Colorectal Cancer

Todd M. Blodgett, MD

Alex Ryan, MD

Omar Almusa, MD

Key Facts

Imaging Findings

PET poorly sensitive for small (< 1 cm) lesions; high positive predictive value
PET insensitive (29%) for small (< 1 cm) regional lymph nodes
Clinical management: PET affects surgical planning in approximately 30% of colorectal cancer patients
PET/CT more sensitive for regional/distant metastases than CT alone
> 95% sensitivity and ˜ 71% specificity for localization of relapse in patients with increased CEA
Staging: PET/CT will often show additional lesions not seen on CT, particularly in the liver
Restaging: Combination of a rising CEA level and a focal abnormality on PET/CT, often without a correlative CT abnormality
May be focal at ileocecal valve

Top Differential Diagnoses

Adenomas
Abscess
Physiologic FDG activity in bowel

Clinical Issues

Recurrence: Rising CEA level, abdominal pain (obstruction)

Diagnostic Checklist

Pre-treatment PET for staging, confirmation of FDG-avid disease
Mucinous adenocarcinoma has variable PET activity
Correlate focal increased activity in bowel on FDG PET with colonoscopy

Graphic shows a circumferential mass in the sigmoid colon

that causes marked narrowing of the colonic lumen. This appearance is often termed “apple core” lesion on barium enema.

Coronal PET (A), axial CT (B) and fused PET/CT (C) show a focal area of intense FDG activity

, corresponding to primary colon carcinoma in the proximal ascending colon

TERMINOLOGY

Abbreviations and Synonyms

Colorectal carcinoma (CRC), colon cancer, adenocarcinoma of the colon, rectal carcinoma

Definitions

Malignancy of the colon &/or rectum

IMAGING FINDINGS

General Features

Best diagnostic clue
- Initial diagnosis: None, usually indicated in history, although incidental focal intense FDG activity may represent an incidental malignant lesion
- Staging: PET/CT will often show additional lesions not seen on CT, particularly in the liver
- Restaging: Combination of a rising CEA level and a focal abnormality on PET/CT, often without a correlative CT abnormality
Location
- Initial diagnosis: Colon/rectum
- Staging: Additional liver lesions will often affect patient management
- Recurrence: Surgical anastomosis, regional lymph nodes, presacral area
Size: Variable, although PET has poor performance with small lesions including carcinomatosis
CMS coverage 2009: Initial diagnosis, staging, restaging; response to therapy not currently covered

