(UroToday.com) The 2025 GU ASCO annual meeting featured a session on emerging trends in germ cell tumors and a presentation by Dr. Axel Heidenreich discussing primary retroperitoneal lymph node dissection (RPLND) in stage II seminoma. The clinical presentation of seminomas is such that <10% of patients present in de novo clinical stage IIA/B. Importantly, 15% of stage I seminoma patients relapse with 90-95% of relapses located in the retroperitoneum. Relapse free survival rates vary between 82-94% and 5-year overall survival is ~95%. Standard treatment for seminoma is (i) 3 cycles of BEP chemotherapy or 4 cycles of EP chemotherapy, (ii) radiation therapy with 30 Gy in CS IIA seminoma and 36 Gy in CS IIB seminoma, (iii) an optional treatment option is radiation therapy + 1 cycle AUC 7. With all of these treatment options, the 5-year overall survival is 95%. The problem with all of these treatments is long-term toxicity, which includes additional solid cancers, leukemia, cardiovascular, and diabetes mellitus:
Late effects affecting mortality do not show up until 20+ years after diagnosis, specifically related to long-term toxicity. In a population-based study (n = 5,707) from Norway [1], over a median follow-up of 18.7 years (IQR 12.7 – 35), the non-testicular cancer death was 12%. Overall excess non-testicular cancer mortality was 23% compared to the general population, with increased risks after platinum-based chemotherapy and radiotherapy:
Dr. Heidenreich notes that among the 86% of seminoma CSI patients, 15-30% relapse, of which 95% relapse in the retroperitoneum, nearly all relapses have good prognosis, and these patients are now CS IIA/B seminoma. The hypothesis of nerve sparing RPLND is as follows:
- Seminoma is a “lymphodular” disease
- Low volume, locoregional lymph node metastases might be cured by locoregional surgery
- Reduction of significant treatment-associated toxicities
- Maintenance of oncological efficacy
The following table highlights the current RPLND trials in seminoma:
These trials comprised mostly high volume, experienced surgeons:
Approximately 90% of relapses in these trials occurred within 2 years, and in field relapses are rare:
To date, >90% of RPLNDs for seminoma have been done via open surgery. Moreover, complication rates in these trials have been acceptable:
Summarizing the available evidence, Dr. Heidenreich notes the body of evidence comprises 234 CS IIA/B marker negative seminomas, with the majority being low volume CS IIB. The median follow-up of the prospective trials is > 3 years, with a relapse rate of 17.9% (95% CI 11.8-30), and rarely in field. More than 80% of patients are chemotherapy free, saving 246 cycles of chemotherapy. The majority of relapses occur within 2 years of follow-up, with a 100% cure rate with salvage chemotherapy. However, these trials are not without issue or controversy:
- pN0 rate of 7.7%
- Relapse rate of 17.9%
- Open RPLDN in >90% of patients
- Only performed at experienced centers
Several ways to potential improve on the pN0 rate of 7.7% is to redo the CT/MRI in low volume clinical stage IIA patients or to use biomarkers such as miR371. To improve on the relapse rate of 17.9%, Dr. Heidenreich notes that we need to respect nodal distribution:
Additionally, we can adapt our surgical techniques:
- Always retrocaval or retroaortal
- Always common iliac down to the iliac bifurcation
- Always lateral to the ureters
- Always resection of the ipsilateral testicular vein and vas deferens
In high risk patients, perhaps we should be doing adjuvant chemotherapy. High risk in these instances is defined as >3 cm nodes or extranodal extension, in which patients may be candidates for BEP x 1 cycle of chemotherapy or EP x 2 cycles of chemotherapy. Dr. Heidenreich states that open RPLND should remain the technique of choice until proven otherwise, given that there is no long term impact for the patient if done by experienced surgeons. Finally, these procedures should only be done in experienced centers, since this is a prerequisite for optimal outcomes.
Dr. Heidenreich concluded his presentation by discussing primary retroperitoneal lymph node dissection in stage II seminoma with the following take-home points:
- Open nerve sparing RPLND:
- Oncologically highly effective in low volume CS IIA/B, marker negative pure seminoma
- Associated with minimal surgical associated morbidity
- 100% cure for 10-30% relapsing patients with salvage chemotherapy
- Avoidance of long-term toxicity due to standard treatment with 3 cycles of BEP chemotherapy or retroperitoneal radiation therapy
- Improvement of outcomes is possible
- Utilization of miR371 to avoid unnecessary surgery
- Think about adjuvant BEP x 1 cycle/EP x 2 cycles of chemotherapy for high risk patients
Presented by: Axel Heidenreich, MD, PhD, University Hospital of Cologne, Cologne, Germany
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025.
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