RT). Given the excellent prognosis, active surveillance minimizes the risks of treatment-associated morbidity. (See "Treatment of stage I seminoma" and "Treatment of stage I seminoma", section on 'Surveillance'.)
●For males who refuse active surveillance and for those who want more aggressive treatment despite their excellent prognosis, we suggest one or two cycles of single-agent carboplatin (dosed at an area under the concentration x time curve [AUC] of 7) rather than adjuvant RT. Single-agent carboplatin is well tolerated and as effective as adjuvant RT in preventing relapse. It is also associated with less morbidity, including lower risks of impaired fertility, second malignancy, or late cardiac disease. (See "Treatment of stage I seminoma", section on 'Patients who are not candidates for surveillance'.)
●For males who refuse active surveillance and are not candidates for chemotherapy, we suggest adjuvant RT. (See "Treatment of stage I seminoma", section on 'Patients who are not candidates for surveillance'.)
Stage II seminoma — Following orchiectomy, the optimal treatment for stage II disease depends on the extent of lymph node involvement (table 1 and table 2). (See "Treatment of stage II seminoma".)
●Stage IIA – For males with stage IIA disease (ie, diameter of involved nodes ≤2 cm), we suggest RT rather than chemotherapy. However, cisplatin-based combination chemotherapy is a reasonable alternative. (See "Treatment of stage II seminoma", section on 'Stage IIA disease'.)
●Stage IIB or IIC – For males with more extensive retroperitoneal adenopathy (ie, diameter of involved nodes >2 cm), we recommend cisplatin-based chemotherapy. (See "Treatment of stage II seminoma", section on 'Stage IIB and IIC seminoma'.)
●Elevated beta-hCG – Although uncommon, males with pure seminoma may have associated elevations in serum beta-human chorionic gonadotropin (beta-hCG; >50 international units/L). While its clinical significance is controversial, we suggest treatment using cisplatin-based chemotherapy. (See "Treatment of stage II seminoma".)
The optimal chemotherapy regimen has not been definitively established. The author's preference is for three courses of bleomycin, etoposide, and cisplatin (BEP (table 3)), but four courses of etoposide and cisplatin (EP) is an alternative. A choice between them should be based on institutional practice and the predicted ability of the patient to tolerate bleomycin.
Nonseminomatous germ cell tumor — The staging of patients with NSGCT is based on tumor markers following radical orchiectomy, as well as on clinical staging. For those patients whose treatment includes retroperitoneal lymph node dissection (RPLND), pathologic staging may result in further changes in treatment.
Stage IA and IB nonseminomatous germ cell tumors — For males with stage IA and IB NSGCTs, management depends on whether factors associated with an increased risk of relapse are present. These include:
●Lymphovascular invasion
●Predominance of an embryonal carcinoma component
●A T3 or T4 primary tumor
Using these risk factors, our approach to stage I NSGCTs is as follows:
●Low risk – For males who do not have any risk factors present, we suggest active surveillance. (See "Active surveillance following orchiectomy for stage I testicular germ cell tumors", section on 'General principles'.)
●High risk – For males with one or more risk factors, active surveillance, chemotherapy, and RPLND are all options. If technical expertise is available, RPLND is an appropriate treatment option. However, chemotherapy (one or two cycles of BEP) is a reasonable alternative (table 3). For males who prefer not to undergo further treatment, active surveillance is a reasonable alternative. However, these males should understand that their risk of relapse, and thus the need for subsequent treatment at a later date, approaches 40 percent. (See "Management of stage I nonseminomatous germ cell tumors".)
Stage IS — Patients with NSGCT limited to the testis on clinical staging but who have persistent elevation of tumor markers following orchiectomy are classified as stage IS. Persistently elevated markers generally indicate the presence of metastatic disease. These patients should be treated with chemotherapy similarly to those with good-risk stage III disease. (See "Initial risk-stratified treatment for advanced testicular germ cell tumors".)
Stage II nonseminomatous germ cell tumors — For patients with stage II NSGCTs, treatment depends on whether disease is documented clinically or pathologically. (See "Management of stage II nonseminomatous germ cell tumors".)
●Clinical stage IIA NSGCT – For males with radiographically abnormal nodal involvement ≤2 cm and normal serum tumor markers, we suggest RPLND. Further treatment will be based on the pathologic stage. (See "Retroperitoneal lymph node dissection for early-stage testicular germ cell tumors", section on 'RPLND-II'.)
