Multicentric Analysis of Predictors of N1 Upstaging After Resection of cStage-I NSCLC (NUTS)

Five papers showed a lower N1 nodal upstaging with video-assisted thoracic surgery (VATS) compared to open surgery in patients with cStage-I NSCLC . This finding questions the oncologic quality of minimal invasive lung cancer surgery, especially the quality of hilar and intrapulmonary lymh node dissection. However, these retrospective studies did not include analysis of central tumor location, although central tumors have a reported higher chance of N1 upstaging . Possibly, this creates a selection bias as surgeons might select central lesions deliberately for open surgery in line with initial VATS feasibility reports

Study Overview

• Status: Completed
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Procedure: Central/Peripheral

Detailed Description

After optimal preoperative staging, 10 to 25% of patients with clinical stage I (cStage-I) non-small cell lung cancer (NSCLC) are found to have unforeseen positive lymph nodes during resection.

Central tumors, even if they are smaller than 3cm (cT1), have a higher incidence of both intrapulmonary or hilar (N1) or ipsilateral mediastinal (N2) lymph node involvement in comparison to peripheral lesions.

In a cohort of patients that underwent identical preoperative mediastinal evaluation and postoperative pathologic tissue examination of equal quality, nodal upstaging can be used as a quality indicator of oncologic thoracic surgery. Or, it can be used as an instrument to compare different techniques, such as thoracoscopic (VATS) versus open lung resections for lung cancer.

Five papers showed a lower N1 nodal upstaging with video-assisted thoracic surgery (VATS) compared to open surgery. These retrospective studies did not include tumor location.

The investigators hypothesize that this creates a bias as surgeons might have chosen an open approach when the tumor was centrally located. This is in line with initial feasibility reports and guidelines that excluded patients with central lesions. This results in a higher prevalence of positive N1 nodes in patients operated with the open approach.

Our single centre analysis showed a one in three chance of nodal upstaging in central located cStage-I tumors , multivariate analysis showed central location to be the only significant predictor for upstaging, and not the surgical technique.

The aim of this multicentric study is to investigate risk factors for nodal upstaging, including tumor location, in patients with cStage-I NSCLC and validate previous findings.

• Study Type: Observational
• Enrollment (Actual): 956

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Per centre, a list of consecutive patients operated for cStage-I NSCLC in 2014 is selected.

cStage-I is decided based on all information before resection is started in accordance to the 7th edition of TNM

Description

Inclusion Criteria:

• Patients operated in 2014
• NSCLC on final pathology
• cStage-I (cT1-2a cN0 cM0 ) before start of incision for anatomical resection.
• This includes: open/VATS/ Robotic Assisted Thoracoscopic Surgery (RATS)
• This includes: lobectomy, bilobectomy, sleeve or pneumonectomy (not wedge)

Exclusion Criteria:

• Higher clinical stage than cStage-I
• Former therapy for lung cancer (chemotherapy, radiotherapy, surgery)
• Metastatic disease
• Induction chemo- or radiotherapy
• Non-anatomical resections (wedge)
• Previous lymph node disease
• No positron emission tomography (PET) or Missing PET report

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
VATS; Patients operated by means of minimal invasive technique (VATS or roboticVATS)	Procedure: Central/Peripheral; Central versus peripheral location of the primary tumor
Open; Patients operated by means of open thoracotomy	Procedure: Central/Peripheral; Central versus peripheral location of the primary tumor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of nodal (N1 and N2) upstaging	Incidence of nodal (N1 and N2) upstaging stratified by 'central' versus 'peripheral' tumor location	immediate postoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	To compare survival after resection by open technique or VATS, stratified for the above predictors	1 yr postoperative

Collaborators and Investigators

• Sponsor: University Hospital, Gasthuisberg
• Investigators: Study Director: Herbert Decaluwé, MD, Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: March 21, 2016
• First Submitted That Met QC Criteria: April 1, 2016
• First Posted (Estimate): April 7, 2016

Study Record Updates

• Last Update Posted (Actual): September 25, 2019
• Last Update Submitted That Met QC Criteria: September 24, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Surgery; Thoracotomy; VATS
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: NUTS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO