Management of Colorectal Cancer Liver Metastases
May 17, 2023 - read ≈ 49 min
Dominic J. Vitello, MD
Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, United States of America
Ryan P. Merkow, MD
Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, United States of America
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in men and women. Over one-half of newly diagnosed individuals will develop liver metastases. Among those with liver-only metastatic disease, only about one in five will be candidates for potentially curable resection. With advances in the management of colorectal liver metastasis (CRLM), overall survival has improved significantly since the 1990s, and continues to increase with significant advances in both medical and surgical management options.[2–4]
This chapter will focus on surgical and oncologic principles to examine the contemporary evaluation, management, and post-treatment surveillance of CRLMs.
Signs and Symptoms
There are three key initial presentations of CRC. Some patients present with suspicious, unexpected signs and symptoms such as pain, weight loss and/or anemia in an otherwise healthy middle-aged adult. These symptoms can be caused but the local tumor, sites of metastatic disease, or both. Other patients may be identified on routine screening such as colonoscopy. Lastly, patients may present acutely with obstruction or perforation.
While changes in bowel habits were previously thought to be the most common local tumor symptom, more recent series suggest that occult blood per rectum may be more common.[5,6] These recent series also demonstrate a much higher prevalence of abdominal pain and anemia than previously reported. There are also several local symptoms which are associated with primary tumor location. Changes in bowel habits are associated with left-sided colon cancers. Conversely, right sided colon cancers are more likely to cause occult bleeding and resultant iron-deficiency anemia.
At the time of presentation approximately one in five patients have distant metastases. The most common metastatic sites are the lymph nodes, liver, lungs and peritoneum. Signs and symptoms associated with advanced disease are right upper quadrant pain, abdominal distension, early satiety, and lymphadenopathy.
Signs and symptoms of CRC confer some degree of information regarding the patient’s prognosis. For example, symptomatic patients tend to have larger tumors, more nodal involvement, and a higher risk of metastatic disease than those who are asymptomatic.[6,8]
Conversely, identification of CRC at screening is associated with decreased risk of death and recurrence. Similarly, patient’s diagnosed at screening have longer overall survival and disease free intervals. Obstruction, perforation, or both are associated with a poorer prognosis, independent of stage.
Colonoscopy is the single, best, currently available test for the diagnosis of CRC. After diagnosis, patients should undergo a staging evaluation which consists of imaging to assess the overall burden of disease. It is at this juncture that patients may be identified as having CRLMs. Metastatic disease may also be identified on post-treatment surveillance imaging.
Biopsy confirmation of CRLMs is generally indicated. Patients who have previously been treated for CRC who have lesions with characteristic features on imaging, an elevated CEA, and potentially resectable disease may not require biopsy. The risk of tract seeding with percutaneous biopsy techniques appears to be low, and is more often associated with primary hepatic neoplasia such as hepatocellular carcinoma.[11–13]
Needle biopsy should be performed intra-operatively if the patient undergoes surgical management for a primary CRC prior to CRLM-directed therapy.
Imaging is a vital component of preoperative evaluation for patients with CLRMs. Adequate imaging is necessary as it provides information regarding the number, extent, and location of the metastatic lesions. The usual imaging modalities for cross-sectional imaging in gastrointestinal malignancy are useful and include computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET).[14–16] It is, perhaps, most important to identify patients that would not stand to benefit from surgical resection of CRLMs. For this reason, the imaging modality with the highest sensitivity for lesion detection is preferred.
Based on available evidence, contrast-enhanced MRI appears to be most sensitive for the detection of CRLMs at 81 percent. MRI may also be further superior to CT in patients with hepatic steatosis, a finding that is common after neoadjuvant therapy.[18,19] MRI with Eovist contrast agent is particularly helpful in identifying hepatic lesions and is our preference.
However, MRI is generally inferior in evaluating vasculature, and therefore we frequently rely on triphasic CT studies to map the portal venous and hepatic arterial anatomy. Nevertheless, MRI may not be widely available, even in well-resourced health systems. Patients may also be ineligible to undergo MRI for a variety of reasons, such as metal implants, insurance coverage issues, or patient-preference.
