Stage II & III Rectal Cancer
Chemotherapy
For patients with pMMR or MSS rectal cancer, chemotherapy is a key part of treatment. The recommended approach is called total neoadjuvant therapy (TNT), where all chemotherapy and radiation are given before surgery. TNT is different from chemoradiation alone — it combines a full course of chemotherapy with chemoradiation, all completed before surgery begins.
Treatment typically begins with 12 to 16 weeks of chemotherapy. The most common regimens are:
- FOLFOX — a combination of folinic acid (leucovorin), fluorouracil (5-FU), and oxaliplatin
- CAPEOX — a combination of capecitabine and oxaliplatin
- FOLFIRINOX— a combination of folinic acid (leucovorin), fluorouracil (5-FU), irinotecan, and oxaliplatin. This regimen contains all the same drugs as FOLFOX plus irinotecan, making it a more intensive option that may be considered in certain cases.
These are given in cycles, with treatment days followed by rest days to let your body recover.
An important note on DPYD testing: If your treatment plan includes 5-FU or capecitabine, ask your care team about DPYD gene testing before starting chemotherapy. Some people have a gene variant that makes it harder for their body to process these drugs safely, which can lead to serious side effects. Knowing ahead of time allows your team to adjust your dose or choose a different treatment.
Immunotherapy
If your tumor is dMMR or MSI-H, immunotherapy is the preferred first treatment. Immunotherapy works differently from chemotherapy — instead of directly attacking cancer cells, it helps your own immune system recognize and destroy them.
The specific type of immunotherapy used for rectal cancer is called a checkpoint inhibitor. Treatment is recommended for up to 6 months.
- If treatment works so well that no cancer can be detected, treatment is finished and close surveillance begins — surgery may not be needed at all.
- If cancer is still present after 6 months, radiation is added next, followed by surgery if needed.
Checkpoint inhibitors have unique side effects that are different from chemotherapy. Because they work by activating your immune system, they can sometimes cause your immune system to attack healthy tissues in the body. It is important to know what to watch for and report any new or unusual symptoms to your care team right away.
If immunotherapy is not an option for you, your care team may recommend total neoadjuvant therapy instead — the same approach used for pMMR/MSS patients, which combines chemotherapy and radiation before surgery. Talk to your care team about which approach is right for your situation.
Radiation
After chemotherapy, radiation is the next step in total neoadjuvant therapy. There are two approaches:
- Long-course chemoradiation — radiation given daily Monday through Friday for 5 to 6 weeks, with chemotherapy (usually 5-FU or capecitabine) given at the same time. Giving chemotherapy alongside radiation makes the radiation more effective at killing cancer cells. This is called chemoradiation.
- Short-course radiation — a higher dose of radiation given over just 5 treatment sessions, without chemotherapy.
Your care team will recommend which approach is best based on your tumor’s location, size, and other factors — and in some cases, research has shown that radiation may not be necessary at all. Ask your radiation oncologist to walk you through what to expect and why they are recommending a particular approach for you.
Surgery
For most people with Stage II or III rectal cancer, surgery follows chemotherapy and radiation. The type of surgery depends on where your tumor is located.
- Low anterior resection (LAR) for tumors in the middle or upper rectum. The rectal tumor and part or all of the sigmoid colon are removed. When possible, the colon is reconnected so bowel function can continue more normally. A temporary ostomy is often created to allow the surgical site to heal and can usually be reversed after a few months.
- Abdominoperineal resection (APR) for tumors in the lower rectum. The rectum, anus, and sphincter muscles are removed, and a permanent colostomy is created for stool to leave the body. Many people with a permanent ostomy live full, active lives, and an ostomy nurse or support group can help with the adjustment.
At least 12 lymph nodes should be removed and tested during surgery to help confirm the cancer stage and guide any decisions about further treatment.
In some cases, chemotherapy and radiation work so well that no cancer can be detected before surgery. If this happens, your care team may discuss whether surgery is still necessary. This decision should be made carefully with your care team.
Watch and Wait
For some patients, treatment works so well that no cancer can be detected in the body at all. This is called a complete response. When this happens, your care team may offer the option to skip surgery and instead monitor the cancer closely — this is called watch and wait.
Watch and wait is only suitable for carefully selected patients and the decision should be made carefully with your care team.