Nuclear Medicine Findings

General
- Physiologic FDG activity
- Very common
  - Range from no activity to intense
- Usually linear in appearance
  - Right colon and cecum more commonly demonstrate increased physiologic FDG activity
  - May be focal at ileocecal valve
  - Short segment or linear FDG activity in bowel without correlative CT abnormality almost always physiologic
  - Focal or short segment moderate to intense activity is also common at the anorectal junction
- PET poorly sensitive for small (< 1 cm) lesions; however, high positive predictive value
- PET has limited sensitivity for peritoneal, omental metastases, highly mucinous tumors (may not be FDG avid)
- Positive predictive value high for detection of omental or peritoneal disease, which may be difficult to detect with CT alone
- Primary colon cancers may be incidentally identified with PET
  - Focal activity on FDG PET should be followed subsequently evaluated with colonoscopy
- 1-3% of patients undergoing PET/CT will have incidental accumulation in GI tract
  - Associated with substantial risk of underlying cancer or pre-cancerous lesion
Initial diagnosis
- Not recommended for screening, but PET/CT may play a role in screening patients with familial polyposis
- PET and PET/CT are CMS-covered but rarely used for initial diagnosis of colon cancer
- Colonoscopy is the preferred method for initial diagnosis
- Colonic adenoma and benign polyps can take up significant FDG and appear similar to carcinoma
- Not used for diagnosis of polyps &/or adenomas
  - However, FDG PET has 84% specificity for detecting colonic adenomas
  - Specificity improves with increasing size and grade of adenoma
Staging
- Clinical management: PET affects surgical planning in approximately 30% of colorectal cancer patients
- Main indication for PET/CT in CRC is assessment for consideration for metastasectomy
  - Goal of avoiding major surgery in patients with undetected nodal/distant metastases
- Consider pre-treatment PET for staging of all high risk patients and confirmation of FDG-avid disease
- PET insensitive (29%) for small (< 1 cm) regional lymph nodes
- Colon metastases most commonly go to liver
- Accuracy of distant staging for colorectal cancer: PET 78%, PET/CT 89%
  - PET/CT more sensitive for regional/distant metastases than CT alone
- Rectal metastases may bypass liver and metastasize to lung
  - Inspection of CT is pertinent to detect small pulmonary nodules that may be missed on PET
- Mucinous adenocarcinoma metastases may show calcification on CT
  - May also be falsely negative on PET
- Consider staging PET or PET/CT in any patient with a high risk primary lesion (> Dukes A lesion at surgery)
Restaging
- Established role for PET/CT in patients with suspected recurrent disease, particularly in patients with rising CEA levels
- Restage to detect locally recurrent disease, isolated metastatic disease in liver/lung, diffuse metastases
- > 95% sensitivity and ˜ 71% specificity for localization of relapse in patients with increased CEA
- PET to differentiate scar/fibrosis after surgery or radiation from tumor in rectal canal
- No evidence to support use of PET in routine surveillance following curative primary surgery
Response to chemotherapy
- Not currently a CMS-covered indication
- Early, i.e., metabolic but not anatomic, response to therapy can be imaged with FDG PET
  - Also can identify those with biologically aggressive disease unsuitable for resection
  - Reduction in SUV after 1-3 cycles of chemotherapy may predict response and correlate with subsequent tumor shrinkage
  - Future chemotherapy that achieves cytostasis over cytotoxicity may benefit from PET imaging

CT Findings

Localized tumor may be seen as intraluminal or intramural mass of soft tissue density adjacent to gasfilled or contrast-filled bowel lumen
- No mural thickening or pericolic fat in stage A tumors
- Some smaller primary tumors may not be visible on CT or PET
More advanced tumors associated with > 6 mm thickening of bowel wall and infiltration of pericolic fat
Annular carcinoma seen as a thickening of bowel wall and narrowing of lumen
- Thickening is concentric given perpendicular scanning plane
Extracolonic tumor spread indicated by loss of tissue fat planes between colon and surrounding structures
- Invaded muscle may be enlarged
- Colonic tumors may invade anterior abdominal wall, liver, pancreas, spleen, or stomach
Intussuscepting tumor may have target-like appearance with alternating rings of soft tissue and fat on CT
- Only seen if mesenteric fat is present between intussusceptum and intussuscipiens
60% of affected lymph nodes are detected by CT
Rectosigmoid tumors may metastasize to external iliac nodes
Liver is most common site of metastasis
- CECT shows well-defined areas of low density (relative to normal parenchyma) in portal venous phase
- In earlier arterial phase, hepatic mets may show rim enhancement or become hyper-/isodense to normal liver
- Other common sites of metastasis are lungs, adrenal glands, peritoneum, and omentum
Adrenal mets may be seen in as many as 14% of patients with CRC
- Typical findings include enlargement (> 2 cm), asymmetry, and heterogeneity
Bony and cerebral mets are uncommon

Imaging Recommendations

Best imaging tool
- PET/CT for initial staging and restaging
- Other modalities: For detection of primary lesion
  - Colonoscopy, double contrast barium enema (low sensitivity for polyps < 1 cm), and virtual colonography (gaining acceptance)
- Imaging of liver
  - PET/CT for high risk patients
  - Improves therapeutic management of patients with liver metastases
  - MR, US for indeterminate cases
- Rectal cancer
  - PET/CT has significant impact on course of treatment through more accurate staging
  - MR is also established in staging by facilitating accurate assessment of mesorectal fascia
Protocol advice
- PET/CT perform with diagnostic rather than noncontrast CT
  - Will help with abdominopelvic lesions adjacent to bowel and also increase confidence level for confirming hepatic lesions

