Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
PRO-CON SESSIONS
SESSION PC01: PRO CON SESSION: INVASIVE MEDIAS-
TINAL STAGING FOR N2 DISEASE
MONDAY, DECEMBER 5, 2016 - 14:30-15:45
PC01.02 INVASIVE STAGING AND RESTAGING
Christophe Dooms
University Hospitals KU Leuven, Leuven/Belgium
The aim of mediastinal staging is to exclude with the highest certainty and
the lowest morbidity patients with mediastinal nodal disease. The concepts
of decision analysis and Bayes’ theorem form the basis for a mediastinal
staging strategy. The goal of the clinical staging strategy is to lower the
post-test probability sufficiently so that it falls below a testing threshold,
which ascertains the clinician that the result is accurate. The ESTS working
group considers a rate of unforeseen mediastinal nodal disease at the time of
anatomic resection with lymph node dissection less than 10% as acceptable. 1
Contrast-enhanced multi-detector CT (computed tomography) scanning
has an excellent spatial resolution but is an imperfect means of staging the
mediastinum. A Cochrane review evaluated integrated positron emission
tomography (PET) - CT for assessing mediastinal lymph node involvement in
NSCLC. 2 The review showed that the accuracy of PET-CT is insufficient to allow
management on PET-CT alone, but PET-CT can be used to guide clinicians in
the next step (either a biopsy or direct to surgery). The suboptimal specificity
of mediastinal lymph nodes positive on PET-CT requires a tissue confirmation.
There are conditions where invasive staging is also mandatory despite a
normal mediastinum on PET-CT as the prevalence of N2/N3 disease remains
significant. These conditions include a primary tumour >3 cm, any central
primary tumour, PET/CT hilar N1 disease, or low FDG uptake in the primary
tumour. 1 Cervical Mediastinoscopy. A conventional cervical mediastinoscopy
through a pretracheal suprasternal incision was introduced in 1959 and
for decades considered the gold standard for invasive mediastinal nodal
staging. Recently, a very large (N=721 patients; prevalence of mediastinal
nodal disease 47 %) retrospective single center study reported on safety and
efficacy of cervical mediastinoscopy performed by general thoracic surgeons. 3
There was no mortality, a low perioperative complication rate at 1.3 %, and an
unexpected hospital (re)admission rate of 0.46 %. The sensitivity, negative
predictive value and post-test probability were 0.90 (95% CI 0.87-0.92), 0.92
(95% CI 0.90-0.94), and 0.09 (95% CI 0.07-0.11), respectively. It is performed
under general anesthesia and allows a full mapping of the ipsilateral and
contralateral superior mediastinal lymph nodes. Since 1995, the use of video
techniques has been introduced leading to video-assisted mediastinoscopy
(VAM) clearly improving visualization and teaching. In addition, VAM allows
bimanual dissection with possibilities to perform nodal dissection and
removal rather than sampling or biopsy. The ESTS working group recommends
performing VAM. 1 Endoscopic ultrasonography (EUS) en endobronchial
ultrasonography (EBUS). In the last decade, the predominant role of cervical
mediastinoscopy has been challenged by EUS and EBUS using a convex probe.
When mediastinal nodal staging is required, systematic nodal sampling seems
feasible but some primary choices have to be made. At least mediastinal nodal
stations 4R, 4L and 7 should be sought. To avoid contamination, the order
of sampling should begin at the level of N3 stations followed by N2 stations
before N1. There is no evidence to suggest that sampling of all visible nodes
in each nodal station is superior to a systematic nodal sampling of the largest
measuring ≥5 mm or PET-positive node in each station. It must be stressed
that EBUS cannot access the prevascular nodes (station 3a), the subaortic
and para-aortic nodes (stations 5 and 6) as well as the paraesophageal and
pulmonary ligament nodes (stations 8 and 9). Some of these nodes (stations
8 and 9) can however be reached from the esophagus. Therefore the use
of the EBUS scope is extended to an esophageal exploration with EUS-B
sampling of stations 4L, 7, 8 and 9. In terms of safety, EBUS and EUS have a low
complication or serious adverse event rate of 1.4 and 0.3%, respectively. 4,5 The
two staging strategies, surgical staging alone on the one hand and combined
EUS/EBUS followed by surgical staging whenever endosonography was
negative on the other hand, were compared in a pivotal randomized controlled
trial (RCT). 6 It was concluded that invasive mediastinal nodal staging
should start with combined linear endosonography, as the trial showed
that a staging strategy starting with combined linear endosonography
(EUS+EBUS) detected significantly (P=0.02) more mediastinal nodal N2/
N3 disease compared to cervical mediastinoscopy alone, resulting in a
significantly higher sensitivity of 0.94 (95%CI 0.85-0.98) compared to 0.79
(95%CI 0.66-0.88), respectively. 6 Another RCT suggested that EBUS-TBNA
is the preferred primary procedure in combined linear endosonography for
mediastinal nodal staging of resectable stage I-III lung cancer. 7 There is no
RCT comparing combined EBUS-EUS(-B) to EBUS-TBNA alone for mediastinal
nodal staging, but a recent meta-analysis suggested that the combined
EBUS-EUS is more sensitive than EBUS-TBNA alone to detect mediastinal
nodal disease. 8 The absolute increase in sensitivity of the combined approach
compared to EBUS-TBNA alone depends on the quality of the EBUS-TBNA
procedure, but published studies suggest an increase in sensitivity up to 10%.
