Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / @xirurgi_2025 / @xirurgi_2025 - 598 - файл
.pdf
16 Management oftheMalignant Colon Polyp: Resection or Surveillance?
https://t.me/medicina_free
Fig. 16.5 Kikuchi SM 3.
(This gure produced
thanks to Dr. Kathleen
Byrnes and Washington
University in St. Louis
Pathology Department)
195
Lymphovascular Invasion
The presence of lymphatics and blood vessels in the submucosa is the reason malignant cells in this layer are able to spread. The majority of published literature on the
risks of lymph node spread have demonstrated that lymphovascular invasion is a
risk factor. Samuolis etal., a recently retrospective study, found that half of specimens with positive lymph nodes had lymphovascular invasion [22]. Butte et al.
demonstrated odds of 5.3 of lymphovascular invasion when lymph nodes are positive [20].
Poor Differentiation
Poor differentiation is another risk factor associated with lymph node spread. The
2014 meta-analysis demonstrated that specimens with positive lymph nodes were
associated with positive margins with an odds ratio 3.52. It was also signicantly
associated with disease-specic mortality [19]. Kim etal. showed that poor differentiation was 7.5 times as likely to have residual disease [21].
Tumor Budding
Tumor budding which is dened as a single cancer cell or a cluster of up to 4 cells
at the advancing edge of the tumor, is not as well studied as the other features.
Nevertheless, more recent studies have demonstrated an association with lymph
node spread. Two studies, Choi etal. and Kye etal. found that tumor budding was
independently associated with 16 and 7.7 increased odds of having lymph node
metastasis respectively [12, 23]. A large meta-analysis encompassing 4510 patients
196
https://t.me/medicina_free
published in 2013 also found that tumor budding was independently associated with
lymph node metastasis (OR 7.74) [7].
A. A. Eltahir and R. K. Smith
Recommendations
Patients who present with malignant colon polyps with no high-risk features can
undergo surveillance with frequent colonoscopies instead of surgical resection with
no increase in risk of adverse outcomes (Recommendation: Strong; Evidence:
Moderate).
The decision to manage malignant colon polyps should be a collaborative
approach between the physician and patient, taking into account the patient’s tness, preference, and ability to adhere to a surveillance schedule. After expert
pathology review demonstrates no high-risk features such as positive margins, poor
differentiation, lymphovascular invasion, deep submucosal invasion, or tumor budding in the colonic polyp, patients can opt for surveillance with a low risk of lymph
node spread or recurrent disease. However, if high-risk features are identied,
patients should consider surgical resection if medically t.
Personal View
Treating colorectal cancer is largely dependent on its potential to metastasize. Given
the scarcity of lymphatic vessels in the colonic mucosa, truly intramucosal carcinomas have no risk of metastasizing to the lymph node [24]. Numerous studies have
demonstrated that endoscopic management of these polyps is cost effective and
associated with lower morbidity and mortality [25, 26]. The potential for morbidity
and mortality of surgery should prompt physicians and patients to avoid surgery if
it does not offer any clinical benets.
With more widespread adoption of colorectal cancer screening, more carcinomas
are detected at an earlier state. Over the last several decades, dozens of articles have
been published to better understand the risk of lymph node metastasis in malignant
polyps allowing for more informed consent and shared decision making. The known
literature points to certain histological features that are known to increase the risk of
spread such as positive margins, lymphovascular invasion, poor differentiation,
deep submucosal invasion and, to some degree, tumor budding. In order to best
evaluate these features, the rst step is an en-bloc resection of the polyp allowing
pathologists to best evaluate the margins and architecture of the specimen.
