Colorectal Endoscopic Stenting Trial (CReST) for Obstructing Left-sided Colorectal Cancer: Randomized Clinical Trial

Incomplete

J Hill. "Colorectal Endoscopic Stenting Trial (CReST) for Obstructing Left-sided Colorectal Cancer: Randomized Clinical Trial". Br J Surg. Oct 14;(11). doi: 10.1093/bjs/znac141. PMID:.. 2022. 109(11):1073-1080.
PubMed • Full text • PDF

Clinical Question

Among patients presenting with malignant left sided bowel obstructions, does stent placement as a bridge to surgery reduce mortality, morbidity, or quality of life compared to emergency surgical intervention?

Bottom Line

Stenting is safe option to temporize patients to with left-sided malignant bowel obstructiosn. Stenting decreases rates of stoma creation.

Major Points

This study sought to elucidate whether obstructing left sided colon cancers treated with stenting as a bridge to surgery reduced morbidity or mortailty compared to surgery alone. Although this study did not show a difference in its primary endpoints of 30 day mortality nor 1 year length of stay, the investigators demonstrated a high stenting success rate (86%) and reduced rates of stoma creation in those undergoing surgery for curative intent (47% stenting vs. 72% surgery). Stent specific perforation rates were low (3.3%).

This study is in line with previous work demonstrating more frequent primary anastomosis and decreased morbidity in a stent first approach. Previous studies have also demonstrated a 30 day mortality difference. , reduction in 60 day morbidity, reduced ostomy rate, and increased rates of primary anastomosis. Stenting in this clinical scenario have also been shown to reduce permanent ostomy rates.

Expert guidelines agree the choice of endoscopic stenting should be individualized depending on local and regional surgical, radiologic, and endoscopic expertise. A national population-based cohort study of obstructing left sided colon cancers comparing endoscopic stenting to primary diverting stoma indicated stenting associated with reduced rates of laparoscopic resection, fewer primary anastomosis, reduced 90 day and 3 year survival.

Guidelines

2022 The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Colon Cancer

• Endoscopic stent or fecal diversion is preferable to colectomy when life expectancy is < 1 year. (Grade 1B recommendation)
• Curable left-sided colon cancer presenting with emergency obstruction can be managed with endoscopic stent decompression, diverting colostomy with interval colectomy, or initial treatment with oncological segmental colectomy. The choice should be individualized based upon patient factors and local expertise of the institution. Grade 1B.

Design

• Setting: in 39 UK hospitals from April 2009 and December 2014
• Randomized control trial, nonblinded
• Enrollment: N=245, 123 stenting, 122 emergency surgery
•  1:1 allocation of participants to 2 groups: stenting or surgical decompression with or without resection of tumor.
  • 739 patients screened for trial
• 245 patients allocated
  • 123 for stenting
  • 122 for emergency surgery
• April 2009 — December 2014
• Follow-up: 6 month in interval group
• Analysis: intention-to-treat
• 90% power to detect a 0.35 standard deviation reduction in time spent in hospital, equivalent to 1-2 days, 90% power to detect difference in mortality (estimated 16% following emergency general surgery, 4% following elective surgery)
• Primary outcome: Coprimary outcomes of 30-day mortality and duration of hospital stay during the first year

Population

Inclusion Criteria

• Age >= 18 years old
• Left sided colon obstruction secondary to colonic malignancy
• Candidate for emergency surgery

  • 217 /245, deemed curative
    • 110 stenting
    • 107 surgery
• Balanced for curative intent, tumor location within colon, and APACHE score

Exclusion Criteria

• Peritonitis
• Perforation
• Obstruction in mid/low rectum necessitating neoadjuvant chemotherapy

Baseline Characteristics

• Stenting (n = 123)
• Age (years)
  • < 50: 7 (5.7%)
  • 50-59: 16 (13%)
  • 60-69: 30 (24.4%)
  • 70-79: 39 (31.7%)
  • 80+: 31 (25.2%)
  • Mean (s.d.): 69.5 (10.4)
  • Median (IQR; range): 71 (61–81; 34–93)
• Sex
  • F: 51 (41.5%)
  • M: 72 (58.5%)
• Tumour site
  • Transverse colon: 3 (2.4%)
  • Splenic flexure: 5 (4.1%)
  • Descending colon: 13 (10.6%)
  • Sigmoid: 68 (55.3%)
  • Rectosigmoid: 28 (22.8%)
  • Rectum: 6 (4.9%)
• Treatment type
  • Potentially curative: 110 (89.4%)
  • Probably curative: 0
  • Possibly curative: 0
  • Palliative: 13 (10.6%)
• APACHE score
  • 1: 23
  • 2: 41
  • 3: 29
  • 4: 18
  • 5: 4
  • 6: 1
  • Unknown: 7
  • Median (IQR): 6 (5–8)
• ASA grade
  • P1 (normal healthy patient): 23 (18.7%)
  • P2 (mild systemic disease): 79 (64.2%)
  • P3 (severe systemic disease): 21 (17.1%)

