Staging of colon cancer RAD Magazine, 43, 510, 27-28

Dr K HickmanSpecialist registrar radiology

Dr S WhitleyConsultant GI radiologist

Addenbrooke’s Hospital, Cambridge katy.hickman@addenbrookes.nhs.uk

IntroductionColorectal carcinoma is one of the most prevalent forms ofcancer worldwide. It is the third leading cause of cancer-related deaths in women and the fourth in men.1 The WorldHealth Organization classifies colorectal carcinoma as a sin-gle entity and therefore much of the literature does not dif-ferentiate colon from rectal cancer.2 However, they areclearly very different diseases in terms of anatomy, diagnos-tic work-up and treatment response.

Current role of CT in staging colon cancer The majority of patients with colon cancer will undergosurgery, either for attempted cure or for palliation.Therefore, definitive staging and decisions regarding adju-vant therapy are largely based on pathology analysis of thesurgical specimen.

While CT is the recommended staging examination forcolon cancer,4 preoperative radiological T and N stage arenot always reported as there has been uncertainty regardingits accuracy.5,6 The European Registration of Cancer Careconsensus document concluded that CT as an imagingmodality is limited in differentiating T1-3 disease and itsreal value is accurately detecting distant metastases.7

Therefore, this local-regional staging information is oftenestablished following surgery.

This means the role of the preoperative CT is two-fold:firstly to aid surgical planning and secondly to assess distantmetastatic spread.8,9 Reports should identify potentially dif-ficult surgical cases such as tumours that infiltrate into adja-cent structures or those presenting with bowel perforation.Detailing the size and site of the lesion will influence thetype of surgical resection performed. Finally, describing thepattern of metastatic spread ensures review of potentiallyresectable disease or identifies patients for whom surgerywould not be appropriate.

CT staging protocol CT of the thorax, abdomen and pelvis is the primary imag-ing investigation. The Royal College of Radiologists recom-mends the following protocol:4

• Oral iodinated contrast medium or one litre of water todelineate small and large bowel

• 100-150ml of intravenous iodinated contrast mediuminjected at 3-4ml/sec

• CT is commenced at 20-25 seconds (thorax) and 70-80seconds (abdomen and pelvis) post-injection.

• Sections should be acquired at 1.25-2.5mm to enablereformatting in the coronal/sagittal and axial planes at2-5mm for viewing.

Staging systems The Tumour Node Metastasis (TMN) classification is theaccepted system for staging of colorectal cancer (table 1,figures 1-5). The TMN classification can be converted intoprognostic staging set out by The American Joint Committeeon Cancer (table 2).10 However, it is not only the stage thatdescribes the risk profile of a tumour, factors such as extra-

mural venous invasion (EMVI) (figure 6) and bowel perfo-ration at presentation (figure 7) have also been shown toeffect prognosis.12-13

Treatment of colon cancer Surgical resection is the treatment for local, regional and,increasingly, distant metastatic disease with adjuvantchemotherapy being used for those with stage III disease.Six months of adjuvant chemotherapy is the standard dura-tion and it is recommended to start within eight weeks post-surgery.13

However, there is debate as to whether those withstage II disease should also receive adjuvant chemotherapy.Two separate meta-analyses did not find a significant sur-vival benefit of adjuvant chemotherapy for stage IIpatients.14,15 Yet, the largest randomised control trial exam-ining this found adjuvant chemotherapy provided a smallsurvival benefit (the five-year survival rates were 80.3% inthe chemotherapy arm compared with 77.4% in the obser-vation arm).16 This remains a contentious area. TheAmerican Society of Clinical Oncology recommends thosewith ‘high risk’ stage II colon cancer should receive adjuvantchemotherapy.15 High risk is defined as those with advancedtumour stage, poor tumour grading, EMVI or tumour perforation.7