Realistically, many of these features are surprisingly difcult to differentiate and
can have poor inter-operator reliability. Given that the decision to forgo surgery will
largely depend on the lack of high-risk features on histological evaluation, expert
pathologic assessment is paramount however this is often times limited by the specimen itself. The original endoscopist must make every effort to resect the polyp
16 Management oftheMalignant Colon Polyp: Resection or Surveillance?
https://t.me/medicina_free
197
completely and in one piece. In almost every study, positive margins were associated with residual disease or lymph node spread. Piecemeal dissection makes it
difcult for the pathologist to evaluate the specimen and can lead to inaccurate or
incomplete interpretation. One study demonstrated there was an increase in recurrence for polyps removed in a piecemeal fashion [27]. Regardless, piecemeal dissection in and of itself is not an indication for surgical resection but it should prompt
the conversation between the patient and physician even if there are no other highrisk features.
Another issue to consider is that the alternative to surgical resection is surveillance with frequent colonoscopies. There are no exact guidelines on the frequency
of these colonoscopies, and they are institution and physician dependent. The
patient and physician must consider the feasibility of patient adherence to the surveillance schedule. If there is a serious risk of not following up with medical care
either due to logistical issues or lack of insurance, then surgical resection should be
weighed more favorably. Ultimately, risks of nodal disease, the patient’s preference,
and their tness for surgery must be clearly considered in the treatment of malignant polyps.
PICO table
Patients
Patients with pT1
malignant colon polyps
Intervention Comparator
Colectomy Surveillance Lymph node metastasis, mortality,
Outcome
recurrent disease
Data summary
Study
Choi [12] 87 Surgery vs
Pizarro [28] 42 Surgery Residual disease 22% Moderate
Di Gregorio
[19]
Butte [20] 143 Surgery Lymph node
Boenicke
[18]
Samuolis
[22]
Kim [21] 148 Surgery Residual disease 10.9% Weak
Okabe [29] 428 Surgery Lymph node
Kye [23] 55 Surgery Lymph node
Patients Intervention Outcome Result
Lymph node
surveillance
105 Surgery vs
surveillance
105 Surgery vs
surveillance
40 Surgery Lymph node
spread
Cancer related
mortality
spread
Lymph node
spread
spread
spread
spread
20% vs 0% Strong
6% vs 0% Moderate
7% Moderate
Odd ratio
(OR) 9.2
12.5% Moderate
10% Moderate
14.5% Moderate
Quality of
evidence
Weak
198
https://t.me/medicina_free
A. A. Eltahir and R. K. Smith
References
1. Aarons CB, Shanmugan S, Bleier JI. Management of malignant colon polyps: current status and controversies. World J Gastroenterol WJG. 2014;20(43):16178–83. https://doi.
org/10.3748/wjg.v20.i43.16178.
2. Netzer P, Forster C, Biral R, etal. Risk factor assessment of endoscopically removed malignant
colorectal polyps. Gut. 1998;43(5):669–74. https://doi.org/10.1136/gut.43.5.669.
3. Hackelsberger A, Frühmorgen P, Weiler H, Heller T, Seeliger H, Junghanns K. Endoscopic
polypectomy and management of colorectal adenomas with invasive carcinoma. Endoscopy.
1995;27(2):153–8. https://doi.org/10.1055/s- 2007- 1005654.
4. Bujanda L, Cosme A, Gil I, Arenas-Mirave JI. Malignant colorectal polyps. World J
Gastroenterol WJG. 2010;16(25):3103–11. https://doi.org/10.3748/wjg.v16.i25.3103.
5. Colorectal Cancer Screening | Cancer Trends Progress Report. Accessed 28 Sept 2022. https://
progressreport.cancer.gov/detection/colorectal_cancer
6. Rex DK, Shaukat A, Wallace MB.Optimal Management of Malignant Polyps, from endoscopic assessment and resection to decisions about surgery. Clin Gastroenterol Hepatol.
2019;17(8):1428–37. https://doi.org/10.1016/j.cgh.2018.09.040.
7. Beaton C, Twine CP, Williams GL, Radcliffe AG.Systematic review and meta-analysis of
histopathological factors inuencing the risk of lymph node metastasis in early colorectal
cancer. Colorectal Dis Off J Assoc Coloproctology G B Irel. 2013;15(7):788–97. https://doi.
org/10.1111/codi.12129.
