Colorectal cancer (CRC)
What are the clinical features of CRC?
- Usual features- Abdominal pain, Change in bowel habit, Haematochezia or melena, Anaemia without other gastrointestinal symptoms, Weight loss.
A change in bowel habit is a more common presenting symptom for left-sided cancers. Occult colonic bleeding occurs more often with caecal and ascending colon tumors. - Unusual features
Malignant fistula formation into adjacent organs, such as bladder or small bowel. This is most common with caecal or sigmoid carcinomas.
Streptococcus bovis bacteraemia and Clostridium septicum sepsis can be due to underlying colonic malignancies.
What are synchronous and metachronous cancers?
Synchronous CRCs are defined as two or more distinct primary tumors separated by normal bowel and not due to direct extension or metastasis. It occurs in upto 5 percent of patients with colon cancer.
Metachronous CRCs are defined as non anastomotic new tumors developing at least six months after the initial diagnosis. It occurs in upto 3 percent of patients in the first five years postoperatively.
Discuss the differential diagnosis of CRC?
Rare malignancies other than adenocarcinoma which are primary to the large bowel;
- Disseminated Kaposi’s sarcoma can involve the colon in patients with AIDS, manifested as characteristic violaceous macules or nodules.
- Primary non-Hodgkin’s lymphoma of large bowel most commonly arises in the cecum, right colon, and rectum. It typically appears as a large solitary mass.
- Colonic carcinoid tumors appear as submucosal nodules.
Discuss the staging for CRC?
Duke’s A- Localized to the mucosa and submucosa
Duke’s B- Extending into or through the muscle layer without lymph node involvement
Duke’s C- Lymph node involvement
Duke’s D- Distant metastases
TNM staging
T1 Tumour invades the submucosa
T2 Tumour invades muscularis propria
T3 Tumor invades through the muscularis propria into the subserosa, or into non-peritonealized pericolic or perirectal tissues
T4 Tumor directly invades other organs or structures, and/or perforates visceral peritoneum
N1- Metastasis in 1-3 regional lymph nodes. N2- Metastasis in >= 4 regional lymph nodes
M0- No distant metastasis M1- Distant metastases
What investigations are needed?
- CT scan of chest/abdomen/pelvis for staging
- MRI- useful for staging of rectal cancer. MRI is better at assessing perirectal node involvement.
- PET scans — it may be useful in localizing site of disease recurrence in patients who have a rising serum CEA level and nondiagnostic conventional imaging evaluation. It may also be used to evaluate patients who are thought to be candidates for resection of isolated colorectal cancer liver metastases.
- EUS – helps in assessing depth of invasion and nodal status in rectal cancer. Both transrectal or endorectal ultrasound (EUS) and MRI with endorectal coils can demonstrate the various layers of the rectal wall, but the EUS is less expensive.
- Tumor markers — Carcinoembryonic antigen (CEA) have a low diagnostic ability to detect primary CRC. However serum CEA has prognostic utility in patients with newly diagnosed CRC. Patients with preoperative serum CEA > 5 ng/mL have a worse prognosis, stage for stage, than those with lower levels. American Society of Clinical Oncology (ASCO) guidelines recommend that serum CEA levels be obtained preoperatively in patients with demonstrated colorectal cancer to aid in staging, surgical treatment planning, and in the assessment of prognosis. Elevated CEA levels should normalize following curative resection; if they do not, residual disease should be suspected.
Discuss the treatment of CRC?
Surgery is the only curative modality for localized colon cancer. The goal of colon cancer surgery is complete removal of the tumor along with the major vascular pedicle feeding the affected colonic segment and the lymphatic drainage basin. Regional lymphadenectomy is of prognostic and therapeutic value. At least 12 lymph nodes should be assessed for adequate staging. The 30-day postoperative mortality rate is around 5 %.
There is great variability in the frequency of postoperative bowel movements following a hemicolectomy. Most patients will have a minimal increase in frequency, and some have at least a temporary increase to four or more movements per day. Such patients may benefit from the addition of dietary fiber, and when necessary, an antimotility agent. The remaining colon will often adapt over a four to six month period, gradually returning to a more normal bowel pattern.