Additionally, there is evidence that those with fewer thanseven lymph nodes examined pathologically are at higherrisk of recurrence, possibly due to inadequate staging at thetime of initial resection, and therefore should also be con-sidered for adjuvant chemotherapy.17,18

Chemo-radiotherapy versus chemotherapy was assessedfor those with T3N1, T3N2 and T4 disease, however, no sur-vival benefit was demonstrated and predictably, toxicity wasgreater with the addition of radiotherapy.19

Hepatic metastasis The liver is the most common site of distant metastatic dis-ease in patients with colon cancer; 50-70% of patients withcolorectal cancer will develop liver metastases and of thesearound 20-30% will be potentially resectable.20,21 Metastaticspread to the liver effects patient prognosis and early detec-tion allows for the opportunity to perform hepatic resectionsand improve outcome.22,23 The five-year survival followinghepatic resection is reported at around 30%, this is comparedto 5% for patients with untreated but potentially resectablemetastases.24,25 Therefore it is imperative that imaging accu-rately identifies liver metastases early on. The imaging tech-nique must be able to both identify the number and size ofthe lesions but also calculate the volume of the remainingliver to ensure resection is feasible.

CT is known to be an excellent modality for detectingliver metastasis with high sensitivity and specificity.26,27

However, MRI has been shown to be even better for identi-fying and characterising liver lesions.21,28

Peritoneal carcinomatosis Peritoneal carcinomatosis as a site of metastatic disease rep-resents a specific entity associated with poor prognosis anddoes not respond well to systemic chemotherapy alone. Thereis an increasing amount of evidence for the role of hyper-thermic intra-peritoneal chemotherapy, offering a chance ofcure in selected patients.7,29 Currently CT is used to assessthe extent of peritoneal carcinomatosis, however, one studyfound it lacked sensitivity, only detecting 33% of lesions.26,30

Future uses of CT in staging colon cancer The role of neoadjuvant chemotherapy in the treatment ofcolon cancer is being evaluated by a multi-centre randomisedcontrolled trial.3 The FOxTROT trial is looking at whethersix weeks of a chemotherapy regimen given preoperativelyto patients with locally advanced but resectable colon cancer

will improve disease-free survival. It is hypothesised thathigh risk patients (advanced T3 and T4 disease, lymph nodepositive and EMVI) will benefit from chemotherapy prior tosurgery.3,11

This places emphasis on the radiologist to make adetailed assessment of T and N stage on initial preoperativeCT to ensure patients in the high risk category do not missout on chemotherapy and low risk patients are not exposedunnecessarily to the side effects of chemotherapy.

Accuracy of CT in staging colon cancer While it is only with the evolution of multi-detector CT thatdescribing in the required level of detail can now be consid-ered, many are still wary of the reliability of CT to do soaccurately. A recent meta-analysis of 13 studies found thesensitivity and specificity of CT predicting invasion beyondthe bowel wall (T3 and T4) was 90% and 69% respectively.31

These results are of comparable accuracy with the earlyassessments of MRI staging of rectal tumours to stratifypatients into those who should and should not receive neo-adjuvant chemotherapy.32 For lymph node involvement, 16studies were included and it was found CT was 71% sensi-tive and 67% specific for detecting positive nodes.31

Given the relative lack of specificity for evaluating lymphnodes, the focus of imaging has been on local tumour inva-sion. However, distinguishing radiologically between invasioninto (T2) versus through the muscularis propria (T3) is dif-ficult. Smith et al suggest a subgroup of patients with T3tumours with greater than 5mm extramural invasion aremost convincingly associated with a poor prognosis and mostlikely to benefit from neoadjuvant chemotherapy.11 Initially,the FOxTROT study used >5mm extramural invasion as acut-off for recruiting high risk patients. However, recentstudies have shown suboptimal accuracy for distinguishingtumour invasion of T1-T3ab versus T3cd-T4.11,34-36 Therefore,the inclusion criteria for the FOxTROT study has beenrelaxed to T3 and above.33

Local staging with MR in colon cancer Neoadjuvant chemotherapy is established in the treatmentof rectal cancer. To facilitate this, preoperative use of MRhas been shown to be accurate at identifying poor prognosticfactors in rectal cancer.37-39 Literature on the use of MR inassessing poor prognostic factors in colon cancer is mixed.One study demonstrated a higher sensitivity but lower speci-ficity when directly compared to CT,40 whereas another paperfound no significant difference in accuracy between the twomodalities.41 Given the potential limited amount of additionalinformation provided by MR, CT remains the preferredimaging modality for assessing local disease in colon cancer.

