Seminom im klinischen Stadium IIA/B – machen oder nicht machen: welchen Stellenwert hat die retroperitoneale Lymphadenektomie?

Zusammenfassung

Ungefähr 10% der Patienten mit einem seminomatösen testikulären Keimzelltumor werden im klinischen Stadium (KS) IIA/B diagnostiziert. Die aktuellen Therapieempfehlungen der S3-Leitlinie beinhalten die systemische Chemotherapie mit 3 Zyklen PEB oder die perkutane Radiotherapie mit 30 bzw. 36 Gy. Beide Behandlungsvarianten führen zu einer hohen Kurationsrate von 90–94 bzw. 82–90% in den Stadien IIA bzw. IIB. Jedoch sind beide Optionen nicht nur mit einer signifikant erhöhten langfristigen therapieassoziierten Toxizität bezüglich sekundäre Malignome, kardiovaskulärer und metabolischer Erkrankungen, sondern auch mit einer erhöhten therapiebedingten Sterberate assoziiert. Die primäre retroperitoneale Lymphadenektomie (RLA) hat sich in 5 prospektiven und retrospektiven Studien als eine valide therapeutische Alternative entwickelt. Die Rezidivrate beträgt nach einem medianen Follow-up von 25–33 Monaten 11–30%, sodass 70–90% der Patienten ohne eine begleitende Chemotherapie kuriert werden konnten. Alle Patienten wurden im Rezidiv meist mit einer Salvage-Chemotherapie kuriert. Die Rate an operationsbedingten Komplikationen Clavien-Dindo ≥3a ist gering und beträgt nur 3–13%. Der Erfolg der Operation ist abhängig von der Erfahrung der jeweiligen Operateure und dem gewählten Template, sodass die nsRLA nur an ausgewiesenen Zentren durchgeführt werden sollte. Die präoperative Bestimmung des molekularen Biomarkers miR371 korreliert streng mit dem Vorhandensein lymphonodulärer Mikrometastasen und könnte in das diagnostische Armentarium vor Therapie der Seminome im klinischen Stadium IIA/B integriert werden.

Abstract

About 10% of patients with seminomatous testicuar germ cell tumors are diagnosed with clinical stage II/B. The current guideline recommended treatment options include systemic chemotherapy with 3 cycles PEB or radiation therapy with 30 Gy for CS IIA and 36 Gy for CS IIB. Despite a high cure rate of 90–94% and 82–90% for CS IIA and CS IIB, respectively, both options are associated with a high rate of treatment-associated long-term toxicities. A significantly increased risk for the development of secondary malignancies, cardiovascular and metabolic disease as well as an increased for treatment-associated mortality has been proven in various studies. Primary nerve sparing retroperitoneal lymph node dissection (nsRPLND) has been evaluated in 5 prospective and retrospective clinical studies and it has emerged as a valid treatment alternative. The relapse-rate after a median follow-up of 25–33 months is in the range of 11–30%, so that 70–90% of patients are cured without being subjected to chemotherapy and potential long-term toxicities. All relapsing patients have been cured with secondary salvage chemotherapy. The frequency of significant surgery-associated complications is low with 3–13%. Therapeutic success depends on the surgical experience of the various surgeons and the chosen template, so that this type of surgical interventions should only be performed in centres of excellence with dedicated surgeons. Preoperative evaluation of the new biomarker miR371 has been shown to predict the presence of metastatic disease with an accuracy of around 100% so that this marker might be used in daily routine prior to active treatment in CS IIA/B seminomas.

