Received: 23 November 2017 | Accepted: 15 January 2018

DOI: 10.1002/ags3.12061

REVIEW ARTICLE

Recent updates in the surgical treatment of colorectal cancer

Takeru Matsuda1 | Kimihiro Yamashita2 | Hiroshi Hasegawa2 | Taro Oshikiri2 |

Masayoshi Hosono2 | Nobuhide Higashino2 | Masashi Yamamoto2 |
Yoshiko Matsuda2 | Shingo Kanaji2 | Tetsu Nakamura2 |
Satoshi Suzuki2 | Yasuo Sumi3 | Yoshihiro Kakeji2

1
Division of Minimally Invasive Surgery,
Department of Surgery, Kobe University Abstract
Graduate School of Medicine, Kobe, Japan Because of recent advances in medical technology and new findings of clinical trials,
2
Division of Gastrointestinal Surgery,
treatment options for colorectal cancer are evolutionally changing, even in the last
Department of Surgery, Kobe University
Graduate School of Medicine, Kobe, Japan few years. Therefore, we need to update the treatment options and strategies so
3
Division of International Clinical Cancer that patients can receive optimal and tailored treatment. The present review aimed
Research, Department of Surgery, Kobe
University Graduate School of Medicine, to elucidate the recent global trends and update the surgical treatment strategies in
Kobe, Japan colorectal cancer by citing the literature published in the last 2 years, namely 2016
Correspondence and 2017. Although laparoscopic surgery is still considered the most common
Takeru Matsuda, Division of Minimally approach for the treatment of colorectal cancer, new surgical technologies such as
Invasive Surgery, Department of Surgery,
Kobe University Graduate School of transanal total mesorectal excision, robotic surgery, and laparoscopic lateral pelvic
Medicine, Kobe, Japan. lymph node dissection are emerging. However, with the recent evidence, superiority
Email: takerumatsuda@nifty.com
of the laparoscopic approach to the open approach for rectal cancer seems to be
controversial. Surgeons should notice the risk of adverse outcomes associated with
unfounded and uncontrolled use of these novel techniques. Many promising results
are accumulating in preoperative and postoperative treatment including chemother-
apy, chemoradiotherapy, and targeted therapy. Development of new biomarkers
seems to be essential for further improvement in the treatment outcomes of col-
orectal cancer patients.

KEYWORDS
colorectal cancer, laparoscopic surgery, lateral pelvic lymph node dissection, robotic surgery,
transanal total mesorectal excision

1 | INTRODUCTION surgical approaches such as transanal endoscopic surgery and

robotic surgery are being innovated. Important results of recent
Colorectal cancer is the fourth most deadly cancer in the world, clinical trials to elucidate the efficacy of laparoscopic versus open
because 700 000 patients die of colorectal cancer every year.1 surgery, lateral pelvic lymph node dissection (LLND), preoperative
Incidence and mortality rates of colorectal cancer are still rising and postoperative therapy, and a watch-and-wait approach are
rapidly in most countries except for some of the most developed accumulating. Several new biomarkers for selecting patients who
countries in the world.2 To overcome this global disease, new would benefit by adjuvant therapy are promising. The use of such

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This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
© 2018 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of
Gastroenterological Surgery

Ann Gastroenterol Surg. 2018;2:129–136. www.AGSjournal.com | 129

130 | MATSUDA ET AL.

