Palliative Care for Colorectal Cancer
May 9, 2023 - read ≈ 22 min
Cara Ferguson BS
University of Michigan, Ann Arbor, MI
Pasithorn A. Suwanabol MD, MS
University of Michigan, Ann Arbor, MI
Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide, and accounts for 8% of all cancer deaths . While surgery is considered the mainstay treatment for CRC, 10-15% of patients present with metastatic disease and may never be eligible for curative therapy .
For those presenting with metastatic CRC, there have been recent shifts toward more aggressive therapies with no one treatment strategy recommended over another. Instead, an individualized and multidisciplinary approach is recommended .
Ultimately, treatment approach is determined by the patient’s symptom burden and potential for resectability, and should be informed by goals of care conversations with the patient and family. In this article, we focus on management of the primary tumor in those with metastatic CRC (i.e., palliative interventions).
Management of Asymptomatic or Minimally Symptomatic Primary Tumors
For patients not experiencing symptoms or experiencing minimal symptoms due to the primary tumor, the decision to pursue surgery is based on resectability of metastatic disease and may include resection of the primary cancer .
For such patients, initial treatment with chemotherapy, then reevaluation for resection is recommended. For patients with disease that responds to chemotherapy or remains stable during the chemotherapy period, resection of both the primary tumor and metastatic sites may be pursued. On the other hand, if there is widespread disease progression during the chemotherapy period, it is unlikely that resection will provide meaningful benefit.
In contrast, for asymptomatic or minimally symptomatic patients with unresectable metastatic CRC, routine resection of the primary cancer to prevent obstruction, bleeding, and pain is not currently recommended. Instead, given that survival depends on control of distant disease, it is strongly recommended that patients receive systemic chemotherapy .
Despite this recommendation, the risk benefit ratio (including improvement in quality of life and prevention of complications) for resecting the primary tumor should be carefully considered as deferring surgery may increase the risk of an emergent presentation with bowel obstruction, perforation, or bleeding. It is important to consider, however, that the risk of postoperative morbidity for patients undergoing primary tumor resection is 20-30% and the risk of mortality is 1-6% .
Additionally, primary tumor resections have been associated with decreased quality of life [6, 7], poorer survival rates , and importantly, may delay the initiation of life-prolonging systemic treatment.
For patients who develop obstruction, perforation, bleeding and/or pain, operative intervention may be appropriate.
Malignant bowel obstruction may be mechanical (i.e., physical obstruction of the intestinal lumen) or functional (i.e., anything that causes adynamic ileus). Bowel obstruction presents with a symptom constellation including worsening abdominal pain, distension, tympany, and nausea and/or vomiting. The diagnosis is most often confirmed with cross-sectional imaging or water-soluble contrast enema .
For a patient who presents with symptomatic bowel obstruction, conservative measures (e.g., nasogastric tube decompression, bowel rest, intravenous fluids) should be considered first as resolution nears 30-40% with this approach. However, recurrence following conservative measures is possible and more aggressive measures (venting G tube, enteric bypass, ostomy or surgical resection) should be offered for persistent or recurrent obstruction. Guidelines from the American Society of Colon and Rectal Surgeons recommend consideration of decompressive stenting before attempting more aggressive measures.
Aggressive measures to treat symptomatic bowel obstruction include procedures to proximally divert the fecal stream, and surgery to remove or divert the affected segment. Proximal diversion may include gastrostomy tube, enteric bypass or stoma placement. Gastrostomy tubes allow bowel decompression, discontinuation of nasogastric tube, and possible discharge from the hospital, but patients are not able to eat. This approach is associated with high success rates and immediate improvement in patient symptoms, but is used as last resort as it doesn’t allow for patients to eat [10, 11].
When considering proximal diversion with a stoma in a patient who has potentially resectable disease, it is important to consider how the placement of a stoma will affect future reconstructive options by restricting colonic mobility or damaging the marginal artery. Additionally, to avoid closed-loop obstruction and perforation, the distal portion of the bowel should be vented. While stomas may relieve symptoms from obstruction, one-third of patients will develop symptoms from their stoma including leakage, prolapse, retraction, skin irritation, pain, or partial necrosis that can negatively impact quality of life . Enteric bypass can be offered for patients with unresectable disease but who able to heal the anastomosis.
