Treatment of stage II seminoma

INTRODUCTION — Germ cell tumors (GCTs) account for most testicular cancers. The most common histologic subtypes of GCTs are nonseminomatous and seminomatous (ie, seminomas) tumors. Stage II seminomas are a highly curable malignancy. (See "Anatomy and pathology of testicular tumors".)

The initial treatment of patients with a clinically confirmed diagnosis of stage II seminoma will be presented here. The clinical presentation, diagnosis, and staging of testicular cancer and the treatment of stage I seminoma are presented separately.

●(See "Clinical manifestations, diagnosis, and staging of testicular germ cell tumors".)

●(See "Treatment of stage I seminoma".)

DEFINITION OF STAGE II SEMINOMA — Patients with clinical stage II seminoma have the presence of pure seminoma in their orchiectomy specimen and imaging studies of the abdomen and pelvis that suggest the disease is limited to the regional (ie, retroperitoneal) lymph nodes (table 1A-B). Per the American Joint Committee on Cancer (AJCC) staging guidelines, potentially involved regional lymph nodes measure at least 1 cm in greatest dimension (ie, on the long axis of cross-sectional imaging). However, repeat imaging and clinical judgment are necessary to determine if these lymph nodes are benign or malignant. (See 'Borderline lymph nodes (1 cm)' below.)

Imaging studies should otherwise demonstrate no evidence of metastatic disease at other distant sites, such as the lungs, thoracic or pelvic lymph nodes, liver, or central nervous system. Approximately 15 percent of all patients initially diagnosed with seminoma present with stage II disease [1]. Further details on the initial diagnostic evaluation of seminoma are discussed separately. (See "Clinical manifestations, diagnosis, and staging of testicular germ cell tumors", section on 'Diagnostic evaluation'.)

Stage II seminomas are further classified into clinical stage IIA, IIB, or IIC disease using the AJCC eighth edition staging system for testicular cancer (table 1A-B). Disease stage is one of the clinical factors used to select therapy. (See 'Treatment' below.)

●Stage IIA seminoma – Any or unknown pathologic tumor (T) stage and clinical N1 disease (metastasis with a lymph node mass ≤2 cm in greatest dimension or multiple lymph nodes, all of which are ≤2 cm in greatest dimension)

●Stage IIB seminoma – Any or unknown pathologic T stage and clinical N2 disease (metastasis with a lymph node mass >2 cm and ≤5 cm in greatest dimension or multiple lymph nodes, with any one mass >2 cm but ≤5 cm in greatest dimension).

•A stage IIB seminoma is further subclassified as "non-bulky" if the regional lymph node(s) are ≤3 cm.

●Stage IIC seminoma – Any or unknown pathologic T stage and clinical N3 disease (metastases with a lymph nodes mass >5 cm in greatest dimension).

Tumor marker studies are obtained postorchiectomy as part of staging to determine serum marker (S) status (table 1A-B). These tumor markers include lactate dehydrogenase (LDH), alpha-fetoprotein (AFP), and beta-human chorionic gonadotropin (beta-hCG). The most important posttreatment tumor marker in pure seminomas is beta-hCG since an elevated LDH is not always specific to testicular cancer, and seminomas do not, by definition, produce AFP.

In stage II seminomas, postorchiectomy tumor markers can either be within normal limits (ie, S0) or elevated within a specific range (S1; defined as LDH less than 1.5 times the upper limit of normal and beta-hCG less than 5000 mIU/mL and AFP less than 1000 ng/mL). (See "Serum tumor markers in testicular germ cell tumors".)

Patients with stage II seminoma and a mild elevation of either LDH OR beta-hCG alone do not meet criteria for S1 disease and are typically treated using a similar approach to those with S0 disease. Such patients may also be evaluated for alternative causes of the isolated tumor marker. (See "Serum tumor markers in testicular germ cell tumors", section on 'Lactate dehydrogenase' and "Serum tumor markers in testicular germ cell tumors", section on 'False-positive hCG'.)

Tumors with postorchiectomy markers studies that are higher than these levels (S2 or S3 disease) or are not available/performed (SX) are classified as advanced GCTs, and their management is discussed separately. (See "Initial risk-stratified treatment for advanced testicular germ cell tumors".)

