COMMENTARY

Complete Resection in Lung Cancer Surgery: From

Definition to Validation and Beyond
Ramón Rami-Porta, MD,a,b,* Christian Wittekind, MD,c
Peter Goldstraw, MBChB, FRCSd,e
a
Department of Thoracic Surgery, Hospital Universitari Mútua Terrassa, University of Barcelona, Terrassa, Barcelona, Spain
b
Network of Centers for Biomedical Research in Respiratory Diseases (CIBERES) Lung Cancer Group, Terrassa, Barcelona,
Spain
c
Institute of Pathology, University Clinic Leipzig, Leipzig, Germany
d
National Heart and Lung Institute, Imperial College, London, United Kingdom
e
Thoracic Surgery, Royal Brompton Hospital, London, United Kingdom

Received 24 July 2020; revised 6 September 2020; accepted 11 September 2020

Available online - 13 October 2020

The International Association for the Study of Lung
Cancer (IASLC) proposed definitions for complete,
incomplete, and uncertain resections in lung cancer 15
years ago.1 The definitions were based on several pre-
vious definitions and on the consideration of different
issues related to the surgical treatment of lung cancer,
that is, the different ways of intraoperative nodal
assessment, the requirements for pathologic absence of
nodal disease (pN0), and the prognostic impact of
pleural lavage cytology. All this was thoroughly dis-
cussed by the members of the IASLC Staging
Committee during several meetings until a true multi-
disciplinary and international agreement was reached.
The publication of the definitions fulfilled one of the
objectives of the International Workshop on Intratho-
racic Staging, organized by Prof. Goldstraw in London in
October 1996 under the auspices of the IASLC.2 This
commentary will deal with the background that led to
the IASLC definitions, their prognostic impact, and the
potential for future refinements.
The R Descriptor
Residual tumor (R) classification was introduced in
TNM classification by the American Joint Committee on
Cancer in 1997, and it was soon accepted by the Union
for International Cancer Control.3
Its four categories describe the residual tumor left
after treatment. These categories are: R0, no residual
tumor; R1, microscopic residual tumor; R2, macroscopic
residual tumor; and RX, the presence of residual tumor
cannot be assessed. The R descriptor provides us with
information on the effect of the treatment, assists us by
indicating additional treatments for residual disease and
modifies the prognosis assigned to a given pathologic
TNM classification.4 Its prognostic impact is well docu-
mented. The analyses of the IASLC database used to
inform the eighth edition of the TNM classification for
lung cancer revealed an absolute difference of 37% be-
tween the survival rates of those patients who had un-
dergone an R0 resection (5-year survival rate of 73%)
and those who had undergone an R1 resection (5-year
survival rate of 36%). The absolute difference was
even greater (45%), when R0 resections were compared
with R2 resections (5-year survival rate of 28%). The
differences between R0 and R1 to R2 (p < 0.0001) were
statistically significant, but not those between R1 and R2
(p < 0.27).5
Important as it is, the R descriptor is not explicit
enough on how the R0 classification was achieved. For
example, there may be no residual tumor, but the
descriptor does not tell us whether a systematic nodal
dissection was performed. Failure to perform an
adequate nodal dissection is associated with lower sur-
vival when compared with survival after some intra-
operative mediastinal nodal assessment. If a systematic
nodal dissection is not performed, involved lymph nodes
*Corresponding author.
Disclosure: The authors declare no conflict of interest.
Address for correspondence: Ramón Rami-Porta, MD, Department of
Thoracic Surgery, Hospital Universitari Mútua Terrassa, University of
Barcelona, Plaza Dr. Robert 5, 08221 Terrassa, Barcelona, Spain.
E-mail: rramip@yahoo.es
ª 2020 International Association for the Study of Lung Cancer.
Published by Elsevier Inc. All rights reserved.
ISSN: 1556-0864
https://doi.org/10.1016/j.jtho.2020.09.006

