Minimally-invasive ICG-guided Retroperitoneal Sentinel Lymph Node Dissection in the Primary Staging of Testicular Cancer Versus Standard of Care

Official title

RAISN 2: Prospective Randomized Trial of Minimally-invasive ICG-guided Retroperitoneal Sentinel Lymph Node Dissection in the Primary Staging of Testicular Cancer Versus Standard of Care

Overview

Testicular cancer is highly curable, but approximately 20-30% of patients with clinical stage I disease harbor occult retroperitoneal lymph node metastases that are not detected by conventional imaging. Current risk-adapted management may lead to overtreatment in some patients while failing to identify others who are at increased risk of relapse. The RAISN 2 study evaluates whether minimally invasive indocyanine green (ICG)-guided retroperitoneal sentinel lymph node dissection can improve primary staging and risk stratification in patients with clinical stage I testicular cancer. Participants will be randomized in a 5:1 ratio to undergo either orchiectomy combined with ICG-guided sentinel lymph node dissection or standard orchiectomy followed by guideline-based surveillance. All participants will undergo structured follow-up according to current clinical guidelines. The primary objective is to estimate the 2-year relapse-free survival of patients undergoing the sentinel lymph node approach. Secondary objectives include assessment of overall survival, relapse patterns, perioperative morbidity, quality of life, psychological outcomes, and the feasibility and safety of the procedure. This multicenter study aims to determine whether sentinel lymph node-guided staging provides more accurate risk stratification while avoiding unnecessary treatment and maintaining oncological safety.

Detailed description

Testicular germ cell tumors are the most common solid malignancy in young adult men and are associated with excellent long-term survival when managed appropriately. In patients with clinical stage I disease, approximately 20-30% harbor occult retroperitoneal lymph node metastases despite the absence of radiologically detectable disease. Current management strategies rely on histopathological risk factors to guide surveillance or adjuvant treatment; however, these factors have limited predictive accuracy and may result in both overtreatment and undertreatment.

Sentinel lymph node (SLN) mapping has been successfully established in several solid malignancies as a minimally invasive method for detecting occult lymphatic metastases. The RAISN feasibility study demonstrated that minimally invasive indocyanine green (ICG)-guided retroperitoneal sentinel lymph node dissection is technically feasible in patients with clinical stage I testicular cancer, achieving a 100% sentinel lymph node detection rate without increasing perioperative morbidity. These findings provide the basis for prospective validation in a larger patient population.

RAISN 2 is a prospective, randomized, multicenter clinical trial designed to evaluate whether ICG-guided retroperitoneal sentinel lymph node dissection improves primary staging and risk stratification in patients with clinical stage I testicular cancer. Eligible participants will be randomized in a 5:1 ratio to receive either minimally invasive ICG-guided sentinel lymph node dissection combined with inguinal orchiectomy (intervention arm) or inguinal orchiectomy followed by guideline-based surveillance (control arm). The unequal allocation was chosen to maximize the prospective evaluation of the novel staging procedure while maintaining a concurrent reference group.

In the intervention arm, indocyanine green is injected into the affected testis immediately before minimally invasive retroperitoneal exploration. Near-infrared fluorescence imaging is used to identify and remove sentinel lymph nodes for histopathological evaluation. After surgery, patients in both study arms undergo guideline-based surveillance without routine adjuvant treatment. In the event of disease recurrence, salvage therapy is administered according to current national and international guidelines.

The primary objective of the study is to estimate the 2-year relapse-free survival of patients undergoing the sentinel lymph node strategy. Secondary objectives include evaluation of overall survival, relapse patterns, time to relapse, perioperative morbidity, postoperative complications, quality of life, psychological outcomes, technical feasibility, and safety of the procedure. In addition, translational analyses using prospectively collected blood and tissue samples will explore clinicopathological and molecular factors associated with oncological outcomes.

The results of this study are expected to determine whether minimally invasive ICG-guided sentinel lymph node dissection can provide more accurate nodal staging, reduce unnecessary treatment, and maintain oncological safety in patients with clinical stage I testicular cancer.

Interventions

• Procedure ICG-Guided Retroperitoneal Sentinel Lymph Node Biopsy
  Minimally invasive laparoscopic or robot-assisted retroperitoneal sentinel lymph node biopsy performed after intratesticular injection of indocyanine green (ICG) using near-infrared fluorescence imaging for sentinel lymph node identification.
• Procedure Radical Inguinal Orchiectomy
  Standard radical inguinal orchiectomy performed according to current clinical guidelines.

