Time to Initiation of Adjuvant Chemotherapy in Colon Cancer: Comparison of Open,Laparoscopic,and Robotic Surgery

Abstract

Background:

The time to initiation of adjuvant chemotherapy (TIC) can be used as a recovery parameter after surgery. The effect of laparoscopic or robotic surgery on TIC has not been thoroughly studied. This study aimed to compare the impact of open, laparoscopic, and robot-assisted surgery on TIC after colon cancer surgery.

Materials and Methods:

Patients who underwent curative resection for stage II or III colon cancer between January 2007 and June 2013 and who received adjuvant chemotherapy from surgeons capable of performing open, laparoscopic, and robotic surgeries were included in this study. Patient demographics, clinicopathologic variables, and TIC were compared among the three groups. Univariate and multivariate analyses were performed to identify factors affecting TIC.

Results:

Of the 252 patients, 40, 161, and 51 patients underwent open, laparoscopic, and robotic colectomy, respectively. The postoperative complication rate was lower in the laparoscopic and robotic groups compared to the open group (P = .002). The length of hospital stay was shorter in the laparoscopic group compared with the open and robotic groups (P < .001). Multivariate analysis revealed that the operation method was the only factor affecting TIC, with laparoscopic and robotic surgery being favorable (regression coefficient −5.1, 95% confidence interval −7.6 to −2.6; P < .001). However, there was no difference in TIC between the laparoscopic and robotic group.

Conclusions:

Laparoscopic and robotic surgeries were associated with shorter TIC. This study demonstrates another benefit of minimally invasive surgery with regard to early initiation of adjuvant chemotherapy.

Introduction

Curative resection is the most important treatment strategy in colon cancer patients. The use of adjuvant chemotherapy following resection with stage III colon cancer is regarded as the standard of treatment. Adjuvant chemotherapy has not yet been conclusively shown to be beneficial for stage II colon cancer patients. Despite the lack of data, adjuvant chemotherapy is considered after receipt of informed consent from patients who have high risk of recurrence on the basis of clinicopathologic outcomes.^1,2

The optimal time to initiation of adjuvant chemotherapy (TIC) for colon cancer is still controversial. Even though no prospective studies have evaluated the associations between TIC and oncologic outcomes, it is generally accepted that adjuvant chemotherapy should be initiated within 8–12 weeks after surgery for better oncologic outcomes in the management of colorectal cancer.^3–6

Postoperative recovery is one of the important factors related to delay of TIC. Laparoscopic surgery has been shown to reduce postoperative complications and length of stay while maintaining similar oncologic outcomes compared to open surgery.^7–9 Recent studies have demonstrated that laparoscopic surgery has a reduced TIC in comparison to open surgery.^10,11 Because faster recovery from surgery is related to early initiation of adjuvant chemotherapy, TIC can be used as a postsurgical recovery parameter. Recent studies have demonstrated similar recovery outcomes between robotic and laparoscopic surgeries,^12–15 nevertheless, the impact of laparoscopic and robotic surgeries on TIC has not been thoroughly investigated in the management of colon cancer.

Thus, this study compared the impacts of open, laparoscopic, and robotic surgery on TIC after colon cancer surgery.

Materials and Methods

Eligibility

All patients who had undergone adjuvant chemotherapy after curative resection for stage II or III colon cancer between January 2007 and June 2013 at Gangnam Severance Hospital, Yonsei University College of Medicine were identified retrospectively from a prospectively maintained database. In our hospital, the regimen and initiation date of adjuvant chemotherapy after colon cancer resection were mostly decided by colorectal surgeons. All surgeries were performed by a total of four colorectal surgeons, two of whom did not perform laparoscopic or robotic surgeries during the study period. For this retrospective study comparing the impact of surgery type on TIC, only patients who were operated on by surgeons capable of open, laparoscopic, and robotic colectomy were included to reduce the effect of surgeon differences in initiation of postoperative adjuvant chemotherapy. Cases for which TIC was decided by a medical oncologist were also excluded. This study was approved by our Institutional Review Board.

