Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second most common cause of cancer-related deaths in the world. Management strategies aimed at improving outcomes in patients diagnosed with CRC were presented at the 2023 ONA Summit Live Virtual Meeting.
Mortality has been progressively declining over the past 3 decades at a rate of approximately 1.6% to 2.0% per year. The decline can be attributed largely to screening practices in persons older than 50 years, identifying colon and rectal polyps before they develop into cancers. In contrast to this decline, over the past 2 decades CRC incidence has been steadily rising worldwide in persons younger than 50 years.
Although the exact cause of CRC is unknown, certain risk factors are strongly linked to the disease, including increasing age, obesity, physical inactivity, and history of inflammatory bowel disease such as Crohn disease and ulcerative colitis. Other factors that increase risk of CRC include a history of other cancers such as ovarian, breast, and endometrial cancers; first-degree family history of CRC, adenomas, or polyps; and known hereditary conditions such as familial adenomatous polyposis or hereditary nonpolyposis CRC (HNPCC or Lynch Syndrome). The risk of CRC is higher for those who eat a high-fat diet, a lot of processed meat or red meat. Moderate to heavy alcohol consumption and smoking also have been linked to CRC risk.
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Primary and secondary prevention strategies that decrease the incidence of CRC are well documented. Lifestyle modification such as following a prudent diet, maintaining physical activity, and a body mass index of less than 25 kg/m2 are strategies that can decrease an individual’s risk.
The United States Preventive Services Task Force (USPSTF) recommendations for screening are endorsed by the American Cancer Society, Center for Disease Control, National Comprehensive Cancer Network, and numerous patient-related organizations. Generally, recommendations for screening average-risk patients start at 50 years of age. In the United States, average-risk patients aged 45 to 75 years have 3 options: stool-based screening tests every 3 years, flexible sigmoidoscopy every 5 years with fecal occult blood test (FOBT) every 3 years, or colonoscopy every 10 years.
CRC can have a variety of presentations. The cancer is discovered on routine screening colonoscopy in an asymptomatic patient. Suspicious signs and symptoms may vary depending on physiology of the bowel and location of the tumor.
Unexplained iron deficiency anemia is associated with cancer of the ascending or right colon. A palpable mass is also associated with cancer of the ascending or right colon.
Hematochezia and melena are associated with cancer in the transverse and descending or sigmoid colon. Changes in bowel habits (diarrhea and or constipation, changes in stool characteristics such as thinning of the stool) are associated with the rectum. Blood from the rectum, thin stools, and tenesmus are common symptoms associated with a mass in the rectum.
Abdominal pain as a single symptom is the least common presentation. Symptomatic patients typically have more advanced disease, and therefore a poorer prognosis, compared with asymptomatic patients. Patients present for an emergency admission with intestinal obstruction, perforation, and sometimes gastrointestinal bleeding. Obstruction and perforation indicate a poor prognosis independent of the stage of the cancer at diagnosis.
Typical clinical staging includes blood tests, such as liver function tests, complete blood cell count, and carcinoembryonic antigen. Imaging may include computed tomography, magnetic resonance imaging, and positron emission tomography (PET) scanning. A PET scan is obtained only if there are questionable findings on previous imaging. Endoscopy procedures include colonoscopy and/or sigmoidoscopy with biopsy of the primary tumor in the colon or rectum. In addition, patients with metastatic disease will have image-guided biopsy or surgical biopsy of the site suspicious for disease. The majority of CRCs are adenocarcinoma, other types of CTC include neuroendocrine tumors, lymphomas, and mesenchymal tumors.
More than half of patients with CRC present with advanced metastatic disease with a median survival of 24 to 30 months with treatment and 6 to 9 months without treatment. In the United States, CRC diagnosis in African Americans, Asian Americans, and Hispanic Americans often occurs when disease is at a later stage.
In addition to assessing pathology and stage, tissue samples should be evaluated with molecular profiling, or tumor genomic profiling. Molecular profiling classifies tumors based on genetic make-up to help diagnose and treat cancer. Using a blood test or biopsy identifies genetic mutations acquired by these cells. The most common somatic mutations found in CRC that have specific targeted therapies are KRAS and NRAS, BRAF, HER2. Microsatellite instability (MSI) is also a feature of some colorectal tumors. This is characterized by many mutations and carries a better prognosis.
