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Metastatic Rectal Cancer Introduction According to the American Joint Committee on Cancer tumor-node-metastasis staging system, stage IV rectal cancer is defined as a tumor that has spread to at least one distant site, commonly the lung and liver. The National Comprehensive Cancer Network (NCCN) notes that for 75%–90% of rectal cancer patients who present with liver metastases at diagnosis, the disease is considered unresectable; nearly all will eventually die of the disease if they cannot undergo surgery. Those sobering statistics mean that patients with metastatic rectal cancer are often treated with a strictly palliative intent, whereby surgery is deferred and chemotherapy is provided not for cure but to prolong overall survival. Recently, the approach has changed for some patients: treatment advances have allowed initially unresectable disease to be “downsized” to resectable status with neoadjuvant chemotherapy and/or combined chemotherapy and radiation therapy (chemoradiation). Owing to those advances, patients diagnosed with metastatic rectal cancer at The University of Texas M. D. Anderson Cancer Center are now considered for curative treatment. The key is the timing and sequence of treatments, which are based on a thorough evaluation before any treatment is given and on continual monitoring and re-evaluation. The individual patient factors that determine the treatment plan are so varied that there is no typical sequence. The plan is a delicate and carefully orchestrated one, and it must be devised and carried out in real-time collaboration among specialists from multiple disciplines. Initial evaluation When a patient is diagnosed with stage IV rectal cancer, a comprehensive treatment plan should be developed before any treatment begins—and the decisions that shape the plan are vital to the patient’s potential survival. “Long-term survival may be possible even if the patient has 10 or more liver metastases,” said Eddie K. Abdalla, M.D., an associate professor in the Department of Surgical Oncology. “The patient’s best hope is a careful initial evaluation and an exquisitely timed and managed treatment sequence.” The first decision is whether a curative approach is possible. To answer that question, the initial evaluation must be thorough and multidisciplinary: the patient should be directly examined by all of the physicians who might be involved in the treatment plan. According to George Chang, M.D., an assistant professor in the Department of Surgical Oncology, the initial evaluation should include a pretreatment proctoscopic examination by the surgeon who will perform the rectal surgery. At M. D. Anderson, the evaluation might also include computed tomography, positron emission tomography, magnetic resonance imaging, and endorectal ultrasonography studies—all of which yield different but complementary information. Among the more important questions to be addressed in the initial evaluation are whether the primary tumor is likely to grow and, if it is, whether it would then become unresectable or symptomatic. “At M. D. Anderson, the treating physicians review each patient’s case individually to determine the optimum sequence of treatment, including the need for surgical or endoscopic intervention.” Treatment modalities Rectal surgery When surgical resection of the primary tumor is performed, it is important to consider whether the goal of treatment is curative or palliative. It is also important to involve a hepatobiliary specialist to determine whether curative resection of any liver tumors can be performed. Depending on the extent of rectal and liver surgery needed, it may be possible to perform both surgeries at the same time and avoid the need for multiple anesthetics, hospitalizations, and recovery periods. The goal should be complete resection of the primary tumor. Following surgery, the colorectal surgeons review the resection specimens face-to-face with the gastrointestinal pathologist, Dr. Chang said. “The advantage for the patient is that there is never a question about the specimen because of confusion about the operative or pathologic findings, for example, and therefore we all have a clearer understanding going forward. This also allows for the best chance for restoring intestinal continuity without a permanent colostomy and without compromising oncologic outcome.” Similar pathology consultations are also valuable when physicians are evaluating tumor response to chemotherapy.
Dr. Chang, who specializes in colorectal tumors, said local recurrences of rectal cancer can be very difficult to treat. Unfortunately, local recurrence is a common type of rectal cancer progression after palliative surgical therapy. Therefore, it is critical that the treatment sequence be devised to yield the optimal conditions for a complete resection of the primary tumor and metastatic disease. This may include neoadjuvant chemoradiation, particularly for large or bulky tumors in the pelvis. “When we operate with the intent to cure, we want to have confidence that the cancer will not recur,” Dr. Chang said. “In addition, as these tumors often respond to chemotherapy and radiation therapy, resulting in tumor downsizing, the adjacent tissue becomes more accessible and we can more readily remove all tumor-bearing tissue and prevent local recurrence.” Based on the group’s experience, the risk for local recurrence after primary resection should be less than 10%—well under the risk for systemic recurrence. Liver surgery PVE is an outpatient procedure performed by a highly skilled interventional radiologist. The procedure blocks blood flow to the part of the liver that contains tumor and will be removed. As a result of PVE, blood flow to the liver is diverted to the disease-free side of the liver, and the diseased side atrophies. The healthy side then grows (hypertrophies), creating additional vital liver tissue—enough to enable the surgeon to remove the disease and leave behind adequate liver reserve. When both lobes have metastases, the surgery is done in stages: one liver surgery is done to remove lesions from the lobe that will ultimately remain, and following PVE, a second surgery to is done to remove the remaining liver containing tumors (if needed). This two-stage approach to bilateral liver metastases has raised the overall survival rate from nearly 0% to more than 80% 3 years after surgery. Dr. Abdalla, who specializes in hepatobiliary surgery, said decisions about the intent of treatment for patients with liver metastases