DIFFERENTIAL DIAGNOSIS

Adenomas

Variable PET activity
Benign adenomas can show intense FDG activity and mimic carcinoma

Inflammatory Bowel Disease

Ulcerative colitis, Crohn disease
Increased activity often seen in affected bowel on PET

Infection

Increased activity in affected segments of bowel
Example: Pseudomembranous colitis

Abscess

Abscess and tumor can both show increased FDG activity
Increased FDG activity surrounding photopenic center = abscess, necrotic tumor
- Time course, prior studies useful to differentiate
Gas + fluid collection more specific for abscess

Physiologic FDG Activity in Bowel

Diffuse activity in part of/or throughout bowel
Usually linear
No corresponding bowel thickening on CT

Seroma

Photopenia on FDG PET; fluid density on CT

Post-Radiation Change

Early: Often difficult to assess due to increased FDG activity secondary to inflammation
Typically resolves in 2-6 months

Post-Surgical Scar/Fibrosis

Mildly increased FDG activity with normal post-surgical healing
Serial FDG PET: Scar/fibrosis has stable or decreased activity

PATHOLOGY

General Features

General path comments
- Colon polyps
  - 10% of all polyps are adenomatous
  - Increased incidence of carcinoma in villous tumors
Genetics: Some genetic predisposition in familial polyposis syndromes
Etiology
- Arises from pre-existing adenomatous polyps in colonic or rectal mucosa
- Age, smoking, diet high in fat and cholesterol, inflammatory bowel disease (mostly ulcerative colitis), genetic predisposition
Epidemiology
- 3rd most common cancer in USA
- 135,000 new cases per year in USA; 55,000 deaths per year
- Lifetime risk in general population: 5.9%
- 2/3 of colorectal cancers arise in colon, 1/3 in rectum

Staging, Grading, or Classification Criteria

Modified Dukes staging system for colorectal cancer
- Dukes A: Carcinoma in situ limited to mucosa or submucosa (T1N0M0)
- Dukes B: Cancer that extends into the muscularis (B1), into or through the serosa (B2)
- Dukes C: Cancer that extends to regional lymph nodes (T1-4, N1M0)
- Dukes D: Modified classification; cancer that has metastasized to distant sites (T1-4, N1-3, M1)

CLINICAL ISSUES

Presentation

Most common signs/symptoms
- GI bleed, seen in 60% of patients presenting with colorectal carcinoma
- Colonic adenoma presents: 50% with abdominal pain; 35% with bowel habit changes; 30% with occult bleeding
Other signs/symptoms: Recurrence indicated by rising CEA level, abdominal pain (obstruction)

Demographics

Age: Peak 7th decade; risk rises over age 40
Gender: Male preponderance for colon polyps

Natural History & Prognosis

Dukes A: 5 year > 90%
Dukes B: 5 year > 70%
Dukes C: 5 year < 60%
Dukes D: 5 year ˜ 5%
Small studies have shown improved disease-free and overall survival in patients evaluated with FDG PET imaging prior to surgery
Untreated patients with metastatic disease have life expectancy of 6-12 months
> 20% of patients who present with hepatic metastases are resectable, but surgery remains only potentially curative therapy
5 year overall survival following complete resection of isolated liver metastasis is 30-40% with 10 year survival of ˜ 25%
75% of patients who undergo liver metastasis resection experience relapse
- Partly due to inaccurate staging with occult extrahepatic metastases that go undetected prior to surgery

Treatment

Surgically curable if detected early
Adjuvant chemotherapy to prolong survival with lymph node positive disease
Rectal adenocarcinomas are sensitive to radiation
Local recurrence: Surgery, chemo ± radiation
Hepatic recurrence: Resection, radiofrequency ablation, hepatic arterial chemotherapy/radiotherapy
Patients with unresectable disease have median survival up to 20 months with non-surgical therapy
Estimation of gross tumor volume in reference to radiotherapy changed significantly in approximately 50% of patients when metabolic imaging was used