Conclusion The potential introduction of neoadjuvant chemotherapy totreat colon cancer requires patients to be staged preopera-tively calling for even greater detail in the description oftumour appearances on initial CT. While CT has good sen-sitivity for the detection of colon cancers, there is large inter-centre (and indeed inter-observer) variation in accuracy.Even with current estimates of specificity, 31% of patientsare unnecessarily exposed to the side effects of chemotherapydue to inaccuracies inherent in CT staging.31 Two studiesexamining the use of CT colonography in staging wereincluded in the recent 2016 meta-analysis.42-43 The sensitivityand specificity values found in these studies were signifi-cantly higher compared with those using standard CT forboth tumour invasion and nodal detection.31 While there aremany considerations including cost, scan time and radiologistexperience, CT colonography seems to improve the radio-logical accuracy of local staging and warrants further inves-tigation if neoadjuvant chemotherapy is to be included inthe management of colon cancer.

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Figure 1T2 tumour that does not invade beyond the bowelwall. There is a smooth mural contour (arrows) andthe tumour demonstrates intraluminal projection.Axial (A) and sagittal (B) CT colonography recon-structed images.

A B

Figure 2T2 tumour that does not invade beyond the bowelwall (arrows) with a smooth mural contour. Sagittalreconstructed CT image.

Figure 3T3 tumour with spread beyond the bowel wall(arrows). Histology confirmed 8mm of extramuralinvasion beyond the muscularis propria.

Figure 4T4a tumour, proven on histology, infiltrating thelateral conal fascia (arrows).

Stage 1 T1/2 N0 M0

Stage IIA T3

Stage IIB T4

Stage IIIA T1/2 N1

Stage IIIB T3/4

Stage IIIC T1/2/3/4 N0/1 M1

Figure 5Enlarged and enhancing rounded lymph node.Histology confirmed N1 disease with multiple posi-tive lymph nodes. Adjacent to the lymph node isseen circumfrential nodular thickening of thedescending colon.

Figure 6T3 tumour with extramural venous invasion (EMVI)as evidenced by nodular spread along the vessels(arrows). EMVI confirmed on histology.

Figure 7Perforated T4b tumour with thickening of the wallof the caecum, invasion into the serosa and an adja-cent fluid and gas collection (arrows). CT coronalreformatted image.

Table 1Definitions of local invasion depth (T stage), lymphnode involvement (N stage) and presence of distantmetastases (M stage) in the sixth edition of theAmerican Joint Committee on Cancer (AJCC)system. Table 2

AJCC sixth edition staging classification.

Category Definition

Tx The primary tumour cannot be assessed

T0 No evidence of primary tumour

Tis Tumour restricted to mucosa

T1 Tumour invades through the mucosa into the submucosa

T2 Tumour invades into, but not beyond, the muscularis propria

T3Tumour invades through the muscularis propria into the subserosa, or into nonperitonealised pericolic or perirectal tissues

T4a Tumour perforates visceral peritoneum

T4b Tumour invades other organs

Nx Regional lymph nodes cannot be assessed

N0 No regional lymph node metastases

N1 Cancer cells detectable in one to three pericolic or perirectallymph nodes

N2 Cancer cells detectable in four or more pericolic or perirectallymph nodes

Mx The presence of distant metastasis cannot be assessed

M0 No distant metastasis

M1 Distant metastasis present