ORIGINAL ARTICLE – COLORECTAL CANCER
High-Risk Stage II Colon Cancer: Not All Risks Are Created
Blake D. Babcock, MD, Mayada A. Aljehani, DrPH, Brice Jabo, MD, MPH, Audrey H. Choi, MD, John W. Morgan,
DrPH, MPH, Matthew J. Selleck, DO, Fabrizio Luca, MD, Elizabeth Raskin, MD, Mark E. Reeves, MD, PhD,
Carlos A. Garberoglio, MD, Sharon S. Lum, MD, and Maheswari Senthil, MD
Loma Linda University Cancer Center, Loma Linda, CA
Introduction. Adjuvant chemotherapy is recommended in
patients with stage II colon cancer with high-risk features
(HRF). However, there is no quantiﬁcation of the amount
of risk conferred by each HRF or the overall survival (OS)
beneﬁt gained by chemotherapy based on the risk factor.
Objective. To assess survival beneﬁts associated with
adjuvant chemotherapy among stage II colon cancer
patients having one or more HRF [T4 tumors, less than 12
lymph nodes examined (\ 12LN), positive margins, high-
grade tumor, perineural invasion (PNI), and lymphovas-
cular invasion (LVI)].
Methods. Patients diagnosed with stage II colon cancer
between 2010 and 2013 were identiﬁed from California
Cancer Registry. Propensity score weighted all-cause
mortality hazard ratios (HR) were calculated for combi-
nations of HRF.
Results. A total of 5160 stage II colon cancer patients
were identiﬁed, of which 2398 had at least one HRF and
510 of 2398 (21%) received adjuvant chemotherapy.
Compared with patients with a single HRF, presence of any
2orC 3 HRF showed increasingly poorer survival [HR
1.42, 95% conﬁdence interval (CI) 1.16–1.73 and HR 2.50,
95% CI 1.96–3.20, respectively]. Chemotherapy was
associated with improved overall survival only among
patients with T4 as the single HRF (HR 0.51, 95% CI
0.34–0.78) or combinations involving T4 as T4/\ 12 LN
(HR 0.31, 95% CI 0.11–0.90), T4/high grade (HR 0.26,
95% CI 0.11–0.61), and T4/LVI (HR 0.16, 95% CI
Conclusions. Not all high-risk features have similar
adverse effects on OS. T4 tumors and their combination
with other HRF achieve the most survival beneﬁt with
adjuvant therapy. Type and number of high-risk features
should be taken into consideration when recommending
adjuvant chemotherapy in stage II colon cancer.
Surgical resection is the mainstay of treatment for stage
II colon cancer. Although the beneﬁt of adjuvant
chemotherapy has been clearly established in stage III
colon cancer, it remains controversial in stage II colon
QUASAR—a randomized, controlled, clinical
trial that evaluated the beneﬁt of 5-ﬂuorouracil–based
adjuvant chemotherapy in stage I-III colon cancer—failed
to demonstrate a survival beneﬁt with adjuvant
chemotherapy in stage II colon cancer (relative risk (RR)
0.86, 95% CI 0.66–1.12).
Similarly, the International
Multicentre Pooled Analysis of B2 Colon Cancer Trials
(IMPACT B2) reported no signiﬁcant survival differences
between stage II patients treated with adjuvant
5-FU ? leucovorin and those treated with surgery alone.
Despite lack of deﬁnitive evidence, many studies have
suggested that a subset of patients with stage II colon
cancer with high-risk features (HRF) might achieve
improved survival with adjuvant chemotherapy.
have been deﬁned throughout the literature as T4 tumors,
perforation, lymphovascular invasion (LVI), perineural
invasion (PNI), less than 12 lymph nodes examined, high-
grade tumors, positive margins, and obstruction.
American Society of Clinical Oncology, despite the lack of
conclusive evidence, recommends consideration of adju-
vant chemotherapy in stage II patients with T4 tumors,
inadequate lymph node sampling, perforation, or poorly
Ó Society of Surgical Oncology 2018
First Received: 11 January 2018;
Published Online: 19 April 2018
B. D. Babcock, MD
Ann Surg Oncol (2018) 25:1980–1985