recent advancements is indispensable for the optimal treatment of survival (DFS). Based on these reports, laparoscopic surgery is con-
colorectal cancer patients. sidered an acceptable standardized approach for colon cancer even
The present study aimed to elucidate recent global trends and with carrying out CME or D3 dissection.
update surgical treatment strategies in colorectal cancer by review- In contrast, there seems to be some controversy about the non-
ing the literature published in the last 2 years. Several important inferiority of laparoscopic surgery to open surgery for rectal cancer
studies published more recently are also referred to as essential (Table 1). Two previous large RCT and several meta-analyses showed
introductory information. similar pathological and oncological outcomes between laparoscopic
and open approaches for rectal cancer,7–10 and the laparoscopic
approach was regarded as a standardized alternative to the open
2 | SURGICAL TREATMENT
approach. However, two more recent RCT showed contradictory
results, and each failed to show the non-inferiority of laparoscopic
2.1 | Laparoscopic versus open approach
rectal resection to open rectal resection.11,12 In the ALaCaRT trial,
Although the previous randomized control trials (RCT) showed the the number of patients with negative circumferential margin (CRM
superiority of laparoscopic surgery for colon cancer over open sur- ≥1 mm) was 222 (93%) of 238 patients in the laparoscopic group
gery in short-term outcomes,3,4 there is critical concern about the and 228 (97%) of 235 patients in the open group (P = .06 for non-
feasibility of complete mesocolic excision (CME) or D3 dissection in inferiority). Primary outcome of successful resection was achieved in
those trials. Just recently, the outcomes of laparoscopic versus open 194 patients (82%) in the laparoscopic group and in 208 patients
D3 dissection for stage II or III colon cancer in a randomized control (89%) in the open surgery group (P = .38 for non-inferiority). In the
trial (JCOG0404) were reported from Japan.5 In this study, the non- ACOSOG Z6051 RCT, surgical success rate was higher in the open
inferiority of laparoscopic surgery to open surgery could not be group versus the laparoscopic group (86.9% and 81.7%, respectively,
shown because 5-year overall survival (OS) of each group was much P = .41 for non-inferiority). From Japan, a large cohort study was
better than expected (90.4% for open surgery and 91.8% for laparo- reported in 2017.13 In this study, the proportion of positive CRM
scopic surgery, P = .073 for non-inferiority). This result suggests cases was not different between the groups (4.53% in the laparo-
laparoscopic D3 surgery could be an acceptable treatment option for scopic group and 4.47% in the open group), and no significant differ-
patients with stage II or III colon cancer. A meta-analysis to examine ence was observed in either 3-year OS or recurrence-free survival
the non-inferiority of laparoscopic CME or D3 surgery versus open between the groups. Postoperative complications were significantly
surgery was reported from the United Kingdom (UK).6 In their analy- less after laparoscopic surgery than open surgery (30.3% vs 39.2%,
sis, there was no difference in short-term mortality and morbidity. P = .005). The most recent meta-analysis concluded that the risk of
Although intraoperative blood loss was significantly less in the unsuccessful resection in rectal cancer was significantly higher in
laparoscopic group, there was only a trend for longer operative time laparoscopic surgery compared with open surgery.14 Therefore, long-
and shorter hospital stay in laparoscopic surgery compared to open term outcomes are awaited to evaluate whether such poor patholog-
surgery. There was no significant difference in OS and disease-free ical outcomes have an adverse effect on DFS or OS.

T A B L E 1 Laparoscopic vs open surgery for rectal cancer

COLOR II COREAN ALaCaRT ACOSOG Z6051
8 7 12
Authors van der Pas et al Jeong et al Stevenson et al Fleshman et al11
Bonjer et al9 Kang et al10
Countries Europe, Canada, South Korea South Korea Australia, New Zealand USA, Canada
Period 2004–2010 2006–2009 2010–2014 2008–2013
No. patients 1103 340 475 462
Lap/Open 739/364 170/170 238/237 240/222
Conversion rate 16.6% 1.2% 8.8% 11.2%
Short-term outcome Less blood loss and Less blood loss and Less blood loss and Less blood loss and
longer operative time in Lap longer operative time in Lap longer operative time in Lap longer operative time in Lap
Long-term outcome, Lap: 74.8% Lap: 79.2% NA NA
3-y DFS Open: 70.8% Open: 72.5%
CRM involvement Lap: 56/588 (9.5%) Lap: 5/170 (2.9%) Lap: 16/238 (6.7%) Lap: 29/240 (12.1%)
Open: 30/300 (10%) Open: 7/170 (4.1%) Open: 7/235 (3.0%) Open: 17/222 (7.7%)
P = .850 P = .770 P = .06
Incomplete mesorectal Lap: 77/666 (11.6%) Lap: 41/170 (24.1%) Lap: 32/238 (13.4%) Lap: 19/240 (7.9%)
excision Open: 28/331 (8.5%) Open: 44/170 (25.9%) Open: 19/235 (8.1%) Open: 11/222 (5.0%)
P = .250 P = .414 P = .06

