Ann Surg Oncol DOI 10.1245/s10434-014-3703-9
ORIGINAL ARTICLE – COLORECTAL CANCER
Laparoscopic Colectomy Decreases the Time to Administration of Chemotherapy Compared with Open Colectomy Vitaliy Poylin, MD, Thomas Curran, MD, Eliza Lee, MD, and Deborah Nagle, MD Colon & Rectal Surgery, Beth Israel Deaconess Medical Center, Boston, MA
ABSTRACT Background. Minimally invasive colon surgery (MIS) has been shown to minimize pain and decrease overall recovery time. No studies have shown a clear oncologic benefit. Some literature suggests that the time to administration of chemotherapy can be important to improve outcomes for advanced colon cancer. The goal of this study is to evaluate the effect of minimally invasive surgery on the timing of chemotherapy administration. Methods. This was a retrospective review of all patients undergoing surgery for colon cancer at a tertiary institution between 2004 and 2013. Results. A total of 668 partial colectomies for cancer were performed; 241 were stage III and above and deemed appropriate for chemotherapy. Eighty-five patients did not receive chemotherapy (patient’s wishes, age/comorbidities or lost to follow-up). Of the 156 patients who received chemotherapy, 57 underwent MIS and 99 had open colectomy. Average time to chemotherapy after MIS colectomy was 42.9 versus 60.3 days for open surgery (p \ 0.001). In the open group, 52 (53 %) people had postoperative complications and readmissions versus 24 (39 %) in the MIS group. Postoperative complications increased the time to chemotherapy for all patients. However, among patients with complications, patients in the MIS group were still able to start chemotherapy earlier (p \ 0.05) than open colectomy patients. Multivariate analysis revealed the MIS approach as the only factor lowering time between surgery and chemotherapy. Conclusions. Laparoscopic colectomy decreases the time interval from surgery to the start of chemotherapy compared with open colectomy. Postoperative complications
Ó Society of Surgical Oncology 2014 First Received: 16 August 2013 V. Poylin, MD e-mail: [email protected]
increase the time to chemotherapy for both open and MIS surgery.
The administration of chemotherapy (adjuvant for stage III and palliative for stage IV) has been shown to improve both overall and disease-free survival after surgery for stage III and IV colon cancer.1–13 Chemotherapy treats macroscopic and microscopic residual disease after surgical resection. It is generally accepted that chemotherapy should start within 12 weeks of the completion of surgery. This practice is based on clinical studies showing poorer outcomes in patients who had chemotherapy delayed for more than 12 weeks after surgery.1–8 A cutoff beyond which adjuvant treatment has no value has not yet been established. Data suggests that an earlier start of adjuvant treatment may be beneficial, but the exact relationship between the timing of initiation of treatment and outcomes is still being debated.2,5,9,14 Postoperative complications such as superficial and deep infection and comorbidities have been shown to significantly delay timing to initiation of chemotherapy.5,9 Laparoscopic surgery has been shown to be as safe and effective for the treatment of colon cancer as open surgery.15–18 Laparoscopic colectomy has been shown to expedite patient recovery and return to work.11 Laparoscopic surgery has also been shown to significantly decrease the incidence of some postoperative complications such as infection, incisional hernia, and intestinal obstruction. Finally, animal studies have shown that laparoscopic surgery reduces the inflammatory response associated with surgery, which may contribute to activation and acceleration of micrometastasis.12 The effect of laparoscopic colectomy on the time to initiation of adjuvant chemotherapy administration has not been studied. We hypothesize that laparoscopic colectomy may lead to significantly earlier commencement of chemotherapy.
