Surgical resection of pulmonary metastases: Outcomes by histology

INTRODUCTION — Lung metastases from a primary extrapulmonary malignancy are often a manifestation of widespread dissemination; however, some patients have no other evidence of disease. Extensive experience with pulmonary metastasectomy in a number of different cancers has confirmed that resection is associated with prolonged relapse-free survival and cure in some patients. Based upon these observations, aggressive resection of isolated pulmonary metastases has become a widely accepted treatment for appropriately selected patients. However, acceptance is not universal, and it is unproven whether surgical metastasectomy substantially improves survival [1].

Questions remain as to whether it is the resection or simply the selection of patients with a more favorable natural history that is responsible for any apparent improvement in survival associated with metastasectomy.

The potential benefits of resection are discussed in more detail elsewhere. (See "Surgical resection of pulmonary metastases: Benefits, indications, preoperative evaluation, and techniques".)

The benefits of resection, and the specific approach to the patient are also dependent upon the histology of the tumor [2]. This topic review will cover the outcomes of pulmonary metastasectomy in various tumor types and the use of adjuvant therapy following resection, where indicated. Specific issues related to patients undergoing resection of lung metastases from soft tissue sarcoma and a general discussion of the benefits of pulmonary metastasectomy, selection criteria, preoperative evaluation, and techniques for surgical resection are discussed elsewhere. (See "Surgical treatment and other localized therapy for metastatic soft tissue sarcoma" and "Surgical resection of pulmonary metastases: Benefits, indications, preoperative evaluation, and techniques".)

The integration of surgery into multidisciplinary therapy for patients with specific malignancies is discussed in the appropriate topic reviews.

OUTCOMES BY HISTOLOGY

Soft tissue sarcoma — Soft tissue sarcomas primarily metastasize to the lungs, and surgery is the only potential curative treatment. The International Registry of Lung Metastases found similar survival rates in patients with epithelial carcinomas and in those with sarcomas [2]. Among 1917 patients with sarcoma pulmonary metastases, overall survival after resection was 31 percent at five years and 26 percent at 10 years, with a median survival of 29 months [2]. These outcomes have been further corroborated by a 2017 analysis of the Memorial Sloan Kettering Cancer Center (MSKCC) database [3]. Over 25 years, 539 patients underwent 760 metastasectomies of soft tissue sarcoma with curative intent. Although there was a short median disease-free survival of 6.8 months, the median overall survival was 33.2 months. Perhaps more importantly, there was a long survival tail to the Kaplan-Meier curve, with 47 percent surviving three years, 34 percent surviving five years, and 23 percent surviving seven years. In another series, the overall survival of patients with leiomyosarcoma pulmonary metastases was particularly favorable, with a median survival of 70 months [4].

The role of surgery in the treatment of lung metastases from soft tissue sarcoma is discussed elsewhere. (See "Surgical treatment and other localized therapy for metastatic soft tissue sarcoma", section on 'Pulmonary metastases'.)

Lung cancer — Synchronous and metachronous metastatic disease to the ipsilateral or contralateral lung is common among patients with primary non-small cell lung cancer (NSCLC). For patients with a limited number of metastatic sites from NSCLC, local therapy may delay progression and occasionally be associated with prolonged disease-free survival. Randomized controlled trial data are limited, but local consolidative therapy for oligometastatic NSCLC may improve survival [5]. Surgical resection of possible pulmonary metastases for patients with lung cancer may have a particular role if it is uncertain whether a new pulmonary lesion represents metastatic disease or a new primary tumor, in which case resection may serve both diagnostic and therapeutic purposes and facilitate collection of tissue adequate for molecular testing. (See "Oligometastatic non-small cell lung cancer".)

Metastatic and recurrent small cell lung cancer is generally treated primarily with systemic therapy. The role of surgical resection for metastatic or recurrent small cell lung cancer is limited, but resection may be considered for the occasional patient with low-volume, slowly progressive disease or in whom the diagnosis is in doubt.

Colorectal cancer — For patients with potentially resectable lung metastases from colorectal cancer resection may prolong overall survival. However, nonsurgical management is also an option for these patients. Although uncontrolled reports suggest that 5- and 10-year survival rates seem better following resection than can be achieved by modern combination chemotherapy, there are no randomized trials proving benefit, and questions remain as whether surgical results are better than those that can be achieved using modern ablative techniques, such as stereotactic body radiation therapy or radiofrequency ablation. A multidisciplinary tumor board discussion for decision-making is preferred in these patients. This position is consistent with guidelines from the National Comprehensive Cancer Network (NCCN) [6] and the American Society of Colon and Rectal Surgeons [7].

