Rectal cancer treatment programs vary by the stage of the disease, and whether it is operable or not. A treatment program may initially be defined at the time of diagnosis based on the "Clinical stage" (see below), and further treatment may be required after surgical removal of the tumor based on the "Pathologic stage" (see below).
Your surgeon or oncologist will determine your Clinical stage at the time you are diagnosed (when a tumor biopsy obtained by colonoscopy/sigmoidoscopy shows cancer) based on radiology scans (CT, MRI, or PET) and endoscopy results, including study of the tumor by endoscopic ultrasound (EUS). A treatment program based on Clinical stage will be developed that may include chemotherapy, radiation, and/or surgery in a variety of combinations and sequences outlined below.
If the tumor is removed-either as the first intervention, or after chemotherapy and radiation therapy, the pathology report will reveal the Pathologic stage based on the size, invasiveness, and spread to lymph nodes of the rectal tumor. You may be asked to undergo additional therapy after surgery with chemotherapy and/or radiation-based on Pathologic stage as also outlined below.
Note 1: The treatment programs for rectal cancer are among the most complex in all of oncology due to the need to utilize all 3 main therapeutic modalities (surgery, chemotherapy, radiation) to achieve the best results for the majority of patients. Treatment can sometimes be arranged with equally good results in different sequences that must be individually tailored to each patient based on tumor properties, age, coexisting diseases, etc. Please discuss the choice of treatment program with your doctors and why it is best for you.
Note 2: It is sometimes a matter of clinical judgment whether a given tumor is in the colon (upper part of large intestine) or rectum (last ~6 inches of large intestine where stool is held prior to a bowel movement). Information provided at the time of sigmoidoscopy/colonoscopy is usually key in determining the tumor location in colon or rectum.
Detailed Guide: Colon and Rectum Cancer - How Is Colorectal Cancer Staged?
Rectal Cancer Treatment ( by Clinical stage at diagnosis )
- Stage I (90% 5-year survival)
- Surgical resection (often transanal for small tumors) followed by observation:
- colonoscopy surveillance for new cancers and recurrence of prior cancer
- checkups and CEA tests every 3-6 months for 3 years, every 6 months for 5 years
- Stage II (60-85% 5-year survival)
- Chemotherapy (low dose Xeloda OR 5-FU delivered by constant pump infusion) + radiation therapy (~6 weeks) followed by surgical resection (LAR vs. APR) (This approach also called "neoadjuvant") OR
- Surgical resection (LAR vs. APR) followed by chemotherapy + radiation (as above)
- Full dose chemotherapy (FOLFOX) may be offered in stage II disease if pathology analysis of the biopsy or resection specimen reveals aggressive appearance of the tumor cells Either followed by observation
- colonoscopy surveillance for new cancers
- checkups and CEA tests every 3-6 months for 3 years, every 6 months for 5 years; CT scans annually for 3 years based on predicted risk of recurrence
- Stage III (27-60% 5-year survival)
- Chemotherapy/radiotherapy (as for stage II) followed by surgical resection (LAR vs. APR) followed by full dose chemotherapy (FOLFOX) OR
- Surgical resection (LAR vs. APR) followed by courses of chemotherapy + radiation (as above) and full dose chemotherapy (FOLFOX)
Either followed by observation
- colonoscopy surveillance for new cancers
- checkups and CEA tests every 3-6 months for 3 years, every 6 months for 5 years; CT scans annually for 3 years
- Stage IV (5-7% 5-year survival)
- 1st line therapy: FOLFOX (or FOLFIRI) + avastin
- 2nd line therapy:FOLFIRI (or FOLFOX) + avastin OR
- Irinotecan + cetuximab (or panitumumab) [if tumor is not mutated at the K-Ras oncogene]
- 3rd line therapy: panitumumab (K-ras non-mutated) OR
- Irinotecan + cetuximab (K-ras non-mutated) OR
- Clinical Trial (if K-Ras mutated)
***If Pathologic staging of a surgical specimen results in upwards revision of original Clinical stage to a higher Pathologic stage, appropriate additional treatment is offered if it has not already been received, i.e.- chemotherapy/radiation (for upstaging to Pathologic stage II or III) and/or full dose chemotherapy (for upstaging to Pathologic stage III)
Rectal Cancer Operations
- Transanal excision- As the name implies, small tumors or polyps of the lower 1/3 of the rectum are excised from the inside of the rectum directly, without having to open the pelvis, and without disrupting the anal sphincter.
- Pros: Minimally invasive, rapid healing time, effective for early stage cancers
- Cons: Inappropriate for larger, more invasive tumors, can have a higher recurrence rate for more advanced stage I tumors
- Low Anterior Resection (LAR)- The surgeon opens the pelvis and excises the tumor and margin of surrounding normal rectum proximal (towards the stomach) and distal (towards but not including the anus) and then reconnects the colon to the remaining rectal stump. Sometimes, for technical reasons, the operation is done in two steps, and the patient is given a temporary colostomy (external bag for stool), and the reconnection happens at a later date (after radiation is completed).