Schlüsselwörter

Seminom - Nichtseminom - miR371 - Chemotherapie - Strahlentherapie

Keywords

Seminoma - miR371 - chemotherapy - radiation therapy - non-seminoma

Publication History

Received: 03 May 2024

Accepted after revision: 24 June 2024

Article published online:
01 August 2024

• Literatur

• 1 Travis LB, Feldman DR, Fung C. et al. Adolescent and Young Adult Germ Cell Tumors: Epidemiology, Genomics, Treatment, and Survivorship. J Clin Oncol 2024; 42: 696-706
• 2 Patrikidou A, Cazzaniga W, Berney D. et al. European Association of Urology Guidelines on Testicular Cancer: 2023 Update. Eur Urol 2023; 84: 289-301
• 3 S3-Leitlinie Diagnostik, Therapie und Nachsorge der Keimzelltumoren des Hodens (Version 1.1, 2020). https://www.leitlinienprogramm-onkologie.de/leitlinien/hodentumoren
• 4 Fung C, Dinh Jr P, Ardeshir-Rouhani-Fard S. et al. Toxicities Associated with Cisplatin-Based Chemotherapy and Radiotherapy in Long-Term Testicular Cancer Survivors. Adv Urol 2018; 2018: 8671832
• 5 Haugnes HS, Oldenburg J, Bremnes RM. Pulmonary and cardiovascular toxicity in long-term testicular cancer survivors. Urol Oncol 2015; 33: 399-406
• 6 Kvammen Ø, Myklebust TÅ, Solberg A. et al. Long-term Relative Survival after Diagnosis of Testicular Germ Cell Tumor. Cancer Epidemiol Biomarkers Prev 2016; 25: 773-779
• 7 Kvammen Ø, Myklebust TÅ, Solberg A. et al. Causes of inferior relative survival after testicular germ cell tumor diagnosed 1953–2015: A population-based prospective cohort study. PLoS One 2019; 14: e0225942
• 8 Chovanec M, Abu Zaid M, Hanna N. et al. Long-term toxicity of cisplatin in germ-cell tumor survivors. Ann Oncol 2017; 28: 2670-2679
• 9 Maroto P, Anguera G, Martin C. Long-term toxicity of the treatment for germ cell-cancer. A review. Crit Rev Incol Hematol 2018; 121: 62-67
• 10 Pierorazio PM, Cheaib JG, Patel HD. et al. Comparative effectiveness of surveillance, primary chemotherapy, radiotherapy and retroperitoneal lymph node dissection for the management of early-stage testicular germ cell tumors: a systematic review. J Urol 2021; 205: 370-382
• 11 Papachristofilou A, Bedke J, Hayoz S. et al. Single-dose carboplatin followed by involved-node radiotherapy for stage IIA and stage IIB seminoma (SAKK 01/10): a single-arm, multicentre, phase 2 trial. Lancet Oncol 2022; 23: 1441-1450
• 12 Mezvrishvili Z, Managadze L. Retroperitoneal lymph node dissection for high risk stage I and stage IIA seminoma. Int Urol Nephrol 2006; 38: 615-619
• 13 Hu B, Shah S, Shojaei S. et al. Retroperitoneal Lymph Node Dissection as First-Line Treatment of Node-Positive Seminoma. Clin Genitourin Cancer 2015; 13: e265-e269
• 14 Daneshmand S, Cary C, Masterson T. et al. Surgery in early metastatic seminoma: a phase II trial of retroperitoneal lymph node dissection for testicular seminoma with limited retroperitoneal lymphadenopathy. J Clin Oncol 2023; 41: 3009-3018
• 15 Hiester A, Che Y, Lusch A. et al. Phase 2 Single-arm Trial of Primary Retroperitoneal Lymph Node Dissection in Patients with Seminomatous Testicular Germ Cell Tumors with Clinical Stage IIA/B (PRIMETEST). Eur Urol 2023; 84: 25-31
• 16 Heidenreich A, Paffenholz P, Hartmann F. et al. Retroperitoneal lymph node dissection in clinical stage IIA/B metastatic seminoma. Results of the Cologne Trial of Retroperitoneal Lymphadenectomy in metastatic seminoma (COTRIMS). Eur Urol Oncol 2024; 7: 122-127
• 17 Tachibana I, Alabd A, Tong Y. et al. Primary Retroperitoneal Lymph Node Dissection for Stage II Seminoma: Is Surgery the New Path Forward?. J Clin Oncol 2023; 41: 3930-3938
• 18 Matulewicz RS, Benfante N, Funt SA. et al. Primary Retroperitoneal Lymph Node Dissection for Seminoma Metastatic to the Retroperitoneum. J Urol 2024; 211: 80-89
• 19 Gilligan T, Lin DW, Aggarwal R. et al. Testicular Cancer, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2019; 17: 1529-1554
• 20 Stephenson A, Eggener SE, Bass EB. et al. Diagnosis and Treatment of Early Stage Testicular Cancer: AUA Guideline. J Urol 2019; 202: 272-281
• 21 Antonelli L, Ardizzone D, Tachibana I. et al. Risk Factors for Relapse in Nonseminomatous Testicular Cancer After Postchemotherapy Retroperitoneal Lymph Node Dissection With Viable Residual Cancer. J Clin Oncol 2023; 41: 5296-5305
• 22 Seelemeyer F, Pfister D, Pappesch R. et al. Evaluation of a miRNA-371a-3p Assay for Predicting Final Histopathology in Patients Undergoing Primary Nerve-sparing Retroperitoneal Lymphadenectomy for Stage IIA/B Seminoma or Nonseminoma. Eur Urol Oncol 2023; 7: 319-322
• 23 Lafin JT, Scarpini CG, Amini A. et al. Refining the serum miR-371a-3p test for viable germ cell tumor detection. Sci Rep 2023; 13: 10558