CRM, circumferential resection margin; DFS, disease-free survival; Lap, laparoscopy; NA, not applicable; Open, open surgery.
MATSUDA ET AL. | 131

Another important concern is the indication for laparoscopic sur- At present, considering the extra financial and time expenses,
gery in elderly patients with colorectal cancer. A systematic review robotic surgery might be selectively applied for those patients who
by Fujii et al15 showed significantly better short-term outcomes of may benefit from this novel technology.
laparoscopic surgery compared with open surgery in terms of esti-
mated blood loss and overall morbidity. They also reported similar
2.3 | Transanal TME
long-term outcomes between laparoscopic and open surgery. Roscio
et al16 evaluated the effectiveness of laparoscopic surgery for col- Transanal TME (TaTME) was first introduced by Sylla et al in
orectal cancer in the very elderly over 80 years old by a prospective 2010.24 Since then, the feasibility and safety of this surgery has
multicenter analysis. They showed similar short-term and oncological been reported by many case studies with acceptable short-term out-
outcomes between laparoscopic and open surgery, and concluded comes.25–28 Most recently, de Lacy’s group reported the pathological
that age was not a risk factor or a limitation for laparoscopic surgery. results of 186 constitutive cases with mid and low rectal cancer.29
A large multicenter study in Japan also showed better short-term Complete TME was achieved in 95.7%, and overall positive CRM
outcomes and a lower morbidity rate in the laparoscopic group com- (≤1 mm) and distal resection margin (DRM) (≤1 mm) were 8.1% and
pared with the open group even in elderly patients with a history of 3.2%, respectively. The international TaTME registry also reported
abdominal surgery.17 They also showed similar oncological outcomes the results of 720 patients.30 In 634 patients with rectal cancer,
between the groups. These reports suggest that laparoscopic surgery complete TME was obtained in 503 (79.3%), and positive CRM and
is safe and is the preferred approach for elderly patients with col- DRM rates were 2.4% and 0.3%, respectively. Perdawood et al31
orectal cancer. carried out a retrospective, case-matched analysis including 300
patients (100 each who underwent TaTME, laparoscopic TME, and
open TME, respectively). The CRM positive rate was comparable
2.2 | Robotic surgery
among the three groups. More favorable outcomes in terms of
In their systematic review of rectal cancer, Prete et al18 reported shorter operation time, less blood loss, and shorter hospital stay
that robotic surgery had a lower rate of conversion to open surgery, were observed in TaTME than in the other two groups. Marks
whereas operating time was significantly longer than by laparoscopic et al32 first reported the long-term outcomes of rectal cancer
surgery. However, perioperative mortality and CRM involvement rate patients who were treated by TaTME. Rates of successful TME, neg-
were similar. Another analysis of costs and outcomes between open, ative CRM, and negative DRM were 96%, 94%, and 98.6%, respec-
laparoscopic, and robotic surgeries of 488 rectal cancer patients tively. Overall local recurrence, distant recurrence, and 5-year OS
showed that operative time was significantly longer in the robotic rates were 7.4%, 19.5%, and 90%, respectively. According to a sys-
19
group. Estimated blood loss, intraoperative transfusion, length of tematic review in 2016, total morbidity of TaTME was 40.3%, which
stay, and postoperative complications were all significantly higher in was comparable with that of conventional laparoscopic TME in a
the open group. Direct cost of hospitalization for primary resection previous large RCT.33 It showed favorable outcomes of low rates of
and total direct cost were significantly greater in the robotic group. anastomosis leakage (5.7%) and conversion (3.0%). The rate of posi-
20
Huang et al reported that robotic surgery might offer a shorter tive CRM was 4.7%, and complete TME was achieved in 87.6%.
learning curve than laparoscopic surgery even in patients who DRM involvement developed in 0.2% only. Importantly, operative
showed more advanced disease after undergoing preoperative and oncological outcomes were better in high-volume centers (>30
chemoradiotherapy (CRT). cases in total) than in low-volume centers (<30 cases in total) includ-
In an analysis of abdominoperineal resection, robotic surgery had ing operative time, conversion rate, major complication rate, TME
a significantly lower conversion rate compared with laparoscopic sur- quality, and local recurrence rate. Currently, a multicenter RCT com-
gery (5.7% vs 13.4%; P < .01).21 However, it had significantly higher paring TaTME versus laparoscopic TME for mid and low rectal can-
total hospital costs compared with laparoscopic surgery (mean differ- cer (COLOR III) is ongoing.34
ence, US$24 890; P < .01). However, technical difficulty of this approach has been well
Concerning total mesorectal excision (TME) rate, a retrospective acknowledged by early adopters of this technique. TaTME registry
analysis of a prospectively maintained database with 20 robotic and data showed visceral injuries during perineal dissection including five
40 laparoscopic surgery cases for rectal cancer was reported.22 In this urethral injuries (0.7%), two bladder injuries (0.3%), one vaginal per-
study, the quality of TME was better in the robotic group. In a Japa- foration (0.1%), and two rectal tube perforations (0.3%).30 The sys-
nese retrospective study, 203 robotic surgery cases were compared tematic review also detected five cases (0.6%) with urethral injury
with 239 laparoscopic cases.23 Significantly lower conversion rate and five cases (0.6%) with bleeding from the pelvic side wall among
(0% vs 3.3%, P = .009), less blood loss (15.4  26.4 vs 794 patients.33
39.1  85.1 mL, P < .001) and shorter hospital stay (7.3  2.3 vs According to a recent survey of the Association of Coloproctol-
9.3  6.7 days, P < .001) were seen in the robotic group. In contrast, ogy of Great Britain and Ireland (ACPGBI) consultant members,
operative time was not significantly different between the groups. TaTME training was the top educational need for surgeons who wish
Rate of urinary retention was significantly lower in the robotic group to start TaTME.35 Penna et al36 reported the beneficial effect of
than in the laparoscopic group (2.5% vs 7.5%, P = .018). human cadaveric training courses conducted in the UK and USA.
132 | MATSUDA ET AL.