●Clinical stage IIB and IIC NSGCT – For males with radiographically detected nodal disease ≥2 cm and/or elevated serum tumor markers following orchiectomy, we suggest primary cisplatin-based combination chemotherapy. BEP for three cycles and EP for four cycles are acceptable regimens (table 3). (See "Management of stage I nonseminomatous germ cell tumors".)
●Pathologic stage II NSGCT – Males with NSGCTs with confirmed pathological node involvement following RPLND have pathologic stage II NSGCTs (table 2). Treatment following RPLND is based on the extent of nodal involvement (see "Management of stage II nonseminomatous germ cell tumors", section on 'Pathologic stage IIA disease'):
•For males with lymph node metastases ≤2 cm in greatest diameter and with fewer than four lymph nodes involved, we suggest surveillance. While adjuvant chemotherapy dramatically reduces the relapse rate, treatment has no significant effect on survival because patients who relapse are treated with chemotherapy for curative intent.
•For males with nodal involvement >2 cm and/or more than four lymph nodes involved, we suggest two cycles of adjuvant cisplatin-based combination chemotherapy (BEP) because the relapse risk is relatively higher.
ADVANCED DISEASE — For males with advanced testicular germ cell tumors (GCTs), management does not differ for seminoma and nonseminomatous germ cell tumors (NSGCTs).
Instead, treatment is selected based on the International Germ Cell Cancer Collaborative Group (IGCCCG) risk stratification system (table 4). Males with seminoma are categorized as having good- or intermediate-risk disease. Males with NSGCTs are categorized as having good-, intermediate-, or poor-risk disease based on the sites of disease involvement and tumor marker levels. (See "Initial risk-stratified treatment for advanced testicular germ cell tumors", section on 'Definition of risk'.)
Good-risk disease — For males with good-risk disease, we recommend cisplatin-based combination chemotherapy. Our standard treatment is three cycles of bleomycin, etoposide, and cisplatin (BEP (table 3)). We prefer BEP rather than etoposide and cisplatin (EP) for males with good-risk GCTs. We reserve four cycles of EP for males with compromised pulmonary function, males with compromised renal function, and those over the age of 50 years. (See "Initial risk-stratified treatment for advanced testicular germ cell tumors", section on 'Good risk'.)
Intermediate- or poor-risk disease — For males with intermediate-risk or poor-risk disease, we recommend four cycles of BEP (table 3). An alternative regimen consists of etoposide, ifosfamide, and cisplatin (VIP (table 5)), which is preferred for patients at risk of bleomycin-induced lung injury.
Although high-dose chemotherapy with autologous stem cell transplantation is a promising approach, we suggest not administering high-dose chemotherapy as first-line treatment for poor-risk GCTs outside of a clinical trial. (See "Initial risk-stratified treatment for advanced testicular germ cell tumors", section on 'Intermediate- and poor-risk advanced disease'.)
For all patients with advanced disease treated with chemotherapy, a computed tomography (CT) scan of the chest, abdomen, and pelvis is obtained after treatment completion; this is particularly important for males who had initial evidence of retroperitoneal adenopathy. The use of surveillance imaging to assess for recurrent disease is discussed separately. (See "Posttreatment follow-up for men with testicular germ cell tumors", section on 'Guidelines for follow-up'.)
MANAGEMENT AFTER PRIMARY TREATMENT — The management of males postorchiectomy depends on the histologic type of germ cell tumor (GCT) and whether or not residual disease is identified:
Seminoma
●We suggest posttreatment surveillance if there is no evidence of residual disease. In addition, we suggest posttreatment surveillance rather than surgical resection if there is any residual mass <3 cm in size. (See "Treatment of stage II seminoma", section on 'Posttherapy residual masses'.)
●We perform a fludeoxyglucose (FDG)-positron emission tomography (PET) scan if there is evidence of residual masses ≥3 cm to determine appropriate treatment.
•If the PET scan is negative, we suggest posttreatment surveillance. (See "Treatment of stage II seminoma", section on 'Posttherapy residual masses'.)
•A positive PET scan indicates the presence of residual disease. In this situation, we suggest resection. Following resection of residual masses that contain viable GCT, we suggest two additional courses of chemotherapy. (See "Approach to surgery following chemotherapy for advanced testicular germ cell tumors".)
•If resection of residual disease is not technically feasible, we recommend surveillance. Second-line chemotherapy should be deferred until there is evidence of disease progression by imaging. (See "Diagnosis and treatment of relapsed and refractory testicular germ cell tumors".)