8. Choi JY, Jung SA, Shim KN, et al. Meta-analysis of predictive clinicopathologic factors
for lymph node metastasis in patients with early colorectal carcinoma. J Korean Med Sci.
2015;30(4):398–406. https://doi.org/10.3346/jkms.2015.30.4.398.
9. Tateishi Y, Nakanishi Y, Taniguchi H, Shimoda T, Umemura S.Pathological prognostic factors predicting lymph node metastasis in submucosal invasive (T1) colorectal carcinoma.
Mod Pathol Off J U S Can Acad Pathol Inc. 2010;23(8):1068–72. https://doi.org/10.1038/
modpathol.2010.88.
10. Kikuchi R, Takano M, Takagi K, etal. Management of early invasive colorectal cancer. Risk
of recurrence and clinical guidelines. Dis Colon Rectum. 1995;38(12):1286–95. https://doi.
org/10.1007/BF02049154.
11. Risio M, Fiocca R.Malignant adenoma: diagnosis, staging, risk factors, lymph node involvement and problems of sampling. Tech Coloproctol. 2004;8(Suppl 2):s253–6. https://doi.
org/10.1007/s10151- 004- 0171- 4.
12. Choi DH, Kyung Sohn D, Jin Chang H, Lim SB, Seong Choi H, Jeong SY.Indications for subsequent surgery after endoscopic resection of Submucosally invasive colorectal carcinomas:
a prospective cohort study. Dis Colon Rectum. 2009;52(3):438–45. https://doi.org/10.1007/
DCR.0b013e318197e37f.
13. Coverlizza S, Risio M, Ferrari A, Fenoglio-Preiser CM, Rossini FP.Colorectal adenomas containing invasive carcinoma. Pathologic assessment of lymph node metastatic potential. Cancer.
1989;64(9):1937–47. https://doi.org/10.1002/1097- 0142(19891101)64:9<1937::aid- cncr2
820640929>3.0.co;2- x.
14. Nivatvongs S, Rojanasakul A, Reiman HM, etal. The risk of lymph node metastasis in colorectal polyps with invasive adenocarcinoma. Dis Colon Rectum. 1991;34(4):323–8. https://doi.
org/10.1007/BF02050592.
15. Ramirez M, Schierling S, Papaconstantinou HT, Scott TJ. Management of the Malignant
Polyp. Clin Colon Rectal Surg. 2008;21(4):286–90. https://doi.org/10.1055/s- 0028- 1089944.
16. Nascimbeni R, Burgart LJ, Nivatvongs S, Larson DR. Risk of lymph node metastasis in
T1 carcinoma of the colon and rectum. Dis Colon Rectum. 2002;45(2):200–6. https://doi.
org/10.1007/s10350- 004- 6147- 7.
17. Tytherleigh MG, Warren BF, Mortensen NJM.Management of early rectal cancer. Br J Surg.
2008;95(4):409–23. https://doi.org/10.1002/bjs.6127.
16 Management oftheMalignant Colon Polyp: Resection or Surveillance?
https://t.me/medicina_free
18. Boenicke L, Fein M, Sailer M, Isbert C, Germer CT, Thalheimer A.The concurrence of histologically positive resection margins and sessile morphology is an important risk factor for
lymph node metastasis after complete endoscopic removal of malignant colorectal polyps. Int
J Color Dis. 2010;25(4):433–8. https://doi.org/10.1007/s00384- 009- 0836- 6.
19. Di Gregorio C, Bonetti LR, de Gaetani C, Pedroni M, Kaleci S.Ponz de Leon M. clinical outcome of low- and high-risk malignant colorectal polyps: results of a population-based study
and meta-analysis of the available literature. Intern Emerg Med. 2014;9(2):151–60. https://doi.
org/10.1007/s11739- 012- 0772- 2.
20. Butte JM, Tang P, Gonen M, etal. Rate of residual disease after complete endoscopic resection
of malignant colonic polyp. Dis Colon Rectum. 2012;55(2):122–7. https://doi.org/10.1097/
DCR.0b013e3182336c38.
