Comparison of Axillary Sentinel Lymph Node Biopsy Versus no Axillary Surgery

Not Applicable

Active, not recruiting

• Conditions: Breast Cancer
• Interventions: Procedure: SLNB versus completion ALND; Procedure: no axillary surgery versus SLNB

• Registration Number: NCT02466737
• Lead Sponsor: University of Rostock

Brief Summary

Although there is no doubt that the presence of lymph node metastases worsens prognosis of a patient, unambiguous evidence to support lymph node dissection is still lacking. For many solid tumors, the role of lymph node dissection is yet controversial, and may depend on the tumor type and the stage of patient presentation for diagnosis. Axillary surgery for breast cancer is now considered as staging procedure that does not seem to influence breast cancer mortality. Women with breast cancer have benefitted greatly from a series of carefully performed randomized controlled trial focusing on axillary surgery. The objective of INSEMA is to show that less axillary surgery is better, in that oncological outcomes are the same and less surgical intervention will result in fewer surgical complications.

Detailed Description

Currently, axillary surgery for breast cancer is considered as staging procedure that does not seem to influence breast cancer mortality, since the risk of developing metastasis depends mainly on the biological behaviour of the primary (seed-and-soil model). Based on this, the postsurgical therapy should be considered on the basis of biologic tumor characteristics rather than nodal involvement.

The goal of the present study is to show that early-stage breast cancer patients with reduced extent of axillary surgery are not inferior regarding disease-free survival outcome compared with the standard arm. All patients will be first randomized to either no axillary surgical intervention or axillary sentinel lymph node biopsy (SLNB). Patients with SLNB and pN+(sn) status will be secondly randomized to either SLNB alone or completion axillary lymph node dissection (ALND) in cases with less than four involved nodes (1-3 macrometastases). Patients with four or more metastatic sentinel lymph nodes should undergo completion ALND.

Postoperative systemic treatment should be based on local multidisciplinary tumor board recommendation according to the current German AGO and S3 guidelines. For women who are treated with breast-conserving surgery, the most common site of local recurrence is the conserved ipsilateral breast itself. Thus, whole-breast radiation therapy after breast-conserving surgery is mandatory and should be performed according to the current guidelines (S3, AGO, DEGRO).

During follow-up, patients will be assessed for disease recurrence according to standard clinical practice. History and physical examination will be performed every 6 months for the first 36 months and yearly thereafter. Annual mammography and sonography will be required; other testing will be based on symptoms and investigator preference. The total number of patients to be randomized into the trial will be approximately 7,095. An event-driven final efficacy analysis will be performed per-protocol for two primary objectives.

Study Timeline

• Study First Submitted: 2015-06-04
• Study First Submitted QC: 2015-06-04
• Study First Posted: 2015-06-09
• Study Start: 2015-09
• Primary Completion: 2024-08-30
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-16
• Last Update Posted: 2024-12-19
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 5505

Inclusion Criteria

• Written informed consent prior to beginning breast-conserving surgery, including expected cooperation of the patients for follow-up, must be obtained and documented according to the local regulatory requirements
• Histologically confirmed unilateral primary invasive carcinoma of the breast (core biopsy or open biopsy). Multifocal or multicentric tumors are allowed if breast-conserving surgery is planned
• Age at diagnosis at least 18 years
• Preoperative imaging techniques with estimated tumor size of <5 cm (iT1/iT2 irrespective of hormone sensitivity or HER2 status)
• Clinically and sonographically tumor-free axilla prior to core biopsy (cN0/iN0)
• In cases with cN0 and iN+, a negative core biopsy or fine needle aspiration (FNA) biopsy of the sonographically suspected lymph node is required before randomization
• No clinical evidence for distant metastasis (M0)
• Planned breast-conserving surgery (R0 resection) with postoperative external whole-breast irradiation (conventional fractionation or hypofractionation)