Primary outcome measures

• 2-Year Relapse-Free Survival (RFS) [Time frame: 24 months after randomization]

Secondary outcome measures (7)

• Overall Survival [Time frame: 24 months after randomization]
• Time to Tumor Recurrence [Time frame: 24 months after randomization]
• Rate of Salvage Therapy [Time frame: 24 months after randomization]
• Perioperative Morbidity [Time frame: up to 30 days after surgery]
• Postoperative Complications [Time frame: up to 24 months after surgery]
• Health-Related Quality of Life [Time frame: Baseline and annually for 5 years]
• Technical Feasibility of Sentinel Lymph Node Biopsy [Time frame: During surgery]

Eligibility criteria

Inclusion criteria

• Male participants aged 18 years or older.
• Clinically suspected testicular germ cell tumor based on physical examination and scrotal ultrasonography, with or without elevated serum tumor markers (AFP and/or β-hCG).
• No radiological evidence of metastatic disease on preoperative contrast-enhanced computed tomography (CT) of the chest and abdomen (clinical stage I).
• Eligible for radical inguinal orchiectomy.
• Able to understand the study procedures and provide written informed consent.
• Willing and able to comply with the study protocol and follow-up schedule.

Exclusion criteria

• Previous scrotal or retroperitoneal surgery unrelated to germ cell tumor treatment, except surgery for cryptorchidism during childhood.
• Previous malignancy requiring abdominal surgery, chemotherapy, or radiotherapy that could interfere with study participation.

Previous radiotherapy involving the retroperitoneum.

• Known hypersensitivity to indocyanine green (ICG), iodine, or sodium iodide.
• Severe medical condition that precludes surgery or study participation.
• Psychiatric disorder or other condition preventing compliance with study procedures.
• Inability to understand the German language sufficiently to provide informed consent and complete study assessments.
• Individuals under legal guardianship or otherwise unable to provide legally valid informed consent.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Germany · 8 centers

• University Hospital Ulm — Ulm
• University Hospital Würzburg — Würzburg
• Asklepios Klinik Altona — Hamburg
• University Hospital Marbug — Marburg
• University Hospital Cologne — Cologne
• University Hospital Düsseldorf — Düsseldorf
• Helios University Hospital Wuppertal — Wuppertal
• University Hospital Dresden — Dresden

Finland · 2 centers

• Helsinki University Hospital — Helsinki
• University of Turku — Turku

Publications

• Vermeulen-Spohn MS, Pongratanakul P, Thy S, Dukart J, Albers P, Che Y. RAISN: Robot-assisted Indocyanine Green-guided Sentinel Node Biopsy in Clinical Stage I Germ Cell Tumor. Eur Urol Open Sci. 2024 Jun 27;66:55-59. doi: 10.1016/j.euros.2024.06.004. eCollection 2024 Aug. PMID 39036045
• Albers P, Siener R, Krege S, Schmelz HU, Dieckmann KP, Heidenreich A, Kwasny P, Pechoel M, Lehmann J, Kliesch S, Kohrmann KU, Fimmers R, Weissbach L, Loy V, Wittekind C, Hartmann M; German Testicular Cancer Study Group. Randomized phase III trial comparing retroperitoneal lymph node dissection with one course of bleomycin and etoposide plus cisplatin chemotherapy in the adjuvant treatment of clini PMID 18458040
• Nayan M, Jewett MA, Hosni A, Anson-Cartwright L, Bedard PL, Moore M, Hansen AR, Chung P, Warde P, Sweet J, O'Malley M, Atenafu EG, Hamilton RJ. Conditional Risk of Relapse in Surveillance for Clinical Stage I Testicular Cancer. Eur Urol. 2017 Jan;71(1):120-127. doi: 10.1016/j.eururo.2016.07.013. Epub 2016 Aug 12. PMID 27527805
• Tanis PJ, Horenblas S, Valdes Olmos RA, Hoefnagel CA, Nieweg OE. Feasibility of sentinel node lymphoscintigraphy in stage I testicular cancer. Eur J Nucl Med Mol Imaging. 2002 May;29(5):670-3. doi: 10.1007/s00259-001-0751-8. Epub 2002 Mar 5. PMID 11976806
• Blok JM, Kerst JM, Vegt E, Brouwer OR, Meijer RP, Bosch JLHR, Bex A, van der Poel HG, Horenblas S. Sentinel node biopsy in clinical stage I testicular cancer enables early detection of occult metastatic disease. BJU Int. 2019 Sep;124(3):424-430. doi: 10.1111/bju.14618. Epub 2019 Mar 28. PMID 30417511

Identifiers

NCT: NCT07699640 · RAISN 2

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