21. Kim KJ, Lee HS, Jeon SW, Jin S, Lee SW. Association of Poor Differentiation or positive vertical margin with residual disease in patients with subsequent colectomy after complete macroscopic endoscopic resection of early colorectal cancer. Gastroenterol Res Pract.
2017;2017:7129626. https://doi.org/10.1155/2017/7129626.
22. Samuolis N, Samalavicius NE, Dulskas A, etal. Surgical or endoscopic management of malignant colon polyps. ANZ J Surg. 2018;88(12):E824–8. https://doi.org/10.1111/ans.14846.
23. Kye BH, Jung JH, Kim HJ, Kang SG, Cho HM, Kim JG.Tumor budding as a risk factor of
lymph node metastasis in submucosal invasive T1 colorectal carcinoma: a retrospective study.
BMC Surg. 2012;12:16. https://doi.org/10.1186/1471- 2482- 12- 16.
24. Risio M.The natural history of pT1 colorectal cancer. Front Oncol 2012;2. Accessed 21 Aug
2022. https://www.frontiersin.org/articles/10.3389/fonc.2012.00022
25. Ma C, Teriaky A, Sheh S, et al. Morbidity and Mortality After Surgery for
Nonmalignant Colorectal Polyps: A 10-Year Nationwide Analysis. Am J Gastroenterol.
2019;114(11):1802–10. https://doi.org/10.14309/ajg.0000000000000407.
26. Jayanna M, Burgess NG, Singh R, etal. Cost analysis of endoscopic mucosal resection vs
surgery for large laterally spreading colorectal lesions. Clin Gastroenterol Hepatol Off
Clin Pract J Am Gastroenterol Assoc. 2016;14(2):271–278.e1-2. https://doi.org/10.1016/j.
cgh.2015.08.037.
27. Hassan C, Repici A, Sharma P, et al. Efcacy and safety of endoscopic resection of large
colorectal polyps: a systematic review and meta-analysis. Gut. 2016;65(5):806–20. https://doi.
org/10.1136/gutjnl- 2014- 308481.
28. Pizarro-Moreno A, Cordero-Fernández C, Garzón-Benavides M, et al. Malignant colonic
adenomas. Therapeutic criteria. Long-term results of therapy in a series of 42 patients in
our healthcare area. Rev Espanola Enfermedades Dig Organo Of Soc Espanola Patol Dig.
2009;101(12):830–6. https://doi.org/10.4321/s1130- 01082009001200002.
29. Okabe S, Shia J, Nash G, etal. Lymph node metastasis in T1 adenocarcinoma of the colon and
rectum. J Gastrointest Surg. 2004;8(8):1032–40. https://doi.org/10.1016/j.gassur.2004.09.038.
199
Stage II Colon Cancer: Towards
https://t.me/medicina_free
anIndividualized Treatment Approach
GideonDosunmu andChih-YiLiao
Introduction
The decision on whether to administer adjuvant chemotherapy in stage II colon
cancer continues to be an ongoing debate. There are no clear-cut guidelines or data
on the majority of cases. Ultimately, every patient is different, and that decision will
vary from patient to patient depending on their unique characteristics and tumor
biology. The problem is that stage II colon cancer is so heterogeneous biologically
with SEER 5-year survival rates ranging from 66% in stage IIA cancers to 37% for
stage IIC disease [1]. In this chapter, we will present the current state of the science
for stage II colon cancer with the hopes of allowing the practitioner to better riskstratify patients and thereby select those who are most likely to benet from adjuvant chemotherapy. We will conclude with our recommendations for specic cases
with the strength of that recommendation based on the evidence.