Exclusion Criteria

• History of malignancy within last 5 years, except curatively treated basalioma of the skin and carcinoma in situ of the cervix
• Time since core biopsy >3 months (optimal <1 month)
• Previous and already (neoadjuvant) treated invasive breast carcinoma
• Histologically non-invasive breast carcinoma
• cT3/T4 or iT3/T4 tumors
• pregnant or lactating patients
• Planned total mastectomy (e.g. multicentric tumors )
• Planned intraoperative radiotherapy (e.g. Intrabeam) or postoperative partial breast irradiation (e.g. multicatheter technique) alone; both procedures are allowed as boost techniques
• Male patients

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
sentinel lymph node biopsy alone	SLNB versus completion ALND	-
no axillary surgery	no axillary surgery versus SLNB	-
completion axillary lymph node dissection	SLNB versus completion ALND	standard arm in second randomization
sentinel lymph node biopsy	no axillary surgery versus SLNB	standard arm in first randomization

Primary Outcome Measures

Name	Time	Method
invasive disease-free survival (IDFS) after breast-conserving surgery	5 years	non-inferiority question

Trial Locations

Locations (150)

Klinikum Mittelbach Brustzentrum; 🇩🇪 Baden-Baden, BW, Germany

Städtisches Klinikum Brandenburg; 🇩🇪 Brandenburg, BB, Germany

BGZ Dornbirn, Gynäkologie; 🇦🇹 Dornbirn, Austria

Landes-Krankenhaus Wolfsberg, Chirurgie; 🇦🇹 Wolfsberg, Austria

Klinikum Ernst von Bergmann; 🇩🇪 Potsdam, BB, Germany

Park-Klinik Weißensee; 🇩🇪 Berlin, BE, Germany

Elisabeth Krankenhaus Kassel; 🇩🇪 Kassel, HE, Germany

Sana Klinikum Offenbach; 🇩🇪 Offenbach, HE, Germany

Gynäkologische Praxisklinik Harburg; 🇩🇪 Hamburg, HH, Germany

Helios Dr. Horst Schmidt Klinikum; 🇩🇪 Wiesbaden, HE, Germany

Kreiskrankenhaus Bergstraße gGmbH; 🇩🇪 Heppenheim, HE, Germany

Klinikum Kassel; 🇩🇪 Kassel, HE, Germany

Universität Greifswald, Frauenklinik; 🇩🇪 Greifswald, MV, Germany

Dietrich Bonhoeffer Klinikum, Brustzentrum; 🇩🇪 Neubrandenburg, MV, Germany

Henriettenstiftung Frauenklinik; 🇩🇪 Hannover, NI, Germany

Euregio-Klinik Brustzentrum Nordhorn; 🇩🇪 Nordhorn, NI, Germany

Asklepios Paulinenklinik; 🇩🇪 Wiesbaden, HE, Germany

Agaplesion Diakonieklinikum, Brustzentrum; 🇩🇪 Hamburg, HH, Germany

Albertinen-Krankenhaus, Brustzentrum; 🇩🇪 Hamburg, HH, Germany

Universitäts-Frauenklinik; 🇩🇪 Rostock, MV, Germany

Stadtkrankenhaus Worms; 🇩🇪 Worms, RP, Germany

Klinikum Hanau GmbH; 🇩🇪 Hanau, HE, Germany