Patients with MSI can receive immunotherapy in the metastatic setting, and patients with earlier stages of CRC, such as stage II, do not need to receive adjuvant chemotherapy. Molecular profiling results have prognostic significance and are relevant to treatment choices. Molecular profiling identifies the unique attributes of a patient’s cancer that can be targeted by specific treatments. Pathology, staging, and molecular profiling all inform treatment decisions.
Treatment Strategies
Over the past 30 years there has been an explosion of agents approved in the United States for the treatment of CRC, including targeted agents such as antiangiogenic factors, endothelial growth factor receptor (EGFR) inhibitors, immunotherapy such as programmed death-ligand 1 (PD-L1) inhibitors, and small molecule agents such as kinase inhibitors. Oncology nurses need to know which adverse events (AEs) can be expected when patients are receiving chemotherapy in addition to new targeted agents and how they should be managed. The AEs associated with targeted agents such as aflibercept differ from those associated with chemotherapy. Because they have greater specificity, targeted agents are generally better tolerated than chemotherapy, but they are also associated with AEs usually thought to be related to their mechanism of action.
Decision making regarding first-line therapy selection may be based on a variety of factors and patient-specific considerations, including the following.
Side-effect profile Oxaliplatin causes more sensory neuropathy, and irinotecan causes more diarrhea, nausea/vomiting, and alopecia.
Past treatments Reintroducing regimens is sometimes effective depending on how much time has passed. Switching regimens may be preferred, particularly in the presence of persistent toxicities from prior regimens. Patients with regression and/or stable disease will continue therapy. Patients with progression will go on to second-line therapy.
Eventually patients will receive both regimens FOLFOX and FOLFIRI, switching from one to the other when progression occurs or when toxicity limits therapy.
Sidedness of the cancer is considered when choosing a first-line regimen. FOLFIRI and FOLFOX with a biologic cannot be used interchangeably as first-line therapy. Patients with left-sided tumors tend to be more responsive to FOLFOX/cetuximab (KRAS wild-type only), whereas patients with right-sided tumors benefit from FOLFOX/FOLFIRI plus an antiangiogenic agent such as bevacizumab.
In metastatic CRC, selecting a second-line regimen will depend on prior chemotherapy exposure, timing of progression after first-line chemotherapy, molecular testing results, tolerance of previous chemotherapy, and patient preference. Patients with BRAF V600E or MSI-H/MMR-D tumors will receive targeted therapy and/or participate in a clinical trial. For other patients, second-line therapy may be the chemotherapy regimen not received previously. After progression on FOLFOX and FOLFIRI, patients with KRAS/NRAS wild-type tumors who have not received an EGFR inhibitor should receive one. This is combined with irinotecan for tumors considered for third-line therapy. Patients with KRAS/NRAS mutant tumors are considered to have refractory disease after progression on second-line therapy.
Two other FDA-approved vascular endothelial growth factor (VEGF) therapies that have been approved for second-line therapy are ziv-aflibercept and ramucirumab. These can be combined with FOLFIRI. Each VEGF inhibitor improves survival by 1 to 2 months.
In BRAF V600E-variant metastatic CRC, targeted therapy with encorafenib or similar drugs is indicated as second- or later-line treatment. Encorafenib is given in combination with an EGFR inhibitor such as cetuximab. BRAF V600E variants are found in 5% to 10% of metastatic CRCs. They are more common in women, older patients, patients with right-sided poorly differentiated tumors, and those with sessile serrated precursors.
Patients with refractory metastatic CRC may receive regorafenib, an oral tyrosine kinase inhibitor, and/or trifluridine-tipiracil.
Metastatic CRC remains incurable for most patients. However, if the disease is limited to a few metastatic foci (ie, in the liver or the lungs) and a surgeon can resect the metastases, long-term cure can be achieved in approximately 20% of patients. Nodal infiltration and occult micrometastasis dissemination is common in these patients.