Management of CRLMs is multidisciplinary and must include a comprehensive discussion of the various options. Available modalities include surgical resection, systemic therapies (e.g., chemotherapy, targeted therapy, immunotherapy), and other liver-directed therapies including stereotactic body radiation therapy (SBRT), transarterial radioembolization (TARE) (e.g., yttrium-90) and hepatic artery infusion (HAI) chemotherapy. Surgical resection and hepatic ablation represent the only current definitive options, while other modalities are important adjuncts and, in some cases, provided a durable long-term response. Liver-directed therapies are almost always combined with systemic therapy since it is the only approach that addresses extrahepatic microscopic metastatic disease.
The sequencing of various modalities and their interplay is the subject of much discussion. Patients who are candidates for resection are often treated with neoadjuvant chemotherapy.[20–22] It is important to note that patients presenting with synchronous CRLMs will require a full course (6 months) of chemotherapy, regardless of the timing with respect to surgery. However, neoadjuvant chemotherapy prior to liver directed therapy has not been shown to increase overall survival, only progression-free survival.[3,23–27] For these reasons, there is no universally accepted timing of chemotherapy with respect to surgery for CRLMs.
Additionally, elements of treatment such as chemotherapy regimen, patient selection, duration of neoadjuvant therapy, treatment sequencing are not well understood. It is, therefore, important to have multidisciplinary input when proceeding with management of CRLMs. These multidisciplinary meetings, often termed “tumor boards,” are an essential requirement when determining the complex management decisions for patients with CRLMs.[28,29]
Neoadjuvant chemotherapy is always a consideration for patients with CRLMs. There are two commonly cited benefits to neoadjuvant therapy. First, pre-operative administration offers the ability to assess CRLM response.[23,25–27] Lesions that progress despite neoadjuvant chemotherapy are presumed to exhibit an aggressive underlying biology and therefore resection for these patients should be approached with caution. Second, systemic therapy may convert unresectable disease to resectable.[3,26,30–32]
However, the ability to convert patients is widely variable and dependent on the reasons for unresectability (technical vs. biological) and is determined on a case-by-case basis. Early and frequent involvement by experienced hepatobiliary surgical oncologists is required when evaluating for potential resectability. The main disadvantage of neoadjuvant chemotherapy is that it can increase perioperative morbidity and mortality.[24,33–36]
Thus, the ideal approach is individualized and represents a balance between the risks and benefits of various treatment modalities. If neoadjuvant chemotherapy is selected, a few important considerations exist that pertain to the subsequent steps in management. The duration of therapy must be thoughtfully considered and the disease burden must be monitored. These endpoints are interlinked, but are largely managed by way of interval imaging to assess tumor response and potential eligibility for surgery. Additionally, contemporary chemotherapy regimens have resulted in near-60 percent response rates. Approximately 5 percent of patients have CRLMs that may disappear entirely on interval imaging.[37–39]
Nevertheless, for the vast majority of patients, these tumors will eventually become observable and resection is still necessary for definitive management. Moreover, with high quality preoperative imaging such as MRI with Eovist, or intraoperative evaluation with ultrasound, these lesions can be discovered and targeted. Consideration should also be given to marking metastases with a fiducial marker if thought to be at risk for disappearing. This technique has been demonstrated to persistently localize CRLM, even after disappearance, at the time of resection or ablation.
We infrequently place fiducial markers given success with high quality imaging and intraoperative ultrasound. Lastly, chemotherapy-related hepatotoxicity is always a consideration when administering preoperative chemotherapy. Steatosis can additionally mask underlying liver lesions on CT imaging, making MRI even more beneficial in these settings.