TREATMENT — For patients with stage II seminoma, treatment options include surveillance, cisplatin-based chemotherapy, and radiation therapy (RT) to the retroperitoneal and iliac lymph nodes (algorithm 1). Selection of therapy is based on disease stage, extent of nodal involvement, and presence or absence of tumor marker elevation after orchiectomy. Since most seminomas can be treated successfully, clinicians must also consider possible long-term treatment-related toxicities when selecting therapy. (See "Treatment-related toxicity in testicular germ cell tumors" and "Approach to the care of long-term testicular cancer survivors".)

These treatment approaches, which are based upon the clinical practice of the UpToDate contributors, are also generally consistent with guidelines from the National Comprehensive Cancer Network (NCCN), the European Society for Medical Oncology (ESMO), and the Canadian Urological Association [2-4].

Stage IIA seminoma (S0)

Borderline lymph nodes (1 cm) — For patients with clinical stage IIA seminoma (S0) and borderline enlarged retroperitoneal lymph nodes (approximately 1 cm in greatest dimension), we observe for six to eight weeks, then repeat imaging (algorithm 1). In patients with clinical stage II seminoma and lymph nodes slightly larger than 1 cm, the rate of pathologic N0 (pN0) disease at retroperitoneal lymph node dissection (RPLND) is approximately 15 to 30 percent [4,5]. These findings suggest that some lymph nodes may be enlarged due to non-malignant etiologies, and a period of observation could prevent overtreatment in this population.

Our approach is to repeat the original imaging study used to detect the lymph nodes in six to eight weeks to re-evaluate the size of the lymph nodes. Imaging options include contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen and pelvis. (See "Clinical manifestations, diagnosis, and staging of testicular germ cell tumors", section on 'Imaging studies'.)

●Patients whose lymph nodes decrease in size to less than 1 cm are likely benign. Such patients can continue surveillance or be treated like those with stage I seminoma. (See "Treatment of stage I seminoma".)

●Patients whose lymph nodes increase in size on repeat imaging can be more confidently treated for stage II seminoma. (See 'Lymph nodes between 1 and 2 cm' below.)

●Patients whose lymph nodes remain stable in size can continue imaging surveillance, which allows time to determine the etiology of the nodes (benign versus malignant) and the appropriate treatment strategy.

Imaging surveillance can help determine the appropriate treatment strategy and avoid over- or under-treatment of borderline lymph nodes. If the nodes are due to metastatic seminoma but the patient is treated for stage I seminoma with adjuvant therapy, this management represents undertreatment and could result in an increased relapse risk. In contrast, if the nodes are benign, but the patient is treated for stage II seminoma, this management represents overtreatment and could result in unnecessary toxicity.

Lymph nodes between 1 and 2 cm — For patients with clinical stage IIA seminoma (S0) and enlarged retroperitoneal lymph nodes between 1 cm and 2 cm in greatest dimension, treatment options include either RT or cisplatin-based chemotherapy (algorithm 1). Further details on treatment regimens are discussed below. (See 'Treatment modalities' below.)

Both treatment approaches have similar relapse rates and result in high disease-free survival (90 percent or greater at five years). The optimal treatment has not been established since RT and chemotherapy have not been directly compared in randomized trials. The selection of therapy is based on multiple factors such as patient and clinician preference and experience; lymph node size, number, and distribution; patient convenience; and toxicity. Our approach, including advantages and disadvantages, is as follows:

●Patients with larger (closer to 2 cm) or more numerous lymph nodes (especially those distributed over a large area of the retroperitoneum) may derive greater benefit from chemotherapy over RT, extrapolating from data in more advanced stage tumors.

In addition, patients treated with RT who develop relapsed or refractory disease may subsequently require chemotherapy. Such sequential multimodality therapy is associated with a higher risk of subsequent malignancies and cardiovascular disease compared with either modality alone [6]. (See "Diagnosis and treatment of relapsed and refractory testicular germ cell tumors".)

●However, RT is typically associated with less acute toxicities than cisplatin-based chemotherapy and may be preferable for some patients, particularly those with smaller lymph nodes. RT also has a shorter treatment duration (approximately three weeks) than chemotherapy (between nine and twelve weeks, depending upon the regimen selected). (See "Radiation therapy techniques in cancer treatment".)

