Investigation of recurrent cancer
Presentation of local recurrence[edit source]
Patients with local recurrence may be symptomatic or asymptomatic.
Symptoms of local recurrence depends on the site of recurrence and therefore can vary between patients:
- In patients with anastomotic or luminal recurrences, symptoms are usually similar to those of patients with primary colorectal cancer in that patients usually present with rectal bleeding, anaemia or altered bowel habits. Depending on the extent of the local recurrence, patients may also present with varying degrees of bowel obstruction. Where there has been a previous low rectal anastomosis, the luminal recurrence may be readily palpable on digital rectal examination during routine follow up. In patients who have previously undergone an abdominoperineal excision, clinical findings may be limited.
- Patients with nodal or surgical bed recurrences may present with pain from mass effect on neighbouring structures (such as obstruction of ureters or neuropathic pain from the sciatic nerve compression) or may present as a palpable mass.
- Patients with pelvic recurrences are typically symptomatic, with pain as the most common presentation.
Asymptomatic patients may present with a rising serum carcinoembryonic antigen (CEA) level or have a new abnormality detected on surveillance imaging or surveillance colonoscopy.
Presentation of systemic recurrence[edit source]
The most common sites of systemic recurrence following curative treatment of colorectal cancer are hepatic followed by pulmonary metastases. Other visceral metastases such as adrenal metastases, metastases to distant nodal basins such as the para-aortic nodes, bony metastases and brain metastases can also occur but do so much less frequently. As with patients with local recurrence, patients with systemic recurrences may be symptomatic or asymptomatic. Symptoms varies depending on the site of recurrence, and may include abdominal pain from hepatomegaly, jaundice, pleuritic chest pain or shortness of breath. Patients with extensive disease may also have anorexia, cachexia and weight loss. Most recurrences present within the first 3 years after curative resection. Asymptomatic disease is usually detected during routine surveillance as a result of an elevated CEA or a new abnormality detected on surveillance CT scan.
Overview of evidence (non-systematic literature review)[edit source]
No systematic reviews were undertaken for this topic. Practice points were based on selected evidence. Please see Guidelines Development for more information.
Investigation of suspected local recurrence[edit source]
Initial assessment of patients with suspected local recurrence should include:
- serum CEA
- (unless contraindicated) contrast computed tomography (CT) scan of the chest, abdomen and pelvis
- positron emission tomography (PET) scan
- pelvic MRI (for pelvic recurrences).
Depending on individual circumstances, additional investigations may also be necessary, including colonoscopy (if appropriate) prior to further surgery, CT or magnetic resonance angiography (MRA) for suspected mesenteric or iliac vessel involvement, or cystoscopy for potential bladder involvement. Particularly with isolated pelvic recurrences, an examination under anaesthesia can be very helpful as pain often limits the utility of clinical examination. Furthermore, an examination under anaesthesia may also permit other investigations or procedures to be undertaken at the same time such as biopsies, cystoscopy with ureteric stent insertion in the event of ureteric obstruction..
As re-operative surgery is usually complex and may be associated with significant surgical morbidity, histological confirmation of recurrent disease should ideally be obtained prior to embarking on surgery. This is also preferable if neoadjuvant chemoradiation is to be considered prior to surgery. Where the recurrence is extra-luminal, options for biopsies include transvaginal biopsies (where the recurrence is adjacent to the vagina) at the time of an examination under anaesthesia or CT-guided percutaneous biopsies. In situations where the recurrence site is difficult to access for histological confirmation and patient history, serum CEA, MRI as well as PET-CT corroborates the diagnosis of recurrence, biopsies may not be necessary following discussion on a multi-disciplinary team meeting. Further, although CT guided biopsies may carry the potential risk of biopsy tract seeding, reports on this are scant and the risk is likely to be negligible. On balance, histological confirmation is preferred because of the potential morbidity of re-operative procedures.
Investigation of suspected systemic recurrence[edit source]
Initial assessment of patients with suspected metastasis should include all of the following:
- serum CEA
- (unless contraindicated) contrast CT scan of the chest, abdomen and pelvis
Depending on the site of the metastasis, further investigations are usually necessary to determine the local extent of the disease so as to facilitate decision making about appropriateness of further surgical intervention.