Assessing a patient for resection candidacy involves three factors. Elements of the patient’s physiology, tumor biology, lesion number, and lesion location are the key considerations. There are studies that have previously attempted to incorporate these, and other factors, into scoring systems to guide patient selection (e.g., Fong Score).[41–44]
While standard lines of thought apply to assessing the operative risk for a patient with CRLMs, it should be noted that liver resection induces a significant amount of physiologic stress. Therefore, patients with advanced age, significant cardiopulmonary comorbidity, and underlying liver disease may result in prohibitive operative risk.
Tumor biology also influence the decision to offer resection of CRLMs, and likely represent the single most important predictor of survival. Many observable and non-observable factors make up each individual patients underlying biology, such as pattern and extent of disease (e.g., right vs. left sided primary tumor location), molecular diagnostics (e.g., BRAF, KRAS status), and timelines of disease (e.g., disease-free interval) and treatment response.
Lastly, resectability is dependent on the precise distribution of disease and relationship to inflow pedicles and outflow hepatic veins. Some patients may have an isolated metastatic lesion in an entirely unresectable location, while other patients may have several lesions that are more straightforward to resect and/or ablate. With this in mind, previous paradigms for approaching anatomic resectability sought to examine just these aspects, the number, size, and location of CRLMs. However, more contemporary thinking defines anatomically resectable CRLMs as any tumor or tumors that may be resected while leaving an adequate liver remnant (future liver remnant [FLR]) with sufficient inflow and outflow vasculature and draining bile duct. After chemotherapy, we prefer the FLR to be >30-40%.
In the case where the estimated future liver remnant will be insufficient, multiple methods may be employed to assure a safe post-resection volume. One such technique is portal vein embolization (PVE). There are several demonstrated benefits to preoperative PVE. First, there is a documented increase in the ability to offer and perform curative resection for patients with CRLMs. The post-resection liver volume in patients with cirrhosis is, observationally, a predictor of mortality.[46,48]
Lastly, PVE permits time between the act of embolization and post-embolization liver imaging. On post-embolization imaging, the liver may fail to hypertrophy, or additional, rapidly progressive disease may occur. Either of these findings may suggest that surgical resection would not be beneficial. We pay particular attention to the growth kinetics. If the FLR does not increase at a rate >1-2% per week, the underlying hepatic function is questioned.
Surgical resection and ablation, when combined with chemotherapy, represent definitive treatment of identified CRLMs. While neoadjuvant chemotherapy has been shown to improve progression-free survival, there are no studies currently demonstrating improved overall survival.
CRLMs may be synchronous or metachronous. While no universally accepted definition exists, in common parlance synchronous metastases are demonstrated at the time of initial presentation or shortly thereafter. CRLMs that appear much after initial presentation, often after treatment for the primary tumor has concluded, are termed metachronous. Prior to surgical treatment of CRLMs, it is important to consider a number of scenarios which add challenges to the management strategy.
CRLMs may be extensive in both size and number. After surgical resection, the FLR volume must generally be at least 30 percent after use of preoperative chemotherapy. For patients that have extensive, bilobar metastases, staged resection is often necessary. This would proceed with an initial operation to remove as many CRLMs as possible, with interval chemotherapy and re-operation once the remaining liver has recovered.
For patients with synchronous CRLMs, an outstanding question remains as to the optimal surgical approach at the time of the index operation. Some presentations may necessitate management of the primary tumor first, such as obstruction, perforation, or bleeding. In these scenarios, it is advisable to address the primary tumor separate from CRLMs. Attempts to identify and plan for CRLMs may delay more urgent or emergent procedures unnecessarily. Second, the additive morbidity of a combined hepatic and colorectal resection dictates the operative approach. For instance, patients with favorable primary tumor characteristics such as right-sided cancers with oligometastatic disease to the liver may undergo a 1-stage operation, where the primary tumor and CRLMs are addressed concomitantly.
The same patient with a heavy disease burden within the liver may require a 2-staged surgical approach. That is to say, the patient may benefit most from an index operation to resect the primary tumor, followed by additional chemotherapy and interval resection of CRLMs, or vice versa, depending on the scenario. When a synchronous approach is not possible, we prefer to address the CRLMs first when the primary tumor is not symptomatic.
