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Advanced and recurrent colorectal cancer


Introduction

The treatment of advanced and recurrent colorectal cancer represents a significant challenge to oncologists and surgeons, requiring a multimodality treatment approach. As a result, the National Institute for Health and Care Excellence (NICE; 2020) colorectal cancer guideline recommends these patients are best managed in specialist centres by an advanced colorectal cancer multi-disciplinary team (MDT).

For the purposes of this chapter, advanced primary colon and rectal cancer is defined as any or all of the following:

  • Tumours that locally invade into adjacent organs or structures (T4a and T4b lesions according to the American Joint Committee on Cancer [AJCC] TNM classification 8th edition). In the case of rectal cancer, these are tumours that have grown beyond the facial plane removed in a total mesorectal excision (beyond-TME).

  • Tumours that have spread to lymph nodes outside their regional lymphatic drainage area (AJCC TNM classification 8th edition, stage 4 disease).

  • Tumours that present with systemic (e.g., liver or lung) or peritoneal (e.g., ovaries or omentum) metastases (AJCC TNM classification 8th edition, stage 4 disease).

Recurrent colorectal cancer is defined as any or all of the following:

  • Local recurrence at site of previous surgery.

  • Peritoneal recurrence (colon or rectal peritoneal metastases – CRPM).

  • Systemic recurrence (non-locoregional nodal or solid organ metastases).

Incidence

Despite improved access to screening, colorectal cancer still presents as advanced primary or recurrent disease. Population-based studies suggest surgery with curative intent for all-stage disease has a 5-year local recurrence cumulative incidence of 13% (23% for rectal cancer), and systemic metastasis cumulative incidence of 26%. , The timing and sites of distant metastases are important to consider:

  • Liver metastases : Synchronous liver metastases are found in 15% of presenting colorectal cancers. Metachronous liver metastases within 5 years of diagnosis occur in 13% of cases.

  • Lung metastases : Synchronous lung metastases are found in 11% of presenting colorectal cancers. Metachronous lung metastases within 5 years of diagnosis occur in 6% of cases.

  • CRPM are found in 10.3% of primary right-sided cancers and 6.2% of left-sided cancers. They are found in up to 27% of primary rectal cancers.

  • Bone metastases : The 5-year incidence is 10%.

  • Brain metastases : The 5-year incidence is 2%.

Survival from surgery for advanced and recurrent colorectal cancer can be presented as relative survival (RS). This is the ratio of observed survival rate to the expected survival rate in a comparable population of patients without colorectal cancer. Longitudinal studies looking at Western populations over the last 40 years have suggested that the volume of surgery taking place for locally recurrent colorectal cancer with curative intent has risen from 16% of cases to 58%, with a 5-year RS of 36%. In the same population over the same time period, the volume of surgery with curative intent for metastatic colorectal cancer has risen from 7% to 24% of cases, with a 5-year RS of 24%. The median overall survival (OS) for patients being treated for metastatic colorectal cancer reported in phase III oncology trials and large observational series is 30 months.

Diagnosis and staging of advanced and recurrent colorectal cancer

Histological confirmation and biomarkers

Histological confirmation through biopsy is important before treatment. Deoxyribonucleic acid (DNA)-based biomarker testing such as RAS and BRAF mutation analysis not only guides epidermal derived growth factor (EGFR)-based antibody therapy (cetuximab and panitumumab), but also has prognostic significance:

Extended RAS analysis to include KRAS exons 2, 3 and 4, and NRAS exons 2, 3 and 4 is recommended. Tumours harbouring any of these RAS mutations respond poorly to EGFR antibody therapy. BRAF should accompany RAS analysis, as this is a significant negative prognostic indicator with regard to OS and may also predict EGFR antibody therapy response.

DNA mismatch repair (MMR) status (by microsatellite instability or MMR- immunohistochemistry) can assist genetic counselling, identification of Lynch syndrome, and have prognostic importance. NICE now recommends this testing in all newly diagnosed colorectal cancers.

In patients with advanced disease and those with local recurrence, colonoscopy may be used to obtain these samples. Other options include radiologically guided biopsy or in selected cases of CRPM, laparoscopic biopsy.

The serial enlargement of a lesion accompanied by either positive positron emission tomography–computed tomography (PET–CT) or rising carcinoembryonic antigen level may be accepted for tumour diagnosis.

In cases where biopsy of the recurrence is not possible, biomarker testing of either the original primary tumour or liver and lung metastasis is adequate with high concordance rates.

Radiology

Computed tomography

CT scanning of the thorax, abdomen and pelvis with oral and intravenous contrast is the gold standard for disease staging. Oral contrast opacifies small bowel and identifies sites of extra-luminal disease ( Fig. 7.1 ). CT also plays an important role in image-guided biopsy.

Figure 7.1, Computed tomography (CT) scan with oral and intravenous contrast demonstrating colorectal peritoneal metastases (CRPM) in the omentum ( arrow ) of a patient who previously had a right hemicolectomy for a T4N1M0 adenocarcinoma of the hepatic flexure. The distinction between this and the adjacent loop of small bowel ( B ), which has been opacified with oral contrast, can easily be made.

Magnetic resonance imaging

Magnetic resonance imaging (MRI) is a discriminatory test to stage tumours in the pelvis. In locally advanced/recurrent rectal cancer and CRPM involving the pelvis, MRI helps identify the planes of dissection and structures that require removal to achieve complete tumour clearance. Pelvic examination under anaesthesia is used alongside MRI to determine whether a clearance of over 1 mm (R0 resection for primary colorectal cancers) can be achieved. MRI liver is more sensitive for lesions over 10 mm in diameter than CT. Its diagnostic accuracy for liver lesions may be improved through contrast enhancers (gadoxetate). MRI small bowel with diffusion-weighted imaging is increasingly used to determine operability of CRPM.

Positron emission tomography

PET–CT is an investigation for the detection of extrahepatic metastases and local recurrence, and has been shown to change management in 8–30% of cases. Its role is limited to selected cases, with no consensus on its routine use.

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