Question

Is PET-CT better able than CT in detecting additional metastases from primary colorectal cancer in terms of specificity, sensitivity, and clinical impact in patients with potentially curable local metastases?

Recommendation

Colorectal liver metastases

If there are colorectal liver metastases, which are considered locally treatable on the basis of chest CT, liver CT and abdomen CT scan, an FDG PET(-CT) should be considered as additional imaging to detect possible extrahepatic metastases that may lead to changes in treatment.

 

Suspected recurrence

If a recurrence is suspected on the basis of an increased serum CEA with negative conventional imaging (including diagnostic CT of the chest and abdomen), an FDG PET-CT should be considered.

Introduction

After the latest search action in the most recent systematic review, five systematic reviews about the accuracy of various imaging techniques to detect colorectal liver metastases were published., among which two meta-analyses, and one prospective study.(1-6) Besides, one randomized clinical trail investigated the clinical impact of PET-CT on patients with potentially resectable liver metastases.(7)

Conclusions

It does not seem plausible that PET-CT more accurately than CT detects liver metastases in patients suspected of having liver metastases and patients known to have liver metastases of primary colorectal carcinoma. Sensitivity and specificity data of both imaging modalities are statistically comparable.

Level 2: B: (Patel S. et al., 2011; Niekel M.C. et al., 2010; Mainenti P.P. et al., 2010 ; Brush J. et al. 2009)

 

It seems plausible that PET-CT is higher sensitive than CT for the detection of extra hepatic metastases in patients suspected of having liver metastases and patients known to have liver metastases of primary colorectal carcinoma. It seems plausible that the specificity of both imaging modalities for the detection of extra hepatic metastases is similar.

Level 2: B: (Patel S. et al., 2011; Niekel M.C. et al., 2010; Mainenti P.P. et al., 2010; Brush J. et al. 2009)

 

There is some evidence that PET-CT in addition to CT reduces the relative risk of futile surgical treatment with 38% in patients with potentially resectable liver metastases of colorectal carcinoma.

Level 3: A2: (Ruers T.J.M. et al., 2009)

 

It seems plausible that PET-CT in addition to CT in 9%-21% of the patients with potentially resectable liver metastases of colorectal carcinoma leads to change of the treatment plan.

Level 2: B: (Patel S. et al., 2011; Chan K. et al., 2012)

 

It seems plausible that PET or PET-CT supports the decision making in patients with CT detected colorectal liver metastases, who are eligible for liver resection, through the detection of additional metastases that CT otherwise would have missed.

Level 3: B: (Chan K. et al., 2012)

Literature summary

Diagnostic accuracy

One systematic review, included only prospective studies on patients suspected of having colorectal metastases and patients known to have colorectal liver metastases. Out of three studies, the authors calculated a patient based pooled sensitivity of 96,5% (95% CI: 94,2%-97,9%) and specificity of 97,2% (95% CI: 92,8%-99,0%) of FDG PET-CT for the detection of colorectal liver metastases. Out of nine studies, a patient based pooled sensitivity of 83.6% (95% CI: 66.9, 92.8) and specificity of 94,9% (95% CI: 92,9%-96,3%) for CT was calculated.(4)

Out of seven prospective and retrospective studies (including 281 patients with known or suspected colorectal liver metastases), Brush et al. calculated a patient based pooled sensitivity of 91% (95% CI 87%-94%) and specificity of 76% (95% CI 58%-88%) of FDG PET-CT for the detection of colorectal liver metastases. For CT, no pooled sensitivity or specificity data were calculated.(3) Six primary studies in this systematic review (362 patients), compared FDG PET-CT with CT, among which four studies with patient level accuracy estimates. Two studies showed better accuracy data, one study showed comparable accuracy data and one study showed lower sensitivity, but higher specificity of FDG PET-CT compared to CT (FDG PET-CT sensitivity, range: 87%–100%, specificity, range: 75%–100%, CT sensitivity, range: 75%–98%, specificity, range: 25%–100%).

Patel et al. reviewed six prospective and retrospective studies (in total 440 patients with known liver metastases) and suggested that PET-CT has a higher patient based accuracy than CT for the detection of intra hepatic metastases and extra hepatic metastases.(2) Based on five studies with 316 patients, PET-CT was suggested to be more sensitive (range: 91%–100%) and more specific (range: 75%–100%) as compared to CT (sensitivity, range: 78%–94%, specificity, range: 25%–98%) for the detection of liver metastases. For extra hepatic metastases, based on three prospective studies with 178 patients, PET-CT was suggested to be more sensitive (range: 61%-97%) than CT (range: 64%-88%), but equally specific: PET-CT range: 95%-96% and CT range: 87%-97%.

