Treatment of Recurrent Rectal Cancer
Medically reviewed by Dr. C.H. Weaver M.D. 5/2020
Recurrent rectal cancer is cancer that has returned or progressed following initial treatment with surgery, radiation therapy and/or chemotherapy. Patients experiencing progression of rectal cancer have been perceived to have few treatment options. However, certain patients can still be cured of their cancer and others derive meaningful palliative benefit from additional treatment.
Treatment of Pelvic Recurrence of Rectal Cancer
Patients treated for rectal cancer may experience a recurrence of cancer near the original site of the cancer. Clinical studies have reported that certain patients with localized recurrence of cancer in the pelvis can undergo surgical removal of disease and be cured in approximately 10 to 20% of circumstances. Depending on the extent of recurrent disease, surgery may involve local excision with or without bowel resection, abdominoperineal resection, or pelvic exenteration (removal of most structures in the pelvis). Patients may also be treated with chemotherapy and radiation therapy. .
Treatment of Metastatic Rectal Cancer
Recurrent rectal cancer may also involve distant sites in the body such as the liver or lung. When the site of metastasis is a single organ, such as the liver, and the cancer is confined to a single defined area within the organ, patients may benefit from local treatment—such as surgery—directed at that single site of recurrence or metastasis. This local treatment may be accompanied by systemic (whole-body) treatment such as chemotherapy, immunotherapy or precision cancer medicines. When cancer is more extensive and surgery is not possible, systemic therapy is the primary approach to treatment.
Treatment of the Liver: When the cancer has spread only to the liver and it’s possible to completely surgically remove all liver metastases, surgery is the preferred treatment. Although surgery offers some patients the chance for a cure, a majority of patients with liver metastases are not candidates for surgery because of the size or location of their tumors or their general health. Some of these patients may become candidates for surgery if initial treatment with chemotherapy shrinks the tumors sufficiently. If the tumors continue to be impossible to remove surgically, other liver-directed therapies may be considered. These other therapies include radiofrequency ablation (use of heat to kill cancer cells), cryotherapy (use of cold to kill cancer cells), delivery of chemotherapy directly to the liver, and radiation therapy. Relatively little information is available from clinical trials about the risks and benefits of these other approaches, but they may benefit selected patients. (1)
Systemic Treatments: Several different treatment regimens are available, and the choice of which to use will depend on factors such as your health, previous treatment history, and the presence of defined cancer driving mutations that can be targeted with precision cancer medicines. In some cases, systemic therapy can shrink the cancer enough that initially inoperable cancers becomes possible to surgically remove.
Chemotherapy may be given in combination with other drugs known as targeted therapies. Targeted therapies are anticancer drugs that interfere with specific pathways involved in cancer cell growth or survival. Some targeted therapies block growth signals from reaching cancer cells; others reduce the blood supply to cancer cells; and still others stimulate the immune system to recognize and attack the cancer cell. Depending on the specific “target”, targeted therapies may slow cancer cell growth or increase cancer cell death.
Targeted therapies that have shown a benefit for selected patients with metastatic colorectal cancer include Avastin® (bevacizumab), Erbitux® (cetuximab), and Vectibix® (panitumumab). Avastin blocks a protein (VEGF) that plays a key role in the development of new blood vessels. By blocking VEGF, Avastin deprives the cancer of nutrients and oxygen and inhibits its growth. Erbitux and Vectibix slow cancer growth by targeting a protein known as EGFR. Cancers with certain gene mutations are unlikely to respond to Erbitux or Vectibix, and tests are available to detect these mutations before treatment decisions are made. All patients with recurrent rectal cancer should undergo genomic testing in order to determine if they have a cancer driving mutation that can be treated with a precision cancer medicine.
If patients are experiencing symptoms from their rectal cancer, they may also receive treatments such as radiation therapy, surgery, or stenting to relieve problems such as bowel obstruction.
Strategies to Improve Treatment
While some progress has been made in the treatment of recurrent or progressive rectal cancer, the majority of patients still succumb to cancer and better treatment strategies are clearly needed. Future progress in the treatment of rectal cancer will result from continued participation in appropriate clinical trials. Patients with recurrent or progressive rectal cancer are usually included in clinical trials of colon cancer. Currently, there are several areas of active exploration aimed at improving the treatment of rectal cancer.
New Approaches to Treating Liver Metastases: Researchers continue to explore news ways to treat cancer that has spread to the liver. One approach that is being evaluated is radioembolization This strategy uses radioactive microspheres (small spheres containing radioactive material). The small spheres are injected into vasculature of the liver, where they tend to get lodged in the vasculature responsible for providing blood and nourishment to the cancer cells. While lodged in place, the radioactive substance spontaneously emits radiation to the surrounding cancerous area while minimizing radiation exposure to the healthy portions of the liver.2 Researchers are also exploring alternatives to radiofrequency ablation for the destruction of liver tumors, as well as new approaches to delivering chemotherapy to the liver.
New Chemotherapy Regimens: Development of new multi-drug chemotherapy treatment regimens that incorporate new or additional anti-cancer therapies is an active area of clinical research.
Precision Cancer Medicines such as Avastin, Erbitux, and Vectibix already play a role in the treatment of selected patients with advanced colorectal cancer, but researchers continue to identify additional cancer driving mutations and develop precision medicines that target those mutations. Patients should ensure they have NGS testing preformed and discuss the role of clinical trials evaluating newer precision medicines with their doctor.
Phase I Trials: New chemotherapy drugs continue to be developed and evaluated in patients with recurrent cancers in phase I clinical trials. The purpose of phase I trials is to evaluate new drugs in order to determine the best way of administering the drug and whether the drug has any anti-cancer activity in patients.
- Alsina J, Choti MA. Liver-directed therapies in colorectal cancer. Seminars in Oncology. 2011;38:651-567.
- Hendlisz A, Van den Eynde M, Peeters M, et al. Phase III Trial Comparing Protracted Intravenous Fluorouracil Infusion Alone or With Yttrium-90 Resin Microspheres Radioembolization for Liver-Limited Metastatic Colorectal Cancer Refractory to Standard Chemotherapy. Journal of Clinical Oncology. 2010;28:3687-94.