St. Josefs-Hospital, Frauenklinik; 🇩🇪 Wiesbaden, HE, Germany

Klinikum Ludwigshafen; 🇩🇪 Ludwigshafen, RP, Germany

Universität Halle/Saale, Frauenklinik; 🇩🇪 Halle/Saale, Saint, Germany

Altmark-Klinikum Brustzentrum; 🇩🇪 Salzwedel, Saint, Germany

Universitätsklinikum Leipzig, Brustzentrum; 🇩🇪 Leipzig, SN, Germany

Helios Klinik; 🇩🇪 Schkeuditz, SN, Germany

Universitätsklinikum Jena; 🇩🇪 Jena, TH, Germany

Diakonissen-Stiftungs-Krankenhaus Speyer; 🇩🇪 Speyer, RP, Germany

Krankenhaus St. Elisabeth und St. Barbara; 🇩🇪 Halle, Saint, Germany

Sana-Klinik; 🇩🇪 Eutin, SH, Germany

Universitätsklinikum Schleswig-Hostein; 🇩🇪 Kiel, SH, Germany

Krankenhaus St. Joseph-Stift; 🇩🇪 Dresden, SN, Germany

Hufeland-Klinik Bad Langensalza; 🇩🇪 Bad Langensalza, TH, Germany

Diakonissenkrankenhaus; 🇩🇪 Dresden, SN, Germany

Klinikum Obergöltzsch Rodewisch; 🇩🇪 Rodewisch, SN, Germany

SRH Waldklinikum; 🇩🇪 Gera, TH, Germany

SRH Zentralklinikum Suhl; 🇩🇪 Suhl, TH, Germany

Universität Dresden, Frauenklinik; 🇩🇪 Dresden, SN, Germany

Städtisches Klinikum; 🇩🇪 Görlitz, SN, Germany

St. Elisabeth Krankenhaus; 🇩🇪 Leipzig, SN, Germany

DRK Krankenhaus, Brustzentrum; 🇩🇪 Sömmerda, TH, Germany

LKH Uni-Klinikum Graz, Gynäkologie; 🇦🇹 Graz, Austria

Ordensklinikum-BHS; 🇦🇹 Linz, Austria

Universitätsfrauenklinik Salzburg; 🇦🇹 Salzburg, Austria

KH der Barmherzigen Brüder; 🇦🇹 St. Veit/Glan, Austria

Hanusch-Krankenhaus, Brustzentrum; 🇦🇹 Wien, Austria

Brustzentrum Donau-Riß; 🇩🇪 Ehingen, BW, Germany

ViDia Christliche Kliniken, Diakonissenkrankenhaus Karlsruhe; 🇩🇪 Karlsruhe, BW, Germany

St. Elisabethen Krankenhaus; 🇩🇪 Lörrach, BW, Germany

Helios Klinik Pforzheim; 🇩🇪 Pforzheim, BW, Germany

Klinikum am Steinenberg; 🇩🇪 Reutlingen, BW, Germany

Universitätsfrauenklinik; 🇩🇪 Tübingen, BW, Germany

Schwarzwald-Baar Klinikum; 🇩🇪 Villingen-Schwenningen, BW, Germany

Klinikum St. Marien; 🇩🇪 Amberg, BY, Germany

Rems-Murr Kliniken; 🇩🇪 Winnenden, BW, Germany

Klinikum Bayreuth GmbH, Frauenklinik; 🇩🇪 Bayreuth, BY, Germany

Kreisklinik Ebersberg; 🇩🇪 Ebersberg, BY, Germany

Gynäkologische Praxis; 🇩🇪 Eggenfelden, BY, Germany

Klinikum Landshut; 🇩🇪 Landshut, BY, Germany

Klinikum Fichtelgebirge gGmbH, Brustzentrum; 🇩🇪 Marktredwitz, BY, Germany

Klinikum Memmingen; 🇩🇪 Memmingen, BY, Germany

Klinikum der Universität München; 🇩🇪 München, BY, Germany

Klinikum Harlaching, Frauenklinik; 🇩🇪 München, BY, Germany

Frauenklinik der Universität Regensburg, Caritas-Krankenhaus St. Josef; 🇩🇪 Regensburg, BY, Germany