Surgery

All patients underwent curative resection based on a standardized technique. For left-side tumors, the inferior mesenteric artery was ligated at the level of its origin from the aorta or just below the left colic artery. In the case of right-side tumors, if the tumor was located at the cecum or proximal portion of the ascending colon, the ileocolic vessels and the right branch of the middle colic vessels were transected. When the tumor was located at the hepatic flexure and proximal transverse colon, the middle colic vessels were ligated from the superior mesenteric vessels at their origin. Oncologic considerations undertaken during the surgery were not different among the open, laparoscopic, and robotic surgeries.

The type of surgery was determined after discussion between surgeons and patients. In Korea, the national health insurance system does not reimburse the cost of robotic surgeries. Therefore, robotic surgeries are mainly selected by patients who have additional private insurance or patients who can afford the high cost.

Adjuvant chemotherapy

Adjuvant chemotherapy has been widely accepted as a standard treatment in stage III colorectal cancer. During the study period, the FOLFOX regimen was the most commonly used adjuvant chemotherapy regimen for stage III colon cancer patients. In the case of stage II colon cancer, patients who were regarded as having high-risk factors such as T4 tumor, preoperative obstruction or perforation, lymphovascular permeation, fewer than 12 harvested lymph nodes, or poorly differentiated histology were managed with FOLFOX regimen. In some patients who did not have high-risk factors, 5-FU/leucovorin was applied according to the surgeon's discretion.

All adjuvant chemotherapy in this study was administered by colorectal surgeons. The decision regarding when to start chemotherapy was dependent on the surgeon's assessment of patient fitness. For determination of the regimen of adjuvant chemotherapy after curative resection of colon cancer, a multidisciplinary team (MDT) discussion was not routinely applied. MDT discussion in our hospital had been mainly focused on the management of stage IV patients or recurrent colorectal cancer patients who failed first- or second-line chemotherapy.

Data collection and definition of delayed chemotherapy

Demographic and clinicopathologic data of patients, including sex, age, body mass index (BMI), tumor stage, ASA grade, tumor location, operation time, conversion, transfusion requirement, complications, and length of hospital stay (LOH), were retrospectively collected from our database and clinical medical records. TIC was defined as the number of days between curative colon cancer surgery and first chemotherapy administration. In our analysis, delayed chemotherapy was defined as initiation of adjuvant chemotherapy delayed more than 33 days after surgical resection.

Statistical analyses

All statistical analyses were performed using IBM SPSS version 20.0 (SPSS, Inc., Chicago, IL). Chi-square test, two-sided t-test, or Fisher's exact test was performed to compare categorical and continuous variables between three groups. Univariate Cox regression analysis was used to assess all factors that were possibly associated with TIC. Multivariate analysis was performed to determine independent factors of induction time of chemotherapy. A P < .05 was considered to indicate significance.

Results

Patient demographics

During the study period, a total of 252 patients met the inclusion criteria. Forty patients underwent open surgery, 161 patients underwent laparoscopic surgery, and 51 patients had robotic colectomy. The baseline characteristics of the patients are shown in Table 1. There were no differences in patient sex, age, BMI, or tumor location among the three groups. There was a significant difference in tumor stage, for which there was a higher proportion of stage III in the laparoscopic and robotic surgeries (45% in open group versus 68.3% in laparoscopic group versus 66.7% in robotic group, P = .021). ASA grade was not the same among the three groups, and grades II and III were more prevalent in the laparoscopic group compared to the other groups (P < .001). Operation time was significantly longer in the robotic group compared to the other surgical approaches (P = .022).

Table 1.

