ESOU 2022: Stage II Seminoma: What Is the Role for Retroperitoneal Lymph Node Dissection?

( The 2022 EAU Section of Oncological Urology (ESOU) Annual Meeting included a session on the early detection and personalized management of testis cancer and a presentation by Dr. Sia Daneshmand discussing the role of retroperitoneal lymph node dissection (RPLND) in stage II seminoma. 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, tinnitus, and increased risk of suicide. So, is there a treatment that can reduce long-term morbidity?

The SEMS trial evaluated surgery in metastatic seminoma (NCT02537548) and was first presented at GU ASCO 2021. 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; at USC, Dr. Daneshmand prefers a midline extraperitoneal approach) 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 over 4 years 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. There was one patient that received adjuvant carboplatin 1 month post-surgery. As follows is the Kaplan-Meier curve for recurrence-free survival and treatment-free survival:

SEMS trial-0.jpg 

There were 4 patients who experienced 6 short-term complications within one year of RPLND, of which 2 were classified as Clavien Dindo III (chylous ascites, pulmonary embolism). No patients have reported long-term complications. Of note, Dr. Peter Albers is running a similar trial in Germany called the PRIMETEST trial, with a side-by-side comparison of the two trials as follows:

SEMS trial-1.jpg 

Dr. Daneshmand’s conclusions from the SEMS trial were as follows: (i) the SEMS trial established RPLND as a therapeutic option as a first-line treatment in early metastatic seminoma with isolated retroperitoneal lymphadenopathy (1-3 cm), (ii) with 2-year median follow-up, systemic treatment free survival was 85% and overall survival was 100%, and (iii) 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.

Dr. Daneshmand also highlighted miRNA 371a-3p is a potential biomarker in germ cell tumors, and in his opinion, will change everything in the management of testicular cancer. Building off of the early work of miRNA, Dr. Daneshmand envisions the next iteration of an RPLND trial to be miRNA biomarker driven:

SEMS trial-2.jpg 

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

  • Patients with stage IIA/B seminoma (<= 3cm) may be offered a primary RPLND to reduce toxicity and morbidity of chemotherapy/radiotherapy
  • Micro-RNA 371 is a useful biomarker, is clinically validated, and will change our treatment algorithms
  • Clinical trials are planned to validate the utility of miRNA in equivocal clinical settings

Presented by: Sia Daneshmand, MD, Director of Urologic Oncology, University of Southern California, Los Angeles, CA

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 EAU Section of Oncological Urology (ESOU) Hybrid Annual Meeting, Madrid, Spain, Fri, Jan 21 – Sun, Jan 23, 2022.