Palliative Surgery in Cancer Patients

Introduction

Palliative surgery is “… used with the primary intention of improving quality of life or relieving symptoms caused by advanced disease. Its effectiveness is judged by the presence and durability of patient-acknowledged symptom resolution.”

Surgical treatment decisions for patients receiving palliative care are challenging. Often they have to be made within a short period of time, and the outcome expectations may vary significantly between the surgeon on one side and the patient/family on the other side. The goals of surgery and those of good palliative care are, however, directly compatible. They often are shared clinical decisions, an evidence base is usually not available, and the consequences of decision-making are profound. Clinical intuition and experience are therefore very important in this situation.

The major prognostic feature is overall well being rather than the organs in which metastases appear. Increasing global frailty is the hallmark of death approaching. If a person is in a catabolic state, anything that accelerates their deterioration is likely to be irreversible. The trauma of surgery compounds the deterioration of the disease itself. Urgent operations are associated with increased risk and 30-day mortality of up to 28% is seen in patients with disseminated malignancy. Despite these risks, patients may experience significant benefits from palliative procedures, with observational studies demonstrating that 80%–90% of patients undergoing palliative surgery experience symptom improvement or resolution. ^, It has also been demonstrated in common solid tumors that the longer a patient survives from the time of diagnosis the more likely they are to survive the next 5 years (conditional survival).

These complexities highlight that when weighing the risks and benefits of surgical intervention in a patient with advanced cancer, the nuances of prognostication are best handled by a multidisciplinary team (MDT). MDTs have been shown to be more accurate at predicting survival than individual clinicians. A multidisciplinary approach is beneficial but due to the wide variation of disease presentation and underlying conditions of patients undergoing palliative surgery only very limited or no studies are available to support treatment decisions. ^,

There is no doubt that decisions in palliative surgery are very difficult but it is important to make every decision in this challenging area of surgery with profound and humble respect for the person who is dying and for their family.

Preoperative Assessment

The overall condition of the patient must be weighed against the proposed intervention in a multifactorial calculus that has little certainty. What is the overall condition of the person? Where might this person be in their disease trajectory either with or without the intervention proposed? What has been the rate of systemic decline in recent weeks and is it reversible? Rapid decline without a reversible cause is likely to delineate a very short prognosis, while a slower decline is likely to indicate a longer prognosis. Ultimately, is this person otherwise going to tolerate this procedure and live long enough to recover from the effects of the procedure to enjoy the benefits offered?

Prognostication is very difficult and clinicians tend to be too optimistic. Gripp et al . showed that patients suffering from metastatic colorectal and breast cancer had a more favorable prognosis, whereas brain metastases, Karnofsky performance status less than 50%, need for strong analgesics, dyspnea, high lactate dehydrogenase (LDH), and leukocytosis were associated with a poor prognosis.

In the preoperative phase it is important to review and clarify the goals of care with the patient and their caregivers, and this should be actively performed by the treating clinicians.

Interventional Radiology

The interventional radiologist can offer less invasive management of complications occurring in patients receiving palliative care.

Complications from vascular thrombosis are the second leading cause of death in patients with malignancy. For larger vessel venous disease, stenting is an option, such as in superior vena cava (SVC) syndrome and less commonly inferior vena cava (IVC). IVC stenting may provide symptomatic relief and can prevent secondary organ failure (renal or hepatic venous involvement).

Hemorrhage can occur in up to 10% of patients with advanced cancer. The role of interventional radiology in management of bleeding lies in embolization of a bleeding vessel, usually after active bleeding has been identified on computed tomography (CT) angiogram. This is performed most commonly via a femoral artery approach.

Embolotherapy can be bland when agents that cause vessel occlusion alone are employed (Gelfoam, polyvinyl alcohol particles, microspheres, coils). ^, Chemoembolization combines chemotherapeutic agents with an embolic agent and is delivered directly to the target tumor by selective cannulation of the feeding artery. This method facilitates increased chemotherapy dose to the tumor. ^,

Radioembolization or selective internal radiation therapy (SIRT) enables delivery of high-dose brachytherapy (BT) to hepatic malignancies by the selective injection of yttrium-90 microspheres, used in the setting of hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM). ^, This treatment exploits the finding that arterial supply to liver tumors is different to normal liver tissue, which is supplied by the portal vein system. There is low penetration of the beta particles from yttrium-90 (approximately 2.5 mm in human tissues), so necrotizing effects are localized.