• Emergency surgery (n = 122)
• Age (years)
  • < 50: 7 (5.7%)
  • 50-59: 11 (9.0%)
  • 60-69: 32 (26.2%)
  • 70-79: 43 (35.2%)
  • 80+: 29 (23.8%)
  • Mean (s.d.): 68.8 (10.2%)
  • Median (IQR; range): 70 (62–76; 36–89)
• Sex
  • F: 45 (36.9%)
  • M: 77 (63.1%)
• Tumour site
  • Transverse colon: 3 (2.5%)
  • Splenic flexure: 5 (4.1%)
  • Descending colon: 13 (10.7%)
  • Sigmoid: 64 (52.5%)
  • Rectosigmoid: 28 (23.0%)
  • Rectum: 9 (7.4%)
• Treatment type
  • Potentially curative: 107 (87.7%)
  • Probably curative: 0
  • Possibly curative: 0
  • Palliative: 15 (12.3%)
• APACHE score
  • 1: 22
  • 2: 33
  • 3: 35
  • 4: 16
  • 5: 8
  • 6: 1
  • Unknown: 7
  • Median (IQR): 7 (5–8)
• ASA grade
  • P1 (normal healthy patient): 27 (22.1%)
  • P2 (mild systemic disease): 75 (61.5%)
  • P3 (severe systemic disease): 20 (16.4%)

• Total (n = 245)
• Age (years)
  • < 50: 14 (5.7%)
  • 50-59: 27 (11.0%)
  • 60-69: 62 (25.3%)
  • 70-79: 82 (33.5%)
  • 80+: 60 (24.5%)
  • Mean (s.d.): 69.1 (10.3%)
  • Median (IQR; range): 71 (61–78; 34–93)
• Sex
  • F: 96 (39.2%)
  • M: 149 (60.8%)
• Tumour site
  • Transverse colon: 7 (2.9%)
  • Splenic flexure: 10 (4.1%)
  • Descending colon: 26 (10.6%)
  • Sigmoid: 132 (53.9%)
  • Rectosigmoid: 56 (22.9%)
  • Rectum: 15 (6.1%)
• Treatment type
  • Potentially curative: 217 (88.6%)
  • Probably curative: 0
  • Possibly curative: 0
  • Palliative: 28 (11.4%)
• APACHE score
  • 1: 45
  • 2: 74
  • 3: 64
  • 4: 34
  • 5: 12
  • 6: 2
  • Unknown: 14
  • Median (IQR): 6.5 (5–8)
• ASA grade
  • P1 (normal healthy patient): 50 (20.4%)
  • P2 (mild systemic disease): 154 (62.9%)
  • P3 (severe systemic disease): 41 (16.7%)

• 25 patients (7 stent, 16 surgery) were found not to have cancer

Interventions

• Before the randomization period, 5 stenting workshops were held for the participating units, minimum of 30 stents placed for obstructing cancers required for unit to participate.
• 123 individuals randomized to receive stenting +/- elective surgery for tumor resection 
* 110 of these 123 were patients who were deemed potentially curable and 13 deemed 
palliative 
* Stenting attempted in 119 of 123 of allocated patients
  • achieved relief of obstruction 98/119 (82.4%)
  •  86/110 in the curative group
  • 12/13 in the palliative group 
* 24/110 in curative group failed/did not attempt stenting 
*99/110 in the curative group went on to have some form of surgery

Potentially curative Stenting (n = 110)

• Intraoperative forms received
  • Patients who had surgery: 99

• Tumour site
  • Transverse colon: 2
  • Splenic flexure: 1
  • Descending colon: 3
  • Sigmoid: 56
  • Rectosigmoid: 28
  • Rectum: 10
  • Missing: 0