Survival depends on the molecular subtype, which informs prognosis by identifying both a tumor’s natural history as well as therapies that are and are not likely to be effective.
Other factors influencing metastatic CRC prognosis include previous receipt of adjuvant chemotherapy, time between adjuvant therapy, and development of metastasis, comorbid conditions, and frailty. Without treatment, survival in metastatic CRC is 6 to 12 months. Multiagent chemotherapy is necessary to achieve survival beyond 18 to 26 months.
The majority of patients with metastatic CRC respond to FOLFIRI or FOLFOX for several months, followed by stable disease. The treatment is eventually limited by toxicity, which typically is either cumulative peripheral neuropathy from FOLFOX or diarrhea and fatigue from FOLFIRI. When patients become intolerant of either regimen, maintenance therapy with 5-FU/leucovorin with/without bevacizumab, cetuximab, or panitumumab is an option. Alternatively, a chemotherapy holiday may be offered until there is evidence of progression on clinical basis and or on diagnostic tests.
Gastric Cancer
The incidence of gastric cancer in the United States has declined over the past several decades. However, globally it remains a major health problem. It is the third leading cause of cancer-related death worldwide. More than 95% of tumors are adenocarcinoma, which are typically classified according to location within the stomach and type of histology. The risk factors include smoking; gastroesophageal reflux disease; a diet high in salty, smoked foods and low in fruits and vegetables; Helicobacter pylori infection; and hereditary gastric syndromes. To date, no screening test is available.
Gastric cancer carries a poor prognosis because diagnosis occurs late in the course of the disease. Systemic therapy can provide palliation of symptoms and improve quality of life and survival in patients with locally advanced and metastatic disease. The implementation of biomarker testing, especially of HER2, MSI status, and the expression of PD-L1, has had a significant effect on patient care.
Systemic chemotherapy includes the fluoropyrimidines, taxanes, and platinum compounds. Often regimens are toxic, and doublet is preferred over triplet combinations. Targeted therapy includes trastuzumab, nivolumab, and pembrolizumab. Monoclonal antibodies, such as ramucirumab, are usually combined with traditional chemotherapy. Small molecule therapy for patients with NTRK gene changes, such as the tyrosine kinase inhibitors larotrectinib and entrectinib, are also an option.
Role of the Oncology Nurse
Oncology nurses play a significant role in the care of patients with gastric cancer and mCRC within the multidisciplinary team, acting as liaison between the patient and the care team. Nurses play a vital role in the management of side effects associated with treatment. They are in a unique position to provide patients with ongoing support and symptom assessment and management.
Nurses can provide support for the psychological, social, behavioral, and physiologic effects of treatment. Successful patient education hinges on establishing and maintaining a strong partnership between the patient and the oncology team. Nurses can encourage identification and reporting of side effects in their pivotal roles as connectors between the patient and the care team.
Written patient and family education materials may include information about side effects of drugs and directions for symptom management. For example, education materials may include directions related to antiemetic regimens, diarrhea management, prevention of cold-induced neuropathy, mouth and skin care management, and infection and bleeding precautions. Some patients will do well with a simple slide presentation or video emphasizing the anticipated side effects of therapy and appropriate management. Patients should be encouraged to keep treatment diaries to assist in side effect reporting. Oncology nurses should identify 1 person in the health care team whom the patient can contact for side effect reporting, problems, and questions.
Nurses are in the ideal position not only to educate patients about the potential toxicities that may be encountered during treatment, but to identify and manage toxicity before they become problematic. Nurses are an asset in empowering patients to participate in shared decision making regarding their cancer care.
Nina Grenon is a nurse practitioner in gastrointestinal oncology at Dana-Farber Cancer Institute Center for Gastrointestinal Oncology in Boston, Massachusetts.
Reference
Grenon NN. Collaborating towards improved outcomes in advanced gastric and colorectal cancers. Oral presentation at: 2023 ONA Summit Live Virtual Meeting; March 17-19, 2023.
This article originally appeared on Oncology Nurse Advisor
