5038 Background: Primary mediastinal non-seminomatous germ cell tumors (PMNSGT) have been categorized as poor risk disease. They are rarely curable with salvage chemotherapy. Our institution has subscribed to a policy of surgically removing any residual disease if deemed resectable after cisplatin-based chemotherapy regardless of serum tumor marker (STM) status. In this study, we retrospectively analyzed outcomes of patients who presented to surgery with rising alphafetoprotein (AFP) or human chorionic gonadotropin (hCG). Methods: All patients with PMNSGT who received platinum based chemotherapy followed by complete surgical extirpation of residual disease at Indiana University between1981–2007 were retrospectively reviewed. Univariate comparisons were performed for multiple variables including STM at time of diagnosis and surgery, presence of lung metastasis, extrathoracic disease, sites of relapse, and outcomes in the subset of patients with rising STM after chemotherapy. Results: Of 158 patients (155 males and 3 females) who underwent post-chemotherapy surgery, 36 patients (35 males and 1 female) had rising STM after chemotherapy. The median age of this subset was 27 (range 19–44). Three patients had rising hCG (21, 92, 1,500 mU/ml), one had rising AFP and hCG (58 mU/ml), and the remaining 32 had rising AFP at the time of surgery, with median AFP 159.5 ng/ml (range 29–8,445). Despite the presence of rising markers post-chemotherapy, 8 patients pathologically demonstrated teratoma and 3 patients necrosis only at time of resection. Thirty patients normalized their tumor markers postoperatively. Twenty-one of 36 died (including three postoperative deaths), five were lost to follow-up, and ten are alive. Of the ten patients alive, 8 are continuously disease-free with median follow up of 73 months (range 4–220). Seven of these 8 patients had germ cell cancer pathologically demonstrated in resected mediastinal mass and 2 in resected lung metastases. Conclusions: Rising markers post-chemotherapy in patients with PMNSGCT connote a poor prognosis. However, selected pts may still be curable with extensive resection by experienced thoracic surgical oncologists No significant financial relationships to disclose.