Introduction

Colorectal carcinoma metastasizes to the lung in 10% to 15% of patients. The decision about whether to perform surgery for a patient with lung metastasis must take into account the patient’s ability to tolerate surgery, as well as the likelihood of achieving long-term survival. Most reports detailing the treatment of lung metastases are single-center retrospective reviews that have used overall survival as the endpoint. During the past 10 to 15 years, several multicenter reviews have been published, and a single prospective randomized trial has been initiated. This chapter will review the indications for resection of metastases to the lungs, prognostic factors derived from prior single and multi-institution reports, the issue of combined lung and liver metastases, the surgical approach, and the concepts behind the development of a prospective randomized trial.

Indications for Resection of Colorectal Metastases

Many factors are involved in the decision of whether to offer the option of surgical resection to a patient with metastatic disease to the lungs. A basic set of criteria has long been adopted by most surgeons:

• 1.
  

  The operative risk for the patient must be acceptable. Severe comorbidities such as recent congestive heart failure, unstable angina, and severe or critical aortic stenosis would preclude most patients from any procedures except for immediately lifesaving operations. In addition, pulmonary capacity and the ability to withstand lung resection must be taken into account. Patients should undergo full pulmonary function testing, including forced expiratory volume in the first second of expiration (FEV1) and diffusion capacities. Commonly held parameters for lung resection dictate that the postoperative FEV1 or diffusion capacity (when adjusted for hemoglobin and total alveolar ventilation) should not be less than 35% to 40% of predicted. Patients with numbers below these values have been shown to have an excess of perioperative complications and postoperative respiratory problems. A preoperative FEV1 is obtained, and the percentage of functioning segments that would be removed is estimated to obtain a number. These calculations are typically used in reference to anatomic resections such as lobectomies or segmental resections. Small, peripheral wedge resections usually do not have a significant effect on lung function and often can be performed even in persons with very poor baseline function.

  
  
• 2.
  

  A complete resection of all metastatic disease should be achievable. This goal has recently been modified with the development of stereotactic body radiation, which delivers fairly good long-term control for lesions smaller than 3 cm in diameter.

  
  
• 3.
  

  The primary malignancy should be removed, and the patient should have no evidence of recurrence.

  
  
• 4.
  

  Patients should have no evidence of disease elsewhere. Certain patients with combined hepatic and lung metastases who may have good long-term outcomes are an exception to this dictum.

Outcomes of Patients Undergoing Resection and Prognostic Factors

More than 100 single-institution reports describing outcomes of patients undergoing resection of colorectal lung metastases have been published. Each report represents what is likely a highly selected group of patients cared for by a unique group of surgeons in a unique facility. The results achieved in these patients by these surgeons in these facilities may not apply to other institutions. Nonetheless, they represent the mainstay of our literature. Girard et al retrospectively reviewed 86 patients with metastatic colorectal cancer who underwent lung resection at a single French hospital. Twenty-one patients underwent bilateral surgery, and 10 had an incomplete resection. The estimated 5-year and 10-year survival was 24% and 20%. Complete resection, the number of lung metastases, and preoperative carcinoembryonic antigen (CEA) levels were all noted to be independent predictors of prolonged survival. Inoue et al retrospectively reviewed 128 patients in Osaka, Japan, who underwent resection. The overall 5-year survival rate was 45.3%. In univariate analysis, the number of metastases, unilateral location, preoperative CEA levels, absence of hilar or mediastinal nodal metastases, and node negativity of colon primary were all predictors of long-term survival. In multivariate analysis, however, only negative nodes in the colon primary cancer resection and the unilateral nature of lung metastases were significant independent predictors. Saito et al reviewed the cases of 165 patients who underwent lung resection for colorectal carcinoma in Japan between 1990 and 2000. In the majority of patients (57%), the site of their primary cancer was in the rectum. Sixty-three percent of the patients who underwent lung operations had a solitary metastasis, 23% had three or more metastases, and 16% had hepatic metastases, which were resected before the lung metastases. The patients in this series were all treated with a thoracotomy. (It should be noted that in the United States today, a significant percentage, and possibly the majority, of these resections at academic institutions are performed by video-assisted thoracic surgery [VATS]). Overall 5-year and 10-year survival rates were 39.6% and 37.2%, respectively. The authors noted that 5-year survival was much better for patients with a prethoracotomy CEA of less than 10 ng/mL (42.7%) than for those with a level of greater than 10 ng/mL (15.1%). The 5-year survival of patients without hilar or mediastinal nodal metastasis was 53.6% versus 6.2% for patients with metastases. The 10-year survival of patients with prior resected hepatic metastases was 34.1% and was not statistically different from that of the patients without hepatic metastases.

