(i) Seminoblastoma Stage I: Radiation therapy (20-30 Gy) should be routinely performed below the diaphragm, including the para-aortic lymph node area, after orchiectomy. Prophylactic mediastinal irradiation is not done because the recurrence rate in this region is extremely low. A subset of patients may opt for simple postoperative follow-up observation without radiotherapy due to the higher risk of radiotherapy complications and the small number of T1 and T2 lesions. The cure rate of both methods for patients with stage I seminomas is almost 100%. However, 15-20% of patients without adjuvant radiotherapy will recur, with a median time of recurrence of 12 months after surgery, and there are also cases of recurrence 5 years after surgery. Recurrence can still be cured by chemotherapy. Stage II: Radiation therapy (35-40 Gy) to the subdiaphragmatic area, including the para-aortic and ipsilateral iliac paravascular lymph nodes, should be performed after orchiectomy. No prophylactic mediastinal irradiation is done. If the patient has horseshoe kidney, radiotherapy is not indicated and chemotherapy is given as per good prognosis GCT. Stages IIC and III: Stage IIC patients with giant retroperitoneal lymph node metastases are treated with chemotherapy according to the GCT with good prognosis (see risk factor classification later). Chemotherapy is followed by observation and follow-up, surgical resection/biopsy, or radiation therapy, depending on the presence of residual tumor on imaging, respectively. If surgery is chosen, retroperitoneal lymph node dissection is not recommended because of technical difficulties in patients with seminomas due to extensive fibrosis, which may lead to serious complications. Rescue therapy is performed if CT suggests progression of the lesion, and chemotherapy is performed in patients with stage III or extragonadal (e.g., mediastinal) spermatogonial tumors, depending on the prognostic grading. With the exception of those with visceral metastases other than lungs, who are at intermediate risk, patients with stage IIIC have a good prognosis, and approximately 90% of late-stage cases can be cured with cisplatin-containing regimens. Recurrence after radiotherapy for stage I and IIA, IIB: 3 cycles of BEP or 4 cycles of EP regimen can be given as chemotherapy for non-seminomatous cell tumors with good prognosis. The cure rate is about 90%. Patients with intermediate prognosis (with visceral metastases other than lung) are given 4 cycles of BEP or enrolled in clinical trials. After chemotherapy, if the residual lesion is larger than 75px consider surgery or radiotherapy or follow up observation. (ii) Non-seminomatous germ cell tumors Treatment based on staging includes observation, chemotherapy, and nerve preserving retroperitoneal lymph node dissection (RPLND). Stage I: Stage IA patients have two options after orchiectomy: observation or RPLND. cure rates are both over 95%. Patients under observation alone must be followed closely to achieve such a high cure rate, and 20-30% of those who recur can be cured with chemotherapy. Lymph node metastases are found in approximately 20% of patients with stage I nonseminomatous plasmacytoma who undergo RPLND. The biggest complication of bilateral clearance in patients undergoing RPLND is infertility due to ejaculatory disorders. The technique of nerve preservation of early symptoms of lung cancer by China Biotherapeutics www.chinaswzl.com杨教授特别指出 preserves ejaculatory function in 90% of cases. If no metastasis is found in the cleared lymph nodes, adjuvant chemotherapy is not necessary after surgery. If there is lymph node invasion, the decision to administer chemotherapy depends on the extent of lymph node invasion and the patient’s compliance with long-term follow-up.There are three options for patients with stage IB: observation, chemotherapy, and RPLND. RPLND is recommended, and 2 cycles of BEP regimen are administered if RPLND is not available. Observation alone is not recommended if the patient is T2 and has vascular invasion. stage IS patients with persistently elevated serum markers suggesting possible distant spread of the tumor should be treated with chemotherapy according to the prognostic GCT. Stage II: Treatment of stage IIA patients after orchiectomy is mainly based on serum marker levels. If elevated, chemotherapy is given and if negative, RPLND or chemotherapy is considered. RPLND patients with PN2 are treated with 2 cycles of postoperative BEP chemotherapy, while PN1 patients are observed.Treatment of IIB patients is based on serum markers and imaging. Patients with extensive lesions should be treated with chemotherapy before considering RPLND and postoperative chemotherapy. Stage IIC and III: Chemotherapy