They proposed a structured training curriculum including reading metastasis varies among the investigators. Ishibe et al47 reported
material, dry-lab purse-string practice, cadaveric training, and post- that a cut-off value of 10 mm was useful for avoiding unnecessary
course mentorship as an excellent teaching model for TaTME. Aigner LLND. Akiyoshi’s group reported that the optimal cut-off value
37
et al also claimed that the training course on cadavers is indispens- before CRT was 8 mm.44 Yamaoka reported an optimal cut-off value
able regarding implementation of TaTME into clinical practice. The of 6.0 mm, with a sensitivity of 78.5% and a specificity of 82.9%.43
International TaTME Educational Collaborative Group proposed a Before the start of preoperative treatment, accurate estimation of
detailed framework for a structured TaTME training curriculum LLN size by MRI is useful.
including guidance on case selection, multidisciplinary training, men- Although JCOG0212 reported that LLND did not increase male
torship, and assessment.38 sexual dysfunction, LLND is considered technically challenging.48
Although TaTME is one of the most attractive and promising Recently, the safety and feasibility of laparoscopic versus open
advancements for colorectal surgeons, the risk of adverse outcomes LLND was shown by a subgroup analysis of a large multicenter
associated with widespread uncontrolled use of this novel technique cohort study from Japan.49 They also showed similar oncological
should be noted. Surgeons are also required to conform to St. Gallen outcomes between the groups.
consensus guidelines for safe implementation and practice of Establishment of criteria to accurately predict LLN status as well as
TaTME.39 standardization of the technique of LLND is necessary in the future.