17
Patient population
Patients with stage II colon
cancer
G. Dosunmu (*) · C.-Y. Liao
Section of Hematology/Oncology, Department of Medicine, University of Chicago,
Chicago, IL, USA
e-mail: gideon.dosunmu@uchicagomedicine.org; andyliao@medicine.bsd.uchicago.edu
© 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_17
Intervention Comparators
Chemotherapy Observation Disease free survival, overall
Outcomes studied
survival
201
202
https://t.me/medicina_free
G. Dosunmu and C.-Y. Liao
Results
Non-Risk-Stratified Patients
In attempting to answer the questions as to whether chemotherapy is important in
stage II colorectal cancer, we will explore available studies. A comprehensive list of
the relevant studies is listed in Table17.1. A noteworthy trial is the QUASAR trial
[2] which explored the use of adjuvant 5-FU based therapy in stage II colon cancer.
Although not a perfect study, with the study power and randomization, it reasonably
answers our question of chemotherapy benet. In the QUASAR trial, 5-FU chemotherapy resulted in a statistically signicant improvement in overall survival and
disease-free survival. The absolute magnitude of the survival benet was 3.6%
(95% CI: 1–6%), and number needed to treat was 28. No other study conrms this
survival advantage statistically, but most suggest a magnitude of benet that is not
inconsistent with the QUASAR results either for overall survival (OS) or at least for
disease-free survival (DFS) [3–10].
A limitation of most of the studies aimed at addressing our question is that they
are either underpowered or are pooled subset analyses of randomized trials which
subjects them to biases inherent in pooled analysis, including a meta-analysis done
by the Cochrane group [3]. MOSAIC and NSABP C-07 are two trials that incorporated oxaliplatin-based chemotherapy. They however did not appear to have shown
a signicant improvement over 5-FU alone for stage II colon cancer patients [5, 10].
Even the 10-year MOSAIC update failed to show an overall survival advantage of
one chemotherapy over the other (78.4% vs. 79.5%) [11]. The limitation of these
studies is that they are underpowered to answer our question with any certainty.
Looking at some registry data which are weaker study types in our table, such as
the BCCA and SEER-Medicare. They showed no advantage to chemotherapy in
stage II colon cancer and even suggest it may be detrimental [12, 13]. However, data
from the National Cancer Database consisting of 153,110 stage II colon cancer
patients showed increased OS in those who received adjuvant chemotherapy compared to those who did not 51% vs 35% [14]. The limitation of these registry studies
is uncontrolled threats to internal validity.
Risk-Stratification: Clinical andPathologic Factors
To better understand risk stratication, let’s clarify the basic terminology surrounding risk stratication, namely the distinction between a prognostic versus a predictive factor. Prognostic factors are features of a disease that tells us about the natural
course and outcomes of the disease. This can help guide in deciding whether to treat
cancer. Predictive factors give information as to whether a patient will benet from
an intervention or not. It is important to note that prognostic is not equal to predictive. A common fallacy to which we are all susceptible is that patients with the worst
prognosis are the ones most likely to benet from aggressive treatment. It is sometimes the case but often it is not.
17 Stage II Colon Cancer: Towards anIndividualized Treatment Approach
https://t.me/medicina_free
Table 17.1 Role of chemotherapy for stage II colon cancer
Stage
II
cancer
Study
QUASAR
[2]
NACCP [9] RCT (subset) 468 5-Fu vs
INT-0035
[8]
Nordic [7] Pooled RCT 812 5-FU vs
IMPACT-B2
[4]
Gill etal.
[6]
MOSAIC
[5], 18
NSABP
C-07 [10]
Cochrane
[3]
SEERMedicare
[13]
BCCA data
base [11]
NR not reported
a=Stage II with no poor prognostic feature (obstruction/perf, T4, poor/undiff histology, >12 LN,
emergent surgery)
Trial type
RCT 2146 5-FU vs
RCT 318 5-Fu vs
Pooled RCT 1016 5-FU vs
Pooled RCT
(IMPACT-B2+2
Additional trials)
RCT (subset) 899 FOLFOX
RCT (subset) 699 FLOX vs
Meta-analysis 7097 Chemo
Registry 6234 Chemo
Registry 1697a Chemo
Pts Therapies
surgery
alone
surgery
alone
surgery
alone
surgery
alone
surgery
alone
1440 5-FU vs
surgery
alone
vs 5-FU
5-FU
vs.
surgery
alone
vs.
surgery
alone
vs.
surgery
alone
RFS (95%
CI)
0.78
(0.66–
0.93)
71% vs.