Thermal ablation techniques involve placement of a specially designed probe/electrode into the center of a lesion, usually under ultrasound (US) +/− CT guidance. The device is connected to an energy source able to generate extremes of temperature to cause irreversible tumor necrosis, ranging from microwave or radiofrequency ablation (RFA) in excess of 60°C to cryotherapy using argon gas under pressure to create subfreezing temperatures. ^{, ,} Chemical ablation has also been described using absolute alcohol and phenol, although thermal ablation is more commonly performed. A 0.5–1.0-cm zone of coagulation necrosis around the lesion is required to enable a tumor-free margin. Because RFA relies on electrical current flow, effective tissue/tumor heating is reduced by adjacent blood vessels >3 mm due to heat sink effect. Microwave ablation can include larger treatment volumes (up to 8 cm diameter), provides optimal heating of cystic masses, causes less pain, and has less heat sink effect than RFA.

Overall, thermal ablative therapies (primarily RFA and microwave) are the preferred treatment option for small lesions, with chemoembolization therapy preferred for larger lesions.

Esophagus

Esophageal carcinoma is the eighth most common cancer worldwide and sixth most common cause of cancer death. ^, Despite recent improvements in treatment and modest survival gains, overall 5-year survival for esophageal cancer remains disappointing at around 17%. Patients with inoperable local disease fare even worse with less than 3% of patients surviving 5 years. The majority of symptoms from advanced esophageal cancer can now be palliated with nonsurgical techniques and, as such, palliative surgery in the form of resection or bypass is rarely performed.

The most troublesome symptoms of incurable esophageal cancer, namely, dysphagia and bleeding, can be alleviated using less invasive methods. Esophageal self-expanding stents (SES), BT, external beam radiotherapy, and endoscopic recannulation techniques are highly effective as unimodal or multimodal therapy and are well tolerated by patients. A 2014 Cochrane Review confirmed that the combination of BT with self-expanding metal stent insertion or radiotherapy should be used as the preferred options for palliative management of dysphagia. Meta-analysis has shown that metallic stents are superior to plastic stents. Patients have been reported to do badly with tumors requiring stents more than 12 cm in length.

BT provides a less instant relief of dysphagia than SES but is associated with a better quality of life (QOL) and survival. The optimal dose is unknown but 8–20 Gy in single or double doses is common. SES can be placed endoscopically often without the need for esophageal dilatation.

Malnutrition is common with advanced esophageal cancer due to malignant dysphagia and the catabolic state. Percutaneous gastrostomies (PEG) and radiologically inserted gastrostomies (RIG) can be placed and permit bolus feeding. The author prefers placement of a PEG tube at the time of esophageal stenting. Occasionally if the esophageal lumen is completely occluded, a surgical gastrostomy or feeding jejunostomy may be required. This can be placed via laparotomy or laparoscopy.

Stomach

Gastric carcinoma represents the second leading cause of cancer-related death worldwide. Despite improvements in overall survival, the majority (60%–70%) of patients diagnosed with gastric cancer present with advanced stages. Bleeding is the most important adverse event caused by locally advanced gastric cancer. Other major complications are gastric outlet obstruction (GOO) and malnutrition.

Hemorrhage and obstruction may often be controlled by endoscopic intervention or with radiotherapy, perforation almost always requires surgical intervention. The effect of palliative surgery in patients with advanced gastric cancer on QOL is unknown. Currently two prospective randomized multicenter trials (RENAISSANCE/Flot5, SURGIGAST) are assessing the role of combined chemotherapy and surgery for patients suffering from stage IV gastric cancer.

Complications due to peritoneal carcinomatosis, i.e., stenosis, bleeding, or perforation, have to be treated considering tumor mass, distribution and localization, performance status, nutritional status, and overall prognosis. Potential surgical therapeutic approaches include small bowel resection, stoma formation, bypass surgery, or PEG placement to drain gastric and small bowel fluid.

