Lungenkarzinom: Gibt es eine Indikation zur Resektion bei persistierendem N2 nach neoadjuvanter Chemotherapie?

Zusammenfassung

Hintergrund: Infolge einiger randomisierter Studien Mitte der 90er-Jahre gilt die Induktionschemotherapie mit nachfolgender Resektion als eine mögliche Therapieoption bei Patienten mit pN2-Lungenkarzinom. Nachfolgende Untersuchungen legten die Vermutung nahe, dass bei persistierendem Lymphknotenbefall (ypN2) die Prognose ungünstig ist und diese Patienten keiner operativen Therapie unterzogen werden sollten. Die vorliegende Untersuchung geht der Frage nach, wie die Überlebenswahrscheinlichkeit bei persistierendem Lymphknotenbefall ist und ob es Prognosefaktoren innerhalb dieser Gruppe gibt. Methode: Wir führten eine retrospektive Kohortenstudie von 50 Patienten nach Induktionschemotherapie bei Stadium IIIA3 N2 NSCLC durch. Es wurde das Langzeitüberleben im Hinblick auf den postoperativen Lymphknotenstatus sowie die Anzahl der involvierten Lymphknoten analysiert. Ergebnisse: 50 Patienten mit potenziell resektablem Stadium IIIA3 N2 gingen in die Analyse ein. In 25 Fällen (50 %) persistierte die N2-Situation nach der Induktionschemotherapie mit 2 Zyklen Cisplatin/Gemcitabin, bei 11 Patienten konnte ein mediastinales Downstaging erreicht werden; 14 Patienten konnten aufgrund von Krankheitsprogress oder Komorbiditäten nach der Induktionschemotherapie nicht operiert werden. Die operative Therapie bestand bei 29 Patienten in einer Lobektomie oder Bilobektomie, bei 2 Patienten in einer Pneumonektomie; 4 Patienten wurden durch Segmentresektionen behandelt und in 1 Fall erfolgte eine atypische Resektion. Bei persistierendem mediastinalen Lymphknotenbefall (ypN2) betrug das mediane Überleben 14,6 Monate, bei mediastinalem Downstaging (ypN0/1) 22,3 Monate (p = 0,172). Die Anzahl der mediastinalen Lymphknoten mit persistierendem Tumornachweis war ein signifikanter Prognosefaktor. Bei weniger als 6 persistierend positiven Lymphknoten betrug das mittlere Überleben 17,5 Monate, bei mehr als 6 befallenen Lymphknoten 8,6 Monate (p < 0,01). Schlussfolgerung: Das mediane Überleben bei persistierender N2-Erkrankung nach Induktionstherapie ist ungünstiger als bei ypN0/1-Patienten. Dennoch beträgt das Langzeitüberleben bei Patienten mit weniger als 6 persistierenden Lymphknoten 17,5 Monate, sodass aus unserer Sicht auch hier eine Operationsindikation besteht und nach Induktionschemotherapie ein Restaging zum Ausschluss eines multiplen Lymphknotenbefalls durchgeführt werden sollte.

Abstract

Background: Induction chemotherapy followed by surgical resection has been a treatment option for stage IIIA3 N2 non-small cell lung cancer since publication of some small randomised trials during the 1990s. Later on other studies suggested a poor prognosis in cases of persistent N2 disease, so surgical treatment for these patients was not recommended. This study analyses the outcome of patients with persisting N2 disease and tries to identify prognostic parameters within that group of patients. Methods: We conducted a retrospective cohort study with 50 patients after induction therapy for stage IIIA N2 NSCLC. We analysed the influence of the postoperative lymph node involvement as well as the number of involved lymph nodes on the overall survival. Results: 50 patients with potentially resectable stage IIIA N2 were included in the analysis. In 25 cases (50 %) a persisting N2 remained after induction therapy with cisplatin/gemcitabine, 11 patients had a mediastinal downstaging. 14 patients did not qualify for surgery because of disease progression or comorbidities. The resection consisted in 29 cases of a lobectomy or bilobectomy; two times pneumonectomy was necessary and 4 segmentectomies and one atypical resection were performed. The median survival of patients with persisting N2 (ypN2) was 14.6 months, if mediastinal downstaging was achieved (ypN0/1) it was 22.3 months (p = 0.172). The number of involved mediastinal lymph nodes was a significant prognostic factor. If less than 6 lymph nodes were involved the mean survival was 17.5 months, while it was 8.6 months in patients with more than 6 involved lymph nodes (p < 0.01). Conclusions: The median survival for patients with persisting N2 disease is less favourable compared to patients with mediastinal downstaging. However, the long-term survival for patients with less than 6 involved lymph nodes is 17.5 months. Therefore surgical resection for these patients seems to be justified. After induction therapy a rigorous restaging should be performed to rule out persisting multilevel N2 disease.

Schlüsselwörter

neoadjuvante Chemotherapie - Thoraxchirurgie - Lymphknotenmetastase - persistierendes N2

Key words

neoadjuvant chemotherapy - thoracic surgery - lymph node metastasis - persisting N2 disease

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