• Perforation present
  • Stent site: 10 (9.1%)
  • Other: 0
  • Cancer: 5

• Resection performed
  • Overall: 93 of 110 (84.5%)
  • Patients who had surgery: 93 of 99 (93.0%)
  • Panproctocolectomy: 3
  • Total colectomy: 8
  • Extended right hemicolectomy: 3
  • Right hemicolectomy: 2
  • Left hemicolectomy: 1
  • Subtotal/segmental colectomy: 27
  • Sigmoid colectomy: 13
  • Hartmann’s procedure: 22
  • Anterior resection: 14
  • Other: 0

• Stoma field
  • Patients who had surgery: 47 of 110 (42.7%)
  • Patients who had surgery (stoma type): 47 of 99 (47.5%)
  • End: 38
  • Loop: 9
  • Unknown: 0

• Assessment of resection
  • Patients who had surgery: 68
  • R0: 61
  • R1: 7
  • R2: 0
  • Unknown: 0
  • Missing: 5

• Transferred to critical care
  • HDU: 34 of 99 (34.3%)
  • ICU: 4 of 99 (4.0%)
  • Unknown: 2

• Any metastases
  • Liver: 18 of 99 (18.2%)
  • Peritoneum: 2
  • Lung: 4
  • Lymph nodes: 2
  • Other: 1

Surgery (n = 107)

• Intraoperative forms received
  • Patients who had surgery: 106

• Tumour site
  • Transverse colon: 4
  • Splenic flexure: 3
  • Descending colon: 9
  • Sigmoid: 54
  • Rectosigmoid: 26
  • Rectum: 10
  • Missing: 0

• Perforation present
  • Stent site: 1
  • Other: 6
  • Cancer: 8

• Resection performed
  • Overall: 101 of 107 (86.9%)
  • Patients who had surgery: 106 of 106 (87.7%)
  • Panproctocolectomy: 0
  • Total colectomy: 6
  • Extended right hemicolectomy: 6
  • Right hemicolectomy: 2
  • Left hemicolectomy: 3
  • Subtotal/segmental colectomy: 22
  • Sigmoid colectomy: 17
  • Hartmann’s procedure: 25
  • Anterior resection: 21
  • Other: 4

• Stoma field
  • Patients who had surgery: 72 of 107 (67.3%)
  • Patients who had surgery (stoma type): 72 of 106 (67.9%)
  • End: 63
  • Loop: 9
  • Unknown: 0

• Assessment of resection
  • Patients who had surgery: 81
  • R0: 73
  • R1: 7
  • R2: 1
  • Unknown: 0
  • Missing: 8

• Transferred to critical care
  • HDU: 36 of 106 (34.0%)
  • ICU: 3 of 106 (2.8%)
  • Unknown: 3

• Any metastases
  • Liver: 19 of 107 (17.8%)
  • Peritoneum: 4
  • Lung: 7
  • Lymph nodes: 2
  • Other: 1

Palliative Stenting (n = 13)

• Intraoperative forms received
  • Patients who had surgery: 13

• Tumour site
  • Transverse colon: 0
  • Splenic flexure: 0
  • Descending colon: 2
  • Sigmoid: 6
  • Rectosigmoid: 3
  • Rectum: 2
  • Missing: 0

• Perforation present
  • Stent site: 0
  • Other: 1
  • Cancer: 0

• Resection performed
  • Overall: 2 of 13 (15.4%)
  • Patients who had surgery: 2 of 4 (50.0%)
  • Panproctocolectomy: 0
  • Total colectomy: 0
  • Extended right hemicolectomy: 0
  • Right hemicolectomy: 0
  • Left hemicolectomy: 0
  • Subtotal/segmental colectomy: 0
  • Sigmoid colectomy: 0
  • Hartmann’s procedure: 0
  • Anterior resection: 0
  • Other: 2

• Stoma field
  • Patients who had surgery: 3 of 13 (23.1%)
  • Patients who had surgery (stoma type): 3 of 4 (75.0%)
  • End: 3
  • Loop: 0
  • Unknown: 0

• Assessment of resection
  • Patients who had surgery: 4
  • R0: 0
  • R1: 0
  • R2: 0
  • Unknown: 0
  • Missing: 0

• Transferred to critical care
  • HDU: 2 of 4 (50.0%)
  • ICU: 0 of 4 (0.0%)
  • Unknown: 0

• Any metastases
  • Liver: 0 of 13 (0.0%)
  • Peritoneum: 0
  • Lung: 1
  • Lymph nodes: 0
  • Other: 0

Surgery (n = 15)

• Intraoperative forms received
  • Patients who had surgery: 15

• Tumour site
  • Transverse colon: 0
  • Splenic flexure: 0
  • Descending colon: 0
  • Sigmoid: 8
  • Rectosigmoid: 5
  • Rectum: 2
  • Missing: 0

