ASCO GU 2021: SEMS trial: Result of a Prospective, Multi-Institutional Phase II Clinical Trial of Surgery In Early Metastatic Seminoma

( The management of stage 2A seminoma has been consistent over the past several years, consisting of either radiotherapy of 30 Gy to the para-aortic and ipsilateral iliac lymph nodes or primary chemotherapy with either three cycles of BEP or four cycles of EP. Cure rates with these approaches are excellent but are also associated with many life years of potential cumulative toxicities. For example, the hazard ratio for cardiac events and secondary malignancy range between 2 and 3 depending on the study. Additionally, there is a risk for bleomycin-induced pulmonary injury, neurotoxicity, and metabolic syndrome. More recently, investigators have been exploring the utility of retroperitoneal lymph node dissection (RPLND) in early metastatic seminoma. This is based on the known effectiveness of RPLND as a primary therapeutic intervention in Stage 1 and 2A non-seminoma, as well as after chemotherapy in both non-seminoma and seminoma. Overall, data suggest lower long-term morbidity with RPLND compared to chemotherapy or radiation therapy. Efficacy data for RPLND as primary management of stage 2A seminoma has been limited. 

Based on a total of 15 published patients with early metastatic seminoma treated with RPLND in three reports from 1997-2014 and no recurrences with short term follow-up, the SEMS (Surgery in Early Metastatic Seminoma) trial was initiated. SEMS (NCT02537548) was designed as a phase 2 study of RPLND as first line treatment for testicular seminoma with isolated retroperitoneal disease measuring 1-3 cm. Patients were eligible for the trial if they had a pure testicular seminoma, either stage 1 with an isolated 1-3 cm relapse or stage 2 with no more than 2 lymph nodes measuring 1-3 cm in any dimension within the RPLND template. Tumor markers were required to be normal with the exception that mildly elevated LDH to 1.5x the upper limit normal was allowed. Patients with potential late relapse biology (relapse after 3 years), or who had received prior chemotherapy or radiotherapy, were excluded. Treatment was an open modified template RPLND, and the primary outcomes was 2-year recurrence-free survival. Key secondary outcomes included 5-year recurrence free survival, pathologic upstaging, treatment free survival, and surgical complications. Surgeons eligible to participate in the study were required to perform more than 8 open RPLNDs per year or more than 24 in the past three years. All procedures were open, photographs were required, and use of the Memorial Sloan Kettering Cancer Center (MSKCC) modified template was required. 

In total 55 patients were accrued to this study over 4 years across the US and Canada. The median age of patients was 34, with 80% identifying as white/Caucasian. 25% of patients enrolled were stage 1 with recurrence, and 75% were stage 2A or 2B at presentation. The median follow-up was 24 months, range 8-52 months. 

The overall recurrence rate was 18%, with 10 patients recurring at a median time of 8 months. The two-year recurrence-free survival was 84% (46/55 patients). Two of the patients who recurred received further surgery, and eight received chemotherapy. There were seven short term complications noted, 2 of which were classified as Clavien Dindo 3 (chylous ascites and pulmonary embolism). There were no long-term complications such as ejaculatory changes. 

Dr. Daneshmand concluded that the SEMS trial establishes additional data for RPLND as a treatment alternative for testicular seminoma with isolated retroperitoneal lymphadenopathy (1-3 cm). Overall survival at the median follow-up of 2 years was 100%, and 85% of patients were free from additional treatment. With further validation, RPLND in this patient population may be a feasible alternative to preserve patient outcomes and limit the morbidity of treatment. 

Presented by: Siamak (Sia) Daneshmand, MDAssociate Professor of Urology Keck School of Medicine USC University of Southern California with Clinical Scholar designation and serves as director of clinical research as well as the urologic oncology fellowship director

Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute, during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021

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Clinical Trial Information: NCT02537548