Role of PET in Colorectal Cancer

Principles

1. Conventional imaging displays anatomy; PET displays metabolic changes.

2. Indications in colorectal cancer are selective but rapidly evolving.

3. Works based on Warburg effect:
- cancer cells exhibit enhanced glycolysis
- and often have increased expression of epithelial glucose transporter proteins, e.g. hexokinase and pyruvate dehydrogenase that lead to enhanced glucose metabolism.

4. 18F-FDG-PET uses radionuclide flurine-18, attached to a glucose analog.
- competes at the glucose binding site.
- but once internalized, accumulate within cells as cannot be metabolized

5. PET Scanners detect positron emission that results from 18F-FDG decay, generates a pattern of distribution
- this can be reconstructed in sagittal, coronal or axial planes.

6. PET now often fused with CT or MRI to correlate anatomic detail with biologic activity.
- proven in numerous studies to increase sensitivity, specificity, positive and negative predictive value.
- e.g. in pelvic rectal Ca recurrence: 98%, 96%, 90% and 97%; with IV contrast CT.

7. Need cautious interpretation as some organs have high glucose metabolism, i.e brain, myocardium
- and some organs shine up where 18F-FDG excreted- kidney, bladder.
- small and large bowel can exhibit physiologic uptake which mustn't be confused with malignancy.

8. Because of competition between glucose and 18F-FDG uptake, must fast patients for 4-6h before the study.
- and not performed in pts with elevated serum glucose due to higher false-positive rates.

9. Sensitivity and specificity depend on various factors including tumour size and biology.
- unreliable for lesions <1cm.
- tumour biology dictates relative 18F-FDG PET avidity
- .e.g less sensitive in detecting mucinous than nonmucinous colorectal Ca.
- degree of dysplasia important: worse = more avid.

10. Commonly used in malignancy but benign conditions may also show up involving high glucose use.
- inflammatory processes e.g. infection, scarring, inflammatory bowel disease
- though in general highest in malignancies, there may be areas of overlap making interpretation equivocal.

11. Timing of PET in relation to therapy is important.
- FDG avidity increased after radiotherapy and reduced after chemo; chemo associated with 40% decrease in tumor cell hexokinase activity.
--> if performed within 4 weeks of chemo, associated with higher false-negative rates.

Screening

Utility in screening unproven; no prospective trials.
It costs $3000-$6000
Any positive finding would require workup.
Given cost limitations, unlikely to be a feasible screening tool.

Staging

Preop staging purpose differs between colon and rectum

In colon, want identify patients with metastatic disease; incl for possible metastasectomy
--> good results are both a result of improved therapy but also perfecting patient selection.
One of the most compelling indications for PET is evaluation of patients undergoing metasectomy
- several studies have demonstrated 18F-FDG PET to be superior to all other conventional imaging in metastatic disease detection: sensitivity 80-100%, specificity 73-100%
--> about 25% of high-risk patients will be ruled out on basis of PET; changes management in 40%.
In the setting of colon cancer staging, 18F-FDG-PET should be considered in patients with high clinical suspicion

In rectum, want to stage not only metastatic disease but also identify advanced locoregional disease who whill benefit from neoadjuvant therapy.
- traditionally have used MRI and ERUS to delineate local disease stage
- additional benefit of PET has been limited limited, as resolution cannot show T stage and signal overlap from tumours to nodes complicates detection.
-- but addition of CT to PET has been an improvement; now patients restaged due to identification of occult lymph node mets
--> changed management in about 25%
Has potential to alter treatment strategies but further studies needed for preoperative staging role.

Treatment Response Assessment

Changes in metabolic activity may preced radiographic evidence of tumour response
- may be 100% sensitive and 60% specific for response.
Correlates with survival outcomes; recurrence-free survival.
Further research needed to see if PET changes correlate with hostopathologic response.
- if correlation exists, such patients may benefit from more aggressive surgical intervention.
May help show radiofrequency ablation response through metabolic change.
- PET may serve a role in assessing RFA completeness and monitoring for recurrence after therapy.

Colorectal Cancer Recurrence

Up to 50% may develop recurrent disease; 10-15% of these being operative candidates.
- recurrence detected clinically, biochemically (CEA) or by changes in conventional imaging.
- PET has highest sensitivity and specificity in both local recurrence and metastatic disease.
- overall sensitivity and specificity of 97% and 76% respectively.

No role in routine surveillance but established role in pts with suspected recurrence; ie:
1. In patients with rising CEA but radiographically occult disease
2. Evaluation of indeterminate or equivocal lesions seen on standard imaging
3. Exclusion of other sites of metastatic disease in patients being considered for metastasectomy.

Up to 70% of pts with asymptomatic recurrence will present with occult disease and rising CEA, often without radiographic findings.
- FDG-PET supplements CT; positive predictive value 89%, negative predictive value 100%
- superior to all other modalities, predicts unresectable disease in 90%
Importantly, MRI and CT struggle in differentiating scar tissue and recurrent disease; combined with FDG, it can.
FDG-PET reduces rates of nontherapeutic laparotomy by better selection.

Also probably reduces costs overall, by elimination of unnecessary procedures.