The last 10 years have seen marked and impressive improvements in survival for patients with metastatic colorectal cancer, attributed in part to the availability of several new active drugs, making this one of the most favorable subgroups to consider for pulmonary metastasectomy.

Very few randomized trials of resection have been conducted [8], and there are no data from high-quality, statistically robust trials to support a survival benefit from resection. However, encouraging results with surgery in prospective uncontrolled series and retrospective reports have led to the general acceptance of aggressive surgical resection in carefully selected patients with pulmonary metastases [9-19]. The range of overall 5- and 10-year survival rates is 35 to 70 percent and 20 to 30 percent, respectively. In general, these rates are higher than those seen with systemic chemotherapy alone (at most 20 percent are still alive at five years [20]). (See "Systemic therapy for metastatic colorectal cancer: General principles", section on 'Systemic therapy versus supportive care'.)

However, whether results such as these are better than those that can be achieved using modern ablative techniques, such as stereotactic body radiation therapy [21-23] or radiofrequency ablation [24], is not clear; randomized trials are not available, and retrospective reports are complicated by the potential for selection bias. (See "Stereotactic body radiation therapy for lung tumors", section on 'Lung metastases'.)

To date, only a single randomized control trial exists from the United Kingdom. The PulMicc trial (NCT01106261) randomly assigned 65 patients with metastatic colorectal cancer to pulmonary metastasectomy or active monitoring [8]. The study was stopped early for low recruitment. The estimated five-year survival among those who participated was 38 percent for metastasectomy and 29 percent for controls, a difference that was not as large as expected and did not achieve statistical significance. The role of molecular features (eg, BRAF and RAS mutations) and systemic chemotherapy (which was administered only to 9 control patients and 12 metastasectomy patients) were not delineated. The high five-year survival (29 percent) in the nonsurgical group and limited statistical power highlight the need for future trials with surgical randomization [1]. (See "Surgical resection of pulmonary metastases: Benefits, indications, preoperative evaluation, and techniques".)

Prognostic factors associated with an improved prognosis following metastasectomy for colorectal cancer include a limited number of nodules, a normal pre-thoracotomy carcinoembryonic antigen (CEA) level, the absence of regional lymph node spread, bilaterality, metachronous rather than synchronous presentation, and a longer duration between cancer onset and the development of metastases [9,11,13,14,16,25-30]. In a series of 378 patients undergoing surgery for pulmonary metastases from colorectal cancer at Memorial Sloan Kettering Cancer Center (MSKCC), recurrence-free survival was 49 percent at three years for those with a single lesion and a disease-free interval of greater than one year [29]. By contrast, there were no survivors beyond three years among the 44 patients with three or more lesions and a <1 year disease-free interval.

Other potential prognostic factors after pulmonary metastasectomy include the presence of certain tumoral mutations and primary colorectal cancer location:

●A single center retrospective review investigating the influence of certain mutations in recurrence or survival after pulmonary metastasectomy found that patients with RAS and TP53 mutations had significantly higher probability of death (RAS HR 3.25, 95% CI 1.39-7.59, p = 0.006; TP53 HR 2.64, 95% CI 1.14-6.10, p = 0.023) and disease recurrence (RAS HR 2.14, 95% CI 1.35-3.39, p = 0.001; TP53 HR 1.80, 95% CI 1.11-2.90, p = 0.017) in any location after pulmonary metastasectomy. Furthermore, those with mutant RAS and wild-type TP53 had low median disease-free survival of only 12 months.

A similar median disease-free survival was noted for those with mutant TP53 and wild-type APC. Conversely, APC mutations appeared to be protective with regards to overall survival (HR 0.29, 95% CI 0.12-0.66; p = 0.003) [31].

●A retrospective study from this same group found that left sided colon cancers were associated with better overall survival in multivariable analysis (HR 0.31, 95% CI 0.10-0.93; p = 0.036). Primary tumor laterality, however, was not associated with disease-free survival [32].

Further investigation into these and other prognostic factors is warranted given the retrospective nature and smaller size of these studies.