V. Poylin et al.
MATERIAL AND METHODS This is a retrospective review of a prospectively collected database of all patients undergoing colon surgery between 2004 and 2013 at the Beth Israel Deaconess Medical Center (BIDMC). This study was approved by the Dana Farber Institutional Review Board (IRB) [protocol #13-292]. Patients operated on for primary colon cancer (diagnosed both pre- and postoperatively) were identified from our BIDMC IRB-approved RedCap database. Patients with stage I and II colon cancer and rectal cancer, and patients for whom adequate follow-up was not available, were excluded (lost to follow-up, received treatment elsewhere without clear data on when chemotherapy was initiated). Demographic data, comorbidities, surgical details, postoperative complications, treatment start time, and carcinoembryonic antigen (CEA) levels were identified via the BIDMC online medical record (OMR). The minimally invasive surgery (MIS) group was defined as colectomy cases having a major portion of the procedure done laparoscopically (multi-port, single-port or robotic) or hand-assisted (laparoscopic mobilization with open division of mesentery and/or bowel). All statistical analyses were conducted using IBM SPSS version 20.0 for Macintosh (IBM Corp., Armonk, NY, USA). Two-sided Student’s t test, Chi-square or Fisher’s exact test were used to compare groups as appropriate. Univariate Cox regression was carried out for all possible predictors of time to chemotherapy. Those factors with a p value B 0.05 on univariate Cox regression analysis were entered into a multivariable Cox proportional hazard model with backward stepwise selection to determine independent predictors of time to chemotherapy as indicated by p B 0.05. Final model parameters included age, postoperative complication occurrence, and use of a minimally invasive surgical approach. Throughout all analyses, statistical significance was determined by a criterion of p B 0.05.
TABLE 1 Patient demographic characteristics and tumor stage MIS
Open
p value
Age (years)
59.4 ? 14.5
61.5 ? 12.4
NS
Male [n (%)]
27 (47)
44 (44)
NS
TNM stage II
2 (4)
9 (9)
\0.05
III
51 (87)
56 (56)
\0.05
IV
4 (9)
34 (34)
\0.05
2.25
2.34
NS
ASA class
MIS minimally invasive surgery, NS not significant, ASA American Society of Anesthesiologists
There was no statistical significance between the MIS and open surgery groups with respect to rates of receiving chemotherapy. Over the study inclusion period, rates of MIS increased. However, groups were significantly underpowered to perform a full analysis and to reach reliable conclusions on whether time to chemotherapy shortened as rates of MIS approach increased. Patients with stage IV disease underwent surgery for the control of local symptoms such as bleeding or obstruction (symptomatic or impending), prior to initiation of planned chemotherapy or metastatic disease being discovered at the time of surgery. Patient Demographics Both groups were similar in age, sex, and American Society of Anesthesiologists (ASA) class (Table 1). Distribution of stages between the open and MIS groups was similar. The proportion of patients undergoing right versus left colectomy was also similar between groups. Left colectomies were 51 % in the MIS group versus 42 % in the open group (p = 0.083). Rates of diabetes mellitus (11 vs. 17 %), coronary artery disease (4 vs. 10 %), congestive heart failure (4 vs. 5 %) and chronic obstructive pulmonary disease (5 % each) were also similar between the MIS and open groups (all p [ 0.05).
RESULTS Postoperative Outcomes A total of 668 patients underwent partial colectomy for cancer between 2004 and 2011; 427 patients had stage II or lower and were excluded. The exceptions were nine patients with stage II disease in the open group and two patients in the MIS group who received chemotherapy due to high-risk lesions. Of the 241 patients deemed appropriate for chemotherapy (stage III and IV), 85 were excluded (40 patients were lost to follow-up and 45 did not receive chemotherapy due to either the patient’s wishes or comorbidities). Of the 156 patients who received chemotherapy, 57 underwent MIS and 99 had an open procedure.
The average length of postoperative hospital stay was lower for the MIS group when compared with the open group (3.9 vs. 6.8 days; p \ 0.001). Complications were seen in 22 patients (39 %) in the MIS group compared with 52 patients (53 %) in the open group (not statistically significant; Table 2). However, only rates of postoperative atrial fibrillation were significantly higher in the open group (7 vs. 0 % in the MIS group). Rates of ileus and anastomotic leak were equivalent between the groups. Readmission rates were relatively high (18 % for the MIS
Laparoscopic Colectomy Decreases Time to Chemo
Overall
Open
Wound infection
25 (16)
19 (19)
UTI
15 (10)
Ileus
34 (22) 4 (3)
DVT/PE
MIS
p value
6 (11)
0.180
12 (12)
3 (5)
0.259
23 (23)
11 (19)
0.688
3 (3)
1 (2)
1.00
Anastomotic leak
4 (3)
2 (2)
2 (4)
0.623
Return to OR
5 (3)
4 (4)
1 (2)
0.653
Readmission Dysrhythmia
21 (14) 7 (5)
11 (11) 7 (7)
10 (18) 0 (0)
0.330 0.047
MIS minimally invasive surgery, UTI urinary tract infection, DVT/PE deep vein thrombosis/pulmonary embolism
80
Time to chemotherapy, days
TABLE 2 Postoperative complications between the MIS and open groups [n (%)]
70 60
60.3
* p
ORIGINAL ARTICLE – COLORECTAL CANCER
Laparoscopic Colectomy Decreases the Time to Administration of Chemotherapy Compared with Open Colectomy Vitaliy Poylin, MD, Thomas Curran, MD, Eliza Lee, MD, and Deborah Nagle, MD Colon & Rectal Surgery, Beth Israel Deaconess Medical Center, Boston, MA