Patient Demographics and Perioperative Outcomes

	Open, N (%)	Laparoscopy, N (%)	Robot, N (%)	P
Gender
Male	26 (65)	88 (54.7)	35 (68.6)	.149
Female	14 (35)	73 (45.3)	16 (31.4)
Age (years)
Mean (SD)	61.3 (11.4)	60.3 (11.3)	60.2 (9.5)	.853
BMI (kg/m²)
Mean (SD)	23.4 (3.9)	23.2 (2.8)	23.5 (3.0)	.850
Stage
II	22 (55)	51 (31.7)	17 (33.3)	.021
III	18 (45)	110 (68.3)	34 (66.7)
ASA grade
I	28 (70)	71 (44.1)	39 (76.5)	<.001^a
II	12 (30)	71 (44.1)	11 (21.6)
III	0	19 (11.8)	1 (2)
Tumor location^b
Proximal colon	17 (42.5)	62 (38.5)	11 (21.6)	.055
Distal colon	23 (57.5)	99 (61.5)	40 (78.4)
Operation time (minute)
Mean (SD)	198.2 (114.7)	220.6 (77.9)	247.6 (80.2)	.022
Open conversion		1 (0.6)		N/A
Transfusion	2 (5)	3 (1.9)	0	0.236^a

Fisher's exact test.

Tumor location: proximal: cecum–transverse colon; distal: descending colon–rectosigmoid junction.

SD, standard deviation; BMI, body mass index; ASA, American Society of Anesthesiologists.

Postoperative morbidities

The overall rate of complications was significantly lower in the laparoscopic group and robotic group than in the open group (9.3% in laparoscopic group versus 9.8% in robotic group versus 30% in open group, P = .002). The rate of wound infection was significantly higher in the open group compared to the other groups (12.5% in open group versus 2.5% in laparoscopic group versus 2% in robotic group, P = .019). Ileus and obstruction were also significantly higher in the open group than the other groups (P = .026). The rates of anastomotic leakage, voiding difficulty, and postoperative bleeding were similar among the three groups (Table 2).

Table 2.

Early Postoperative Complications and Management

Complications	Open, N (%)	Laparoscopy, N (%)	Robot, N (%)	P
Overall
	12 (30)	15 (9.3)	5 (9.8)	.002
Anastomotic leakage	0 (0)	1 (0.6)	1 (2)	.593^a
Wound infection	5 (12.5)	4 (2.5)	1 (2)	.019^a
Ileus/obstruction	4 (10)	4 (2.5)	0 (0)	.026^a
Voiding problem	2 (5)	5 (3.1)	1 (2)	.756
Postoperative bleeding	0 (0)	0 (0)	1 (2)	.361^a
Other	1 (2.5)	1 (0.6)	1 (2)	.296^a
Management
Conservative	10 (76.9)	13 (86.7)	4 (80)	.865^a
Intervention	1 (7.7)	1 (6.7)	0 (0)
Reoperation	2 (15.4)	1 (6.7)	1 (20)

Fisher's exact test.

LOH and TIC

The LOH was shorter in the laparoscopic group compared with the open group and robotic group (P < .001). There was a significant difference in TIC among the open, laparoscopic, and robotic groups (open group, 36.0 versus laparoscopic group, 27.8 versus robotic group, 25.2 days, P < .001). Comparing between the laparoscopic and robotic group, the TIC was shorter in the robotic group than in the laparoscopic group (P = .035).

In a subgroup analysis comparing patients without perioperative complications, LOH was shortest in the laparoscopic group (P < .001). Specifically, the laparoscopic group showed a significantly shorter LOH than the robotic group (7.3 days in laparoscopic group versus 8.8 days in robotic group, P = .007). In contrast, the robotic group showed a shorter TIC than the laparoscopic group (24.9 days in robotic group versus 27.7 days in laparoscopic group, P = .028) (Table 3).

Table 3.

Length of Hospital Stay and Time to Initiation of Chemotherapy

		Open	Laparoscopy	Robot	P
Length of hospital stay (days)
Overall, (N = 252)	Mean (SD)	15.5 (9.2)	7.7 (4.1)	10.0 (5.7)	<.001
Complication group, (N = 32)	Mean (SD)	22.0 (10.9)	11.6 (7.9)	21.2 (13.0)	.025
No complication group, (N = 220)	Mean (SD)	12.6 (6.9)	7.3 (3.4)	8.8 (2.4)	<.001
Time to initiation of chemotherapy (days)
Overall, (N = 252)	Mean (SD)	36.0 (23.5)	27.8 (7.0)	25.2 (8.5)	<.001
Complication group, (N = 32)	Mean (SD)	35.2 (13.5)	28.5 (5.9)	28.2 (11.7)	.212
No complication group, (N = 220)	Mean (SD)	36.4 (26.9)	27.7 (7.2)	24.9 (8.2)	<.001

SD, standard deviation.