2.4 | Lateral pelvic lymph node dissection 2.5 | Preoperative therapy

The beneficial effect of lateral pelvic lymph node dissection (LLND) Currently, fluorouracil-based chemoradiotherapy is the golden stan-
had been under debate for a long time until the results of the dard of preoperative therapies for locally advanced rectal cancer.50
40
JCOG0212 trial were published in 2017. Five-year OS, and 5-year However, the beneficial effect of addition of oxaliplatin to CRT is con-
local-recurrence-free survival in the mesorectal excision (ME) with troversial. In 2016, initial results of the Chinese FOWARC randomized,
LLND and ME-alone groups were 92.6% and 90.2%, and 87.7% and phase III trial comparing the three arms (fluorouracil-radiotherapy,
82.4%, respectively. Local recurrence rates were 7.4% and 12.6% in n = 155; mFOLFOX6-radiotherapy, n = 157; mFOLFOX6, n = 163)
the ME with LLND and ME-alone groups, respectively (P = .024). were reported.51 mFOLFOX6-radiotherapy resulted in a higher patho-
41
Kanemitsu et al also reported the outcomes from a total of 1191 logical complete response (pCR) rate than fluorouracil-radiotherapy
consecutive patients with lower rectal cancer who underwent TME and mFOLFOX6 (27.5% vs 14.0% and 6.6%, respectively). However,
with LLND. They described that dissection of the internal iliac nodes higher toxicity and more postoperative complications were observed
and obturator nodes yielded similar therapeutic benefits to those in patients who received radiotherapy. Long-term outcomes of the
expected from dissection of the superior rectal artery nodes. They ACCORD12 trial, comparing 45 Gy radiation + capecitabine and
also showed that the relative risk for local recurrence was 2.0 for 50 Gy radiation + capecitabine + oxaliplatin, reported contradictory
patients with unilateral LLND compared with those with bilateral results in 2017.52 There was no difference between the groups for
LLND. Based on these results, ME with LLND is still a standard either DFS or OS. A meta-analysis including eight clinical trials
treatment in Japan. It should be noted that patients with lateral between 2011 and 2015 was reported in 2017.53 Additional oxali-
lymph nodes (LLN) larger than 10 mm were excluded and that no platin to preoperative CRT significantly improved pCR rate (P = .002),
patient received any preoperative treatments in JCOG0212. decreased local recurrence rate (P = .012), and improved DFS
The effect of additional LLND after preoperative treatment is (P = .000). However, it can increase CRT-related toxicities, and had no
unclear. Ishihara et al42 reported that the incidence of LLN metastasis beneficial effects on R0 resection rate, mortality, and OS.
was estimated to be 8.1% (18/222) even after preoperative CRT. There is increasing interest in a watch-and-wait approach as a
Yamaoka et al also reported that LLN metastasis was detected in management option for patients with rectal cancer who received
seven out of 19 patients who underwent preoperative CRT, suggest- preoperative therapy. The OnCoRe project, which was a propensity-
ing preoperative CRT followed by ME alone is not sufficient, espe- score matched cohort study, was reported in 2016.54 In that project,
43
cially when LLN involvement is clinically suspicious. Ishihara’s group 129 patients were managed by the watch-and-wait approach
carried out TME + LLND for patients with swollen LLN following because of clinical complete response (cCR) after preoperative CRT,
preoperative CRT.42 Akiyoshi’s group also carried out LLND with a and 228 patients who did not have cCR received surgical resection
similar theory and reported 3-year relapse-free survival of 75.1% for if eligible. Of the 129 patients in the watch-and-wait group, 44
patients with LLN metastasis.44 Currently, RCT to assess the efficacy (34%) had local regrowth with a 3-year actual rate of 38%, and three
and safety of LLND after preoperative CRT for rectal cancer patients of those 44 patients had synchronous luminal regrowth and distant
with suspicious LLN metastases is ongoing in China.45 metastasis. Thirty-one (76%) of 41 underwent subsequent salvage
Kusters et al reported that the lateral local recurrence rate was surgery and five patients (12%) underwent radiotherapy. The 3-year
significantly higher in patients with LLN larger than 10 mm than in non-regrowth DFS rates for the watch-and-wait and surgery groups
patients with smaller nodes despite the use of preoperative radia- were 88% and 78%, respectively (P = .022 by the log-rank test). The
tion.46 The optimal cut-off value of LLN size for prediction of systematic review published in 2017 reported that the regrowth rate
MATSUDA ET AL. | 133

