HIGHLIGHTS OF THE NCCN 2022 ANNUAL CONFERENCE

Updates in Screening Recommendations for

Colorectal Cancer
Presented by Reid M. Ness, MD, MPH

ABSTRACT

In the past 2 years, several significant changes have been made to the NCCN Guidelines for Colorectal Cancer (CRC) Screening. The age for initi-
ation of screening average-risk adults has been lowered from age 50 to 45 years—without differentiation by age and race—and from age
50 to 45 years for those with second- and third-degree relatives with CRC. For several groups, surveillance intervals have been changed. Patients
with 1 or 2 low-risk adenomas at index colonoscopy, on the other hand, can now wait 10 years rather than 5 to 7 years between surveillance
examinations. The first surveillance examination following resection of large adenomas or sessile serrated polyps (SSPs) with unfavorable-risk
characteristics or that were removed piecemeal should now occur at 6 months. For patients with $10 adenomas and SSPs on a single colonos-
copy, time to first surveillance was lowered to 1 year. J Natl Compr Canc Netw 2022;20(5.5):603–606
doi: 10.6004/jnccn.2022.5006

In an effort to prevent colorectal cancer (CRC), the
NCCN Clinical Practice Guidelines in Oncology (NCCN
Guidelines) provide recommendations for screening
based on a variety of risk factors and patient profiles. In
the past 2 years, the NCCN Guidelines for CRC Screening
have undergone several significant changes, reflecting
recommendations that will spare some patients unneces-
sary interventions and, in other cases, detect cancers ear-
lier. The updated recommendations were presented at
the NCCN 2022 Annual Conference by Reid M. Ness,
MD, MPH, Associate Professor of Medicine, Vanderbilt-
Ingram Cancer Center, and Chair of the NCCN Guide-
lines Panel for Colorectal Cancer Screening.
“The first and most significant change in the NCCN
Guidelines was a lowering of the initial screening age for
average-risk individuals from 50 to 45 years. The second
biggest change is the recommendation to extend the sur-
veillance period from 5–7 years to 10 years for patients
with only 1 to 2 small tubular adenomas at the index
colonoscopy,” Dr. Ness announced.
In other changes, the NCCN Guidelines panel now
recommends lowering the age for first screening in per-
sons with second- and third-degree relatives with CRC
from 50 to 45 years; shortening the time to first surveil-
lance examination to 6 months following resection of
large adenomas or sessile serrated polyps (SSPs) with
unfavorable-risk characteristics or that were removed
piecemeal; and shortening the time to first surveillance to
1 year for patients found to have $10 adenomas or
SSPs at a single colonoscopy. However, several other
important recommendations re-mained unchanged,
including:
 Age for initiation of screening in persons with
affected first-degree relatives with CRC or advanced
adenomas/SSPs remains 40 years.
 Surveillance colonoscopy interval in those with only
1 or 2 low-risk SSPs remains at 5 years.
 The surveillance colonoscopy interval following the
identification of most high-risk adenomas/SSPs remains
at 3 years.
 Initiation of surveillance remains at 8 years for most
patients with inflammatory bowel disease, and surveil-
lance intervals remain at 1 to 3 years, depending on
measures of underlying CRC risk.
Lowering Screening Age
“The impetus for lowering the initial screening age is based
on well-publicized trends in CRC incidence,” Dr. Ness said.
Since 1980, there has been a 40% overall decrease in CRC
incidence among patients aged .50 years in the United
States. Unfortunately, this has been accompanied by a more
recent increasing incidence of CRC among adults aged 20 to
49 years.1 Because data are lacking on CRC screening in per-
sons aged ,50 years, the American Cancer Society and the
US Preventive Services Task Force (USPSTF) relied on model-
ing exercises that demonstrated “small but significant”
amounts of life-years gained from CRC screening beginning
at age 45 years.2,3 Cost-effectiveness was not addressed in the
analyses, and some experts maintained that “the absolute
cost of such a policy change would be unacceptably high,”
Dr. Ness said. “Despite these concerns, the panel felt that the
cost-to-benefit trade-off was acceptable, and in April 2021,
the recommended age to initiate average-risk CRC screening
was lowered to 45 years.”