65% (OR
crosses 1)
7years:
79% vs
71%
(p=0.1)
NR 79% vs 79%
5year:
76% vs
73%
(p=0.061)
5year:
76% vs.
72%
(p=0.049)
5year:
83.7% vs
79.9%
(p=0.258)
5year:
82.1% vs.
80.1%
HR 0.83
(0.77–
0.92)
NR 5year: 70%
5year:
87.1% vs.
92%
(p=0.18)
OS (95%
CI)
0.82 (95%
CI:
0.7–0.95)
5year: 78%
vs 70% (OR
crosses 1)
7year: 72%
vs 72%
(p=0.83)
(p=0.81)
Year: 82%
vs. 80%
(p=0.057)
5year: 81%
vs 80%
(p=0.1127)
6year OS:
86.9 vs 86.8
(0.986)
10year OS:
79.5%
78.4%
(0.980)
89.7 vs 89.6 Moderate
HR 0.96
(0.91–1.02)
vs. 69.5%
5year: 82.9
vs 83.3
(p=0.561)
203
Strength
High
Moderate
Moderate
Moderate
Moderate
Moderate
Moderate
Moderate
Moderate
Moderate
204
https://t.me/medicina_free
The most commonly recognized prognostic factors in stage II colon cancer are as
follows: T4 disease, inadequate lymph node sampling (<12 lymph nodes), poorly
differentiated histology (in MSI-L/S patients), perforation, obstruction, lymphovascular invasion, perineural invasion, and positive resection margins [15]. It is very
important that the reader pays special attention to the high-grade tumor histology
and the importance of interpreting this in the context of the mismatch repair (MMR)
or microsatellite instability (MSI) status of the tumor. As we will go into detail
below, tumors with MMR deciency or MSI-H phenotype are often high grade yet
have an excellent prognosis. Whether these adverse risk factors are predictive of the
benet of chemotherapy is less clear. The strongest data to suggest a benet of chemotherapy in high-risk groups comes from the British Columbia Cancer Agency
(BCCA) registry which found a signicant survival advantage for patients with T4
tumors who received 5-FU chemotherapy (HR 0.5 95% CI: 0.33–0.77) [12]. The
National Cancer Database also showed that the high-risk group beneted from adjuvant chemotherapy at 57% vs 76% (P<0.001) [14]. A study of the California cancer
registry Showed that patients with T4 disease as the single highest risk factor had
improved OS with chemotherapy (HR 0.51, 95% CI 0.34–0.78) [16]. In contrast,
the SEER registry study could discern any differential chemotherapy advantage for
high versus low-risk groups [6, 13].
The MOSAIC study utilizing oxaliplatin-based therapy suggested a disease-free
survival advantage in the high-risk stage II group only with 5-year DFS of 82.3%
versus 74.6% (HR 0.72; 95% CI: 0.5–1.02) for FOLFOX versus infusional 5-FU
[5]. 10-year OS was 79.5% versus 78.4% in 5-FU/LV versus FOLFOX arms [11].
Although there was a statistically signicant improvement in DFS and OS, the benet of FOLFOX was less pronounced with only a small absolute improvement in
DFS and OS.Overall, the MOSAIC study provides some evidence supporting the
use of an oxaliplatin-based regimen in patients with stage II colon cancer with highrisk features. The benet is however less clear than in stage III colon cancer patients.
Therefore, treatment and chemotherapy decisions should be individualized based
on patient and disease characteristics.
