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The CEAwatch multicenter randomized trial examined different frequencies of
CEA serum testing after curative surgery for colorectal cancer, and if CEA rose
twice consecutively, used this to trigger cross-sectional imaging. From 2010 to
2012, 3223 patients were included. More frequent CEA testing found recurrences
sooner (HR 1.45, 95% CI 1.08–1.95, p=0.013); this also led to higher rates of curative treatment (OR 3.12, 95% CI 1.25–6.02, p=0.0145) [8]. However, there were
no differences in overall survival or cancer specic survival with the intensive surveillance regimen (HR 0.73, 95% CI 0.46–1.17; HR 0.78, 95% CI 0.48–1.28,
respectively). The more intensive regimen tended to nd recurrences before they
were symptomatic, and this was associated with better survival than when subjects
developed symptoms from their recurrence (HR 0.39, 95% CI 0.25–0.63) [9].
Patients did not report adverse psychological effects associated with more intense
follow up [10].
An updated Cochrane review published in 2019 collated data on surveillance
strategies for non-metastatic colorectal cancer [11]. There were 19 studies with
13,216 subjects included, and meta-analysis was performed using data from 16 of
the studies. As seen with the individual trial discussed above, there was no difference in overall survival or colorectal cancer specic survival with intensive follow
up regimen. Symptomatic recurrences were less frequent with intensive surveillance, and salvage surgery for recurrence was more frequent as well. When colonoscopy is part of surveillance, this can lead to more complications from bleeding or
perforation. Intensive surveillance did not have a measurable effect on quality of
life, anxiety, or depression. Cost may be increased with more intensive follow up
[11]. Table12.2 summarizes the results of these trials and meta-analyses.
An updated Cochrane review examined the role of serum CEA levels in detecting
colorectal cancer [12]. This review focused on the pooled sensitivity and sensitivity
of different cutoff values for CEA for detecting colorectal cancer recurrence. They
concluded that CEA was insufciently sensitive or specic to be used alone, even
with low cutoff values, for surveillance. Additionally, 20% of recurrences showed
no increase in CEA [12].
12 Is Intensive Surveillance Necessary After Curative Resection forColon Cancer?
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Moderate
Quality of
evidence
Outcomes of intensive
regimen
Variable -reduced overall
mortality
-no difference in cancer
specic mortality
-early detection
-more asymptomatic
Moderate
recurrence detection
-more amenable to
surgery
-better chance of
curative resection
Recurrence found 5.9
Ofce visit and CEA q 4
mo earlier
No difference in overall
or disease free survival
Similar HQoL
mo
Colonoscopy at year 1
and 2
-liver u/s at 4months and
Moderate
Similar OS and CSS
Higher rates of surgery
with curative intent for
recurrence
No scheduled follow up
except CT c/a/p at
12–18months if
16months
requested
(continued)
CT and CEA combined
did not have higher
yield than either alone
labs
CEA
CXR
FOBT
1966–2007 2923 Variable, including:
Years of
accrual N Intensive regimen Control regimen
Meta-
analysis
Study type
Study
Tjandra
Table 12.2 Randomized controlled trials and meta-analyses included
2007
liver u/s
CT
then yearly
q6mo×2years, then
yearly
q6mo×3years, with
single CT c/a/p at
colonoscopy
19–9 q 4mo
CXR and colonoscopy yearly
Liver u/s q 4mo×4, then
yearly
RCT 1998–2006 1228 Ofce visit, CEA, CBC, CA
GILDA
2016
FACS 2014 RCT 2003–2009 1202 Either:
CEA and CT c/a/p
CT c/a/p q6mo×2years,
12–18months if requested
CEA q3mo×2years, then
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T. J. PaulOlson
Quality of
evidence
Moderate
Outcomes of intensive
regimen
No difference in OS and
CSS
No difference in CRC
recurrence
CT c/a and CEA at 12 and
36 mo
Endoscopy and pelvic CT
at discretion of treating
Moderate
More recurrences
detected
More surgically
treatable
More denitive surgical txNo difference in OS,
MD
Year 1–3: CEA q 3mo,
output clinic visit, u/s
liver, CXR q6mo
Year 4–5: CEA q6mo,
annual clinic visit, u/s
liver, CXR
CSS
No difference in adverse
psych events
Strong
CSS
Recurrence found while
asymptomatic
More frequent salvage