in the watch-and-wait group was 21.3% and salvage surgery was improved OS was associated with adjuvant chemotherapy regardless
possible in 93.2% of these patients.55 Another meta-analysis com- of treatment regimen, patient age, or high-risk pathological risk fac-
pared the oncological outcomes of the patients who had watch-and- tors in stage II colon cancer.64 For rectal cancer, a review published
wait after cCR versus those who had radical surgery after cCR or in 2017 concluded that data from the adjuvant rectal cancer trials did
versus patients with pCR after surgery.56 There was no significant not support the use of postoperative adjuvant chemotherapy for
difference among those three groups in terms of non-regrowth patients with rectal cancer treated with preoperative CRT.65
recurrence, cancer-specific mortality, or OS. However, DFS was bet- Selecting patients who actually benefit from adjuvant therapy is
ter in the patients with pCR identified after surgery compared with also important. A retrospective analysis using 570 tumor specimens
the watch-and-wait patients (HR 0.47, 95% CI 0.28-0.78). Although from patients with colon cancer showed that fluoropyrimidine adju-
this approach is attractive for patients, confirming long-term safety vant chemotherapy benefited patients with stage II or III colon can-
in more prospective studies is mandatory. cer with microsatellite-stable tumors or tumors showing low-
In contrast, there is a movement to eliminate the use of radiation frequency microsatellite instability (MSI) but not those with tumors
from preoperative therapy. Results of a study comparing outcomes showing high-frequency MSI.66 A retrospective pooled analysis using
using the National Cancer Data Base in the USA between neoadju- 2141 tumor specimens showed that patients with deficient DNA
vant chemoradiotherapy (NACRT) and neoadjuvant multiagent mismatch repair (MMR) colon cancers have reduced rates of tumor
chemotherapy (NAC) for stage II and III rectal cancer were recurrence and improved survival rates compared with proficient
reported.57 Although treatment-related toxicities were not available MMR colon cancers.67 They also showed distant recurrences were
in that study, the 5-year OS rate for the NACRT group was signifi- reduced by fluorouracil-based adjuvant treatment in deficient MMR
cantly better than that of the NAC group (75% vs 67.2%, P < .01), stage III tumors. The MOSAIC study compared fluoropyrimidine
suggesting that NAC should not be recommended outside of a clini- monotherapy and fluoropyrimidine and oxaliplatin combination ther-
cal trial. FOLFOXIRI is one of the first-line chemotherapy regimens apy, and hazard ratios for DFS and OS benefit in the combination
for metastatic colorectal cancer although it induces high toxicity. So therapy arm were 0.48 (95% CI 0.20-1.12) and 0.41 (95% CI, 0.16-
far, only one prospective, phase II study of FOLFOXIRI for resectable 1.07), respectively, in patients with MMR deficiency stage II and III
colon cancer has been available.58 A total of 23 patients with colon cancer.68 Unlike fluoropyrimidine monotherapy, fluoropyrim-
cT4N2M0 colon cancer received FOLFOXIRI followed by surgery. idine and oxaliplatin combination therapy seems to offer a survival
Twenty patients (87.0%) had marked reductions in tumor volume benefit for MMR deficiency stage II and III colon cancer patients.
after neoadjuvant treatment. Thirteen patients (56.5%) had grade 3- Recently, lack of caudaltype homeobox transcription factor 2 (CDX2)