Resection of the affected segment or a subtotal colectomy should be considered for those patients presenting with obstruction who are able to tolerate lengthier procedures and who have resectable primary tumors. Historically, three-stage approaches (diverting colostomy, resection, and reanastamosis) were preferred, however it was found that two-stage procedures (subtotal colectomy and reanastamosis) were equally effective and associated with shorter hospital stays. One-stage approaches have equal mortality rates  and have been adopted by some centers.
For patients with advanced disease and significant symptoms, low anterior resection (LAR), abdominoperineal resection (APR), or pelvic exenteration may be indicated. These procedures pose unnecessary risk to terminally ill patients however and may only be suitable for patients with longer life expectancies.
Bowel perforation is a life-threatening emergency requiring thoughtful patient and family counseling to determine appropriate next steps in treatment. Due to the high morbidity and mortality (43-60% and 5-40%) of bowel perforation in the setting of CRC, it is critical that patients have a clear understanding of the risks and benefits of surgical intervention [14, 15, 16].
Bowel perforation may be managed by diversion or resection. When operative intervention is appropriate, the type of procedure will depend on the site of perforation, whether intra-abdominal sepsis is present, and the feasibility of resection. If the perforation is proximal to the obstructing tumor, both the affected bowel and oncologic resection should be performed. If the perforation occurs at the site of the tumor, the involved structures should be resected en bloc if possible. For free perforation with peritonitis, resection of the involved segment and fecal diversion with a stoma is indicated. Of note, anastomosis is contraindicated in patients with fecal peritonitis, and instead a staged procedure should be performed.
Ideally resection should follow oncologic principles, however aggressive en bloc resection of vital structures may not be possible for an emergent perforated tumor and metastatic disease. In this case, source control of the intra-abdominal infection should be prioritized. If the perforation is contained and percutaneous or surgical drainage is possible, a simple diversion with drainage may be appropriate.
Chronic blood loss due to the primary tumor does not require surgical intervention, however patients who present with acute massive blood loss should be aggressively resuscitated and closely monitored if unstable. There should be high clinical suspicion for significant acute bleeding in patients who require chronic anticoagulation or patients with tumors that involve the mesenteric vascular structure.
Depending on the location and size of the tumor as well as the rate of bleeding, management may include radiation, surgical resection, or endovascular management. For surface bleeding at the site of the tumor, especially for rectal cancer, radiation provides effective palliation .
For significant hemorrhage or more proximal cancers, palliative resection is preferred and should be informed by the functional status of the patient, resectabilty of the tumor, and volume of metastatic disease. Indications for surgical resection in the setting of acute bleeding include hemodynamic instability despite six units of blood products, inability to stop bleeding with endoscopic techniques, recurrent bleeding after initial stabilization or accompanied by shock, or bleeding that requires more than 3 units of blood products per day .
For particularly frail, high-risk patients with life-threatening hemorrhage, endovascular management provides effective and less invasive management . Endovascular treatments include tumor embolization, parent vessel occlusion, and/or placement of covered stents.
Endoscopic Management for Palliation
Intraluminal stent placement
Endoscopic stenting may be an alternative or antecedent to surgical intervention for patients presenting with bowel obstruction, especially those patients who demonstrate poor performance status or those with unacceptably high operative risk. Additionally, stenting is advantageous in the setting of metastatic disease as it allows the initiation or continuation of systemic chemotherapy.
Functionally, self-expandable stents (SEMS) are placed across the tumor, expand over the course of 24-72 hours, and become embedded into the tumor by pressure necrosis thus increasing the patency of the bowel lumen. Compared to surgical palliation, SEMS allows earlier administration of chemotherapy and has been shown to have a faster recovery time and shorter hospital stays [19, 20].
Despite these advantages and the overall low mortality rate of SEMS at 1% , perforation and stent migration are possible complications. In a 2004 pooled analysis of 1,198 patients, perforation was reported in 3.76%, and stent migration in 11.81% .