RT and chemotherapy have similar relapse rates for stage IIA seminoma. In a systematic review and meta-analysis of thirteen observational studies, 890 patients with stage II seminoma were treated with either cisplatin-based chemotherapy or RT. Among those with clinical stage IIA seminoma, the pooled relapse rate (RR) was similar between RT (RR 0.05, 95% CI 0.02-0.07) and chemotherapy (RR 0.07, 95% CI 0-0.19) [7]. Similar results have been demonstrated in subsequent observational studies comparing relapse rates for RT and chemotherapy [8].

RT and chemotherapy also result in similarly high disease-free survival for stage IIA seminoma. In observational studies, the five-year disease-free survival for RT is approximately 90 percent or greater [4,7-11], which is similarly high for chemotherapy [12]. As an example, chemotherapy (four cycles of etoposide plus cisplatin [EP] or three cycles of bleomycin plus etoposide plus cisplatin [BEP]) was evaluated in 72 patients with stage IIA or IIB seminoma in a trial from the Spanish Germ Cell Cancer Group [12]. Among the 18 patients with IIA disease, there were no relapses, and the five-year progression-free survival (PFS) was 100 percent. The five-year overall survival rate for the entire study population was 95 percent, with only one death secondary to progressive seminoma.

Long-term toxicity profiles also differ between RT and chemotherapy and should be discussed with the patient. RT can be associated with the risk of secondary (ie, subsequent) malignancies and gastrointestinal disease, whereas chemotherapy can be associated with secondary malignancies, cardiovascular disease, hypertension, hyperlipidemia and metabolic syndrome, neuropathy, tinnitus, and infertility [13]. (See "Treatment-related toxicity in testicular germ cell tumors" and "Approach to the care of long-term testicular cancer survivors".)

Stage IIA seminoma (S1) — We offer cisplatin-based chemotherapy to patients with clinical stage IIA seminoma and S1 disease (algorithm 1). Such patients have persistently elevated or rising tumor markers within a specific range, particularly serum beta-HCG levels, postorchiectomy (table 1A-B). These tumors, which are classified as "good-risk" disease using the International Germ Cell Consensus Classification criteria (table 2), are treated with either four cycles of EP (table 3) or three cycles of BEP (table 4).

Further details and data for this risk-stratified approach in advanced testicular germ cell tumors (GCTs) are discussed separately. (See "Initial risk-stratified treatment for advanced testicular germ cell tumors", section on 'General approach to advanced disease'.)

Stage IIB seminoma (S0) — For most patients with clinical stage IIB seminoma (S0), we suggest cisplatin-based combination chemotherapy rather than RT (algorithm 1). Chemotherapy has high overall survival rates (95 percent or greater), and observational studies suggest a lower risk of relapse with chemotherapy compared with RT. For patients with non-bulky stage IIB disease (lymph nodes ≤3 cm) and S0 disease, RT is an appropriate alternative to chemotherapy.

In a systematic review and meta-analysis of thirteen observational studies, 890 patients with stage II seminoma were treated with either cisplatin-based chemotherapy or RT. Among those with clinical stage IIB seminoma, the pooled relapse rate was 0.05 for chemotherapy (95% CI 0-0.11) and 0.12 for RT (95% CI 0.06-0.17), although this difference was not statistically significant [7]. In another systematic review of observational studies, among patients with stage IIB seminoma, the range of relapse rates was 0 to 14 percent for those receiving chemotherapy versus 10 to 21 percent for those treated with RT [8].

Long-term survival outcomes for chemotherapy were evaluated in a trial from the Spanish Germ Cell Cancer group [12]. In this study, 72 patients with stage IIA or IIB seminoma received either four cycles of EP or three cycles of BEP. Among the 54 patients with IIB disease, relapses were seen in six patients (11 percent), and the five-year PFS was 87 percent. The overall survival rate at five years was 95 percent, with only one death secondary to progressive seminoma.

Stage IIB seminoma (S1) — We offer cisplatin-based chemotherapy to patients with clinical stage IIB seminoma and S1 disease (table 1A-B and algorithm 1). These tumors, which are classified as "good-risk" disease using the International Germ Cell Cancer Collaborative Group (IGCCCG) criteria (table 2), are treated with either four cycles of EP (table 3) or three cycles of BEP (table 4). Further details and data for this risk-stratified approach in advanced testicular GCTs are discussed separately. (See "Initial risk-stratified treatment for advanced testicular germ cell tumors", section on 'General approach to advanced disease'.)