Journal of Thoracic Oncology Vol. 15 No. 12: 1815–8

1816 Rami-Porta et al
are likely to have been left behind, and an R1 resection
gets disguised as an R0 resection.
Previous Definitions of Complete
Resection
To complement the information provided by the R
descriptor, several authors and institutions proposed
different definitions of complete resection. These defi-
nitions, in addition to achieving an R0 resection, needed
certain conditions to be fulfilled for considering a
resection as complete. For example, in Japan, the defi-
nition of complete resection was very strict. The mere
involvement of the visceral pleura and of the removed
mediastinal lymph nodes was a criterion of incomplete
resection. Complete lymph node dissection and the
integrity of the margins were essential to define a
resection as complete.6 In North America, in addition to
the margins and the responsibility of the surgeon in
removing all the known disease, the concepts of the most
distant lymph node and of the nodal capsule were
introduced: both had to be free from tumor to consider a
resection as complete.7 Others even considered that a
complete resection implied lobectomy or pneumonec-
tomy, but not smaller resections, such as segmentectomy
or wedge resections.8 In Europe, the following key ele-
ments of the other definitions were adopted for pro-
spective use by a national working group: margins,
complete mediastinal lymphadenectomy, the nodal
capsule, and the most distant lymph nodes.9
The IASLC Definitions
The IASLC Staging Committee members agreed on a
definition of complete resection that included the
integrity of all margins, a systematic nodal dissection, as
defined by the IASLC in 1996,2 or a lobe-specific sys-
tematic nodal dissection (a dissection of three medias-
tinal nodal stations, always including the subcarinal,
chosen depending on the lobar location of the primary
tumor, and three hilar-intrapulmonary stations, so that
the final specimen includes at least six lymph nodes),
and the integrity of the nodal capsule in those nodes
removed separately and of the highest mediastinal
lymph node.1 This definition includes the concept of the
R0 descriptor, but provides more information on the
resection performed.
By contrast, an incomplete resection had positive
margins, extracapsular nodal involvement of the nodes
removed separately, positive nodes left in the operative
field, or positive pleural or pericardial effusion. This
definition coincides exactly with the R1 and R2
descriptors.1
Considerable time was spent in discussing the situa-
tion in which there was no evidence of residual disease,
Journal of Thoracic Oncology Vol. 15 No. 12
but the conditions of complete resection were not ful-
filled. After a thoughtful discussion, the resection in
which there was no evidence of tumor left behind, but
the intraoperative nodal evaluation did not meet the
requirements of systematic nodal dissection or lobe-
specific systematic nodal dissection, the highest medi-
astinal node removed was involved, there was carcinoma
in situ at the bronchial margin, or the pleural lavage
cytology specimen was positive was called uncertain
resection.1 This resection had no equivalent among the R
categories.
The definitions of the type of resection are indepen-
dent from the procedures used for clinical staging and
are based on intraoperative findings and on the defini-
tive pathologic study of the resected specimen.
Furthermore, the definitions are independent of preop-
erative therapies and are unmodified whether the
resection has been performed after induction therapy or
as salvage surgery. The adjacent structures (chest wall,
diaphragm, pericardium, etc.) removed with the lung
specimen are peripheral margins and should be studied
together with the bronchial and vascular margins.
In the past one and a half decades, the definitions
have been used in clinical practice and have been quoted
in articles on the surgical treatment of lung cancer, but
until very recently, they lacked any validation of their
prognostic value.
Prognostic Validation of the IASLC
Definitions
Between 2017 and 2020, three different studies
confirmed the prognostic value of the IASLC definitions.
Gagliasso et al.10 confirmed the prognostic differences
among the three types of resection in a series of 1277
patients who had undergone lung cancer resection be-
tween 1998 and 2007 in a single institution. The 5-year
survival rates for complete, uncertain, and incomplete
resections were 58.8%, 37.3%, and 15.7%, respectively
(p ¼ 0.0001).10 Edwards et al.5 analyzed 14,712 patients
of the IASLC database, used to inform the eighth edition
of the TNM classification of lung cancer, who had un-
dergone lung cancer resection and had information on
the R status. They found that, in the population of pa-
tients with pN0 and pN-positive, the prognosis of the
three types of resection was significantly different. For
pN0, the 5-year survival rates for complete, uncertain,
R1, and R2 were 82%, 79%, 46%, and 38%, respectively
(uncertain versus complete, p ¼ 0.04; complete and
uncertain versus incomplete, p < 0.0001; R1 versus R2,
p ¼ 0.65). The corresponding rates for the pN-positive
group were 55%, 45%, 34%, and 22%, respectively
(uncertain versus complete, p ¼ 0.001; uncertain versus
incomplete, p ¼ 0.002; R1 versus R2, p ¼ 0.10).5 Finally,
December 2020
Osarogiagbon et al.11 analyzed the results of 3361 pa-
tients who had undergone lung cancer resection in a
population-based multicenter study in the United States
between 2009 and 2019. Statistically significant differ-
ences were also found in the 5-year survival rates of
complete, uncertain, and incomplete resections at 75%,
67%, and 42%, respectively (p < 0.0001). These differ-
ences were maintained both in the pN0 and pN-positive
populations.11
Because of the distinct prognosis of the uncertain
resection, a new category in the R descriptor was added
in the seventh edition of the TNM classification: the R0
(uncertain) indicates that there is no evidence of resid-
ual disease, but the nodal assessment falls below the
minimum recommended or the highest mediastinal
lymph node removed is positive.12
Future Refinements
There are two situations in which cancer cells are
found in places where they should not be, but these are
not yet coded in the TNM classification. Cells that spread
through air spaces (STAS) beyond the tumor margin are
associated with a significant increase of recurrence when
sublobar resections, but not lobectomies, are per-
formed.13 Perhaps, a sublobar resection with STAS
should be considered an incomplete resection or, at
least, an uncertain resection. Circulating tumor cells and
tumor cell products, such as DNA and RNA, can be
identified in the blood. Their presence after lung cancer
resection confers a worse prognosis.14 The association of
the findings of liquid biopsy to TNM would refine the
prognosis of the disease and could justify the indication
of adjuvant treatment.15 In addition to STAS, circulating
tumor cells or their components could be used to revise
the definition of complete resection.
Another important issue that will need to be clarified
in the future is the margin of sublobar resections. The
trials of the Cancer and Leukemia Group B
(CALGB140503) and of the Japan Clinical Oncology
Group (JCOG0802 and 0804) will set the indications for
wedge resection and segmentectomy in part-solid and
solid NSCLCs that are 2 cm or less in the greatest
dimension. Once the indications are established, it will
be important to find the adequate margins required for
an oncologically sound operation.
Conclusions
Three independent groups have validated the prog-
nostic value of the IASLC definitions of complete, un-
certain, and incomplete resections with institutional,
international, and population-based databases. The
definition of complete resection and the differentiation
of uncertain resection are clinically important and add
Complete Resection in Lung Cancer Surgery 1817
information to that provided by the R descriptor.
Therefore, the IASLC definitions should be used in clin-
ical practice to complement the R descriptor. The defi-
nitions should be refined with the incorporation of the
cells STAS and those found in the bloodstream, and
adequate tumor margins should be determined for
sublobar resections.
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