There are three major surgical techniques currently deployed for the operative management of CRLMs anatomic resection, parenchymal-sparing resection, and ablation. Anatomic resection refers to removal of liver tissue according to the Couinaud segments. Current standard approaches have moved away from anatomic resection in favor of parenchymal-sparing strategies, when possible. There is no evidence demonstrating increased survival with anatomic when compared to parenchymal-sparing resection.
Furthermore, there are improved perioperative outcomes with parenchymal-sparing resection such as decreased length of stay, lower estimated blood loss, lower transfusion requirement, and lower morbidity.[53,54] Importantly, since 50-75% of patients will have a recurrent liver metastatic disease, a parenchymal sparing approach allows for additional surgical options in the liver to clear all disease. Resection may be achieved through an open or minimally invasive surgical approach.
As part of a parenchymal-sparing approach, hepatic ablation can be used to definitively treat CRLMs. Ablation is, in a sense, a subset of parenchymal-sparing surgical techniques that use electrical or electromagnetic energy to thermally ablate hepatic tumors.[55,56] Ablation can be performed using radiofrequency electrical current, or electromagnetic radiation in the form of microwaves. While various technologies exist, the central mechanism is the same. First, the energy device is inserted into the desired location under guidance and then energized. In radiofrequency ablation (RFA), electrical current passes through the patient in connection with a dispersion pad. In microwave ablation (MWA), the tip of the energy device emits electromagnetic radiation. The energy from this radiation causes atomic and molecular excitation, manifesting as thermal energy, to raise the temperature and cause coagulative necrosis of the target tissue. Ideally, the region of coagulative necrosis encompasses the site of the tumor and 10 mm of surrounding healthy tissue. This is in keeping with the principle of a 10 mm resection margin for CRLMs.
While initially used for CRLMs that were not amenable to surgical resection, the role for ablation is now an essential component to treat liver metastases while maintaining a parenchymal sparing approach. With growing understanding of the side effect profile, ablation is regularly performed laparoscopically, concomitantly with surgical resection, or percutaneously with interventional radiology.
Currently, MWA represents the standard of care for hepatic ablation of CRLMs. There are a variety of advantages to MWA, making it favorable to RFA.[57–63] One such advantage is that multiple energy devices may be used simultaneously during a single encounter. Furthermore, the physical mechanism by which MWA generates thermal energy has more favorable characteristics. For instance the region of ablated tissue is more predictable. While tissue charring and vascular flow can influence the region of treated tissue during RFA, MWA is less affected by these factors. Furthermore, MWA requires 20-30 percent less time per treatment than RFA.
Complications of MWA are usually mild, as the procedure is well-tolerated. Pain, fever, and transaminase elevation are common. Major complications such as abscess, biliary leak, off-target tissue injury, and tract seeding are rare when used correctly by an experienced operator.[62,65] Outcomes after MWA ablation are favorable, with good local tumor control supported by observational data.[65,66]
Like most gastrointestinal neoplasia, achievement of an R0 resection is desirable and is an important component of survival.[67,68] Historically, the recommended resection margin for CRLMs has been 10 mm. However, there exists some controversy surrounding the true margin needed.[69,70] Several studies have demonstrated that an R0 resection margin of less 10 mm does not impair overall survival.[71,72]
Most importantly, efforts in CRLM resection should be focused on obtaining an initial R0 resection. There has been additional focus on resolving whether intraoperative re-resection to obtain a negative margin is beneficial. Alas, the studies demonstrated that performing intraoperative re-section does not confer improved survival, although the range varies widely.[73–75] Long-term follow up data are sparse.