surgery for recurrence
No difference in QoL,
anxiety, depression
24, and 36 mo
Endoscopy and pelvic CT at
discretion of treating MD
Years of
accrual N Intensive regimen Control regimen
Study type
RCT 2006–2010 2509 CT c/a and CEA at 6, 12, 18,
Study
COLOFOL
Table 12.2 (continued)
2018
Year 1–3: Annual CT and,
output clinic visit
Year 4–5: Annual output
clinic visit
RCT 2010–2012 3223 CEA q 8weeks
CEAWatch
2017
1966–2019 13,216 Variable Variable No difference in OS and
Meta-
analysis
Jeffrey
2019
QoL health-care related/quality of life, OS overall survival, CSS cancer specic survival, CRC colorectal cancer
Abbreviations: CEA carcinoembryonic antigen, CXR chest xray, FOBT fecal occult blood test, u/s ultrasound, RCT randomized clinical trial, mo month, HQoL/
12 Is Intensive Surveillance Necessary After Curative Resection forColon Cancer?
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Recommendations Based onData
There are no compelling results to link any particular intensive surveillance regimen
compared with minimal to less frequent surveillance to improved overall or cancerspecic survival. However, high quality studies have consistently shown that more
intensive surveillance is correlated with earlier detection of recurrences, detection
of recurrence while asymptomatic which associated with improved outcomes [13],
and increased rates of both surgically treatable recurrences and successfully resected
recurrences. (Evidence: moderate; recommendation: strong).
The trials and meta-analyses presented here used a variety of different blood
tests, imaging modalities, and timing of surveillance, making it difcult to recommend an exact unied surveillance regimen. Additionally, colonoscopy is an important part of post-resection surveillance for colorectal cancer, but this modality was
inconsistently included in the trials reviewed in this chapter. That being said, the
value of colonoscopy is established for detection of luminal recurrence [14]. Finally,
given the variety of ways colorectal cancer can recur, any modality in isolation is
unlikely to be adequate for meaningful surveillance.
Personal View oftheData
The data examining the role of more intensive vs less intensive surveillance after
curative resection for non-metastatic colorectal cancer is vexing. Despite the fact
that numerous well-designed studies, as well as a multitude of case series and cohort
studies, show that more frequent surveillance by whichever regimen is being studied correlates with earlier detection of recurrence, detection before recurrence
becomes symptomatic, and at a point when recurrences are more likely to be surgically salvageable, this has not translated to improvements in overall survival or
cancer specic mortality. How to make sense of this discrepancy?
One reason may be the evolving landscape of cancer treatments. While these trials were appropriately powered based on older rates of recurrence seen with colorectal cancer, there were decreases in recurrence with concurrent changes in adjuvant
and neoadjuvant therapy. As Popp etal. discuss in their analysis of the combined
results of the GILDA, FACS, and COLOFOL trials, between lower than expected
accrual rates to these studies as well as possibly decreased recurrence rates than
were included in power calculations, these studies may not have been adequately
powered to detect a small survival benet from curative surgery when recurrences
happened [15]. As there is evidence to suggest that treatment of recurrences, whether
with surgery or palliative chemotherapy, can provide benet, intensive surveillance
regimens that allow detection of recurrences before they become symptomatic make
it more likely that patients can receive these treatments [13]. The consistent signal
in the trials and meta-analyses that more subjects were able to receive salvage surgery of recurrences is encouraging and a reason to continue close monitoring of
colorectal cancer patients despite the lack of obvious survival benet. Additionally,
better outcomes associated with asymptomatic detection of recurrences support the
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T. J. PaulOlson
practice of close monitoring in colorectal cancer patients after curative surgery
[13, 16].
The most efcacious combination of surveillance tests is also not entirely settled.