Importantly, there are several contraindications to the use of colon and rectal stents. Some evidence suggests patients who use the antiangiogenic agent, bevacizumab, have a higher risk of perforation after stent placement, and therefore colonic stenting is not recommended in these patients [23, 24, 25].
However, this recommendation is based on data from retrospective studies conducted in 2010 and 2011, and there is a need for more robust data. Additionally, anatomical characteristics of the tumor, including significant angulation or increased tumor length, may increase the risk of perforation . Additionally, the life expectancy of the patient should be considered, given that 106 days is the mean duration of stent patency .
Local tumor ablation
Laser ablation or electrofulguration are additional non-surgical palliation treatment options for patients presenting with partial bowel obstruction or bleeding. For patients experiencing bowel obstruction, laser ablation may also serve as a bridge to surgical resection.
The neodymium- doped yttrium-aluminum-garnet (Nd:YAG) laser has been used since the 1980s and has success rates as high as 85-95% . This laser can be used without general anesthesia in the outpatient setting and penetrates approximately 4mm into the gastrointestinal mucosa. Endoscopic argon plasma coagulation (APC) is another form of laser therapy and has been shown to have a similarly high success rate of 85% . Argon plasma coagulation penetrates more superficially, only 2-3mm, and therefore poses less risk of perforation than the Nd:YAG laser but is also less effective at relieving obstruction.
Bleeding may be controlled by a single laser treatment session, however significant and ongoing symptom relief from obstruction may require multiple sessions and the risk of perforation increases with repeated sessions. Of note, laser therapy has not been shown to prolong life, and does not reduce pain related to tumor invasion.
Chemotherapy and Radiation Management
Palliative chemotherapy and radiation are important components of metastatic CRC care, and specific details of treatment are beyond the scope of this chapter. In general, however, recommendations for chemotherapy include using predictive biomarkers (e.g., RAS, BRAF) to guide therapeutic decision-making, using combination chemotherapy rather than sequential single agents, and earlier initiation of chemotherapy ideally before patients become symptomatic .
In addition to chemotherapy, neoadjuvant radiation therapy may be considered to improve resectability for initially inoperable non-metastatic CRC. Radiation techniques include 3D conformal radiation therapy, intensity-modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT). Patients electing to undergo radiation should be counseled regarding the impacts of radiation on their reproductive organs and should be offered supportive care in the setting of vaginal stenosis, premature menopause, sexual dysfunction, and radiation to the uterus.
Integrated Palliative Care
For all patients confronting serious life-limiting illness, offering integrated palliative care services should be considered the standard of care. The National Comprehensive Cancer Network describes the goals and scope of palliative care as follows, “to anticipate, prevent, and reduce suffering; promote adaptive coping; and support the best possible quality of life for patients/families/caregivers, regardless of the stage of the disease or the need for other therapies. Palliative care can begin at diagnosis; be delivered concurrently with disease-directed, life-prolonging therapies; and facilitate patient autonomy, access to information, and choice” .
Such care can only be provided by a multidisciplinary team and includes the aforementioned surgical, endoscopic, and systemic treatment as well as treatment from palliative care specialists. Groenewoud et al. describe a model of integrated proactive palliative care pathway that includes 8 crucial elements:
- Early and proactive identification of the palliative care phase (“Would I be surprised if this patient was to die in the next 12 months?”);
- Assessing the needs of patients in the physical, social, practical and spiritual domains;
- Weekly multidisciplinary meeting;
- Medication review;
- Timely conversations about end-of-life wishes and needs;
- Coordination between health care professionals covering the entire care cycle;
- Postmortem interview with the caregiver(s)
- Continuous monitoring of desired outcomes (i.e., quality of death and dying) .
Proactive palliative care measures have been repeatedly correlated with quality-of-life benefits for patients and families and lower healthcare use and cost. While some fear early end-of-life discussions may have negative implications on patient and family well-being, such discussions are not associated with higher rates of major depressive disorder or more worry. On the contrary, patients who are given access to early palliative services often elect to de-escalate care, undergo fewer aggressive interventions, and simultaneously report better quality of life. In addition, more aggressive interventions are associated with higher risk of major depression in bereaved caregivers .