Bile leak is a significant postoperative complication that occurs in approximately 10 percent of patients. In efforts to minimize this, some surgeons perform intraoperative air cholangiography. To do this, a catheter is inserted into the cystic duct stump and secured with a suture. The cholangiogram has two parts. During the first part, an ultrasound probe is placed onto the liver and the intrahepatic bile ducts are viewed. Air is injected through the catheter while digital pressure is applied to the common bile duct. Pneumobilia visible on the ultrasound confirms duct patency. Failure to visualize pneumobilia may suggest the presence of an occluded duct, transected duct, a large bile leak, or incomplete digital occlusion of the common duct. Once pneumobilia is achieved, the right upper quadrant is submerged in irrigation solution. The cholangiogram is then repeated, observing for the presence of bubbles. The site of these bubbles represent areas of potential bile leak, and may be suture ligated. This process is repeated until no bubbles are seen. Drains should not be placed routinely as they are demonstrated in observational studies to lead to negative consequences and are unlikely to reduce the need for additional post-operative drainage procedures.[77–79]
Postoperative care for patients undergoing hepatic resection for CRLM often depends on the extent of resection. Most patients are able to be extubated and transferred to a monitored, inpatient care setting. Depending on the resources and staff available, some patients may be appropriate for a regular floor while others may require intensive care monitoring. Particularly with large-volume hepatic resection, intensive care is needed for hemodynamic monitoring and frequent laboratory collection. Nearly all patients have a degree of hypophosphatemia. While the mechanism of hypophosphatemia is under investigation, hepatocyte regeneration and alterations in renal physiology after hepatectomy leading to phosphaturia are thought to play a role.[80–84]
Hypophosphatemia should be corrected deliberately. Furthermore, blood glucose levels can be labile, requiring prompt attention and rectification. The true incidence of post-resection coagulopathy and bleeding are difficult to ascertain due to varying definitions and degrees of severity. Coagulation studies should be monitored in the immediate post-operative period. The serum bilirubin should also be measured in post-hepatectomy patients. These laboratory values are used to monitor for hepatic failure, the most consequential complication. We perform emergent liver Doppler ultrasonography in patients with clinical features concerning for post-hepatectomy hepatic failure. This permits identification of structural abnormalities such as hepatic inflow/outflow issues for which corrective procedures may be offered. With contemporary perioperative medical practices, mortality in patients who undergo resection for CRLM is less than 5 percent. High-volume, specialized centers have reported mortality rates of approximately 1 percent. Morbidity rates range from 5 to 50 percent, depending on the study and the predefined extent of resection.
In patients with CRLMs, five year overall survival remains low without surgery, with ranges less than 11 percent with chemotherapy alone. All told, the benefit of successful resection cannot be understated, with five- and ten-year overall survival at 60 and 24 percent respectively.[41,87,88] To reiterate, perhaps the most important factor in outcomes as a whole is tumor biology. While the underpinnings of this are the substance of basic scientific investigation, two gene mutations, RAS and BRAF, have been associated with poorer outcomes. Mutations in the RAS oncogene appear to portend decreased overall survival. Indeed, the mutation type and location influences the clinical pattern of disease.
The effect on various other process measures is not as linear. The pattern of metastatic burden seems to somehow play a role in outcomes, with hepatic resection being affected negatively by RAS mutation while metastatectomy at other sites is not. Multiple studies also support the assertion that mutations in the BRAF gene, particularly the V600E mutation, are associated with worsened oncologic outcomes, including overall survival.[92–96]
It is estimated that 50-75 percent of patients will have a recurrence after hepatic resection for CRLM with the most common site of recurrence being the liver. With the same principles for patient selection and preparation, patients may undergo repeat surgery for CRLMs. While all available data are currently observational, survival rates at two to five years range from 20 to 73 percent.[99–103]
The benefit appears to be most pronounced in patients that have a relapse-free interval of greater than one year.[104,105] The pattern of recurrence appears to be away from the surgical margin, suggesting that the etiology is that of micrometastatic disease.[69,106]
About 80 percent of patients with CRC are not candidates for hepatic resection at the time of diagnosis. For these patients, systemic therapy as well as non-surgical local therapy can be deployed in an attempt to convert the burden of disease to resectability. Depending on the study and methods used, conversion rates vary from 15 to 50 percent.[108–111]
Nonsurgical, local therapy, refers to any treatment for CRLMs outside of anatomic hepatic resection or parenchymal-sparing hepatic resection. Hepatic ablation of CRLMs is increasingly, and in some centers, heavily used in combination with surgical therapy. As such, the discussion of its use is grouped accordingly. Additional local therapies include stereotactic body radiotherapy (SBRT), hepatic intra-arterial chemotherapy, and transarterial embolization. As previously discussed, the selection of a treatment strategy for patients with CRLMs is complex and influenced by many factors. The decision of whether to use nonsurgical, local therapy and which modality is selected is similarly nuanced. Therefore, nonsurgical, local therapy may be used in combination with systemic therapy and resection for an attempted cure. It is, however, important to note that the subsequently mentioned therapies may not be used alone as curative-intent management of CRLMs.