Nonseminomatous germ cell tumor
●For males who have normalized their serum tumor markers but have imaging evidence of ≥1 retroperitoneal lymph node(s) larger than 1 cm, we perform a retroperitoneal lymph node dissection (RPLND). If RPLND is not performed, we proceed with posttreatment surveillance. (See "Approach to surgery following chemotherapy for advanced testicular germ cell tumors".)
●There is no consensus on the best approach to manage males with persistently elevated serum tumor markers that are either stable or sluggishly declining at the end of treatment. Although they are at a high risk of relapse, we do not suggest administration of additional chemotherapy. We offer either postchemotherapy RPLND or surveillance. A choice depends on patient preference and whether the expertise to perform an RPLND is available. (See "Approach to surgery following chemotherapy for advanced testicular germ cell tumors", section on 'Retroperitoneal lymph node dissection'.)
POSTTREATMENT SURVEILLANCE — Guidelines for surveillance following treatment are a function of histology (seminoma versus nonseminomatous germ cell tumor [NSGCT]) and the stage of disease at presentation. These guidelines are discussed in detail separately. (See "Posttreatment follow-up for men with testicular germ cell tumors", section on 'Guidelines for follow-up'.)
Periodic surveillance of the serum concentrations of beta-human chorionic gonadotropin (beta-hCG) and alpha-fetoprotein (AFP) is the most sensitive means of detecting early relapse for males with NSGCTs.
For males with seminoma, the value of monitoring serum tumor markers is unclear, as relapse is almost always detected by examination or by imaging. (See "Serum tumor markers in testicular germ cell tumors" and "Posttreatment follow-up for men with testicular germ cell tumors".)
Most patients who relapse do so within the first one to two years after their initial treatment. Relapses after two years are uncommon, and relapses after five years are rare. The intensity of follow-up is dictated by the histology of the original tumor (seminoma versus NSGCT), and the stage and risk of recurrence at original presentation.
TREATMENT OF RELAPSED OR REFRACTORY GERM CELL TUMORS — The optimal treatment of relapsed germ cell tumors (GCTs) depends on the response to prior therapy, the location and timing of the relapse, and the tumor histology. (See "Diagnosis and treatment of relapsed and refractory testicular germ cell tumors".)
●Males who are chemotherapy naïve at the time of recurrence should be treated with a cisplatin-based combination regimen (bleomycin, etoposide, and cisplatin [BEP] or etoposide and cisplatin [EP] (table 3 and table 6)). Retroperitoneal lymph node dissection (RPLND) is an alternative to chemotherapy in properly selected patients. (See "Initial risk-stratified treatment for advanced testicular germ cell tumors".)
●For males who relapse following postorchiectomy chemotherapy, we recommend combination chemotherapy using etoposide, ifosfamide, and cisplatin (VIP (table 5)). Other options include vinblastine or paclitaxel with ifosfamide plus cisplatin (VeIP (table 7) or TIP (table 8)).
●For males who were not previously treated with etoposide, we suggest VIP (table 5) or TIP (table 8), as discussed separately. (See "Diagnosis and treatment of relapsed and refractory testicular germ cell tumors", section on 'Treatment after initial chemotherapy'.)
●Males who relapse during or within four weeks after initial chemotherapy have platinum-refractory disease. These males have a poor prognosis and should be treated with a high-dose chemotherapy regimen with autologous hematopoietic cell transplantation (HCT) or in a clinical trial. (See "Diagnosis and treatment of relapsed and refractory testicular germ cell tumors", section on 'Platinum-refractory disease'.)
●Late-relapsing tumors are uncommon and tend to grow slowly. Treatment consists of an aggressive surgical approach and systemic chemotherapy. Surgical resection appears to be crucial for long-term survival. (See "Diagnosis and treatment of relapsed and refractory testicular germ cell tumors", section on 'Late relapse'.)
●Brain metastases may present as an isolated manifestation of metastatic disease or in conjunction with other systematic metastases. Systemic chemotherapy is usually preferred for initial treatment. However, in selected cases, chemotherapy may be used in combination with brain radiation therapy and/or surgical resection. (See "Diagnosis and treatment of relapsed and refractory testicular germ cell tumors", section on 'Brain metastases'.)