G. Dosunmu and C.-Y. Liao
Risk-Stratification: Molecular Factors
The strongest data for both a prognostic and predictive factor exists for a deciency
in the mismatch repair pathway. It is beyond the scope of this chapter to explain the
nuances of MMR deciency and testing for it; but in brief, patients with defective
MMR tumors either have a germline loss of one of the MMR proteins (MLH1,
MSH2, MSH6, PMS2) or epigenetic silencing of the MLH1 promoter [17]. The
former is associated with Lynch syndrome and the latter is often in the setting of a
CpG Island methylator phenotype (CIMP). Defective MMR tumors can either be
tested for using a PCR panel of 5 reference microsatellite sites; if at least 2 show
instability then the tumor is characterized as MSI-H.More often in the clinical setting, immunohistochemistry testing (IHC) is used to stain for the presence or
17 Stage II Colon Cancer: Towards anIndividualized Treatment Approach
https://t.me/medicina_free
205
absence of one of the MMR proteins. By convention in the literature, we call a
tumor as defective MMR.
(dMMR) if they are either MSI-H or have an absence of an MMR protein by
IHC. Table 17.2 lists the major studies which have explored the prognostic and
Predictive value of MMR testing in stage II colon cancer. The majority of these
studies clearly show that those with dMMR stage II tumors have a superior prognosis compared to those with pMMR with hazards of recurrence or death often 50%
lower [18–22]. In the study by Sargent, etal. [21] patients with dMMR tumors who
received chemotherapy had a hazard of death which was nearly three times those
who were on observation (HR 2.95; 95% CI: 1.02–8.54). The reason why this may
be the case is speculative, but we know patients with dMMR often have an intense
immune response to their tumors and are in fact the only colon cancer cohort to date
where immune checkpoint inhibitors appear to be effective in the metastatic setting
[23]. It is suggested that chemotherapy may blunt this immune response. This
hypothesis is further corroborated by recent data suggesting that if there is a chemotherapy benet for these patients, it is only for those with germline tumors which
tend not to express the hyper-mutated phenotype [24]. These ndings of a detrimental impact have not been corroborated by the other studies listed in Table 17.2.
However, no study has found a clearly benecial impact of chemotherapy for this
cohort, who have an otherwise excellent prognosis. It is important to note that all of
Table 17.2 Role of dMMR as prognostic and predictive marker for stage II colon cancer
dMMR
colon
Study
Sargent etal.
[21]
Jover etal. [27] 76 (38
Kim etal.
(NSABP
c01-c04) [28]
Klingbiel etal.
(PETACC-3)
[20]
Hutchings etal.
(QUASAR) [19]
Gavin etal
(NSABP
C07-C08) [18]
dMMR defective DNA mismatch repair, pMMR procient mismatch repair, NR not reported
a
Includes only patients not treated with chemotherapy
b
Includes stage II and III
patients Therapies
102 (stage
II)
stage II)
98 (II and
III)
86 (stage
II)
167 (stage
II)
207 (93
stage II)
5-FU vs
surgery
alone
5-FU vs
surgery
Alone
5-FU vs
surgery
alone
FOLFIRI vs
5FU
5-Fu vs
surgery
alone
FOLFOX HR 0.48
DFS (vs
pMMR)
0.51 (95%
CI:
0.29–0.89)a
6year: 71%
vs 63%
(p=0.3)
HR 0.77
(95% CI:
0.4–1.48)
HR 0.26
(95% CI:
0.1–0.65)
RR 0.44
(95% CI:
0.29–0.67)
(95% CI:
0.3–0.7)
a
OS (vs
pMMR)
0.47
(0.26–0.83)
6year: 57.7%
vs 67.6%
(p=0.6)
Interaction
p=0.68
HR 1.27
(0.65–2.49)
2year: 2.2%
vs 5.1%
Interaction
p=0.55
Interaction
0.97
a
b
b
OS w/chemo
vs w/o chemo
2.95 (95%
CI:1.02–8.54)
69.2% vs
73.5%
(p=0.8)b
Interaction
p=0.62b
HR 1.47
(0.65–3.36)
NR
Interaction
p=0.848
Соседние файлы в папке @xirurgi_2025