Colorectal cancer can follow several patterns of recurrence. There can be luminal,
anastomotic recurrences. Local recurrences are also seen in surrounding lymphatic
tissue and nodal basins. Common sites of distant metastases include lung or liver
lesions. Additionally, while some tumors produce carcinoembryonic enzymes, elevations in this tumor marker are not universally seen. Because of these myriad presentations, a panel of complementary surveillance tests are needed to monitor
colorectal cancer patients. This is demonstrated by the various modalities included
in the trials discussed here, and reect the ongoing attempts to nd the most accurate, most effective surveillance strategy. In particular, the move from chest radiographs and liver ultrasonography to CT imaging is seen in the trials reported here.
Other imaging modalities are also being studied to see if there is any role in colorectal cancer surveillance, such as PET-CT.There is not currently data to support incorporation of this into surveillance, but this may continue to evolve [17, 18]. Likewise,
ongoing studies working to determine better use of serum CEA to maximize the
sensitivity and specicity of this testing could prove benecial for improved surveillance [12, 19, 20].
Another area to potentially improve the granularity of surveillance could be to
incorporate specic pathologic or histologic features into risk estimates for recurrence. A number of groups have been correlating factors such as perineural invasion, number of lymph nodes retrieved, lymphovascular invasion, and novel
classication of log odds of positive lymph nodes to clarify risk of recurrence and
better tailor surveillance regimens [21–24]. While large randomized trials are useful
in providing an aggregate view of a population, some of the ner details can be
obscured in the process. Likewise, the practice of combining colon and rectal cancers in these studies may obscure divergence in outcomes, as the treatments for
these malignancies are evolving differently.
Two of the three large trials discussed here included only stage II and III subjects. How to appropriately surveil stage I patients as well as resected stage IV
patients are ongoing questions that are likely not appropriate for extrapolation from
current trial data. Regarding stage I patients, while there is a low risk of recurrence,
certainly pathologic markers may warrant closer surveillance [22, 25, 26]. Attempts
are also being made to clarify surveillance protocols for resected stage IV patients
as well, as there is little data to guide this management [27].
One important consideration is how the data on surveillance after resection for
colorectal cancer is actually being used. Multiple studies surveying practitioners
internationally show that there is hesitancy or difculty in arranging the degree of
surveillance that is recommended by current guidelines [28–31]. This could reect
lack of buy-in by practitioners to high intensity surveillance, logistical difculties in
arranging follow up for patients, lack of robust systems for tracking patients, or
some combination of these and other elements. If controlled studies with high rates
of retention and adherence to surveillance protocols could demonstrate only indirect
improvements and benets, this degree of low engagement in “real world” settings
12 Is Intensive Surveillance Necessary After Curative Resection forColon Cancer?
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149
suggests that implementation of high intensity surveillance programs will have a
hard time demonstrating noticeable benets.
As a nal point, while I do think there is benet in close and careful surveillance
with complementary modalities in patients after surgery for colorectal cancer, there
is certainly room for improvement of current recommended protocols. It will be
interesting to see what changes might arise from improved incorporation of pathologic data or more targeted use of different imaging modalities, as well as diverging
treatment strategies for colon and rectal cancer. Another promising modality is circulating tumor cell technology; the role of this as part of surveillance regimens is
still very much a work in progress, and it will be intriguing to see if this becomes
incorporated in surveillance going forward.