Chan et al., compared the accuracy of PET, PET-CT and CT between seven prospective studies.(1) The authors suggest an additional value of PET and PET-CT to CT, especially for patients suspected of having colorectal liver metastases, who are eligible for liver resection. In those patients, PET and PET-CT may support the decision making, through the detection of additional metastases that CT otherwise would have missed. The authors based their conclusion on lesion based analysis.

The study design of the primary studies mentioned above, probably has introduced various forms of bias: sampling bias, differential bias, partial verification bias, and interpretation bias. These biases may have either underestimated, or overestimated the accuracy data. Therefore, the level of evidence of the conclusions of the systematic reviews is limited.

In the most recent prospective study (on 34 patients with histologically proven colorectal adenocarcinoma), that used bimanual palpation at laparotomy and intra operative ultrasound staging (IOUS) as gold standard, PET-CT had a sensitivity of 100% en a specificity of 96% for the detection of liver metastases. Multi detector row computed tomography (MDCT) in this study, had a sensitivity of 83% and a specificity of 96%. The differences between PET-CT and MDCT were non significant.(6)

Table 1: patient based sensitivity and specificity data of PET-CT and CT for the detection of liver metastases and extra hepatic metastases of colorectal carcinoma.

 

Liver metastases

Extra hepatic metastases

 

Sensitivity % (range)

Specificity % (range)

Sensitivity % (range)

Specificity % (range)

 

PET-CT

CT

PET-CT

CT

PET-CT

CT

PET-CT

CT

Niekel, 2010 (pooled)

96.5 (95% CI   94.2, 97.9)

83.6 (95% CI   66.9, 92.8)

97.2 (95% CI   92.8, 99.0)

94.9 (95% CI   92.9, 96.3)

 

 

 

 

Brush, 2011 (pooled)

91% (95% CI 87 - 94)

 

 76% (95% CI   58 - 88)

 

 

 

 

 

Brush, 2011 (range)

87%–100%

75%–98%

75%–100%

25%–100%

 

 

 

 

Patel et al, 2011

 

 

 

 

 

 

 

 

Bellomi, 2007

100 (80-100)

94 (71-100)

100 (93-100)

98 (90-100)

75 (35-97)

100 (63-100)

NA

100 (94-100)

Chua, 2007

94 (85-98)

91 (82-97)

75 (35-97)

25 (3-65)

 

 

 

 

Ramos, 2008

55 (46-64)

78 (70-85)

100 (66-100)

56 (21-86)

 

 

 

 

Rappeport, 2007

93 (76-99)

100 (88-100)

100 (29-100)

33 (1-91)

83 (52-98)

58 (28-85)

96 (78-100)

87 (66-97)

Selzner, 2004

91 (81-97)

90 (80-96)

90 (55-100)

88 (47-100)

89 (74-97)

64 (46-79)

95 (83-99)

97 (87-100)

Mainenti,   2011

100

83

96

96

 

 

 

 

 

Clinical impact

The randomized clinical trial, with 150 patients and three years follow-up, calculated a significant decrease of the percentage futile laparotomies in patients with liver metastases in the PET-CT arm (28%), as compared to the CT arm (45%). The relative risk reduction was 38% (95% CI: 4%-60%, p=0,042).(7) Overall survival (OS) and disease free survival (DFS) were comparable between the PET-CT arm and the CT arm (PET-CT arm: OS: 61.3%, DFS: 35.5%; CT arm: OS: 65.8%, DFS: 29.8%, p= 0.378 en p= 0.194 respectively). Besides, based on five studies one systematic review overviewed the effect of PET-CT on the treatment policy of patients with potentially treatable liver metastases.(2) After restaging with PET-CT, 13%-21% of the patients avoided surgery, 8%-13% of the patients had a change in surgery, and 9%-21% of the patients had a change in treatment plan.(1,2)

 

Considerations

FDG PET-CT as additional research is used after spiral CT or MRI still doubts about the nature of the lesions persist, but especially for the detection of extrahepatic disease. Although the literature is limited, FDG PET-CT seems to be a sensitive technique for local recurrence after local ablative therapy of liver metastases (RFA, cryoablation) for early detection (8; 11; 7; 17).

Several studies, including the Dutch POLEM study, show that FDG PET-CT is of value to show additional colonic disease in patients who are considered to be potentially resectable based on CT thorax and abdomen. In these patients FDG PET-CT has a clinically relevant impact on (selection of) treatment.

