ORIGINAL ARTICLE – HEPATOBILIARY TUMORS
The Prognostic Impact of Determining Resection Margin Status
for Multiple Colorectal Metastases According to the Margin
of the Largest Lesion
Kazunari Sasaki, MD
, Georgios A. Margonis, MD, PhD
, Kosuke Maitani, MD
, Nikolaos Andreatos, MD
Jaeyun Wang, BSc
, Emmanouil Pikoulis, MD
, Jin He, MD, PhD
, Christopher L. Wolfgang, MD, PhD
Matthew Weiss, MD
, and Timothy M. Pawlik, MD, MPH, PhD
Division of Surgical Oncology, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD;
First Department of Surgery, Laiko Hospital, University of Athens, Athens, Greece
Background. Although the prognostic role of surgical
margin status after resection of colorectal liver metastasis
(CRLM) has been previously examined, controversy still
surrounds the importance of surgical margin status in
patients with multiple tumors.
Methods. Patients who underwent curative-intent surgery
for CRLM from 2000 to 2015 and who presented with
multiple tumors were identiﬁed. Patients with R1 resection
status determined by the closest resection margin of the
non-largest tumor were classiﬁed as R1-Type 1; patients
with R1 status determined by the resection margin of the
largest tumor were deﬁned as R1-Type 2. Data regarding
surgical margin status, size of tumors, and overall survival
(OS) were collected and assessed.
Results. A total of 251 patients met inclusion criteria; 156
patients (62.2%) had a negative margin (R0), 50 had an R1-
type 1 (19.9%), and 45 had an R1-type 2 (17.9%) margin.
Median and 5-year OS in the entire cohort was
56.4 months and 48.0%, respectively. When all R1 (Type
1 ? Type 2) patients were compared with R0 patients, an
R1 was not associated with worse prognosis (P = 0.05). In
contrast, when R1-type 2 patients were compared with R0
patients, an R1 was strongly associated with worse OS
(P = 0.009). On multivariate analysis, although the prog-
nostic impact of all R1 was not associated with OS (hazard
ratio [HR] 1.56; P = 0.08), R1-Type 2 margin status
independently predicted a poor outcome (HR 1.93;
P = 0.03).
Conclusions. The impact of margin status varied accord-
ing to the size of the tumor assessed. While R1 margin
status deﬁned according to the non-largest tumor was not
associated with OS, R1 margin status relative to the largest
index lesion was associated with prognosis.
Liver resection is generally recognized as the best
potentially curative modality for patients with colorectal
liver metastases (CRLM).
Although hepatectomy for
CRLM can be performed with low short-term morbidity and
mortality, long-term prognosis remains guarded as up to 50%
of patients experience intrahepatic recurrence after curative-
Much attention has been devoted to
identifying potentially modiﬁable factors that may inﬂuence
the risk of intrahepatic recurrence among patients with
CRLM. In particular, the prognostic implications of the
resection margin (RM) following resection of CRLM have
been extensively studied.
Traditionally, a RM width of at
least 10 mm was widely considered the gold standard.
With the introduction of effective modern chemotherapy
regimens, numerous studies have demonstrated, however,
that subcentimeter or even submillimeter margin widths
were not associated with worse survival.
In fact, some
recent studies have questioned the negative prognostic
impact of microscopically positive (R1) resections, in cases
where R0 resections are technically unfeasible.
The rationale underlying the resection of additional
macroscopically nontumorous tissue around the index
Kazunari Sasaki and Georgios A. Margonis contributed equally to this
Ó Society of Surgical Oncology 2017
First Received: 1 November 2016;
Published Online: 10 July 2017
T. M. Pawlik, MD, MPH, PhD
Ann Surg Oncol (2017) 24:2438–2446