Univariate analysis demonstrated that sex, age, BMI, ASA grade, tumor location, tumor stage, and postoperative complication were not correlated with TIC. Only type of operation was a factor associated with early initiation of adjuvant chemotherapy in the univariate analysis. In the multivariate analysis, operation method was determined to be the only factor associated with TIC (regression coefficient −5.1, 95% confidence interval −7.6 to −2.6; P < .001) (Table 4).

Table 4.

Factors Associated with Time to Initiation of Chemotherapy (n = 252)

		Univariate analysis		Multivariate analysis
	N	TIC, mean (SD)	P	Regression coefficient (95% CI)	P
Gender
Male	149	27.6 (9)	.138	2.5 (−0.4 to 5.7)	.100
Female	103	29.9 (15.2)
Age (years)
<65	153	28.3 (14.0)	.718	0.2 (−2.8 to 3.3)	.874
≥65	99	28.9 (7.8)
BMI (kg/m²)
<25	179	28.3 (13.0)	.634	1.5 (−1.6 to 4.8)	.338
≥25	73	29.1 (9)
ASA grade
I	138	28.2 (14.7)	.798	0.3 (−1.9 to 2.7)	.303
II	94	28.9 (7.8)
III	20	29.9 (6.2)
Tumor location
Proximal	90	29.6 (9.7)	.314	−0.5 (−3.6 to 2.5)	.739
Distal	162	28.0 (13.1)
Stage
Stage II	90	27.7 (9.7)	.389	2.4 (−0.6 to 5.5)	.116
Stage III	162	29.0 (13)
Complications
Yes	32	31 (10.5)	.227	−2.1 (−6.6 to 2.2)	.336
No	220	28.2 (12.1)
Operation method
Open	40	36 (23.5)	<.001	−5.1 (−7.6 to −2.6)	<.001
Laparoscopy	161	27.8 (7)
Robot	51	25.2 (8.5)

ASA, American Society of Anesthesiologists; BMI, body mass index; CI, confidence interval; TIC, time to initiation of adjuvant chemotherapy.

To compare the effect of laparoscopic and robotic surgeries, a subgroup analysis was performed. In the univariate analysis, BMI, ASA grade, tumor location, and operation method (favoring robotic surgery) were found to be significantly associated with TIC. In the multivariate analysis, only BMI was significantly correlated with TIC. There was no difference in TIC between laparoscopic and robotic surgeries (Table 5).

Table 5.

Factors Associated with Time to Initiation of Chemotherapy in Patients Who Perform Laparoscopy or Robot Surgeries (n = 212)

		Univariate analysis		Multivariate analysis
	N	Time to initiation of chemotherapy: mean (SD)	P	Regression coefficient (95% CI)	P
Gender
Male	123	26.5 (7.3)	.124	1.9 (−0.2 to 4.0)	.077
Female	89	28.1 (7.7)
Age (years)
<65	129	27 (8.1)	.747	0.0 (−2.8 to 2.1)	.962
≥65	83	27.4 (6.5)
BMI (kg/m²)
<25	149	26.4 (6.9)	.031	2.5 (0.2 to 4.7)	.027
≥25	63	28.9 (8.5)
ASA grade
I	110	26 (7.8)	.042	1.4 (−0.1 to 3.0)	.082
II	82	28 (7)
III	20	29.9 (6.2)
Tumor location
Proximal	73	28.5 (8.6)	.049	−1.4 (−3.5 to 0.7)	.190
Distal	139	26.4 (6.8)
Stage
Stage II	68	27.1 (8.8)	.925	0.5 (−1.6 to 2.6)	.647
Stage III	144	27.2 (6.8)
Complications
Yes	20	28.4 (7.4)	.432	−1.9 (−5.4 to 1.4)	.261
No	192	27 (7.5)
Operation method
Laparoscopy	161	27.8 (7)	.035	−1.5 (−4.0 to 0.9)	.220
Robot	51	25.2 (8.5)

ASA, American Society of Anesthesiologists; BMI, body mass index; CI, confidence interval.