Stage IIC seminoma — For patients with clinical stage IIC seminoma, regardless of the absence or presence of postorchiectomy tumor marker status (S0 or S1), we recommend cisplatin-based chemotherapy rather than RT (algorithm 1), as chemotherapy is associated with a lower risk of disease relapse in this population. Options for chemotherapy regimens include three cycles of bleomycin, etoposide, and cisplatin or four cycles of etoposide plus cisplatin. (See 'Chemotherapy' below.)

In observational studies of stage IIC seminoma, the risk of relapse with RT is approximately 20 percent or greater [10,14], and such patients would subsequently need systemic therapy. Although cisplatin-based chemotherapy can still successfully treat patients with bulky seminoma who relapse after prior RT, it may also be less effective after treatment with extensive RT compared with limited-field RT [15,16]. (See "Diagnosis and treatment of relapsed and refractory testicular germ cell tumors".)

By contrast, seminoma is highly sensitive to chemotherapy. Clinical trials and observational studies have documented the favorable outcome in this population, with 90 percent of patients achieving long-term relapse-free survival. In a prospective observational study conducted by SWENOTECA, 42 males with stage IIC seminoma were treated with four cycles of etoposide plus cisplatin [11]. The five-year cancer-specific and overall survival rates were 97.6 and 95.1 percent, respectively; there were six relapses and three deaths due to progressive cancer.

TREATMENT MODALITIES — For patients with stage II seminoma, treatment options include cisplatin-based chemotherapy and radiation therapy (RT) to the retroperitoneal lymph nodes.

Radiation therapy — The total radiation dose to areas of gross adenopathy is 30 Gy for stage IIA seminoma and 36 Gy for stage IIB seminoma. Standard RT following orchiectomy for patients with stage IIA/stage IIB disease (see 'Definition of stage II seminoma' above) consists of low-dose treatment to the paraaortic lymph nodes and superior ipsilateral pelvis (20 to 25 Gy) followed by a cone down to the involved nodal areas [17].

The "modified dog-leg" field has become the standard in stage II seminoma. A study conducted by the German Testicular Cancer Study Group (GTCSG) evaluated the "modified dog-leg" field where the inferior border of the RT field was placed at the top of the acetabulum. This field modification led to no increase in pelvic relapses [9,18,19].

The scrotum, inguinal and lower pelvic lymph nodes, and mediastinum are not routinely treated with RT [20]. All patients should use a clamshell shield to reduce the radiation dose to the contralateral testicle [20]. A clamshell shield should also be used for patients who have completed sperm banking to preserve both spermatogenesis and testosterone production [20]. (See "Treatment of stage I seminoma", section on 'Adjuvant radiation therapy'.)

The toxicities of RT for stage II seminoma are similar to those seen with the treatment of stage I seminoma. Further details are discussed separately. (See "Treatment of stage I seminoma", section on 'Adjuvant radiation therapy'.)

Chemotherapy — All patients with stage II seminoma, by definition, have disease limited to the lymph nodes and are classified as having good-risk disease by the International Germ Cell Cancer Collaborative Group (IGCCCG) (table 2) [21]. (See "Initial risk-stratified treatment for advanced testicular germ cell tumors", section on 'Seminomas'.)

Like other good-risk testicular germ cell tumors (GCTs), patients with stage II seminoma who are treated with chemotherapy can receive either three cycles of bleomycin, etoposide, and cisplatin (BEP) (table 4) or four cycles of etoposide plus cisplatin (EP) (table 3). Selecting between these regimens is discussed separately. (See "Initial risk-stratified treatment for advanced testicular germ cell tumors", section on 'Seminomas' and "Initial risk-stratified treatment for advanced testicular germ cell tumors", section on 'Good risk'.)

POSTTHERAPY RESIDUAL MASSES — All patients with stage II seminoma who have completed treatment (either chemotherapy or radiation therapy [RT]) should undergo imaging to assess for posttherapy residual retroperitoneal masses. Imaging options include either contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI).

Patients with seminoma can have residual retroperitoneal masses on imaging following treatment, particularly those with bulky disease who received chemotherapy [22,23]. For such patients, management is based on the size of the residual disease, which is discussed in more detail separately. (See "Approach to surgery following chemotherapy for advanced testicular germ cell tumors", section on 'Seminoma' and "Approach to surgery following chemotherapy for advanced testicular germ cell tumors", section on 'Normalized tumor markers with abnormal imaging findings'.)