SPECIAL CONSIDERATIONS DURING THE COVID-19 PANDEMIC — The COVID-19 pandemic has increased the complexity of cancer care. Important issues include balancing the risk from treatment delay versus harm from COVID-19, minimizing the use of immunosuppressive cancer treatments whenever possible, mitigating the negative impacts of social distancing during care delivery, and appropriately and fairly allocating limited healthcare resources. These and other recommendations for cancer care during active phases of the COVID-19 pandemic are discussed separately. (See "COVID-19: Considerations in patients with cancer".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Testicular cancer".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Testicular cancer (The Basics)")
●Beyond the Basics topic (see "Patient education: Testicular cancer (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Prognosis – Testicular germ cell tumors (GCTs) are among the most curable solid neoplasms, with five-year survival rates of approximately 95 percent. (See 'Introduction' above.)
●Diagnosis – The diagnosis of a testicular malignancy is generally established at radical orchiectomy, which also serves as the initial treatment for the primary tumor. (See "Clinical manifestations, diagnosis, and staging of testicular germ cell tumors".)
●Risk stratification – Optimal therapy requires estimating the likelihood of recurrence so that therapy can be limited when appropriate. Key elements in risk stratification include the histology (seminoma versus nonseminomatous germ cell tumor [NSGCT]), the presence or absence of metastases, and the degree of elevation in serum tumor markers (table 4). (See 'Introduction' above.)
●Semen cryopreservation – Whenever possible, a baseline sperm count and sperm banking should be performed prior to diagnosis and staging. Semen cryopreservation should be made available to all males prior to instituting therapy if they wish to preserve fertility. (See "Clinical manifestations, diagnosis, and staging of testicular germ cell tumors", section on 'Cryopreservation of sperm'.)
●Initial management of early stage seminoma – The initial management of early stage seminoma is as follows (algorithm 1):
•Stage I seminoma – For patients with a stage I seminoma, an extremely high cure rate can be achieved with radical orchiectomy. This is typically followed by active surveillance, but radiation therapy (RT) to paraaortic lymph nodes or single-agent carboplatin chemotherapy may be indicated if active surveillance is not appropriate. (See 'Stage I seminoma' above and "Treatment of stage I seminoma".)
•Stage II seminoma – Males with stage II seminoma are usually managed with RT or cisplatin-based combination chemotherapy, depending on the extent of retroperitoneal disease. (See 'Stage II seminoma' above and "Treatment of stage II seminoma".)
●Initial management of early stage NSGCT – The initial management of early stage NSGCT is as follows (algorithm 3):
•Stage IA and IB NSGCTs – For males with stage IA and IB NSGCTs, the management approach is based on the presence or absence of specific risk factors for recurrence: vascular or lymphatic invasion, embryonal carcinoma comprising >40 percent of the total tumor volume, the presence of yolk sac elements, or elevated serum tumor markers prior to orchiectomy that do not decrease by expected half-life. (See 'Stage IA and IB nonseminomatous germ cell tumors' above and "Management of stage I nonseminomatous germ cell tumors".)
-For males who do not have any risk factors present, we suggest active surveillance. (See "Active surveillance following orchiectomy for stage I testicular germ cell tumors".)
-For males with risk factors, we suggest a retroperitoneal lymph node dissection (RPLND). However, two cycles of a cisplatin-based regimen are a reasonable alternative to surgery and are frequently the treatment of choice in Europe. (See "Retroperitoneal lymph node dissection for early-stage testicular germ cell tumors".)
•Stage IS NSGCTs – Males with persistently elevated tumor markers following orchiectomy but without other evidence of disease (stage IS) should be treated with chemotherapy similar to those with good-risk stage III disease. (See "Initial risk-stratified treatment for advanced testicular germ cell tumors", section on 'Good risk'.)
•Stage II NSGCTs – For males with stage II NSGCTs, treatment depends on the extent of disease and whether retroperitoneal lymph node involvement is documented pathologically or is based on imaging studies. Treatment options include RPLND, surveillance, or the use of cisplatin-based combination chemotherapy. (See 'Stage II nonseminomatous germ cell tumors' above.)
For males with pathologic stage II NSGCTs following RPLND, treatment is based on the extent of nodal involvement (see "Management of stage II nonseminomatous germ cell tumors", section on 'Pathologic stage IIA disease'):
-For males with lymph node metastases ≤2 cm in greatest diameter, we suggest surveillance (Grade 2C).
-For males with nodal involvement >2 cm, we suggest adjuvant combination chemotherapy (Grade 2C). Our approach is to use two cycles of cisplatin-based chemotherapy.