- Pros: Maintains stool continence in most cases, no colostomy/bag
- Cons: Prolonged healing time, change in bowel habits/incontinence due to loss of rectum and capacity to store stool
- Abdominal Perineal Resection (APR)- For many years the "gold standard" rectal cancer operation. It involves the removal in one piece of the rectum and anus and floor of the perineum, with diversion of stool through a permanent colostomy (bag). This operation is now reserved for tumors that are too close to the anus to allow for reconnection of the colon, and other situations where an LAR is technically impossible.
- Pros: Low recurrence rate, no incontinence
- Cons: Prolonged healing time, wound infection, permanent colostomy
Chemotherapy Drugs for Colon and Rectal Cancer
- 5-FU (also: 5-fluorouracil)- the oldest drug in continuous use for colon cancer. It is now the anchor drug in many combinations (see below), and rarely used alone. It can be given as a quick injection or as a slow infusion over a number of days using a wearable pump. Main side effects: Diarrhea, mouth sores, rash/pain of hands and feet, weight gain. Uncommon side effects: Vertigo/dizziness, excessive tearing, chest pain. A small percentage of women are intolerant of 5-FU due to an inherited enzyme deficiency (which can be screened for), and can become seriously ill even from small doses of 5-FU.
- Leucovorin- is not formally a chemotherapeutic, but a B-vitamin derivative that potentiates the effects of 5-FU. It is given as a 2 hour infusion (for larger doses). There are no serious side effects.
- Oxaliplatin- is the mainstay of first line treatment of stage II-IV colon cancer, in combination with 5-FU, Leucovorin and avastin (avastin in stage IV disease only). It is given as a 2-3 hour infusion every 2 weeks. Main side effects: Neuropathy (deadening of nerve endings in hands/feet/mouth) with paradoxical pain, extreme cold sensitivity of hands and mouth (usually 1-5 days after an infusion), nausea/vomiting, elevation of liver tests. Neuropathy is usually reversible after a dose, but can become permanent and debilitating after repetitive dosing, so constant monitoring is essential. Women are prone to laryngeal dysesthesia during or immediately after the infusion, where the sensation of the throat closing occurs, though it is not physically happening. Oxaliplatin can suppress the bone marrow, causing white cell, red cell, and platelet deficiencies, though its effects are modest compared with most other chemotherapy drugs.
- Irinotecan-often used in 2 nd line/3 rd line therapy, in various combinations with 5-FU, leucovorin, cetuximab, and avastin, but only in stage IV disease. It is given as a 90 minute infusion on schedules that vary based on the regimen. The main toxicity is diarrhea, which can be severe or even fatal if not monitored and treated. Patients are given specific instructions on how to deal with diarrhea at home, using OTC anti-diarrheals or other prescription medications. Irinotecan also suppresses the bone marrow to varying degrees, and causes hair loss, nausea and vomiting.
- Capecitabine (Xeloda)- pill form of 5-FU, which is turned into 5-FU in cells of the tumors. Side effects: as for 5-FU, with more pronounced diarrhea, hand/foot syndrome, mouth sores.
All patients on chemotherapy are at risk for possibly fatal infection if white cell counts drop, and must report any fever (especially if >100.5 F), chills, or other infective symptoms to their doctor immediately or otherwise report to an emergency room without delay.
Chemotherapy Combination Regimens for Colon and Rectal Cancer
- FOLFOX- 5-FU (as injection and as 46 hour infusion by pump), Leucovorin (injection), oxaliplatin (injection). Repeated every 2 weeks for 6 months---or longer. Can be combined with avastin.
- FOLFIRI- 5-FU (as injection and as 46 hour infusion by pump), Leucovorin (injection), irinotecan (injection). Repeat every 2 weeks for 6 months-or longer. Can be combined with avastin.
- Irinotecan/cetuximab- both as injections- cetuximab weekly and irinotecan at varying scedhules based on MD preference (K-ras non-mutated).
- XELOX- combination of capecitabine (daily for 14 days every 3 wks) + oxaliplatin (once every 3 weeks), where capecitabine substitutes for 5-FU and leucovorin. Sometimes used for convenience, instead of FOLFOX. Appears to be therapeutically equivalent to FOLFOX.
Biologic Agents for Colon Cancer Biology
- Cetuximab- an antibody that targets the EGF receptor on tumor cells. It can only be used against K-ras mutated tumors. It is given weekly as a 60 minute infusion. It can cause infusion reactions (chills, fever, etc.) and steroids and other premedications are used to prevent reactions. Cetuximab is generally used with irinotecan in 2 nd or 3 rd line therapy. Side effects include possibly severe skin rash (treated with topical creams or antibiotic pills), diarrhea.
- Panitumumab- Also an EGFR inhibitor antibody but given every 2 weeks. Side effects as per cetuximab.
- Avastin-antibody against the blood vessel promoting substance in the body VEGF, in the hope it would starve tumor of blood supply. Avastin is given as a 15-30 min infusion on varying schedules, usually with FOLFOX or FOLFIRI combinations in stage IV colon cancer. Main side effects include: bleeding, clotting, high blood pressure, protein in the urine. Serious but rare side effect is perforation of the intestine. Avastin impairs wound healing and must be avoided 6-8 weeks before and after major elective surgery.