Klinikum Starnberg; 🇩🇪 Starnberg, BY, Germany

Kliniken Nordoberpfalz AG, Brustzentrum Weiden; 🇩🇪 Weiden, BY, Germany

Klinikum Traunstein; 🇩🇪 Traunstein, BY, Germany

Klinikum Mitte, Missio Brustzentrum; 🇩🇪 Würzburg, BY, Germany

St. Joseph Stift; 🇩🇪 Bremen, HB, Germany

DIAKO Krankenhaus Bremen; 🇩🇪 Bremen, HB, Germany

Klinikum Frankfurt Höchst; 🇩🇪 Frankfurt am Main, HE, Germany

Agaplesion Markus Krankenhaus; 🇩🇪 Frankfurt, HE, Germany

Main-Kinzig-Kliniken Gelnhausen; 🇩🇪 Gelnhausen, HE, Germany

Brustzentrum Nordsachsen; 🇩🇪 Borna, SN, Germany

St. Gertrauden Krankenhaus; 🇩🇪 Berlin, BE, Germany

Klinikum Ludwigsburg; 🇩🇪 Ludwigsburg, BW, Germany

Helios Klinik Rottweil; 🇩🇪 Rottweil, BW, Germany

Klinikum Fürth; 🇩🇪 Fürth, BY, Germany

Klinikum Passau; 🇩🇪 Passau, BY, Germany

Rotkreuzklinik Würzburg; 🇩🇪 Würzburg, BY, Germany

Bonifatius-Hospital, Brustzentrum; 🇩🇪 Lingen, NI, Germany

Universitätsfrauenklinik Bonn; 🇩🇪 Bonn, Nordrhein, Germany

Marienhospital Bottrop; 🇩🇪 Bottrop, Nordrhein, Germany

Uniklinik Köln; 🇩🇪 Köln, Nordrhein, Germany

St. Elisabeth Krankenhaus, Brustzentrum; 🇩🇪 Köln, Nordrhein, Germany

Klinikum Lünen, Brustzentrum; 🇩🇪 Lünen, Nordrhein, Germany

St. Marienkrankenhaus, Frauenklinik; 🇩🇪 Siegen, Nordrhein, Germany

BZ Mittelrhein Koblenz+Mayen; 🇩🇪 Koblenz, RP, Germany

St. Josef-Hospital, BZ Rhein-Sieg; 🇩🇪 Troisdorf, Nordrhein, Germany

Katharinen-Hospital, Brustzentrum; 🇩🇪 Unna, Nordrhein, Germany

Marien-Hospital; 🇩🇪 Wesel, Nordrhein, Germany

Harzklinikum, Brustzentrum Harz; 🇩🇪 Wernigerode, Saint, Germany

DIAKO Diakonissenkrankenhaus; 🇩🇪 Flensburg, SH, Germany

Westpfalz Klinikum; 🇩🇪 Kaiserslautern, RP, Germany

Johanniter-Krankenhaus, Frauenklinik; 🇩🇪 Stendal, Saint, Germany

Universitätsklinikum Schleswig-Holstein, Campus Lübeck; 🇩🇪 Lübeck, SH, Germany

Helios Klinikum Meiningen, Brustzentrum; 🇩🇪 Meiningen, TH, Germany

Kepler Universitätsklinikum; 🇦🇹 Linz, Austria

Ev. Krankenhaus, Frauenklinik; 🇩🇪 Ludwigsfelde, BB, Germany

Sana Klinikum Berlin-Lichtenberg; 🇩🇪 Berlin, BE, Germany

DRK-Kliniken Westend; 🇩🇪 Berlin, BE, Germany

Klinikum Esslingen; 🇩🇪 Esslingen, BW, Germany

Universitätsfrauenklinik Ulm; 🇩🇪 Ulm, BW, Germany

Hämatologisch-onkologische Praxis; 🇩🇪 Augsburg, BY, Germany

Universitätsklinikum Brustzentrum; 🇩🇪 Frankfurt, HE, Germany

Helios Kliniken Schwerin; 🇩🇪 Schwerin, MV, Germany