is given according to different prognostic grading of patients. Patients with CR after chemotherapy and those with residual tumor may be given observation follow-up, surgical resection, or rescue chemotherapy depending on the situation, respectively. Initial studies on combination chemotherapy for GCT began in the 1970s, and the BVP regimen of bleomycin (BLM), vincristine (VLB), and cisplatin (DDP) for the treatment of metastatic GCT resulted in complete remission (CR) in 70-80% of patients. However, this regimen is associated with serious immediate and long-term adverse effects, including neurotoxicity, myelosuppression, nephrotoxicity, ototoxicity, BLM-associated pulmonary toxicity, and the possibility of leukemia and Raynaud’s phenomenon due to VP16. Due to the high effectiveness and severe toxicity of chemotherapy, stratification of patients and administration of appropriate treatment according to different prognostic characteristics have been continuously explored to avoid over- and under-treatment. Studies have found a strong relationship between disease stage and serum markers and prognosis, therefore, patients had been categorized into two groups with good prognosis and poor prognosis. Dr. Yang, WWW.458SWZL.com, Biotherapy Center, Guangzhou Cancer Hospital, introduced the early symptoms of stomach cancer and recently proposed the International Germ Cell Tumor Conference Classification (International Germ Cell Tumor Cooperative Group, 1997) and added the prognostic grouping to the AJCC staging criteria for germ cell tumors. This classification categorizes patients into three groups: good prognosis, intermediate prognosis and poor prognosis (see table below). And the BEP regimen with pedunculopontin (VP16) instead of VLB resulted in a significant reduction in the incidence of neurotoxicity. Risk classification Risk status Non-seminomatous spermatogonia Seminomatous spermatogonia Good prognosis Primary in testis or retroperitoneum and no visceral metastases other than lungs and mildly elevated serum markers AFP<1,000 ng/ml HCG<5,000iu/L LDH<1.5< span="">times the upper limit of normal value Primary at any site and no visceral metastases other than lungs and normal APF Any degree of HCG elevation Any degree of LDH elevation 5-year period Any degree of elevated LDH 5-year PFS, 89%; 5-year OS, 92% 5-year PFS, 82%; 5-year OS, 86% Intermediate prognosis Primary to testis or retroperitoneum and no visceral metastases other than lungs and moderately elevated serum markers AFP 1,000-10,000 ng/ml HCG 5,000-50,000 iu/L LDH 1.5-10 times upper limit of normal Any Primary at any site and visceral metastases other than lungs and normal APF Any degree of HCG elevation Any degree of LDH elevation 5-year PFS, 75%; 5-year OS, 80% 5-year PFS, 67%; 5-year OS, 71% Poor prognosis Primary in the mediastinum or visceral metastases other than lungs or serum markers are severely elevated AFP > 10,000ng/ml HCG > 50,000iu/L LDH > 10 times upper limit of normal No prognosis 10 times upper limit of normal values No subgroups with poor prognosis 5-year PFS, 41%; 5-year OS, 48% Patients who do not achieve CR on first-line chemotherapy with BEP or BVP regimens or who relapse after CR may be considered for salvage with VIP regimens of VLB + isocyclophosphamide (IFO) + DDP. CR rates of about 50% and 25% sustained CR. In the case of patients with one-sided testicular tumors, a history of achieving CR on first-line chemotherapy, low marker values, and low tumor loads, patients may be considered for salvage with VLB + isocyclophosphamide (IFO) + DDP. and low tumor load, a good outcome may be achieved with chemotherapy. The standard of care is 4 cycles of DDP + IFO + VLB or paclitaxel Predictors of poor outcome with conventional-dose chemotherapy include failure to achieve a CR with first-line chemotherapy, or if the patient requires third-line chemotherapy for salvage, high-dose chemotherapy in combination with autologous hematopoietic stem cell transplantation may be considered or enrolled in a clinical trial. 2 cycles of high-dose carboplatin (CBP) + (VP16) with or without cyclophosphamide (CTX) or IFO may achieve 15-20% persistence. A sustained CR of 15-20% can be obtained. one-sided testicular tumors with elevated markers during first-line therapy may be considered for high-dose chemotherapy as second-line therapy. Factors predictive of poor outcome with high-dose CBP-containing regimens include high serum HCG, mediastinal primary, and insensitivity (absolute resistance) to DDP, and these patients may be considered for a clinical trial or surgical resection of a single metastatic lesion. Patients who do not achieve CR with high-dose chemotherapy are incurable and should be given palliative care.