Factors associated with delayed chemotherapy

This study included only 2 patients (0.7%) with a TIC longer than 56 days (8 weeks). Therefore, we defined delayed chemotherapy as delaying initiation of adjuvant chemotherapy for more than 33 days. A total of 62 patients (24.6%) were classified into the delayed chemotherapy group. In the multivariate analysis, ASA grade, complications, and operation method were significantly associated with delayed chemotherapy (Table 6).

Table 6.

Factors Associated with Delayed Chemotherapy (n = 252)

		Univariate analysis		Multivariate analysis
	N	N (%)	P	HR (95% CI)	P
Gender
Male	149	35 (23.5)	.622	1
Female	103	27 (26.2)		1.5 (0.8–2.9)	.198
Age (years)
<65	153	36 (23.5)	.623	1
≥65	99	26 (26.3)		1.0 (0.5–2.0)	.823
BMI (kg/m²)
<25	179	41 (22.9)	.327	1
≥25	73	21 (28.8)		1.6 (0.8–3.3)	.132
ASA grade
I	138	28 (20.3)	.176^a	1
II	94	29 (30.9)		2.2 (1.1–4.4)	.023
III	20	5 (25)		1.7 (0.5–6.0)	.369
Tumor location
Proximal	90	22 (24.4)	.965	1
Distal	162	40 (24.7)		1.3 (0.7–2.7)	.329
Stage
Stage II	90	25 (27.8)	.383	1
Stage III	162	37 (22.8)		0.9 (0.5–1.9)	.978
Complications
Yes	32	14 (43.8)	.007	1
No	220	48 (21.8)		0.4 (0.1–0.9)	.041
Operation method
Open	40	21 (52.5)	<.001	1
Laparoscopy	161	34 (21.1)		0.2 (0.0–0.4)	<.001
Robot	51	7 (13.7)		0.1 (0.0–0.4)	<.001

Fisher^'s exact test.

ASA, American Society of Anesthesiologists; BMI, body mass index; CI, confidence interval; HR, hazard ratio.

Discussion

This study demonstrated that laparoscopic and robotic surgery, in comparison to open surgery, resulted in earlier initiation of adjuvant chemotherapy for stage II or III colon cancer patients. This could be another potential benefit of minimally invasive surgery. There was no difference in TIC between laparoscopic and robotic colon resection.

The benefits of laparoscopic surgery for colon cancer include early recovery with reduced LOH.^7,8 Earlier recovery in laparoscopic surgery has been confirmed even in the setting of an enhanced recovery program.¹⁶ Reduced small bowel obstruction or incisional hernia is regarded as one of the long-term benefits of laparoscopic colectomy.^17,18 Since the introduction of robotic surgery in the management of colorectal disease, the feasibility and safety, including long-term oncologic outcomes comparing laparoscopic and robotic surgery for treatment of colon cancer, have been reported in the literature.^12–15

Recently, Poylin et al. demonstrated that minimally invasive surgery, including laparoscopic and hand-assisted surgeries, was associated with shorter time to initiation to chemotherapy than open surgery (42.9 versus 60.3 days, P < .001).¹⁰ For rectal cancer patients, Strouch et al. showed that mean time to postoperative chemotherapy was decreased for patients undergoing laparoscopy in comparison to open surgery (50.1 versus 75.2 days, P < .001).¹¹ A recent systematic review revealed that age older than 75 years, unmarried status, low socioeconomic status, worse comorbidity status, low tumor grade, prolonged length of stay, and readmission were associated with delayed initiation of postoperative adjuvant chemotherapy.¹⁹ Laparoscopic surgery in comparison to open surgery was also a significant predictor of delayed adjuvant chemotherapy.¹⁹ These prior results demonstrate another benefit of laparoscopic surgery with regard to early initiation of adjuvant chemotherapy.