Overall, a confirmatory VAM is still warranted for the individual patient with a
negative combined linear endosonography as this further lowers the post-test
probability. This has been shown within ASTER for patients with clinical N2/3
disease on PET-CT (prevalence of mediastinal nodal disease 63%), as the posttest
probability of a negative linear combined endosonography of 20% could
be lowered to 5% by adding a cervical mediastinoscopy. 9 A recent prospective
cohort study on clinical stage II lung cancer based on N1 disease on imaging
(prevalence of mediastinal nodal disease 24%) showed that the post-test
probability of a negative endosonography was 19%, which could be lowered
to 9% by adding a cervical mediastinoscopy. 10 In conclusion, combined EBUS-
EUS(-B) linear endosonography is the standard for initial baseline mediastinal
nodal staging, but a VAM is still recommended after a negative (or incomplete)
combined linear endosonography. Mediastinal restaging after induction
therapy for locally advanced stage III NSCLC is an important prognostic factor.
In the context of a 40-50% prevalence of residual mediastinal disease after
induction therapy, a first cervical VAM as a restaging technique seems to be
the most accurate method for nodal assessment. 1 Overall, limited literature
reported a sensitivity and NPV for linear endosonography that is lower than
for a first mediastinoscopy.
Keywords: NSCLC, mediastinal nodal staging, mediastinal nodal restaging,
invasive
SESSION PC02: BY 2030 CHEMOTHERAPY WILL REMAIN
STANDARD OF CARE FOR THE MAJORITY OF PATIENTS
WITH NSCLC STAGES I-IV
TUESDAY, DECEMBER 6, 2016 - 14:30-15:45
PC02.02 PRO CHEMOTHERAPY
Nasser Hanna
Simon Cancer Center, Indiana University School of Medicine, Indianapolis/IN/
United States of America
Despite the reduction in cigarette consumption in many parts of the world,
the incidence and mortality rate of lung cancer will remain high in the year
2030 1 . Over the last 50 years major advances in the treatment of lung cancer
have included early detection by screening CT, improved cure rates with
neo-adjuvant and adjuvant chemotherapy, the successful integration of
chemotherapy with radiation for locally advanced disease, and prolonged
survival times with chemotherapy in the metastatic setting. More recently,
the discovery of targetable mutations and development of a myriad of small
molecule tyrosine kinase inhibitors have transformed the natural history of
lung cancer in select subsets. Furthermore, immunotherapy is now a reality
in the treatment of patients with stage IV non-small cell lung cancer (NSCLC).
Today, the integration of targeted agents and immunotherapy are being
investigated in earlier stages of disease. With these recent advances, what
does the future of chemotherapy hold in the treatment of stage I-IV NSCLC? Is
there a future at all? Can we eliminate the need for chemotherapy altogether
for most patients at any point in their disease history? The dream of replacing
chemotherapy with more active, less toxic, and more convenient therapy for
patients with stage I-IV NSCLC is a laudatory goal. Is it realistic by the year
2030? Certainly not. Chemotherapy is currently the only systemic therapy
that has ever been known to cure patients in the neo-adjuvant or adjuvant
setting for stage I-III NSCLC 2 . While many targeted agents can prolong
life in the metastatic setting, to date all of those tested in the adjuvant
setting have failed to improve upon standard therapy 3-5 . The graveyard of
negative trials in the adjuvant setting includes those evaluating angiogenesis
inhibition, epidermal growth factor tyrosine kinase inhibition, and vaccine
therapy. The same can be said for locally advanced, unresectable NSCLC.
While the integration of chemotherapy with radiation improves survival rates
compared with radiation alone 6 , thus far no other agents have successfully
done so, including tyrosine kinase inhibitors, angiogenesis inhibitors, or
monoclonal antibodies 7-8 . In the metastatic setting, chemotherapy improves
survival whether given as induction therapy or as maintenance therapy.
Chemotherapy is also more active than targeted therapy in the vast majority
of patients who do not harbor targetable mutations. Even with the stunning
success of immunotherapy for some patients with advanced NSCLC, it
appears this will not be curative in this setting and nearly all patients will
still be getting chemotherapy at some point of their disease history. In other
words, chemotherapy works for patients with stage I-IV NSCLC. Just as we
will do with targeted therapy and immunotherapy, we will not abandon
what works, but rather we will improve upon it. Chemotherapy works in a
broad group of patients with lung cancer. It targets DNA, topoisomerase,
and the mitotic spindle, which are the key targets in all cells. The majority of
patients’ tumors do not have targetable mutations and most patients do not
respond to immunotherapy. While gains are expected over the next 15 years
in targeted therapy and immunotherapy, it is likely that we will discover the
plateau in the benefit to these strategies and eventually nearly all patients
Copyright © 2016 by the International Association for the Study of Lung Cancer
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