In an era where CT and MRI are readily available, the role of liver ultrasound is somewhat limited although it remains a useful investigation in patients with extensive liver metastases where curative resection is impossible. The reported sensitivity of liver ultrasound varies between 50% and 76%, but it is noteworthy that not only is ultrasound user-dependent but also size-dependent. Sensitivity of liver ultrasound can be as low as 20% for lesions under 10mm. For most patients with hepatic metastases, magnetic resonance imaging (MRI) of the liver is currently considered the most accurate staging modality for liver metastases. The addition of diffusion weighted imaging may improve the yield of MRI in detecting smaller liver metastases. MRI using a liver-specific contrast agent, disodium gadoxetate (Gd-EOB-DTPA; Primovist)) is currently the most sensitive and specific test for liver metastases. A recent systematic review has confirmed its superiority over CT.
The purpose of a PET scan in patients with systemic recurrences is to confirm the presence of metastatic disease, but it is also useful for further systemic staging to rule out the presence of extra-hepatic disease. A recent study from Adelaide found PET to be superior CT in staging extra-hepatic disease and that this was useful in guiding patient selection for consideration of liver resection.
Intra-operative ultrasound of the liver is a useful adjunct in patients to rule out the presence of small hepatic metastases that may otherwise be otherwise missed on other imaging modalities. It also allows the surgeon to assess the anatomical relations between the metastasis and hepatic vascular and biliary anatomy so as to determine the best surgical approach. Liver biopsies are generally not needed to confirm the diagnosis of liver metastases as imaging alone is usually sufficient for diagnosis. Nor is this recommended, because of concerns of biopsy tract seeding. Biopsying colorectal liver metastases has been shown to cause tumour dissemination and adversely affect survival.
As most colorectal cancer related lung metastases are usually located within the lung parenchyma in the periphery of the lung, the most important diagnostic investigations are CT scan of the chest and a PET scan. Comparison with previous imaging is important as interval changes are usually significant. While most patients do not require additional investigations, depending on the anatomic location of the metastasis, diagnostic certainty or whether or not there may be co-existing abnormalities such as questionable uptake within mediastinal nodes, additional investigations such as endobronchial ultrasound, bronchoscopy, or even mediastinoscopy, may be required.
Patients with metastatic disease should be fully assessed with imaging (MRI, PET scan) or additional tests prior to commencement of any chemotherapy. Chemotherapy may render small metastatic tumour deposits invisible on subsequent imaging, although 80–90% of these will reappear after surgery or cessation of chemotherapy.
Initial assessment of patients with suspected local or systematic recurrence should include serum CEA, contrast CT scan of the chest, abdomen and pelvis (unless contraindicated) and PET.
- Kinkel K, Lu Y, Both M, Warren RS, Thoeni RF. Detection of hepatic metastases from cancers of the gastrointestinal tract by using noninvasive imaging methods (US, CT, MR imaging, PET): a meta-analysis. Radiology 2002 Sep;224(3):748-56 Available from: http://www.ncbi.nlm.nih.gov/pubmed/12202709.
- Vreugdenburg TD, Ma N, Duncan JK, Riitano D, Cameron AL, Maddern GJ. Comparative diagnostic accuracy of hepatocyte-specific gadoxetic acid (Gd-EOB-DTPA) enhanced MR imaging and contrast enhanced CT for the detection of liver metastases: a systematic review and meta-analysis. Int J Colorectal Dis 2016 Nov;31(11):1739-1749 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27682648.
- Wong GY, Kumar R, Beeke C, Ullah S, Chen J, Karapetis C, et al. Survival Outcomes for Patients With Indeterminate 18FDG-PET Scan for Extrahepatic Disease Before Liver Resection for Metastatic Colorectal Cancer: A Retrospective Cohort Study Using a Prospectively Maintained Database to Analyze Survival Outcomes for Patients With Indeterminate Extrahepatic Disease on 18FDG-PET Scan Before Liver Resection for Metastatic Colorectal Cancer. Ann Surg 2017 Feb 6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28169837.
- Jones OM, Rees M, John TG, Bygrave S, Plant G. Biopsy of resectable colorectal liver metastases causes tumour dissemination and adversely affects survival after liver resection. Br J Surg 2005 Sep;92(9):1165-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15997444.
- Kuhlmann K, van Hilst J, Fisher S, Poston G. Management of disappearing colorectal liver metastases. Eur J Surg Oncol 2016 Dec;42(12):1798-1805 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27260846.