While it is well documented that use of inpatient palliative care consultation decreases healthcare utilization at the end-of-life [34, 35, 36, 37, 38], optimal timing of palliative care intervention is still being considered. A 2019 study from Delisle and Ward et al. examined this specifically among CRC patients and compared healthcare utilization across very early, early, late, and never palliative care delivery groups. Consistent with other studies, early and very early palliative care was associated with decreases in emergency department visits, hospital admissions, in-hospital deaths, and health care costs. Furthermore, there was no differences in healthcare utilization or costs for patients who never received palliative care and those who received it within 14 days of death .
Despite literature outlining the advantages to early initiation of palliative care for CRC patients, the use of palliative care as an adjunct to surgical or systemic treatment remains alarmingly low . Patients who are older, have lower income, are diagnosed in earlier years, and who receive their treatment at nonacademic facilities are most at risk for experiencing this gap in palliative care use .
In USA, Black, Hispanic, and Asian American groups are also impacted by the gaps in palliative care services for reasons not yet well investigated by empiric research. Some potential systemic barriers to equal access to palliative care by these populations include the absence of minority staff, interpreters, and outreach to diverse communities.” .
To improve access to high quality end-of-life care, researchers have investigated the barriers to palliative care use. Such findings may help identify potential targets for intervention. Barriers to palliative care use can be characterized by patient/family factors, provider factors, and system level factors.
All of these factors can negatively impact effective palliative and end-of-life care. Patient and family barriers to effective palliative care include unrealistic expectations about prognosis or effectiveness of treatment (i.e., families desiring aggressive intervention despite poor prognosis) and discordance among family members or between patient/family and care team. Provider level barriers include absence of knowledge or training in palliative and end-of-life care, inadequate communication across care teams and/or between patients and families, difficulty with accurate prognostication, and personal factors (e.g., stress, lack of awareness of cultural norms, fear of legal liability in end-of-life circumstances).
System level barriers to effective palliative care include lack of documentation (e.g., absence of advance directives, lack of surrogate decision maker), lack of resources (e.g., restrictive eligibility criteria for entry into specialist palliative care programs), and health system culture (e.g., lack of understanding of the limitations of medical care, stigmatization of death) [43, 44].
An awareness of the common challenges in providing effective palliative care may better equip providers and researchers to improve care delivery and guide the development of effective interventions.
- For patients not experiencing symptoms or experiencing minimal symptoms due to the primary tumor, the decision to pursue surgery is based on resectability of metastatic disease and may include resection of the primary cancer.
- In contrast, for asymptomatic or minimally symptomatic patients with unresectable metastatic CRC, routine resection of the primary cancer to prevent obstruction, bleeding, and pain is not currently recommended
- For patients who develop obstruction, perforation, bleeding and/or pain, operative intervention may be appropriate.
- Symptomatic bowel obstruction should be managed by conservative measures first, followed by consideration of stenting, and finally more aggressive measures including ostomy, bypass or surgical resection.
- Bowel perforation may be managed by diversion or resection.
- Depending on the location and size of the tumor as well as the rate of bleeding, management for acute bleeding may include radiation, surgical resection, or endovascular management.
- Endoscopic stenting may be an alternative or antecedent to surgical intervention for patients presenting with bowel obstruction, especially those patients who demonstrate poor performance status or those with unacceptably high operative risk.
- Laser ablation or electrofulguration are additional non-surgical palliation treatment options (including acting as a bridging therapy to surgical resection) for patients presenting with partial bowel obstruction or bleeding.
- Palliative chemotherapy and radiation are important components of metastatic CRC care.
- For all patients confronting serious life-limiting illness, integrated palliative care services offered by a multidisciplinary team (including the consideration of surgical, endoscopic, and systemic treatment as well as treatment from palliative care specialists) should be the standard of care.
- Proactive palliative care measures have been repeatedly correlated with quality-of-life benefits for patients and families and lower healthcare use and cost.
- Despite literature outlining the advantages to early initiation of palliative care for CRC patients, the use of palliative care as an adjunct to surgical or systemic treatment remains alarmingly low.
- An awareness of the common challenges in providing effective palliative care may better equip providers and researchers to improve care delivery and guide the development of effective interventions.
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