should take into account the improved survival rate. “We do see patients who have had incomplete rectal surgery—treatment that was approached as palliative rather than curative—after which they might receive chemotherapy and even liver surgery but later have a recurrence from the primary site,” Dr. Abdalla explained. “Patients with a primary local tumor recurrence don’t have a long-term survival benefit from the resection of metastases.” For such patients, involvement of the colorectal specialist for “completion” rectal surgery is sometimes considered at the time of liver surgery to ensure the best possible patient outcome. Chemotherapy The goal of neoadjuvant chemotherapy is to decrease tumor burden—or downsize the tumor—to make successful surgical removal of both the primary and metastatic tumors more likely. In effect, this approach can convert disease initially deemed “unresectable” to “resectable.” Conversion is successful in 10%–15% of cases, Dr. Eng said. “Although the percentage seems small, those patients have dramatically better outcomes,” she said. The 5-year overall survival rate for patients with surgically unresectable disease is about 10%, compared with 25%–65% for patients with metastatic but resectable disease. If the patient is a candidate for surgery, chemotherapy must be delivered carefully to avoid chemotherapy-induced liver toxicity, since the liver may be compromised by cancer and chemotherapy toxicity could compromise surgical candidacy. “We treat until the disease is resectable,” Dr. Eng said, “not until the limits of tolerance are reached.” Surgical recovery is another consideration, and chemotherapy agents likely to compromise wound healing are avoided for a specified period of time. Timing is a factor—for example, if antiangiogenic agents (which inhibit blood vessel growth) are used, at least 5–6 weeks must elapse between the end of chemotherapy and when surgery is done. For each patient, the risk of disease progression during breaks in therapy must be weighed against the potential benefit of the agent. There is an additional benefit to neoadjuvant chemotherapy: it gives the medical oncologist the opportunity to directly observe the response of the cancer to the agents used, and thus it helps better determine which agents are to be used in the adjuvant setting. Chemoradiation Factors in the treatment sequence In the past, a common approach to the treatment of metastatic rectal cancer was to surgically resect the primary tumor, and then perform surgery to address metastases and to give chemotherapy before and/or after surgery. Today, there is no typical treatment plan. The initial treatment might be the first stage of liver surgery, or it might be combination chemotherapy and radiation therapy. Choreographing the treatment plan for an individual patient requires careful evaluation, monitoring, and collaboration among specialists, including the medical and radiation oncologists, the surgical oncologists who will operate on the primary tumor and the metastases, and the pathologist. Symptoms Tumor resectability The size and location of the primary tumor obviously have consequences for whether it is likely to be resectable, whether it will be amenable to radiation, and what type and severity of symptoms the patient experiences. The metastatic tumor burden likewise is a factor in the treatment sequence—dictating, for example, whether more than one liver surgery will be necessary. Resectability is monitored and re-evaluated as the treatment plan unfolds and the response to therapy is observed. The course of neoadjuvant chemotherapy is calibrated to achieve a response while limiting liver effects. The initial response to chemotherapy is also an important indicator of prognosis and therefore is helpful in the very careful selection of patients who will benefit from further surgery. For example, when disease is seen to progress instead of diminish after chemotherapy and the first stage of PVE, the treatment team might re-evaluate whether further liver surgery will be potentially curative or therapeutic. “However, when there is a disease response to chemotherapy and first-stage PVE, the 3-year overall survival rate after surgery is 86%—almost double that of other approaches,” Dr. Abdalla said. Based on published experience from their group, he estimates that about two-thirds of patients are able to proceed to second-stage surgery and potentially experience a survival benefit, while those who would not benefit are spared unnecessary surgery. Patient health and habitus Required breaks in therapy A break or recovery time of several weeks between treatments must be allowed—between chemoradiation and surgery to allow for local tissue inflammation and swelling to subside, between chemotherapy or chemoradiation and surgery to allow for the fullest possible tumor downsizing to occur, or between surgery and adjuvant chemotherapy to allow postoperative recovery. These breaks in treatment must be very carefully managed, as they could also give the disease an opportunity to progress. In rare cases, liver surgery is chosen as the first intervention (after neoadjuvant chemotherapy), since the patient can move to chemoradiation in preparation for rectal surgery shortly thereafter. “When we’re able to do the liver surgery first, it limits the duration of treatment-free intervals,” Dr. Abdalla said. Communication between surgery, medical oncology, and radiation oncology specialists is imperative, and the risks and benefits of each treatment modality and how each impacts the others must be considered. For example, it is often preferable for chemotherapy to precede chemoradiation and for rectal surgery to be done shortly after chemoradiation, since the scarring that develops 3–6 months after chemoradiation makes the surgery more difficult and the tumor could grow if surgery is delayed. However, an ideal course for each patient can be developed depending on the factors detailed above. “The use and sequencing of all modalities must be individualized in order to reach the optimal outcome,” Dr. Crane said. References National Cancer Institute Surveillance, Epidemiology and End Results (SEER)
For more information on this topic or for questions about M. D. Anderson’s treatments, programs, or services, call askMDAnderson at (877) MDA-6789. Other articles in OncoLog, October 2009 issue: Home/Current Issue | Previous Issues | Articles by Topic | Patient Education ©2009 The University of Texas M. D. Anderson Cancer Center |
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