Reply to Peng et al.

European Journal of Cardio-Thoracic Surgery, vol. 62

Abstract

With interest, we read the letter to the editor by Peng et al. in reference to our recently published paper [1]. Peng et al. conclude that surgery should remain the first choice of treatment for operable patients with stage I non-small cell lung cancer (NSCLC), referring to their published meta-analyses [2, 3]. Indeed, our study revealed better overall and progression-free survival after minimally invasive lobectomy compared to stereotactic ablative radiotherapy (SABR) in unadjusted analyses, but direct comparison of these outcomes is hampered by confounding by indication. Propensity score-weighted analyses did not show significant differences between the two treatment modalities. Our study was intended to assess the feasibility of performing a nationwide data collection project and was insufficiently powered to detect significant differences with propensity score analyses. In our extended study, in which 38 Dutch hospitals are participating, data on at least 1880 patients are being collected to determine the preferable treatment for patients with stage I NSCLC. Results from three randomized controlled trials (RCTs) (STABLE-MATES, POSTILV and VALOR) are being awaited; however, these trails are currently recruiting patients and it is unknown whether inclusion targets will be met. Several attempts to complete an RCT have already been made: the STARS, ROSEL and ACOSOG Z4099 trials were all prematurely closed due to poor accrual. Furthermore, the SABRTOOTH study in the UK was stopped due to unwillingness of patients to be randomized between surgery and SABR. Also, RCTs are mainly suitable for determining the best treatment for fit patients with no or few comorbidities, while well-designed retrospective studies offer the opportunity to investigate the optimal treatment for other patient groups (e.g. patients with cardiopulmonary comorbidity or different age groups) as well. This will be explored in our extended research project in addition to the main comparison of minimally invasive lobectomy and SABR. A theoretical advantage of surgery over SABR is the removal of draining lymph nodes during the resection, potentially leading to better locoregional control. Moreover, distant control might be improved by adding adjuvant systemic therapy in case of unforeseen nodal metastases. In our study, 13.5% of operated patients had nodal upstaging and 12.6% received adjuvant systemic therapy. Based on our results, it remains unclear whether surgical lymph node evaluation and eventual use of adjuvant therapy impact recurrence and survival significantly. With an average 5-year survival rate of 59% and the recurrence rate of 26% among the patients included in our study, the prognosis of stage I NSCLC patients remains poor. Therefore, current RCTs are focussing on further improvement of systemic control by adding (neo)adjuvant immunotherapy (e.g. IMpower010, CheckMate 816) or targeted therapy (e.g. ADAURA) to local treatment of the primary tumour. Adequate determination of additional treatment is only possible after accurate pathological diagnosis on a biopsy or resection specimen, of which the latter is always available after surgery. In conclusion, whether SABR can yield similar survival outcome to surgery will be investigated in our extended research project. Aside from these results, we believe that surgery will keep an important role in the future treatment of early-stage NSCLC with respect to the growing contribution of pathological examination of the resected tumour and lymph nodes in decision-making for additional systemic treatments.

Authors 4

1. Julianne Cynthia de Ruiter

   The Netherlands Cancer Institute

   Affiliation as printed

   Department of Surgery, Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital , Amsterdam, Netherlands

2. Egbert Frederik Smit Aachen Department of Pulmonary Diseases

   Leiden University Medical Center · The Netherlands Cancer Institute

   Affiliation as printed

   Department of Pulmonary Diseases, Leiden University Medical Center , Leiden, Netherlands

   Department of Thoracic Oncology, Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital , Amsterdam, Netherlands

3. Vincent van der Noort

   The Netherlands Cancer Institute

   Affiliation as printed

   Department of Statistics, Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital , Amsterdam, Netherlands

4. Koen Johan Hartemink corresponding

   The Netherlands Cancer Institute

   Affiliation as printed

   Department of Surgery, Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital , Amsterdam, Netherlands