INVESTIGATIONAL APPROACHES — It is important to reduce the risk of treatment toxicities in testicular cancer survivors. For patients with stage II seminoma, there are long-term toxicities associated with cisplatin-based chemotherapy regimens and radiation therapy. Various methods have been evaluated to reduce these toxicities, such as de-intensified chemotherapy, chemoradiation, and retroperitoneal lymph node dissection. These approaches remain investigational, and interested patients should be encouraged to enroll in clinical trials, where available.

De-intensified chemotherapy — The use of single-agent carboplatin is not established in stage II seminoma, as data are mixed for the efficacy and toxicity of this approach [24-26].

Some studies have demonstrated high relapse rates with three to four cycles of single-agent carboplatin (AUC = 7) [24]. Randomized trials also suggest that single-agent carboplatin has inferior overall survival compared with cisplatin-based combination chemotherapy [27]. In contrast, other studies have demonstrated excellent outcomes for three to four cycles of single-agent carboplatin at higher doses (AUC = 10), including low relapse rates and five-year overall survival greater than 95 percent [28]. However, data are lacking for long-term toxicities and quality of life in this study. In addition, carboplatin resulted in significant hematologic toxicity, including the need for blood product transfusions.

There is interest in investigating risk-adapted strategies to de-intensify chemotherapy in patients with seminoma. In a non-randomized phase II trial (SEMITEP), 102 patients with good prognosis stage IIB/C or stage III seminoma were treated with two cycles of EP followed by an FDG-PET/CT scan to evaluate treatment response [26]. Patients with residual FDG-avid disease on PET-CT received two additional cycles of EP (EP x 4), whereas those with no residual FDG-avid disease received one additional cycle of carboplatin (AUC = 7). In the entire study population, 67 patients (69 percent) had a negative FDG-PET/CT after two cycles of EP and proceeded to single-agent carboplatin. Patients who received two cycles of EP followed by single-agent carboplatin had similar progression-free survival (PFS) compared with those who received EP x 4 (three-year PFS of 91 and 90 percent, respectively) with lower rates of peripheral neuropathy and ototoxicity.

Chemoradiation — The sequential use of chemotherapy and radiation remains investigational in stage II seminoma, and further long-term follow-up on outcomes and toxicities is necessary.

In a phase II trial (SAKK 01/10), 116 patients with stage IIA/B seminoma were treated with one cycle of single-agent carboplatin (AUC = 7) followed by RT to the involved regional lymph nodes [25]. RT administered to the lymph nodes was expanded by 3 cm in craniocaudal dimension and 2 cm in axial dimensions, which differs from the typical "modified dog-leg" field used to treat stage II seminoma. (See 'Radiation therapy' above.)

At median follow-up of 4.5 years, the three-year progression-free survival (PFS) was 93.7 percent in the entire population, narrowly missing the prespecified primary endpoint [25]. In addition, the incidence of late toxicities is unknown for this approach. Prior studies have demonstrated greater risks of secondary malignancies and cardiovascular disease among patients treated with radiation and chemotherapy as compared with either modality alone [6].

Retroperitoneal lymph node dissection — Retroperitoneal lymph node dissection (RPLND) has been investigated in stage II seminoma as a potential method of avoiding the long-term sequelae of radiation and chemotherapy [29-31]. This approach remains investigational, as data from clinical trials have been mixed for its efficacy [5,32].

●In a single-arm phase II trial (Surgery in Early Metastatic Seminoma; SEMS), 55 patients with testicular seminoma and isolated retroperitoneal lymphadenopathy (no larger than 3 cm) were treated with an open modified template RPLND [5]. The median sizes of the largest clinical and pathologic (post-RPLND) lymph nodes were 1.6 and 2.3 cm, respectively. The rates of pathologic N0, N1, N2, and N3 disease were 16, 22, 56, and 5 percent, respectively. At median follow-up of 33 months, two-year recurrence-free survival was 81 percent [5]. Recurrences were seen in 12 patients (22 percent) who were treated with chemotherapy (10 patients) or additional surgery (2 patients). All patients with recurrences were disease-free at follow-up, and the two-year overall survival was 100 percent.

●By contrast, a similar study (PRIMETEST) demonstrated a higher risk of recurrence with RPLND (30 percent) in stage IIA/B seminoma, which did not meet the prespecified study endpoint [32].