SBRT for CRLMs is similar to its use for other radio-sensitive malignant neoplasms. SBRT uses imaging guidance to deliver targeted doses of ionizing radiation. It has an advantage over traditional radiotherapy in that it is able to minimize damage to surrounding healthy tissue. It is, perhaps, physiologically advantageous as it does not require procedural sedation. SBRT is, however, resource-intensive, and demands that patients present to a center with the available technology for multiple encounters. Local control for SBRT is generally defined as disappearance, decrease in size, or stability of a treated lesion. In all, successful completion of SBRT has demonstrated good local tumor control, with two to three year rates ranging from 59 to 91 percent.[112–116]
Despite this, SBRT is not able to definitively treat CRLMs. A dose of approximately 70 Gy is generally needed to destroy an adenocarcinoma. However, the maximum lifetime dose to the liver is 35 Gy. With this in mind, the development of methods to deliver higher, more-targeted doses of radiation are of biotechnological interest. MRI-guided Linear Accelerator (LINAC) is a promising tool which integrates both MRI and radiation to improve localization, and therefore, allows higher more ablative doses delivered to CRLMs. [117,118]
Hepatic Arterial Infusion Pump
Hepatic arterial infusion pump (HAIP) chemotherapy is a treatment modality that utilizes an implantable pump to deliver therapeutic agents via a catheter to the liver, increasing target tissue agent concentration. HAIP is based upon the understanding that hepatic tumors, derive their blood supply primarily from the hepatic artery. Therefore, HAIP is able to deliver high local concentrations of chemotherapy to CRLMs as well as micrometaststic lesions not seen on imaging, at 300-400x the dose of systemic chemotherapy.
Furthermore, agents with significant systemic toxicity, but readily inactivated by hepatic metabolism, can be used by the targeted nature of the infusion. To deploy this modality, a hepatic artery mapping with a CT or MR arteriogram is obtained to fully define the hepatic arterial anatomy. Placement may proceed if suitable anatomy exists. After gaining exposure to the porta hepatis, an extensive lymphadenectomy and mobilization of the common hepatic, proper hepatic and gastroduodenal arteries are performed. This ensures adequate vascular exposure for placement of the hepatic artery catheter, as well as decreases off-target perfusion can result in complications. Next, accessory or replaced hepatic vessels are completely ligated. The gastroduodenal artery is most commonly selected for catheter placement. The hepatic artery infusion pump is placed into a subcutaneous pocket, which is loaded with heparinized saline. To ensure proper perfusion of the liver and the absence of off-target perfusion, fluorescein or methylene blue are injected. The liver, stomach, and duodenum are then visually inspected for distal perfusion of the dye. Postoperatively, a Tc-99m, macro-aggregated albumin scan is needed to confirm proper target tissue perfusion. After successful placement, chemotherapeutic regimens can be delivered by way of the infusion pump. Treatment with floxuridine (FUDR) is able to be started two weeks from surgery.