JNCCN.org | Volume 20 Issue 5.5 | May 2022 603

 HIGHLIGHTS OF THE
NCCN 2022 ANNUAL CONFERENCE Ness

“All CRC screening guidelines in the United States
have been brought into accord,” he said. The same rec-
ommendation was subsequently made by the USPSTF in
May 2021 and the Multi-Society Task Force on CRC
Screening in November 2021.3,4
Because half of all patients who present with CRC
before age 50 years do so before they even reach 45 years
of age, NCCN also recommends that those presenting with
symptoms suggestive of a possible diagnosis for rectal can-
cer, such as iron deficiency and rectal bleeding, be evalu-
ated with colonoscopy in a timely fashion, he added.5 In
addition, the NCCN Guidelines panel considered whether
the initial screening age should be lowered for average-risk
non-Hispanic Black individuals, but determined that the
model was reassuring in that 45 years of age is appropriate
for all sex- and race-based groups.6
Extending Surveillance Period to 10 Years
“The recommendation to extend the surveillance period
after the finding of a low-risk adenoma is based upon
very strong cohort data,” Dr. Ness said (Figure 1). These
data come from a meta-analysis of 8 cohort studies that
evaluated the risk of CRC in 10,139 persons with low-risk
adenomas on index colonoscopy compared with persons
with normal baseline colonoscopies. In the former group,
the investigators found a small but statistically significant
increase in future advanced adenomas (relative risk, 1.55;
P5.0001).7 The pooled 5-year cumulative incidence of
advanced adenomas was 3.3% for the no-adenoma
group, 4.9% for the low-risk adenoma group, and 17.1%
for patients with advanced adenomas at baseline.
Combined data from the Nurses’ Health Study and
the Health Professional Follow-Up Study, which followed
122,899 patients for a median of 10 years after colonos-
copy, showed that the hazard ratios (HRs) for patients
with 1 or 2 small tubular adenomas was not significantly
increased over those with no polyps at baseline.8
A prospective cohort study from Kaiser Permanente
Northern California published in 2020 followed 64,422
patients for 8 years.9 The investigators found that the
HRs for CRC incidence and death in patients with low-
risk adenomas at baseline were not significantly different
from those of patients with normal findings. In contrast,
patients with high-risk adenomas at baseline had a sig-
nificant increase in age-adjusted CRC after 5 years.
“Although the guidelines recommend extending the sur-
veillance period for patients with 1 to 2 low-risk adenomas,
we did not extend the surveillance period for patients with
only low-risk SSPs on index colonoscopy, secondary to a per-
ceived paucity of data. Nonetheless, there are current studies

PERSONAL HISTORY OF POLYP FOUND COLONOSCOPYq

RISK STATUS CLINICAL FINDINGS FOLLOW-UP OF CLINICAL FINDINGSh
Low-risk adenoma: Repeat
≤2 polyps colonoscopy Negative/
<1 cm between 7–10 yw No adenoma Repeat colonoscopy
or SSP in 10yw

Low-risk SSP:
No dysplasia Repeat Positive/ Repeat colonoscopy
≤2 polyps colonoscopy in adenoma or according to clinical
<1 cm 5 yw SSP findings

High risk (advanced or multiple polyps):u,v Repeat

Personal history TSAs or
of adenomatous High-grade dysplasia or SSP-d or
colonoscopy
polyp(s), SSPs,g Villous or tubulovillous histology or
in 3 yw
traditional serrated Between 3 and 9 adenomatous polyps Negative Repeat colonoscopy
adenoma (TSA), and/or SSPs or in 5 yw
or large (≥1 cm)
Adenoma or any SSP ≥1 cm or
hyperplastic Large (≥ 1cm) hyperplastic polyosq See CSCR-6
polypsq found at
colonoscopyt

Colonoscopy in 1 y Repeat colonoscopy

≥10 adenomatous polyps and/ or SSP in a according to clinical findings
singal colonoscopy
See NCCN Guidelines for
Consider polyposis Genetic/Familial High-Risk
syndrome Assessment: Colorectal
≥20 cumulative adenomatous polyps and/
or SSPu
Individual managementx

Malignant polyp See NCCN Guidelines for colon cancer or

See NCCN Guidelines for Rectal cancer

Figure 1. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colorectal Cancer Screening: personal history of polyp found at
colonoscopy [CSCR-4]. Version 1.2022.
#2022 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the
express written permission of NCCN®. To view the most recent and complete version of these NCCN Guidelines, go to NCCN.org.