Postoperative complications are well-known independent predictors of delayed adjuvant chemotherapy.^10,20 In our study, complications per se did not impact the TIC. However, TIC showed some differences according to the category of complications. For example, patients with ileus/obstruction showed a trend for longer TIC than patients without ileus/obstruction (36.5 versus 28.3 days, respectively, P = .058, data not shown). In addition, when we analyzed the factors associated with delayed chemotherapy, which was defined as delaying initiation of adjuvant chemotherapy for more than 33 days, complication was an independent risk factor associated with delayed chemotherapy in the multivariate analysis. The overall complication rate in our study was 12.7%, and this relatively low rate of complications might be one reason for the discordant results.

It has been reported that delaying initiation of adjuvant chemotherapy after surgery adversely affects patient oncologic outcome.^5,6,20 In our group, the proportion of patients who received adjuvant chemotherapy more than 8 weeks after surgery was extremely low (0.2%). Chan et al. reported that it took an average of 15 days from surgery to referral, 21 days from referral to medical oncology consultation, and 20 days from medical oncology consultation to initiation of chemotherapy.²¹ Patient expected recovery status with adjuvant chemotherapy might differ between surgeons and medical oncologists.¹⁰ The absence of referral time from surgeon to medical oncologist might explain the low rate of delayed chemotherapy in our group. However, this needs further evaluation in other clinical settings.

In this study, there are two distinctive points that deserve to be mentioned. First, as far as we know, in these previous studies comparing the TIC between laparoscopic and open surgery, medical oncologists determined the timing of start of adjuvant chemotherapy. In contrast, in our study, the surgeons decided the date of initiation of adjuvant chemotherapy. Although Strouch et al. insisted that chemotherapy performed by a medical oncologist could eliminate the surgeon bias with regard to initiation of chemotherapy,¹¹ it has not been clearly determined that surgeon bias actually impacts the start of adjuvant chemotherapy in comparison to medical oncologist. To start adjuvant chemotherapy after colon cancer resection, full patient recovery after the operation is the most important factor. Because surgeons understand the impact of the surgical procedure in more detail than the medical oncologists, it might be easier for them to estimate the patients' general condition. The strength of the present study is that all chemotherapies were determined by the operating surgeons, and the decision criterion for when to start adjuvant chemotherapy was not different among open, laparoscopic, and robotic surgeries. Second, our study included patients who underwent robotic surgery. As far as we know, the impact of robotic surgery on TIC has not yet been investigated. Under these circumstances, our results demonstrated that the robotic group and the laparoscopic group are associated with reduced time to adjuvant chemotherapy.

There were several limitations in this study. First, although the LOH was shorter in the laparoscopic group compared to the open or robotic group, a mean of 7.7 days of LOH is relatively longer than other results from Western studies.^9,22 This longer LOH, even in open and robotic surgeries, might be due to the specific socioeconomic background of South Koreans. Because the out-of-pocket cost of hospital stays is low in South Korea, few patients wish to be discharged early. In addition, an enhanced recovery program was not adopted during the study period. Second, the selection of surgery type was dependent on various factors such as surgeon's preference or patients' decision. However, the exact reason for selection of a specific type of surgery could not be identified in this retrospective study. There were also some differences in patient characteristics according to surgery type. To reduce the inherent bias among the groups, we conducted a multivariate analysis. Third, because this study was conducted at a single academic institution with a relatively small number of patients who underwent adjuvant chemotherapy performed by the operating surgeons, it is not clear that our results would be reproducible in the general population.

In summary, our study indicates that laparoscopic and robotic surgeries are associated with reduced TIC in the setting of chemotherapy decision determined by the operating surgeons. Further analysis is warranted to evaluate the impact of surgeon-oriented chemotherapy results in comparison to medical oncologist-oriented chemotherapy results.

Footnotes

Disclosure Statement

No competing financial interests exist.

References

Watanabe

, Itabashi

, Shimada

, et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2014 for treatment of colorectal cancer. Int J Clin Oncol, 2015; 20:207–239.

Schmoll

, Van Cutsem

, Stein

, et al. ESMO consensus guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Ann Oncol, 2012; 23:2479–2516.

Hershman

, Hall

, Wang

, et al. Timing of adjuvant chemotherapy initiation after surgery for stage III colon cancer. Cancer, 2006; 107:2581–2588.