●Advanced disease – Males with advanced disease are classified into good-, intermediate-, and poor-risk groups using the International Germ Cell Cancer Collaborative Group (IGCCCG) risk stratification system (table 4). The IGCCCG system takes into account primary tumor site, metastatic disease, and serum tumor marker levels. (See 'Advanced disease' above and "Initial risk-stratified treatment for advanced testicular germ cell tumors".)
•Good-risk disease – For males with good-risk disease, we recommend cisplatin-based combination chemotherapy (Grade 1A). Our standard treatment is three cycles of bleomycin, etoposide, and cisplatin (BEP (table 3)). However, males with compromised pulmonary function or those who are at risk for bleomycin-induced lung injury should be treated with etoposide and cisplatin (EP) (table 6).
•Intermediate-risk or poor-risk disease - For males with intermediate-risk or poor-risk disease, we recommend four cycles of BEP. An alternative regimen consists of etoposide, ifosfamide, and cisplatin (VIP) and is preferred for patients at risk of bleomycin-induced lung injury (table 5).
●Management after primary treatment – Following adjuvant treatment, a posttreatment computed tomography (CT) scan should be obtained. This is particularly important for males who had initial evidence of retroperitoneal adenopathy. (See 'Management after primary treatment' above.)
•Seminoma – For males with seminoma with evidence of residual disease <3 cm in size, we suggest posttreatment surveillance rather than surgical resection. We perform a fludeoxyglucose (FDG)-positron emission tomography (PET) scan to better characterize residual masses ≥3 cm. (See 'Seminoma' above.)
-If the PET scan is negative, we suggest posttreatment surveillance.
-If the PET scan is positive, we suggest resection of residual disease. If resection is not technically feasible, we suggest surveillance rather than initiation of second-line chemotherapy. (See "Treatment of stage II seminoma", section on 'Posttherapy residual masses' and 'Treatment of relapsed or refractory germ cell tumors' above.)
•NSGCTs – For males with NSGCTs, residual masses are commonly seen on postchemotherapy imaging studies.
-For males who have normalized their serum tumor markers following treatment but have imaging evidence of ≥1 retroperitoneal lymph node(s) larger than 1 cm in diameter, an RPLND should be performed. If RPLND is not performed, we proceed with posttreatment surveillance. (See "Approach to surgery following chemotherapy for advanced testicular germ cell tumors", section on 'Retroperitoneal lymph node dissection'.)
-For males with persistently elevated serum tumor markers that are either stable or sluggishly declining at the end of treatment, we offer either postchemotherapy RPLND or surveillance. A choice depends on patient preference and whether the expertise to perform an RPLND is available. (See "Approach to surgery following chemotherapy for advanced testicular germ cell tumors", section on 'Retroperitoneal lymph node dissection'.)
●Posttreatment surveillance – Periodic surveillance of the serum concentrations of beta-human chorionic gonadotropin (beta-hCG) and alpha-fetoprotein (AFP) is the most sensitive means of detecting early relapse for males with NSGCTs. For males with seminoma, the value of monitoring serum tumor markers is unclear, as relapse is almost always detected by examination or by imaging. (See 'Posttreatment surveillance' above.)
●Treatment of relapsed or refractory disease – The optimal treatment of relapsed GCTs depends on the response to prior therapy, the location and timing of the relapse, and the tumor histology. (See 'Treatment of relapsed or refractory germ cell tumors' above.)
•Males who are chemotherapy naϊve at the time of recurrence should be treated with a cisplatin-based combination regimen (eg, BEP (table 3)). RPLND is an alternative to chemotherapy in properly selected patients. (See "Initial risk-stratified treatment for advanced testicular germ cell tumors".)
•For males who relapse following postorchiectomy chemotherapy without previous exposure to etoposide, we administer either VIP (table 5) or paclitaxel, cisplatin, and ifosfamide (TIP (table 8)), as discussed separately. (See "Diagnosis and treatment of relapsed and refractory testicular germ cell tumors", section on 'Treatment after initial chemotherapy'.)
•Males who relapse during or within four weeks after initial chemotherapy have platinum-refractory disease. These males should undergo high-dose chemotherapy with autologous hematopoietic cell transplantation (HCT). (See "Diagnosis and treatment of relapsed and refractory testicular germ cell tumors", section on 'Platinum-refractory disease'.)
•Relapses after two years are uncommon. An aggressive surgical approach in addition to systemic therapy should be adopted in these patients, since resection appears to be crucial to achieving long-term survival. (See "Diagnosis and treatment of relapsed and refractory testicular germ cell tumors", section on 'Late relapse'.)