604 © JNCCN—Journal of the National Comprehensive Cancer Network | Volume 20 Issue 5.5 | May 2022

CRC Screening Guidelines Updates
that could lead to our extending the surveillance period rec-
ommendation in the near future,” Dr. Ness said.
The guidelines panel reviewed how serrated polyp size
and location affected risk. The Nurses’ Health Study and
Health Professionals Follow-Up Study showed that the HR
for metachronous CRC associated with small serrated polyps
was 1.25—not significantly different than that for patients
without baseline polyps—whereas large, serrated polyps car-
ried an HR of 3.35.9 Interestingly, neither the number nor
location of these polyps significantly affected the risk of
metachronous CRC. However, in a study from Li et al10 of
233,393 patients, serrated polyps in the rectosigmoid colon
did not increase CRC risk, whereas both small and large pol-
yps in the proximal colon did significantly increase risk.
“We kept the recommended surveillance interval for
patients with $3 low-risk adenomas and SSPs, and most
higher-risk adenomas and SSPs, at 3 years. We also con-
tinue to recommend consideration of genetic testing for
a polyposis syndrome in all patients with $10 adenomas
or SSPs on a single colonoscopy or with a lifetime cumu-
lative incidence of at least 20. In contrast, the guidelines
now recommend that any person with $10 polyps at
colonoscopy who does not have a polyposis syndrome
have repeat colonoscopy within 1 year,” he said.
Dr. Ness acknowledged that there are few data to
inform those 2 recommendations. In one study from
Harvard, the odds of diagnosing an underlying polyposis
syndrome were increased in persons with $10 cumula-
tive adenomas.11 In another often-cited article from
South Korea, patients with .10 adenomas versus those
with 3 to 10 adenomas had a 2.25 elevated risk for
advanced colorectal neoplasia.12
Management of Large Polyps
The surveillance interval has been shortened for patients
with large ($1 cm) adenomas and SSPs either with unfa-
vorable-risk factors for local recurrence or removed in
INCREASED RISK BASED ON POSITIVE FAMILY HISTORY
(Not meeting criteria for consideration of a hereditary cancer syndrome or appropriate testing for hereditary cancer syndrome non-
diagnostic or not done)yy
FAMILY HISTORY CRITERIA
≥1 first-degree relative with CRC at any age
Second- and third-degree relatives with CRC
at any age
First-degree relative with confirmed advanced
adenoma(s) (ie, high-grade dysplasia, ≥1 cm,
villous or tubulovillous histology, TSA), or
advanced SSPs (≥1 cm, any dysplasia) at any
age aaa,eee,fff
Figure 2. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colorectal Cancer Screening: increased risk based on positive
family history [CSCR-12]. Version 1.2022.
#2022 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the
express written permission of NCCN®. To view the most recent and complete version of these NCCN Guidelines, go to NCCN.org.
JNCCN.org | Volume 20 Issue 5.5 | May 2022
HIGHLIGHTS OF THE
NCCN 2022 ANNUAL CONFERENCE
piecemeal fashion. The guidelines now recommend the
first surveillance colonoscopy at 6 months, rather than
12 months, with the second occurring 12 months later,
even without evidence of recurrence at the first surveil-
lance examination. A number of studies support this rec-
ommendation,13–15 showing a sizable recurrence rate at
6 months, a much higher risk of recurrence after piece-
meal resection than en bloc resection, and an increasing
risk of recurrence associated with increasing size of the
resected polyp.
Recommendations Based on Family History
Individuals with a first-degree relative with (1) CRC or
endometrial cancer who were diagnosed before age
50 years or (2) synchronous or metachronous Lynch syn-
drome–related cancers regardless of age should undergo
genetic evaluation. Otherwise, for persons with a first-
degree relative with CRC, the guidelines panel recom-
mends colonoscopy beginning at age 40 years, or 10 years
before the earliest familial CRC diagnosis, with surveillance
at least every 5 years (Figure 2). This recommendation is
based on data published almost 30 years ago from a cohort
study of .119,000 adults undergoing their first screening
who were then followed for 6.5 years. The study deter-
mined the age-adjusted relative risk for CRC for those with
a first-degree relative with CRC, and essentially validated
the 10-year earlier shift in diagnosis, based on the presence
of a family history.16
A more recent long-range case-control study of Utah
residents aged 50 to 80 years determined the HR for
developing CRC was 1.6 to 2.5 among individuals with a
first-degree relative with CRC, with the highest risk seen