ABSTRACT Background. Minimally invasive colon surgery (MIS) has been shown to minimize pain and decrease overall recovery time. No studies have shown a clear oncologic benefit. Some literature suggests that the time to administration of chemotherapy can be important to improve outcomes for advanced colon cancer. The goal of this study is to evaluate the effect of minimally invasive surgery on the timing of chemotherapy administration. Methods. This was a retrospective review of all patients undergoing surgery for colon cancer at a tertiary institution between 2004 and 2013. Results. A total of 668 partial colectomies for cancer were performed; 241 were stage III and above and deemed appropriate for chemotherapy. Eighty-five patients did not receive chemotherapy (patient’s wishes, age/comorbidities or lost to follow-up). Of the 156 patients who received chemotherapy, 57 underwent MIS and 99 had open colectomy. Average time to chemotherapy after MIS colectomy was 42.9 versus 60.3 days for open surgery (p \ 0.001). In the open group, 52 (53 %) people had postoperative complications and readmissions versus 24 (39 %) in the MIS group. Postoperative complications increased the time to chemotherapy for all patients. However, among patients with complications, patients in the MIS group were still able to start chemotherapy earlier (p \ 0.05) than open colectomy patients. Multivariate analysis revealed the MIS approach as the only factor lowering time between surgery and chemotherapy. Conclusions. Laparoscopic colectomy decreases the time interval from surgery to the start of chemotherapy compared with open colectomy. Postoperative complications
Ó Society of Surgical Oncology 2014 First Received: 16 August 2013 V. Poylin, MD e-mail: [email protected]
increase the time to chemotherapy for both open and MIS surgery.
The administration of chemotherapy (adjuvant for stage III and palliative for stage IV) has been shown to improve both overall and disease-free survival after surgery for stage III and IV colon cancer.1–13 Chemotherapy treats macroscopic and microscopic residual disease after surgical resection. It is generally accepted that chemotherapy should start within 12 weeks of the completion of surgery. This practice is based on clinical studies showing poorer outcomes in patients who had chemotherapy delayed for more than 12 weeks after surgery.1–8 A cutoff beyond which adjuvant treatment has no value has not yet been established. Data suggests that an earlier start of adjuvant treatment may be beneficial, but the exact relationship between the timing of initiation of treatment and outcomes is still being debated.2,5,9,14 Postoperative complications such as superficial and deep infection and comorbidities have been shown to significantly delay timing to initiation of chemotherapy.5,9 Laparoscopic surgery has been shown to be as safe and effective for the treatment of colon cancer as open surgery.15–18 Laparoscopic colectomy has been shown to expedite patient recovery and return to work.11 Laparoscopic surgery has also been shown to significantly decrease the incidence of some postoperative complications such as infection, incisional hernia, and intestinal obstruction. Finally, animal studies have shown that laparoscopic surgery reduces the inflammatory response associated with surgery, which may contribute to activation and acceleration of micrometastasis.12 The effect of laparoscopic colectomy on the time to initiation of adjuvant chemotherapy administration has not been studied. We hypothesize that laparoscopic colectomy may lead to significantly earlier commencement of chemotherapy.
V. Poylin et al.
MATERIAL AND METHODS This is a retrospective review of a prospectively collected database of all patients undergoing colon surgery between 2004 and 2013 at the Beth Israel Deaconess Medical Center (BIDMC). This study was approved by the Dana Farber Institutional Review Board (IRB) [protocol #13-292]. Patients operated on for primary colon cancer (diagnosed both pre- and postoperatively) were identified from our BIDMC IRB-approved RedCap database. Patients with stage I and II colon cancer and rectal cancer, and patients for whom adequate follow-up was not available, were excluded (lost to follow-up, received treatment elsewhere without clear data on when chemotherapy was initiated). Demographic data, comorbidities, surgical details, postoperative complications, treatment start time, and carcinoembryonic antigen (CEA) levels were identified via the BIDMC online medical record (OMR). The minimally invasive surgery (MIS) group was defined as colectomy cases having a major portion of the procedure done laparoscopically (multi-port, single-port or robotic) or hand-assisted (laparoscopic mobilization with open division of mesentery and/or bowel). All statistical analyses were conducted using IBM SPSS version 20.0 for Macintosh (IBM Corp., Armonk, NY, USA). Two-sided Student’s t test, Chi-square or Fisher’s exact test were used to compare groups as appropriate. Univariate Cox regression was carried out for all possible predictors of time to chemotherapy. Those factors with a p value B 0.05 on univariate Cox regression analysis were entered into a multivariable Cox proportional hazard model with backward stepwise selection to determine independent predictors of time to chemotherapy as indicated by p B 0.05. Final model parameters included age, postoperative complication occurrence, and use of a minimally invasive surgical approach. Throughout all analyses, statistical significance was determined by a criterion of p B 0.05.