Laparoscopic resection is a reasonable option to open colectomy for potentially curative resection of colon cancer. Approximately 20 percent will require conversion to an open approach.
What is the role of adjuvant therapy?
- Node positive cancer- Adjuvant systemic therapy (5-FU based) is routinely used. Such treatment is associated with an approximately 30 percent reduction in the risk of disease recurrence, and a 22 to 32 percent reduction in mortality.
- Node negative cancer- ASCO guidelines suggest that a course of 5-FU-based adjuvant chemotherapy be considered for patients with incomplete sampling of the regional lymph nodes (ie, fewer than 12 nodes in the surgical specimen) or high-risk stage II disease (perforation, T4 lesions, poorly differentiated histology)
- The evidence is inconclusive as to the benefit of adding radiotherapy (RT) to chemotherapy for patients at high risk of local recurrence (ie, those with positive resection margins, perforation of the visceral peritoneum, or invasion of other adjacent organs). It is reasonable to consider RT on a case-by-case basis for such patients.
Discuss the palliative options?
I. Palliation of obstruction
- For unresectable distal obstructing tumors of the sigmoid colon, palliation involves a diverting colostomy and the creation of a mucous fistula with the distal bowel segment. The colostomy diverts the fecal stream and the mucous fistula decompresses the secretions from the distally obstructed bowel.
Patients with more proximal unresectable colon cancers can usually be bypassed with a side-to-side anastomosis from proximal bowel to a distal segment. This circumvents the obstruction, permitting internal decompression of the obstructed segments while avoiding a colostomy. - Colorectal self-expanding metal stents (SEMS) can be placed in poor operative candidates. It can be placed under endoscopic guidance with the aid of fluoroscopy. The most common complications are perforation (5%) and stent migration; less commonly, abdominal pain and bleeding.
II. Palliation of bleeding — Unresectable bleeding tumors present difficult situation. The continued presence of the fecal stream contributes to the bleeding process. The bleeding may resolve or improve with a colonic diversion or bypass. If this fails to control the bleeding, external beam RT may be successful.
Discuss the treatment of rectal cancer?
I. Neoadjuvant therapy- Chemoradiotherapy (5-6 week course, 5-FU based) should be considered in
- Patients with distal mobile rectal cancers, not amenable to local excision
- Patients with more proximal rectal tumors that are large, locally invasive, or clinically node-positive (ie, T3/4, N1).
- All patients who undergo neoadjuvant chemoradiotherapy followed by surgery for low-lying rectal cancers should receive postoperative adjuvant 5-FU-based chemotherapy (4 cycles), even if they have no residual tumor in the surgical specimen.
II. Surgery-The number of lymph nodes sampled is an important predictor of outcome. The surgical specimen should contain at least 12 lymph nodes. The criteria for unresectability are not clearly defined. Locally advanced rectal cancer is defined by some to be T3/4 or N1 disease and/or clinically bulky
There are three surgical options for rectal cancer:
- Abdominal perineal resection (APR) — It is the gold standard for surgical therapy of distal rectal cancers. It involves removal of the tumor along with a complete proctectomy. This results in the need for a permanent colostomy.
Neoadjuvant chemoradiotherapy may facilitate the conversion of a planned APR to a sphincter-sparing LAR by promoting tumour regression. Thus, the preferred approach for patients with T2/T3 low-lying rectal cancers is neoadjuvant chemoradiotherapy that may, in some cases, permit a sphincter-preserving procedure to be performed rather than APR. - Low anterior resection & colo-anal anastomosis — for rectal cancers involving the upper third of the rectum, as long as the surgeon can obtain a distal margin of at least 2 cm (some say 1cms).