If bleeding is significant and cannot be controlled by endoscopic intervention, or if bleeding recurs more than once following endoscopic treatment, the following options remain:

• Angiography and selective embolization of the bleeding vessel (angiography is only capable to visualize bleedings of 1 mL/min or more; the stomach is perfused via five different arteries limiting the chances of successful embolization)

• Palliative gastrectomy

• Palliative radiation

In a meta-analysis comparing endoscopic stenting to gastroenterostomy, stenting was found to be associated with higher clinical success, a shorter time to starting oral intake, reduced morbidity, a lower incidence of delayed gastric emptying, and a shorter hospital stay, while there was no significant difference between the two methods for severe complications or 30-day mortality. Surgical gastroenterostomy, however, appears to allow for longer symptom-free survival.

In some patients, insertion of a jejunal feeding tube (percutaneous endoscopic jejunostomy, PEJ) is the only option to maintain enteral nutrition. In patients with an otherwise untreatable GOO, palliative placement of a PEG is indicated to drain gastric fluid (venting PEG). Palliative (partial) gastrectomy may prolong survival by as much as 3 months when compared with a bypass procedure. This comes with a significant risk of morbidity and mortality and should therefore only be performed in selected cases.

Although gastrectomy remains a successful intervention for GOO related to gastric cancer, endoscopic stenting might be a preferable option for patients with limited life expectancy or where surgery is not possible. There are, however, no data on QOL outcomes postendoscopic stenting and the technology of duodenal stenting seems to lag behind that of biliary stents, and thus laparoscopic or open gastric bypass remains an important consideration.

Radiation has been associated with good palliation in gastric cancer causing obstruction with symptom control rates of 80% in a small series and has the advantage of also controlling bleeding.

Pancreas

Approximately 80% of newly diagnosed patients with pancreatic adenocarcinoma cannot benefit from a curative strategy. When the diagnosis of unresectable disease is made, nonsurgical endoscopic approaches should be prioritized in order to keep hospital stay as short as possible without delaying systemic chemotherapy. If an unresectable disease is diagnosed at laparotomy, an appropriate palliative surgical treatment should be considered to prevent biliary and enteral obstruction, as well as pain exacerbation due to tumor invasion. A more aggressive approach toward palliative resection can be justified only in specific circumstances. Hepatic metastases constitute a contraindication for resection of pancreatic adenocarcinoma. With treatment, median survival for locally advanced inoperable disease approaches 12 months in contemporary clinical trials and 6–8 months for metastatic disease.

The assessment of life expectancy in pancreatic cancer is difficult. Jamal et al . developed a symptom-based score (McGill-Brisbane Symptom Score, MBSS), which can be assessed during the first interview. They reported four symptoms independently predicting poor survival and weighted them regarding their influence on survival:

• Weight loss >10% (8 points)

• Pain (5 points)

• Jaundice (4 points)

• Smoking (4 points)

A low score (0–9 points) predicted an overall median survival of 14.6 months versus 6.3 months in the patient group with a high score (12–21 points).

Patients with an estimated survival of less than 6 months benefit more from interventional stent placement in terms of morbidity and length of hospital stay. Patients with a life expectancy exceeding 6 months may benefit from a more lasting solution with a decreased need for reinterventions over time. In these patients, a surgical bypass procedure should be performed, especially if the diagnosis of unresectable disease is made at laparotomy. These patients will benefit from double bypass procedures as this approach can reduce the incidence of GOO and obstructive jaundice. The double bypass procedure including gastrojejunostomy does not increase postoperative morbidity compared with biliary bypass alone. The retrocolic gastrojejunostomy is associated with a lower rate of postoperative delayed gastric emptying. Some authors reported 20% morbidity and 4% mortality rates after palliative biliary bypass surgery. ^,

A Cochrane Review published in 2014 addressed the question whether resection of the pancreas with involved vessels (locally advanced pancreatic cancer) provides better outcome than palliative treatment alone. This review identified some evidence that pancreatic resection increases survival and decreases costs compared with palliative treatment for selected patients (40% survival in resection group vs. 0% in palliative treatment group at 3 years follow up).

At diagnosis, approximately one-third of pancreatic cancer patients complain of pain and 90% of them experience severe pain at end-stage disease. Therefore any good palliation must focus on pain management in order to improve QOL. Percutaneous and/or intraoperative neurolysis should always be attempted for pain relief.