Cheung

, Neville

, Earle

. Etiology of delays in the initiation of adjuvant chemotherapy and their impact on outcomes for Stage II and III rectal cancer. Dis Colon Rectum, 2009; 52:1054–1063; discussion 1064.

Bayraktar

, Chen

, Bayraktar

, et al. Does delay of adjuvant chemotherapy impact survival in patients with resected stage II and III colon adenocarcinoma?. Cancer, 2011; 117:2364–2370.

Des Guetz

, Nicolas

, Perret

, Morere

, Uzzan

. Does delaying adjuvant chemotherapy after curative surgery for colorectal cancer impair survival? A meta-analysis. Eur J Cancer, 2010; 46:1049–1055.

Veldkamp

, Kuhry

, Hop

, et al. Laparoscopic surgery versus open surgery for colon cancer: Short-term outcomes of a randomised trial. Lancet Oncol, 2005; 6:477–484.

Jayne

, Guillou

, Thorpe

, et al. Randomized trial of laparoscopic-assisted resection of colorectal carcinoma: 3-year results of the UK MRC CLASICC Trial Group. J Clin Oncol, 2007; 25:3061–3068.

COST. A comparison of laparoscopically assisted and open colectomy for colon cancer. N Engl J Med, 2004; 350:2050–2059.

10.

Poylin

, Curran

, Lee

, Nagle

. Laparoscopic colectomy decreases the time to administration of chemotherapy compared with open colectomy. Ann Surg Oncol, 2014; 21:3587–3591.

11.

Strouch

, Zhou

, Fleshman

, Birnbaum

, Hunt

, Mutch

. Time to initiation of postoperative chemotherapy: An outcome measure for patients undergoing laparoscopic resection for rectal cancer. Dis Colon Rectum, 2013; 56:945–951.

12.

Park

, Choi

, Park

, Kim

, Ryuk

. Randomized clinical trial of robot-assisted versus standard laparoscopic right colectomy. Br J Surg, 2012; 99:1219–1226.

13.

Luca

, Ghezzi

, Valvo

, et al. Surgical and pathological outcomes after right hemicolectomy: Case-matched study comparing robotic and open surgery. Int J Med Robot, 2011; 7:298–303.

14.

Lim

, Min

, Kim

, et al. Robotic versus laparoscopic anterior resection of sigmoid colon cancer: Comparative study of long-term oncologic outcomes. Surg Endosc, 2013; 27:1379–1385.

15.

deSouza

, Prasad

, Park

, Marecik

, Blumetti

, Abcarian

. Robotic assistance in right hemicolectomy: Is there a role?. Dis Colon Rectum, 2010; 53:1000–1006.

16.

Kennedy

, Francis

, Wharton

, et al. Multicenter randomized controlled trial of conventional versus laparoscopic surgery for colorectal cancer within an enhanced recovery programme: EnROL. J Clin Oncol, 2014; 32:1804–1811.

17.

Bartels

, Vlug

, Hollmann

, et al. Small bowel obstruction, incisional hernia and survival after laparoscopic and open colonic resection (LAFA study). Br J Surg, 2014; 101:1153–1159.

18.

Burns

, Currie

, Bottle

, Aylin

, Darzi

, Faiz

. Minimal-access colorectal surgery is associated with fewer adhesion-related admissions than open surgery. Br J Surg, 2013; 100:152–159.

19.

Malietzis

, Mughal

, Currie

, et al. Factors implicated for delay of adjuvant chemotherapy in colorectal cancer: A meta-analysis of observational studies. Ann Surg Oncol, 2015; 22:3793–3802.

20.

Tevis

, Kohlnhofer

, Stringfield

, et al. Postoperative complications in patients with rectal cancer are associated with delays in chemotherapy that lead to worse disease-free and overall survival. Dis Colon Rectum, 2013; 56:1339–1348.

21.

Chan

, Woods

, Kennecke

, Gill

. Factors associated with delayed time to adjuvant chemotherapy in stage iii colon cancer. Curr Oncol, 2014; 21:181–186.

22.

King

, Blazeby

, Ewings

, et al. Randomized clinical trial comparing laparoscopic and open surgery for colorectal cancer within an enhanced recovery programme. Br J Surg, 2006; 93:300–308.