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 5^th to 6^th 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 10^th to 12^th 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 topics (see "Patient education: Testicular cancer (The Basics)")

●Beyond the Basics topics (see "Patient education: Testicular cancer (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition – Patients with clinical stage II seminoma have pure seminoma in their orchiectomy specimen and imaging studies that suggest the disease is limited to the regional (retroperitoneal) lymph nodes. Postorchiectomy tumor markers can either be within normal limits (ie, S0) or elevated within a specific range (S1) (table 1A-B and algorithm 1). (See 'Definition of stage II seminoma' above.)

●Clinical stage IIA seminoma (S0) – The treatment of patients with clinical stage IIA seminoma (S0) is as follows (see 'Stage IIA seminoma (S0)' above):

•Borderline enlarged lymph nodes – For patients with borderline enlarged retroperitoneal lymph nodes (approximately 1 cm in greatest dimension), we observe for six to eight weeks, then repeat imaging.

-Lymph nodes that decrease in size to less than 1 cm are likely benign. Such patients can continue surveillance or be treated like those with stage I seminoma. (See "Treatment of stage I seminoma".)

-Patients whose lymph nodes increase in size on repeat imaging can be treated for stage II seminoma. (See 'Borderline lymph nodes (1 cm)' above.)

-Patients whose lymph nodes remain stable in size can continue imaging surveillance, which allows time to determine the etiology of the nodes (benign or malignant) and the appropriate treatment strategy.

•Lymph nodes between 1 and 2 cm – For those with enlarged retroperitoneal lymph nodes between 1 cm and 2 cm in greatest dimension, treatment options include either radiation therapy (RT) or cisplatin-based chemotherapy. (See 'Lymph nodes between 1 and 2 cm' above.)

-Patients with larger (closer to 2 cm) or more numerous lymph nodes (especially those distributed over a large area of the retroperitoneum) may derive greater benefit from chemotherapy over RT, extrapolating from data in more advanced stage tumors.

-However, RT is associated with less acute toxicity and shorter duration of therapy, and may be preferable for some patients, particularly those with smaller lymph nodes.

-Long-term toxicity profiles differ between these modalities and should be discussed with the patient. For example, RT is associated with second malignancies (especially in those who relapse and require subsequent chemotherapy), while chemotherapy is associated with cardiac disease, neuropathy, tinnitus, and infertility, among other toxicities.

●Clinical stage IIB seminoma (S0) – For most patients with clinical stage IIB seminoma (S0), we suggest cisplatin-based combination chemotherapy rather than RT (Grade 2C). RT is an alternative for stage IIB seminoma with lymph nodes ≤3 cm. (See 'Stage IIB seminoma (S0)' above.)

●Clinical stage IIA/B seminoma (S1) – We offer cisplatin-based chemotherapy to patients with either clinical stage IIA (S1) or stage IIB (S1) seminoma (table 3), as discussed separately. (See "Initial risk-stratified treatment for advanced testicular germ cell tumors", section on 'Good risk'.)

●Clinical stage IIC seminoma – For patients with clinical stage IIC seminoma, regardless of postorchiectomy tumor marker status (S0 or S1), we suggest cisplatin-based chemotherapy rather than RT (Grade 2C). (See 'Stage IIC seminoma' above.)

●Treatment modalities

•Cisplatin-based combination chemotherapy – When chemotherapy is chosen for stage II seminoma, options include either three cycles of bleomycin, etoposide, and cisplatin (BEP) (table 4) or four cycles of etoposide plus cisplatin (EP) (table 3). Selecting between these regimens is discussed separately. (See 'Chemotherapy' above and "Initial risk-stratified treatment for advanced testicular germ cell tumors", section on 'Good risk'.)

•Radiation therapy – For those treated with RT, the total radiation dose to areas of gross adenopathy is 30 Gy for stage IIA seminoma and 36 Gy for stage IIB seminoma. (See 'Radiation therapy' above.)

●Residual retroperitoneal mass – For patients with stage II seminoma and residual retroperitoneal masses after treatment completion, the management is dependent on the size of the residual disease, as discussed separately. (See 'Posttherapy residual masses' above and "Approach to surgery following chemotherapy for advanced testicular germ cell tumors".)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Clair J Beard, MD, and William K Oh, MD, who contributed to earlier versions of this topic review.