The evidence on the use of FDG PET-CT in elevated CEA levels with negative conventional diagnostics (including CT of the thorax / abdomen) is limited, but experience shows that FDG PET-CT may be of value, especially for detection of extrahepatic disease. It is unclear what upper limit for the CEA should be used.

Authorization date and validity

Last review : 16-04-2014

Last authorization : 16-04-2014

The validity of this guideline and its associated modules is five years. For various reasons, it may be necessary to edit modules sooner than intended. The National Working Group on Gastrointestinal Cancers therefore annually assesses the content of the guideline and its associated modules. By 2016 it is decided whether a new multidisciplinary working group should be installed to revise the entire guideline.

Initiative and authorization

Initiative : Nederlandse Vereniging voor Radiotherapie en Oncologie

Authorized by:
  • Nederlandse Internisten Vereniging
  • Nederlandse Vereniging van Maag-Darm-Leverartsen
  • Nederlandse Vereniging voor Heelkunde
  • Nederlandse Vereniging voor Klinische Geriatrie
  • Nederlandse Vereniging voor Nucleaire geneeskunde
  • Nederlandse Vereniging voor Pathologie
  • Nederlandse Vereniging voor Radiologie
  • Nederlandse Vereniging voor Radiotherapie en Oncologie
  • Vereniging Klinische Genetica Nederland

General details

All members were mandated by a scientific, professional or patient association. In the composition of the working group we tried to take national distribution, input from participants from both academic and general hospitals and representatives of various disciplines into account. Patients are also represented by delegation into the working group, as well as a focus group meeting.

Scope and target group

Goal

This guideline and its associated modules are - as much as possible - based on scientific research and / or consensus. It is a document with recommendations to support the daily practice of health care professionals involved in patients with (possible) colon cancer, rectal cancer or colorectal liver or lung metastases. It provides recommendations for diagnosis, treatment, follow-up and organization of care. The guideline and its associated modules are thus seeking to improve the quality of care, to increase transparency of choice for treatment and reduce diversity.

 

Target population

Each year colorectal cancer is identified in approximately 13,000 new patients. Rectal carcinoma occurs in about 1 in 3 patients of this. In the Netherlands, the colorectal cancer in both men and women rank third place in incidence of oncological diseases. The expected number of patients diagnosed with colorectal cancer are increased in 2020 to about 17,000, reflecting a slight increase in incidence (especially in men), population growth and aging.

Colorectal cancer is slightly more common in men than in women and ninety percent of patients 55 years or older. More information about the Dutch population can be found at the Netherlands Cancer Registry: www.cijfersoverkanker.nl

This guideline is applicable to all adult patients with (suspected) a primary colorectal carcinoma and patients with metastatic disease. Particular attention is given to the elderly. A separate guideline is available for adult patients with an increased risk of hereditary colon cancer.

Target Audience

This guideline and its associated modules are intended for all professionals involved in the diagnosis, treatment and rehabilitation of patients with (metastatic) colorectal cancer, such as surgeons, general practitioners, consultants, internists, gastroenterologists, (specialist) nurses, clinical geneticists, paramedics, pathologists, radiologists and radiotherapists. The complete guideline is used to develop a patient education text from the Dutch patients Consumer Federation (NPCF).

 

Members of the guideline panel

Name

Function

Hospital

Mandated

Mw. prof. dr. C.A.M. Marijnen chair

Radiotherapist

LUMC Leiden

NVRO

Mw. prof. dr. R.G.H. Beets-Tan

Radiologist

MUMC Maastricht

NVVR

Mw. S. de Bruijn

Specialist nurse

Renier de Graaf hospital Delft

V&VN

Mw. dr. A. Cats

Gastroenterologist

NKI-AVL Amsterdam

NVMDL

Prof. dr. E.F.I. Comans

Nuclear doctor

VUMC Amsterdam

NVNG

Dr. A.R. van Erkel

Intervention radiologist

LUMC Leiden

NVVR

Mw. dr. M.A.M. Frasa

Clinical chemist

Groene Hart hospitalGouda

NVKC

Mw. C. Gielen

Specialist nurse

MUMC Maastricht

V&VN

Dr. E.J.R. de Graaf

Surgeon

IJsselland hospital Capelle a/d IJssel

NVVH

Mw. dr. M. Hamaker

Geriatrician

Diakonessenhuis Utrecht

NVKG

Mw. dr. J.E. van Hooft

Gastroenterologist

AMC Amsterdam

NVMDL

Mw. H.J.A.M.. Kunneman

Researcher

LUMC Leiden

n.v.t.