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T. J. PaulOlson
Surgical Versus Endoscopic Options
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forManagement ofMalignant Large
13
Bowel Obstruction
MarcoBertucci Zoccali andAthanasiosAngistriotis
Introduction
The incidence of colorectal cancer (CRC) has been steadily increasing overtime,
representing the fourth most common malignancy and the third leading cause of
cancer related death worldwide [1]. With advances in early diagnosis and treatment
strategies, CRC mortality has progressively decreased, with a reported 64% 5-year
relative survival rate for all colon cancer stages combined in the US [2]. Elective
colon resection remains the mainstay of treatment for locoregional disease, with
low morbidity and mortality rates, particularly after the widespread adoption of
minimally invasive techniques [3]. Despite the intensication of screening, large
bowel obstruction (LBO) is still the initial presentation of up to 30% of colon cancers [4]. Emergency surgery (ES) has traditionally represented the treatment of
choice for these patients, with reported higher complication rates and worse oncologic outcomes compared to elective operations [5, 6]. In an effort to avoid the
morbidity associated with emergency surgery, the use of endoscopically placed selfexpanding metal stents (SEMS) has been proposed and implemented over the last 3
decades for the restoration of intestinal ow in patients presenting with malignant
LBO [7]. While initially proposed as denitive palliation for unresectable tumors or
in patients unt for surgery, overtime SEMS have been commonly used as a bridge
to surgery (BTS), with the aim of converting a surgical emergency into a condition
amenable to a safer elective procedure [8]. Despite some concerns related to potentially worse oncologic outcomes in the event of an iatrogenic perforation during
stent placement, this approach has gained popularity, as data regarding its safety and
efcacy, particularly in avoiding the need for a stoma, has accumulated in the
M. Bertucci Zoccali (*) · A. Angistriotis
Division of Colorectal Surgery, Columbia University Irving Medical Center- New York
Presbyterian Hospital, New York, NY, USA
© The Author(s), under exclusive license to Springer Nature
Switzerland AG 2023
K. Umanskiy, N. Hyman (eds.), Difcult Decisions in Colorectal Surgery,
Difcult Decisions in Surgery: An Evidence-Based Approach,
https://doi.org/10.1007/978-3-031-42303-1_13
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Table 13.1 PICO table
P (patients)
Patients with
malignant LBO
I (intervention) C (comparator)
ES (colectomy,
diversion)
SEMS
placement
M. Bertucci Zoccali and A. Angistriotis
O (outcomes)
Short term (morbidity, mortality),
long term (oncologic outcomes),
quality of life.
literature [9, 10]. This chapter provides a critical review of the current literature on
the topic, discussing advantages and disadvantages of the use of SEMS over emergency surgeries in the setting of malignant LBO, with some special considerations
for right sided and rectal cancers as well as extracolonic malignancies (ECMs)
(Table13.1).
Search Strategy
For the purposes of this chapter, a literature search was performed on the management of malignant SBO to identify all the English language publications on the
Cochrane Database of Collected Research, EMBASE, MEDLINE, and PubMed
from inception to 2021, with particular focus on those published after 2015. Key
words used for the search included: “colon cancer”, “rectal cancer”, “obstruction”,
“stent”, “stenting”, “surgery”, “emergency”, “stoma”, “colostomy”, “diversion”.
Randomized controlled trials (RCT), systematic reviews and large retrospective
studies were reviewed in details and ndings were summarized in table form in the
results section (Table13.2). Small retrospective series were also assessed and referenced as appropriate.
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153
Quality of
evidence
Emergent
surgery
Technical
success of
stenting Outcome SEMS
16 days
days
Hospital stay 15.5
45% 69%
a
1-year complication rate 60.7% 69.4%
Stoma rate
19.6% 39%
15 days 11 days
7.2% 30.5% Moderate
a
a
a
Stoma rate
Hospital stay
89.9% 30-day morbidity
4 days 8 days
73.9% 94.4%
a
a
Hospital stay
30-day mortality 0 5.5%
Maintenance of decompression
until death
Long-term morbidity 21% 11%
a
30-day mortality 6.3% 6.4%
244 days
days
14.3% 84%
Stoma rate
Mean survival 279
65 56 Moderate
a
180-day Karnofsky 58 52
(continued)
4 days 9.8 days
a
Hospital stay
1-year survival 25% 29%
Study Intent N Design
Table 13.2 Summary of the most notable studies published in the literature to date
1 Hill 2016 BTS 246 RCT 82% 30-day mortality 5.3% 4.4% High
RCT 87.5% 60-day complication rate 51.8% 57.6% High
59 surgery
2 Arezzo 2017 BTS 56 BTS
Retrospective
cohort
36 surgery
3 Siddiqui 2017 Palliative 69 SEMS
Meta-analysis 87.3% 30-day Morbidity 36.5% 24.2% High
(125 total)
4 Ribeiro 2018 Palliative 4 RCT
RCT – 30-day Karnofsky
17 surgery
5 Fiori 2019 Palliative 16 SEMS
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