DIAGNOSTIC CHECKLIST

Consider

PET/CT with diagnostic CT for staging and for restaging patients which elevated CEA levels
Also consider PET/CT when the differential diagnosis is scar vs. residual or recurrent tumor

Image Interpretation Pearls

Mucinous adenocarcinoma has variable PET activity
Correlate focal increased activity in bowel on FDG PET with colonoscopy
Rectal cancer: FDG PET to differentiate scar/fibrosis after surgery or radiation vs. tumor

SELECTED REFERENCES

1. de Geus-Oei LF et al: Chemotherapy response evaluation with FDG-PET in patients with colorectal cancer. Ann Oncol. 19(2):348-52, 2008

2. Dresel S et al: PET in colorectal cancer. Recent Results Cancer Res. 170:109-24, 2008

3. Fletcher JW et al: Recommendations on the use of 18F-FDG PET in oncology. J Nucl Med. 49(3):480-508, 2008

4. Geus-Oei LF et al: Predictive and prognostic value of FDG-PET. Cancer Imaging. 8:70-80, 2008

5. Inoue K et al: Diagnosis supporting algorithm for lymph node metastases from colorectal carcinoma on 18F-FDG PET/CT. Ann Nucl Med. 22(1):41-8, 2008

6. Kristiansen C et al: PET/CT and histopathologic response to preoperative chemoradiation therapy in locally advanced rectal cancer. Dis Colon Rectum. 51(1):21-5, 2008

7. Shin SS et al: Preoperative staging of colorectal cancer: CT vs. integrated FDG PET/CT. Abdom Imaging. 33(3):270-7, 2008

8. Sobhani I et al: Early detection of recurrence by 18FDG-PET in the follow-up of patients with colorectal cancer. Br J Cancer. 98(5):875-80, 2008

9. Soyka JD et al: Staging pathways in recurrent colorectal carcinoma: is contrast-enhanced 18F-FDG PET/CT the diagnostic tool of choice? J Nucl Med. 49(3):354-61, 2008

10. Tan MC et al: A prognostic system applicable to patients with resectable liver metastasis from colorectal carcinoma staged by positron emission tomography with [18F]fluoro-2-deoxy-D-glucose: role of primary tumor variables. J Am Coll Surg. 206(5):857-68; discussion 868-9, 2008

11. Tsunoda Y et al: Preoperative diagnosis of lymph node metastases of colorectal cancer by FDG-PET/CT. Jpn J Clin Oncol. 38(5):347-53, 2008

Image Gallery

DDx: Focal FDG Uptake in Bowel

(Left) Axial CECT shows a short segment area of diffuse circumferential colonic mucosal thickening

in this patient who underwent a recent colonoscopy with biopsy showing adenocarcinoma. Small pericolonic lymph nodes are present

; one adjacent to a colonic mass almost always represents metastatic regional nodes. (Right) Specimen from a partial colectomy shows mass-like diffuse circumferential colonic wall thickening

and luminal narrowing

(Left) Axial CECT in the same patient with an unknown primary metastatic lesion to the liver shows an enhancing mass

near the rectosigmoid junction with adjacent perirectal lymph nodes

. (Right) Axial CECT shows a mass in the distal sigmoid colon

causing focal narrowing, compatible with colon carcinoma.

(Left) Axial CECT shows a short segment mass involving the proximal transverse colon

. Although a subtle finding, the patient was subsequently referred for colonoscopy, which proved a primary colonic adenocarcinoma. (Right) Axial CECT shows a low attenuation lesion within the caudate lobe of the liver

in this patient without a history of malignancy or a known primary.

(Left) Coronal PET (A), axial CT (B) and fused PET/CT (C) show a focal area of intense FDG activity in the distal ascending colon

that corresponds to an area of questionable thickening on the CT portion of the exam

. (Right) Axial CECT (top) and PET/CT (bottom) show intense FDG activity correlating with a focal mass within the lateral aspect of the proximal ascending colon