- Local excision- superficially invasive small cancers may be effectively managed with local excision by transanal approach within 10 cm of the anal verge. Minimally invasive endoscopic techniques such as transanal endoscopic microsurgery (TEM) have expanded the possibility of transanal excision to otherwise inaccessible lesions that are within reach of the endoscope (up to 18 cm from the dentate line)
III. Adjuvant therapy
In contrast to colon cancer, in which the failure pattern is predominantly distant metastases, the site of first failure in rectal cancer patients is equally distributed locally (ie, pelvis) and in distant sites (eg, liver, lung). Local recurrence is mainly related to difficulties in obtaining optimal surgical clearance of the radial margin
- Postoperative adjuvant radiation and chemotherapy (5-FU based) should be offered to all patients with transmural or node-positive disease
- For patients with favorable histology T1 rectal cancer, local excision alone suffices. Postoperative irradiation and chemotherapy should follow local excision procedures for patients with unfavorable histology T1 and all T2 tumors.
IV. Locally recurrent rectal cancer
The choice of therapy depends upon prior therapy and the local extent of the recurrence. Surgery or RT may permit successful salvage. Local re-radiation alone may provide palliation, but does not prolong survival
Discuss localization of rectal tumours at endoscopy?
The most reliable landmark is the dentate line, where the squamous mucosa of the anus transitions to the columnar mucosa of the rectum. The dentate line is located in the middle of the anorectal ring, which is comprised of the sphincters (internal and external). These muscles are responsible for fecal continence and usually extends 1 to 3 cm proximal to the dentate line. A tumor has to be located high enough above the top of the anorectal ring to allow for an adequate distal margin if sphincter preservation is to be achieved.
Discuss resection of colorectal cancer liver metastases?
a. Patients with extrahepatic disease that should be considered for liver resection include:
- resectable/ablatable pulmonary metastases
- resectable/ablatable isolated extrahepatic sites—for example, spleen, adrenal, or respectable local recurrence
- local direct extension of liver mets to, for e.g., diaphragm/adrenal that can be resected.
Contraindications to liver resection-
- non-treatable primary tumour;
- widespread pulmonary disease;
- locoregional recurrence;
- peritoneal disease;
- extensive nodal disease, such as retroperitoneal, mediastinal or portal nodes;
- bone or CNS metastases.
b. Normally, colorectal cancer resection & liver resection would not be performed synchronously. Lesions discovered at operation should not be biopsied. Patients with potentially resectable liver disease and who have undergone radical resection of the primary tumour should be considered for liver resection before consideration of chemotherapy. Patients with unfavourable primary pathology such as perforated primary tumour or extensive nodal involvement should be considered for adjuvant chemotherapy prior to liver resection and be restaged at three months.
c. The natural history of metastatic colorectal cancer is variable. Median survival without treatment is less than eight months from presentation but the prognosis is better for those patients with isolated hepatic metastases. However, even in the group of patients with limited metastatic liver disease, survival at five years is exceptional. Several recent large series on resection for colorectal liver metastases have reported five year survival ranging from 25% to 44%, with operative mortality of 0–6.6%.
d. It has been argued that the limiting factor to the number of lesions that can be resected is whether it is technically possible to remove all tumours. Patients with solitary, multiple and bilobar metastatic disease are candidates for liver resection. The surgeon should define the acceptable residual functioning volume, approximately one third of the standard liver volume, or the equivalent of a minimum of two segments
e. Recent data suggest that if lung metastases of colorectal origin are resectable, five year survival following thoracotomy is similar to that observed in patients after resection of colorectal liver metastases.
f. Recurrence may occur in up to 60% of patients (usually in the first 2 years) following liver resection for colorectal metastases with the most common site being in the liver. These may be suitable for re-resection. The reported morbidity and mortality rates and long term survival rates of re-resection are similar to those reported for the original hepatectomy despite the greater technical difficulty of the procedure.
g. Chemotherapy for metastatic colorectal cancer can improve survival and should be considered in all patients not suitable for surgery. NICE now recommend the use of oxaliplatin based regimens as first line therapy for all patients with non-resectable disease. There is no evidence to support ‘‘pretreatment’’ with neoadjuvant chemotherapy in patients with resectable disease.
Ref-