among those whose relatives were diagnosed before age
40 years.17 Other studies have found a much lower risk
for persons with second- and third-degree relatives with
CRC.18 “After much discussion, the guidelines panel contin-
ued to only recommend colonoscopy screening beginning
SCREENINGbbb
Repeat every 5 yzz,bbb,ccc,ddd
Colonscopy beginning at age 40 y or
or if positive, repeat per
10 y before earliest diagnosis of CRC
colonoscopy findings
Repeat every 10 y
Colonscopy beginning at age 45 yzz or if positive, repeat per
colonoscopy findings
Colonscopy beginning at age 40 y or Repeat every 5-10 ybbb,ccc
at age of onset of adenoma in relative, or if positive, repeat per
whichever is first colonoscopy findings
605
 HIGHLIGHTS OF THE
NCCN 2022 ANNUAL CONFERENCE
at age 45 years for persons with CRC limited to second- and
third-degree relatives,” he said (Figure 2).
Finally, for adults with first-degree relatives that have
confirmed advanced adenoma or advanced SSPs at any
age (Figure 2), the recommendations are similar to those
for patients with an affected first-degree relative with
CRC. Hong Kong investigators determined the odds of
finding adenomas among 200 persons who also had sib-
lings with advanced adenomas compared with 400 adults
without an affected sibling.19 Those with affected siblings
had a matched-sex odds ratio of 3.29 for any adenoma
and 6.05 for advanced adenomas.
Screening Modalities and Evaluation
of Findings
No significant changes have been made regarding the rec-
ommended modalities and strategies for evaluation of
screening findings. The panel continues to endorse colo-
noscopy every 10 years, fecal immunochemical testing
every 1 year, multitargeted stool DNA testing every 3 years,
CT colonoscopy every 5 years, and flexible sigmoidoscopy
every 5 to 10 years.
Summarizing the characteristics of the various diag-
nostic modalities employed in CRC, Dr. Ness noted that
with adherence to the recommended screening intervals,
all screening strategies are cost-effective compared with
no screening. Nonetheless, to achieve the best results,
CRC screening should be done as part of a systematic
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606 © JNCCN—Journal of the National Comprehensive Cancer Network
Ness
population-based program that includes direct outreach
to patients and in-clinic focused interventions to increase
screening rates, reduce mortality, and minimize dispar-
ities by race and ethnicity.
Patients With Inflammatory Bowel Disease
The panel made no significant changes to the recom-
mendations for CRC screening in patients with underly-
ing Crohn’s disease or ulcerative colitis. Surveillance
should be started 8 years after the onset of symptoms
and be conducted with high-definition, white-light
endoscopy or chromoendoscopy with targeted biopsies.
Exceptions to this schedule are patients with primary
sclerosing cholangitis, who should start yearly surveil-
lance upon diagnosis, and patients with a family his-
tory of CRC or advanced neoplasia where age of the
family member at diagnosis may supersede the stan-
dard recommendations for inflammatory bowel dis-
ease, he said.
The frequency of surveillance after initial colonoscopy
ranges between 1 and 3 years, depending on personal and
family histories, disease activity, and other findings (such
as invisible dysplasia and chronic stricture).
Disclosures: Dr. Ness has disclosed receiving grant/research support from
Guardant Health.
Correspondence: Reid M. Ness, MD, MPH, Vanderbilt University, 1301 Medical
Center Drive, Suite 1745B, Nashville, TN 37232. Email: reid.ness@vumc.org
10. Li D, Liu L, Fevrier HB, et al. Increased risk of colorectal cancer in individuals
with a history of serrated polyps. Gastroenterology 2020;159:502–511.
11. Grover S, Kastrinos F, Steyerberg EW, et al. Prevalence and phenotypes
of APC and MUTYH mutations in patients with multiple colorectal adeno-
mas. JAMA 2012;308:485–492.
12. Park SK, Hwang SW, Kim KO, et al. Risk of advanced colorectal neo-
plasm in patients with more than 10 adenomas on index colonoscopy:
a Korean Association for the Study of Intestinal Diseases (KASID) study.
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endoscopic mucosal resection of nonpedunculated colorectal lesions:
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endoscopic resection of large, nonpedunculated colorectal lesions: a pro-
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19. Ng SC, Lau JY, Chan FK, et al. Risk of advanced adenomas in siblings of
individuals with advanced adenomas: a cross-sectional study. Gastroen-
terology 2016;150:608–616.
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