Mw. dr. M.E. van Leerdam

Gastroenterologist

NKI-AVL Amsterdam

NVMDL

Dr. H. Martijn

Radiotherapist

Catharina-hospital Eindhoven

NVRO

Mw. dr. A.M. Mendez

Romero

Radiotherapist

EMC Cancer Insititute Rotterdam

NVRO

Mw. prof. dr. I.D. Nagtegaal

Pathologist

UMCN St Radboud Nijmegen

NVVP

Dr. L.A. Noorduyn

Pathologist

Lab. Voor Pathologie Dordrecht e.o.

NVVP

Mw. A. Ormeling

Patient

Stomavereniging

NFK

Drs. T.A.M. van Os

Klinisch Geneticus

AMC Amsterdam

VKGN

Dr. F.T.M. Peters

Gastroenterologist

UMCG Groningen

NVMDL

Mw. J. Pon

Patient

NFK/SPKS

NFK

Mw. dr. J.E.A. Portielje

Medical oncologist

Haga hospital Den Haag

Gerionne

Prof. dr. C.J.A. Punt

Medical oncologist

AMC Amsterdam

NIV

Mw. dr. H. Rütten

Radiotherapist

UMCN Radboud Nijmegen

NVRO

Prof. dr. H.J.T. Rutten

Surgeon

Catharina-hospitalEindhoven

NVVH

Prof. dr. J. Stoker

Radiologist

AMC Amsterdam

NVVR

Dr. P.J. Tanis

Surgeon

AMC Amsterdam

NVVH

Dr. J.H. von der Thüsen

Pathologist

MC Haaglanden Den Haag

NVVP

Prof. dr. H.M.W. Verheul

Medical oncologist

VUMC Amsterdam

NIV

Prof. dr. C. Verhoef

Surgeon

EMC Cancer Insititute Rotterdam

NVVH

Dr. Tj. Wiersma

General practitioner

NHG

NHG

 

 

Name

Function

Location

Mw. drs. A.Y. Steutel

process manager

Utrecht

Drs. T. van Vegchel

process manager

Amsterdam

Mw. S. Janssen-van Dijk

secretary

Rotterdam

M.P.  van den Berg

Researcher

Bilthoven

P.F. van Gils

Researcher

Bilthoven

Mw. J. Robays

Methodologist

Brussels

Mw. drs. Y Smit

Methodologist

Germany

Mw. A. Suijkerbuijk

Researcher

Bilthoven

Mw. dr. L. Veerbeek

Methodologist

Groningen

Mw. dr. L. Verheye

Methodologist

Brussels

Mw. dr. G.A. de Wit

Researcher

Bilthoven

 

Patient involvement

Two patient experts have been part of the guideline development group. One on behalf of the Dutch Ostomy Association and on behalf of SPKS/NFK. Based on a focus group meeting experiences of patients regarding care were collected. The guideline also has been used to develop a patient education text for the Dutch patients Consumer Federation (NPCF).

Method of development

Evidence based

Implementation

Promoting the use of recommendations begins with a broad (digital) distribution of the guideline, using direct mailing and an article published in the Dutch Journal of Oncology. In other journals or training sessions, for example, the guideline is brought to the attention. An implementation plan for this guideline contains the key recommendations and an overview of barriers and facilitators for implementation.

Methods and proces

The working group met in July 2012 for the first time. Based on an initial list of problems by working group members a survey among professionals involved in patients with colorectal carcinoma was held. Through this survey, sixty professionals supplied and prioritized possible subjects for revision. Also, a focus group meeting was held, collection patients' experiences. The eleven most relevant questions were answered, and translated into English. Also, alle recommendations were translated into English.

 

Each clinical question was andwered by a subgroup within the development group. External methodologists provided the literature search, review, critical assessment, evidence tables and a draft literature review. Workgroup members suggested other considerations and recommendations.

Responsibility

The Comprehensive Cancer Organisation the Netherlands (IKNL) promotes that people with cancer and their families have access to a consistent and qualitatively adequate care as close to home as possible. IKNL was established to improve treatment, care and clinical research in oncology. It also has a role in setting up and supporting networks for palliative care. IKNL supports multidisciplinary guideline development for oncology and palliative care and facilitates the maintenance, management, implementation and evaluation of these guidelines.

AGREE was used to check the methodological quality of the guideline.

Search strategy

Searches are available upon request. Please contact the Richtlijnendatabase.