In a recent publication, Onaitis et al reviewed the experience at Duke Medical Center and Memorial Sloan Kettering Cancer Center. Three hundred seventy-eight patients who underwent pulmonary resection for colorectal metastases between 1998 and 2007 were identified. The rectum was the primary site of disease in 52%, with the left colon accounting for 26% and right colon 16%. Forty-four percent of patients in this series had undergone resection of extrathoracic metastasis prior to lung surgery. The median disease-free interval was 24 months. Sixty percent of patients had a solitary metastasis resected, twenty percent had two metastases resected, 10% had three metastases resected, and 10% had four or more metastases resected. Overall 3-year survival was 78%, but 3-year disease-free survival was only 28%. Multivariate analysis showed that age younger than 65 years, female sex, a disease-free interval of less than 1 year, and more than three metastases were independent predictors of recurrence. None of the 44 or more patients with three or more metastases and a disease-free survival of less than 1 year was cured. The large number of patients with prior resection of extrathoracic metastases differs from many other series and reveals the difficulty in comparing these results across institutions and populations. It should be noted that in the group of patients undergoing surgical resection by thoracoscopy (VATS), no perioperative deaths occurred.

It is apparent from prior single and multiple-institution studies that a variety of preoperative factors correlate with better long-term survival. These factors include a longer disease-free interval from the time of colon resection, fewer metastatic lesions, lower prelung resection CEA, and absence of intrathoracic lymph node involvement. In an attempt to mitigate single-institution bias and obtain larger numbers, retrospective multi-institution reviews have been performed. Pfannschmidt et al reviewed articles published after 1990 involving the surgical treatment of at least 40 patients. Fifteen studies were found, reporting a 5-year survival between 40% and 68% after resection of lung metastases. Five-year disease-free survival was between 19.5% and 34.4%. The perioperative mortality rate ranged from 0% to just 2.4%. (The low mortality numbers may illustrate the highly selected nature of retrospective reviews because institutions with high mortality rates are less likely to publish their data.) The studies in general found improved survival with metachronous presentation of metastasis, a longer disease-free interval, and the presence of more than one metastasis. The presence of intrathoracic lymph node metastasis was a negative predictive factor in two of the studies but was not a negative predictive factor in five studies.

Another meta-analysis reported in 2013 focused on surgical studies of more than 40 patients published since 2000. Most of the studies had between 40 and 80 patients. The meta-analysis included 25 studies with a total of 2925 patients, and overall 5-year survival ranged from 27% to 68%. Factors associated with increased risk of death after resection of lung metastasis were a short disease-free interval (hazard ratio [HR], 1.59; confidence interval [CI], 1.27-1.98), multiple lung metastases (HR, 2.04; CI, 1.72-2.41), intrathoracic lymph node involvement (HR, 1.65; CI, 1.38-2.02), and pre–lung resection CEA level (HR, 1.91; CI, 1.57-2.32). It should be noted that only 14 to 19 of the studies were used for each risk factor analysis because not every variable was described in each of the 25 studies. Nonetheless, this is one of the most comprehensive and recent studies incorporating multiple prior retrospective single-institution studies.