TABLE 1 Patient demographic characteristics and tumor stage MIS
Open
p value
Age (years)
59.4 ? 14.5
61.5 ? 12.4
NS
Male [n (%)]
27 (47)
44 (44)
NS
TNM stage II
2 (4)
9 (9)
\0.05
III
51 (87)
56 (56)
\0.05
IV
4 (9)
34 (34)
\0.05
2.25
2.34
NS
ASA class
MIS minimally invasive surgery, NS not significant, ASA American Society of Anesthesiologists
There was no statistical significance between the MIS and open surgery groups with respect to rates of receiving chemotherapy. Over the study inclusion period, rates of MIS increased. However, groups were significantly underpowered to perform a full analysis and to reach reliable conclusions on whether time to chemotherapy shortened as rates of MIS approach increased. Patients with stage IV disease underwent surgery for the control of local symptoms such as bleeding or obstruction (symptomatic or impending), prior to initiation of planned chemotherapy or metastatic disease being discovered at the time of surgery. Patient Demographics Both groups were similar in age, sex, and American Society of Anesthesiologists (ASA) class (Table 1). Distribution of stages between the open and MIS groups was similar. The proportion of patients undergoing right versus left colectomy was also similar between groups. Left colectomies were 51 % in the MIS group versus 42 % in the open group (p = 0.083). Rates of diabetes mellitus (11 vs. 17 %), coronary artery disease (4 vs. 10 %), congestive heart failure (4 vs. 5 %) and chronic obstructive pulmonary disease (5 % each) were also similar between the MIS and open groups (all p [ 0.05).
RESULTS Postoperative Outcomes A total of 668 patients underwent partial colectomy for cancer between 2004 and 2011; 427 patients had stage II or lower and were excluded. The exceptions were nine patients with stage II disease in the open group and two patients in the MIS group who received chemotherapy due to high-risk lesions. Of the 241 patients deemed appropriate for chemotherapy (stage III and IV), 85 were excluded (40 patients were lost to follow-up and 45 did not receive chemotherapy due to either the patient’s wishes or comorbidities). Of the 156 patients who received chemotherapy, 57 underwent MIS and 99 had an open procedure.
The average length of postoperative hospital stay was lower for the MIS group when compared with the open group (3.9 vs. 6.8 days; p \ 0.001). Complications were seen in 22 patients (39 %) in the MIS group compared with 52 patients (53 %) in the open group (not statistically significant; Table 2). However, only rates of postoperative atrial fibrillation were significantly higher in the open group (7 vs. 0 % in the MIS group). Rates of ileus and anastomotic leak were equivalent between the groups. Readmission rates were relatively high (18 % for the MIS
Laparoscopic Colectomy Decreases Time to Chemo
Overall
Open
Wound infection
25 (16)
19 (19)
UTI
15 (10)
Ileus
34 (22) 4 (3)
DVT/PE
MIS
p value
6 (11)
0.180
12 (12)
3 (5)
0.259
23 (23)
11 (19)
0.688
3 (3)
1 (2)
1.00
Anastomotic leak
4 (3)
2 (2)
2 (4)
0.623
Return to OR
5 (3)
4 (4)
1 (2)
0.653
Readmission Dysrhythmia
21 (14) 7 (5)
11 (11) 7 (7)
10 (18) 0 (0)
0.330 0.047
MIS minimally invasive surgery, UTI urinary tract infection, DVT/PE deep vein thrombosis/pulmonary embolism
80
Time to chemotherapy, days
TABLE 2 Postoperative complications between the MIS and open groups [n (%)]
70 60
60.3
* p