Disadvantages of HAIP include high-resource utilization as well as those associated with the procedure itself. As is evidenced, HAIP requires centers with expertise in this technique. Patients must present for multiple encounters to undergo preoperative and postoperative testing. Early complication rates are low, approximately less than 5 percent. They do include hepatic artery injury, hepatic artery thrombosis, incomplete hepatic perfusion, off-target tissue perfusion, and pump pocket complications such as hematoma or surgical site infection.[119,120]
Benefits of HAIP chemotherapy are demonstrated when used in combination with surgery or systemic chemotherapy. There are multiple, modern studies demonstrating the benefit adjuvant HAIC after resection of CRLMs. Improvements are seen in various perioperative outcomes as well as disease-free and overall survival.[121–123]
For many patients, the burden of disease or refractory nature to curative-intent treatment may necessitate other strategies such as transarterial chemoembolization (TACE) or radioembolization (TARE). While TACE and TARE are not considered curative, they may be selected to improve quality of life and prolong survival based on local expertise, patient preference, and disease characteristics. TACE is technique that introduces a catheter into the hepatic artery via percutaneous access for the introduction of drug-eluding beads. Retrospective data demonstrate that 40 to 60 patients with liver-predominant metastatic CRC can achieve disease stability.[124–126]
Some studies also have demonstrated some advantages of TACE when compared to systemic therapy for the aforementioned patient population.[127,128] Similar, in concept, is the possibility of TARE for patients with refractory, liver-predominant metastatic CRC. Because the scarcity and expense of this management strategy, a consensus panel from the Radioembolization Brachytherapy Oncology Consortium suggested that radioembolization be limited to patients that have a life expectancy of at least 3 months, favorable gastrointestinal flow patterns, minimal pre-treatment intrinsic liver disease, and acceptable risk of off-target radiation delivery.
The technique employs arterial embolization with radioactive elemental isotopes. Available data mainly have shown modest benefit analyzing TARE as sole treatment modality as refractory therapy.[130–135]
Post-Treatment Surveillance and Long-Term Outcomes
After completion of therapy, patients transition into the post-treatment surveillance phase of management. Post-treatment surveillance is not indicated for patients who undergo palliative-intent therapy. However, interval assessment and imaging may be warranted if further palliative-intent modalities align with a patient’s goals of care. For patient who completed curative-intent therapy, there are no data to guide surveillance recommendations. Clinical practice is largely extrapolated form data pertaining to the knowledge of surveillance for patients with lower anatomic stage disease.[136,137]
Using this information, most guidelines recommend history, physical examination and CEA testing every three to six months for two to five years. Circulating tumor DNA (ctDNA) is being increasingly used in addition to CEA to monitor for recurrent disease and treatment response.[138–141] Most guidelines also recommend CT scanning annually over the same interval. As previously discussed, PET and MRI are sensitive for CRLMs at the cost of increased resource utilization, but are not included within currently formulated guidelines. Finally, colonoscopy is nearly universally recommended at one year. Thereafter, colonoscopy is spaced to every three to five years if normal.
Colorectal cancer is a common malignancy. A significant proportion of these individuals have, or will develop, CRLMs. Despite its frequency, the management of CRLMs is complex, and requires multidisciplinary input. Pretreatment evaluation and assessment for the various available treatment modalities is critical. High quality liver imaging, such as with MRI with Eovist, is important for defining the burden of disease within the liver. Patients are sequenced to receive chemotherapy and surgery, with the order being tailored to each individual. Definitive surgical management for CRLMs seeks to resect or ablate all lesions with 1 cm margins, while maintaining an adequate FLR. Despite advances in technology, many patients never complete curative-intent therapy. For these patients, many options exist that delay disease progression, and in some instances prolong survival. Overall five-year survival for patients with CRLMs receiving systemic therapy alone is less than 11 percent. However, for patients that undergo fully curative-intent treatment, five-year survival has risen to 60 percent. This illustrates the benefit of surgical therapy in appropriate candidates. While complex, emerging understanding and novel approaches demand that all health systems address the medical and surgical approach to patients with CRLMs.
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