Background & Purpose: Testicular cancer has become one of the most curable solid neoplasms, with several available treatment options for patients with clinical stage I nonseminomatous germ cell tumors (CSI NSGCT), which afford a 98% to 99% survival rate. These high cure rates have resulted in a shift in focus towards reducing treatment-related morbidity, and tailoring of management according to a risk-adapted approach. In the current study, a clinical trial was undertaken to compare surveillance and retroperitoneal lymph node dissection (RPLND) in a prospectively followed cohort of CSI NSGCT patients that included a group of high-risk patients.Patients and Methods: The study was conducted at Indiana University and included 96 patients who were assigned to either surveillance (45 patients) or primary RPLND (51 patients), and who were followed for a minimum duration of 18 months. A number of risk factors were investigated to assess their impact on outcome. The two treatment strategies were compared regarding rate of relapse, overall and disease-specific survival, treatment related morbidity and need for chemotherapy.Results: The overall rate of relapse in the surveillance arm was 25%, while in the RPLND arm pathologic stage II was detected in 21.6% of patients and the relapse rate was 9.8%. Lymphovascular invasion and embryonal carcinoma predominance were significant predictors of metastasis / relapse in both groups. The newly characterized lymphangiogenic growth factor VEGF-C and its receptor VEGF-R3 showed promise as potential markers for metastatic disease. Complications occurred in 7.8% of patients undergoing RPLND, with preservation of antegrade ejaculation in all 42 patients who underwent a nerve-sparing procedure. All relapses were salvageable with chemotherapy with or without post-chemotherapy surgery, and the overall and disease-free survival rates were 100% in both groups.Conclusion: The presence of high risk features is associated with an increased risk of metastasis and relapse. However, initial management with either surveillance or primary RPLND -combined with chemotherapy for relapses- offers excellent overall cure rates.