4 toxicity, but the toxicity did not affect the subsequent surgery. expression was identified as a possible prognostic biomarker to pre-
These results suggest that FOLFOXIRI might be a promising preoper- dict benefit from adjuvant chemotherapy in stage II colon cancer.69
ative regimen for resectable colorectal cancer in the future. Development of such new biomarkers would allow further progress
For stage IV colorectal cancer with synchronous unresectable in adjuvant therapy.
metastasis, the impact of primary tumor resection is considered con-
troversial. However, recent large-scale retrospective studies showed
that primary tumor resection with systemic chemotherapy con- 3 | CONCLUSION
tributed to significantly better overall or cancer-specific survival com-
pared with chemotherapy alone. In a retrospective cohort study of In the present review, we updated advancements mainly in the surgi-
the National Cancer Data Base from 2004 to 2012, which included cal treatment field of colorectal cancer based on recent important
65 543 patients, Maroney et al59 reported that primary tumor resec- findings. Although surgical technologies including TaTME and robotic
tion was associated with improved overall survival. Gulack et al60 also surgery are rapidly evolving, surgeons need to carry out their prepa-
reported similar results by using the National Cancer Data Base from rations with the most studious care to prevent unfavorable out-
2004 to 2012 in a retrospective study of 1446 patients. A recent comes in patients. Even for laparoscopic surgery, surgeons should
61
meta-analysis by Lee et al showed patients receiving primary tumor keep in mind that recent RCT, the ALaCaRT and ACOSOG Z6051
resection plus chemotherapy/radiotherapy had longer overall survival trials could not show non-inferiority of laparoscopic surgery to open
than those treated with chemotherapy/chemoradiotherapy alone surgery for rectal cancer in terms of pathological results. The recent
(hazard ratio [HR 0.59], 95% confidence interval [CI] 0.51-0.68; progress of preoperative and postoperative treatment is also promis-
P < .001). For a more definitive conclusion, the results of ongoing ing. However, development of new biomarkers seems essential for
randomized controlled trials62,63 are awaited. further improvement in the treatment outcomes of colorectal cancer
patients.

2.6 | Adjuvant chemotherapy

DISCLOSURE
Although adjuvant chemotherapy for stage II colon cancer patients
has been controversial, a recent large-cohort study including 153 110 Conflicts of interest: Authors declare no conflicts of interest for this
patients from National Cancer Data Base in the USA showed that article.
134 | MATSUDA ET AL.

ORCID 17. Yamamoto S, Hinoi T, Niitsu H, et al. Influence of previous abdomi-

nal surgery on surgical outcomes between laparoscopic and open
Takeru Matsuda http://orcid.org/0000-0002-9541-856X surgery in elderly patients with colorectal cancer: subanalysis of a
Shingo Kanaji http://orcid.org/0000-0002-8698-8923 large multicenter study in Japan. J Gastroenterol. 2017;52:695–704.
18. Prete FP, Pezzolla A, Prete F, et al. Robotic versus laparoscopic mini-
Satoshi Suzuki http://orcid.org/0000-0002-7287-6998
mally invasive surgery for rectal cancer: a systematic review and
meta-analysis of randomized controlled trials. Ann Surg. 2017; [Epub
ahead of print]. https://doi.org/10.1097/SLA.0000000000002523.
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