ASCO GU 2021: Surgery In Early Metastatic Seminoma, The Phase II SEMS Trial

(UroToday.com) Chemotherapy or radiotherapy are standard treatments for stage II seminoma, though they are associated with significant long-term treatment-related toxicities. Long-term morbidity from chemotherapy and radiotherapy is real, as these are young patients with excellent cure rates thus potentiating cumulative toxicities. These toxicities may include cardiac events, secondary cancers (hematologic and solid tumors), metabolic syndrome, bleomycin-induced pulmonary injury, infertility, neurotoxicity, and tinnitus. Retroperitoneal lymph node dissection (RPLND) is an established treatment for testicular germ cell tumors (primary RPLND for stage I and IIA NSGCT; post-chemotherapy RPLND) but little data exists on its efficacy as a front-line treatment in early metastatic (stage II) seminoma. At the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), Dr. Sia Daneshmand presented results of the SEMS single-arm, multi-institutional (NCT02537548), phase II study of RPLND as first-line treatment for testicular seminoma with isolated retroperitoneal disease.


This trial included 12 sites in the United States and Canada that prospectively enrolled patients (16 years of age or older) with testicular seminoma and isolated retroperitoneal lymphadenopathy between 1-3 cm in size. Patients were excluded if they received prior therapy (except orchiectomy) for testicular cancer or if the patient’s relapse was greater than three years from diagnosis. Open, modified-template RPLND was performed by qualified surgeons (>= 8 open RPLND in 1 year or >24 open RPLND in 3 years) with a primary endpoint of 2-year recurrence-free survival. Secondary endpoints included 5-year recurrence free survival, complication rates (short and long-term), pathologic up/downstaging, recurrence patterns, adjuvant therapies, and treatment-free survival.

A total of 55 patients were enrolled in SEMS and underwent RPLND. Fourteen patients had initial stage I disease who developed isolated retroperitoneal relapse while 41 patients had clinical stage IIA-B at presentation. The median age was 34 years of age (range: 21-64) with 80% of patients being white. With a median follow-up of 24 months (range: 8-52 months), there were a total of 10 recurrences. The overall recurrence rate was 18% with a median time to recurrence of 8 months; the two-year recurrence free survival rate was 84%. Of the recurrences, eight underwent chemotherapy (6 BEP x 3, 1 EP x 4, 1 carbo/etoposide) and two underwent additional surgery. As follows is the Kaplan-Meier curve for recurrence-free survival and treatment-free survival:


ASCOGU21_Siamak_Daneshmand_SEMS_1.png

There were 7 (13%) patients who experienced short-term complications within one year of RPLND. Of these, 5 (9%) were classified as Clavien Dindo I-II and 2 (3.6%) were classified as Clavien Dindo III (chylous ascites, pulmonary embolism). No patients have reported long-term complications.

Dr. Daneshmand concluded his presentation with the following take home messages: 

  • The SEMS trial established RPLND as a therapeutic option as a first-line treatment in early metastatic seminoma with isolated retroperitoneal lymphadenopathy
  • With 2-year median follow-up, systemic treatment free survival was 84% and overall survival was 100% 
  • The surgery offers cancer control rates similar to those seen in non-seminomatous germ cell tumors and is an attractive option given the favorable long-term morbidity of RPLND

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

Related Content: 
Clinical Trial Information: NCT02537548.

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021