Vinzenzkrankenhaus Hannover; 🇩🇪 Hannover, NI, Germany

Klinikum Wolfsburg, Frauenklinik; 🇩🇪 Wolfsburg, NI, Germany

Klinikum Böblingen; 🇩🇪 Böblingen, BW, Germany

Klinikum Tuttlingen; 🇩🇪 Tuttlingen, BW, Germany

Charite Campus Mitte; 🇩🇪 Berlin, BE, Germany

Ostalb-Klinikum, Brustzentrum Aalen; 🇩🇪 Aalen, BW, Germany

Sana-Klinikum Biberach; 🇩🇪 Biberach, BW, Germany

Fürst-Stirum-Klinik; 🇩🇪 Bruchsal, BW, Germany

Universitätsklinikum Freiburg; 🇩🇪 Freiburg, BW, Germany

Universitätsklinikum Heidelberg; 🇩🇪 Heidelberg, BW, Germany

Städtisches Klinikum Karlsruhe; 🇩🇪 Karlsruhe, BW, Germany

Siloah St. Trudpert Klinikum; 🇩🇪 Pforzheim, BW, Germany

Rems-Murr Klinik; 🇩🇪 Schorndorf, BW, Germany

Helios Klinikum Gifhorn; 🇩🇪 Gifhorn, NI, Germany

MHH Frauenklinik; 🇩🇪 Hannover, NI, Germany

Klinikum Märkische Kliniken, Brustzentrum; 🇩🇪 Lüdenscheid, Nordrhein, Germany

Universitätsklinikum Münster; 🇩🇪 Münster, Nordrhein, Germany

Helios Klinikum, Klinik für Gynäkologie; 🇩🇪 Berlin-Buch, BE, Germany

DRK Kliniken Köpenick; 🇩🇪 Berlin, BE, Germany

Krankenhaus Waldfriede; 🇩🇪 Berlin, BE, Germany

Caritas-Krankenhaus Brustzentrum Tauberfranken; 🇩🇪 Bad Mergentheim, BW, Germany

Universitätsklinikum Hamburg, Brustzentrum; 🇩🇪 Hamburg, HH, Germany

AKH Celle, Brustzentrum; 🇩🇪 Celle, NI, Germany

St. Bernward Krankenhaus; 🇩🇪 Hildesheim, NI, Germany

Agaplesion Ev. Klinikum, Brustzentrum Schaumburg; 🇩🇪 Obernkirchen, NI, Germany

Klinikum Osnabrück; 🇩🇪 Osnabrück, NI, Germany

Diakoniekrankenhaus, Frauenklinik; 🇩🇪 Rotenburg, NI, Germany

Augusta-Klinik; 🇩🇪 Bochum, Nordrhein, Germany

Carl-Thiem-Klinikum; 🇩🇪 Cottbus, BB, Germany

Evang. Waldkrankenhaus Spandau; 🇩🇪 Berlin, BE, Germany

Krankenhaus Bietigheim; 🇩🇪 Bietigheim, BW, Germany

Frauenklinik Freudenstadt; 🇩🇪 Freudenstadt, BW, Germany

AN regiomed Klinikum Ansbach; 🇩🇪 Ansbach, BY, Germany

Klinikum Aschaffenburg; 🇩🇪 Aschaffenburg, BY, Germany

Klinikum Kempten-Oberallgäu; 🇩🇪 Kempten, BY, Germany

Franziskus Hospital Harderberg; 🇩🇪 Georgsmarienhütte, NI, Germany

Universitätsklinikum Essen Frauenklinik; 🇩🇪 Essen, Nordrhein, Germany

Klinik St. Marienstift; 🇩🇪 Magdeburg, Saint, Germany

Frauenklinik der H.-Heine-Universität; 🇩🇪 Düsseldorf, Nordrhein, Germany

Kliniken Essen-Mitte; 🇩🇪 Essen, Nordrhein, Germany

St. Franziskus-Hospital; 🇩🇪 Münster, Nordrhein, Germany

Marienkrankenhaus; 🇩🇪 Schwerte, Nordrhein, Germany