Multimodality Treatment of Advanced Non-small Cell Lung Cancer: Where are we with the Evidence?
Curr Surg Rep
Multimodality Treatment of Advanced Non-small Cell Lung Cancer: Where are we with the Evidence?
Christopher M. Jones 0 1 2 3 4 5
Alessandro Brunelli 0 1 2 3 4 5
Matthew E. Callister 0 1 2 3 4 5
Kevin N. Franks 0 1 2 3 4 5
0 Radiotherapy Research Group, Leeds Cancer Centre, The Leeds Teaching Hospitals NHS Trust , Leeds , UK
1 Leeds Institute of Cancer & Pathology, Faculty of Medicine & Health, University of Leeds , Leeds , UK
2 & Kevin N. Franks
3 Department of Respiratory Medicine, The Leeds Teaching Hospitals NHS Trust , Leeds , UK
4 Department of Thoracic Surgery, The Leeds Teaching Hospitals NHS Trust , Leeds , UK
5 School of Molecular & Cellular Biology, Faculty of Biological Sciences, University of Leeds , Leeds , UK
Purpose of review The majority of patients with non-small cell lung cancer (NSCLC) present with advanced disease and overall survival rates are poor. This article outlines the current and outstanding evidence for the use of multimodality treatment in this group of patients, including in combination with an increasing number of treatment options, such as immunotherapy and genotype-targeted small molecule inhibitors. Recent findings Optimal therapy for surgically resectable stage III disease remains debatable and currently the choice of treatment reflects each individual patient's disease characteristics and the expertise and opinion of the thoracic multi-disciplinary team. Evidence for a distinct oligometastatic state in which improved outcomes can be achieved remains minimal and there is as yet no consensus definition for oligometastatic lung cancer. Whilst there is supporting evidence for the aggressive management of isolated metastases, the use of consolidative therapy for multiple metastases remains unproven. Summary Evolution of new RT technologies, improved surgical technique and a plethora of interventional-radiology-guided ablative therapies are widening the choice of available treatment modalities to patients with NSCLC. In the setting of resectable locally advanced disease and the oligometastatic state, there is a growing need for randomised comparison of the available treatment modalities to guide both treatment and patient selection.
Lung cancer; Treatment; Radiotherapy; Stereotactic ablative radiotherapy; Chemotherapy; Surgery; Locally advanced; Oligometastatic
Introduction
Lung cancer is the most common malignancy worldwide
with over 1.8 million new cases diagnosed each year [
1
].
Overall survival is poor and only around 15% of patients
are alive 5 years after their initial diagnosis [
1
].
Approximately 80–85% of lung cancers are non-small cell lung
cancer (NSCLC), a classification that amongst others
encompasses squamous cell carcinoma, adenocarcinoma
and large cell, or undifferentiated, carcinoma of the lung.
For patients with NSCLC, treatment options vary
significantly by disease extent but have considerably evolved
across all disease stages as a consequence both of the
identification of a raft of targetable, clinically significant
molecular aberrations, and of significant innovation in
surgery and technical radiotherapy (RT). This article
outlines the current and emerging impacts of these advances
on the multimodality treatment of advanced NSCLC within
the specific settings of locally advanced and
oligometastatic disease.
Early NSCLC: Stages I and II
Effective from January 2017, staging of NSCLC is
assessed using the 8th version of the TNM staging system [
2
].
For the small proportion of patients who present with early
(stages I and II) NSCLC, resection remains the
gold-standard treatment [
3
]••, [
4
]. Overall survival following
lobectomy is encouraging; 52–89% of patients with stage I
disease and between 33 and 52% with stage II cancer
survive 5 years [3••]. Post-operative recurrence is however
a concern and the role of adjuvant RT (post-operative
radiotherapy; PORT) and chemotherapy has been
extensively studied, both in the context of patients with
confirmed early NSCLC and for those who are upstaged based
on pathology following resection.
There is high-level evidence confirming a lack of benefit
from either chemotherapy or PORT in the setting of
confirmed stage I disease and neither are routinely
recommended [
3
]••, [
5
]•, [
6, 7
]. It has however been suggested
that adjuvant chemotherapy may be of benefit in a subset of
patients with stage IB tumours exceeding 4 cm in size.
Supporting this, the 2008 Lung Adjuvant Cisplatin
Evaluation (LACE) meta-analysis pooled individual patient data
for 4585 patients from five trials in which adjuvant
chemotherapy using a cisplatin backbone had been
evaluated [8]. Hazard ratio (HR) for death was 1.4 for stage IA
disease but improved to 0.9 in IB disease. Similarly, in a
2008 Cancer & Leukaemia Group B randomised controlled
trial (RCT) focussed specifically on IB disease, a
significant survival advantage was seen for patients with a tumour
size of greater than 4 cm who received doublet
ch (...truncated)