• Perforation present
  • Stent site: 0
  • Other: 4
  • Cancer: 0

• Resection performed
  • Overall: 10 of 15 (66.7%)
  • Patients who had surgery: 10 of 13 (76.9%)
  • Panproctocolectomy: 0
  • Total colectomy: 0
  • Extended right hemicolectomy: 0
  • Right hemicolectomy: 1
  • Left hemicolectomy: 0
  • Subtotal/segmental colectomy: 1
  • Sigmoid colectomy: 1
  • Hartmann’s procedure: 4
  • Anterior resection: 2
  • Other: 2

• Stoma field
  • Patients who had surgery: 10 of 15 (66.7%)
  • Patients who had surgery (stoma type): 10 of 13 (76.9%)
  • End: 8
  • Loop: 2
  • Unknown: 0

• Assessment of resection
  • Patients who had surgery: 13
  • R0: 1
  • R1: 0
  • R2: 0
  • Unknown: 0
  • Missing: 0

• Transferred to critical care
  • HDU: 4 of 13 (30.8%)
  • ICU: 0 of 13 (0.0%)
  • Unknown: 0

• Any metastases
  • Liver: 5 of 15 (33.3%)
  • Peritoneum: 0
  • Lung: 1
  • Lymph nodes: 0
  • Other: 0

Outcomes

Comparisons are Stenting with Interval Surgery vs. Surgery.’’

Primary Outcomes

30-day Mortality

4 (3.6%) vs. 6 (5.6%) (HR 0.63, 95% CI 0.18 — 2.25, P= 0.48)

Hospital Length of Stay

19 days (IQR 11 — 34) vs. 18 (IQR 10 — 28)(RR 1.01, 95% CI 0.75 — 1.37, P = 0.94)

• (IQR = interquartile ratio)

Secondary Outcomes

Stoma formation at initial time of surgery

49/99 (47.5%) vs. 72/106 (67.9%); (P=0.003)

Stenting Completion

98/119 (82%) stent success rate

Clavien-Dindo III or Worse Complications

22 (17.9%) vs. 27 (22.1%); P = NS (not presented)

6 month survival

14/110 (12.7%) vs. 10/107 (9.3%)(HR 1.32, 95% CI 0.58 — 2.96, P=0.51)

3 year recurrence

47/110 (42%) vs. 36/107 (33%)(HR 1.24, 95% CI 0.80 — 1.91, P=0.34)

Adherence to chemotherapy (Chemotherapy ever)

54/116 (46%) vs. 44/106 (41%), P = 0.68

Quality of life analysis

Not significant at 3 or 12 months, no analysis presented

Subgroup Analysis

• None

Adverse Events

• Stenting complications reported for 98 patients in whom stenting relieved the obstruction

Immediate (< 24 h)

• Patients experiencing any complication: 5 of 98 (5.1%)

• Perforation: 1 (1.0%)

• Haemorrhage: 0 (0%)

• Infection: 0 (0%)

• Respiratory depression: 0 (0%)

• Hypotension: 0 (0%)

• Migration: 3 (3.1%)

• Reobstruction: 0 (0%)
• Any degree of sensation: 0 (0%)
• Other: 1 (1.0%)

Intermediate (1–7 days)

• Patients experiencing any complication: 12 of 97 (12.4%)

• Perforation: 2 (2.1%)
• Haemorrhage: 0 (0%)

• Infection: 4 (4.1%)

• Respiratory depression: 1 (1.0%)

• Hypotension: 0 (0%)

• Migration: 0 (0%)

• Reobstruction: 4 (4.1%)

• Any degree of sensation: 0 (0%)
• Other: 2 (2.1%)

Late (7–28 days)

• Patients experiencing any complication: 17 of 97 (17.5%)

• Perforation: 1 (1.0%)
• Haemorrhage: 0 (0%)

• Infection: 1 (1.0%)

• Respiratory depression: 0 (0%)

• Hypotension: 0 (0%)

• Migration: 0 (0%)

• Reobstruction: 3 (3.1%)

• Any degree of sensation: 10 (10.3%)

• Other: 2 (2.1%)

Criticisms

• Despite the purported benefit of reduced stoma creation, there was no difference in quality of life between the stenting and surgery groups
• Significant resources invested in training stenting endoscopists may not be translatable to community practice

Funding

• Funded by Cancer Research UK, no conflicts of interest