Significance of synchronous or metachronous liver metastases — The presence of both liver and lung metastases or a history of previously resected hepatic metastases does not necessarily represent a contraindication to initial pulmonary metastasectomy as long as a complete resection of all sites of disease can be accomplished. However, outcomes may not be as favorable as for those with isolated intrathoracic metastases [33-36]. On the other hand, the presence of liver metastases at initial lung metastasectomy is an adverse prognostic feature in patients who are being considered for repeated lung resection [37]. These patients warrant a multidisciplinary tumor board discussion.

Benefit of postresection adjuvant therapy — Although there is a paucity of high-quality evidence from clinical trials that prove a survival benefit, we suggest a six-month course of adjuvant systemic chemotherapy following resection of isolated colorectal cancer lung metastases. We prefer an oxaliplatin-based regimen, such as oxaliplatin plus leucovorin and short-term infusional fluorouracil (FOLFOX (table 1)) or capecitabine plus oxaliplatin (CAPOX/XELOX (table 2)), as is used following resection of colorectal cancer liver metastases. (See "Potentially resectable colorectal cancer liver metastases: Integration of surgery and chemotherapy", section on 'Postoperative management'.)

The benefit of chemotherapy following resection of lung metastases is incompletely defined; there are few randomized trials [38], and the results of retrospective series have been mixed with some suggesting benefit, and others, no benefit [39-42]. The following data pertain to this issue:

●The benefit of adjuvant chemotherapy after a potentially curative resection of either liver (85 percent of the study cohort) or lung (less than 10 percent) colorectal cancer metastases was addressed in a meta-analysis of two randomized trials of similar design (both using six months of systemic fluorouracil and leucovorin chemotherapy) that were initiated in the early 1990s (the French Fédération Francophone de Cancérologie Digestive [FFCD] 9002 and European Organisation for Research and Treatment of Cancer [EORTC]/National Cancer Institute of Cancer [NCIC] trials); both were closed prematurely because of slow accrual [38]. In a combined analysis of both trials (totaling 278 patients), the differences in median progression-free survival in chemotherapy-treated versus non-chemotherapy-treated patients (28 versus 19 months, p = 0.058) and overall survival (62 versus 47 months), while potentially meaningful, were not statistically significant.

Notably, the chemotherapy used in these trials is considered inferior by modern standards. For patients with unresectable metastatic colorectal cancer, the introduction of newer drugs, such as oxaliplatin, irinotecan, bevacizumab, and cetuximab, has been accompanied by a marked improvement in median survival, from 6 to 7 months to 20 to 24 months. (See "Systemic therapy for nonoperable metastatic colorectal cancer: Selecting the initial therapeutic approach".)

●The impact of more modern chemotherapy regimens was addressed in a retrospective series of 221 patients undergoing pulmonary metastasectomy for metastatic colorectal cancer (some of whom had previously undergone potentially curative hepatic metastasectomy), 80 percent of whom received some form of adjuvant chemotherapy [39]. The specific regimen was oxaliplatin-based combination therapy, irinotecan-based chemotherapy, and fluoropyrimidine monotherapy in 42, 31, and 25 percent of treated patients, respectively.

At a median follow-up of 34 months, the adjuvant chemotherapy group had a markedly longer disease-free survival than did those undergoing surgery alone, although the difference was not statistically significant (median 32.7 versus 11.2 months, p = 0.076). Adjuvant chemotherapy did not improve overall survival (median 89.6 versus 86.8 months). In this study, the patients with limited metastatic disease had a greater benefit from adjuvant chemotherapy than those patients with evidence of more widely metastatic disease.

●Additional information is available from a meta-analysis of eight studies (total 1936 patients) addressing the survival impact of perioperative chemotherapy after pulmonary metastasectomy for metastatic colorectal cancer; none were randomized trials [43]. The use of perioperative chemotherapy had a significant, favorable effect on both overall survival (hazard ratio [HR] 0.83, 95% CI 0.75-0.92) and disease progression/recurrence (HR 0.67, 95% CI 0.53-0.86). These conclusions are limited by the fact that the analysis was based on retrospective studies, which are subject to bias (ie, healthier, more fit patients get selected for more aggressive therapy).

Despite the paucity of evidence, guidelines from the NCCN [6] suggest a six-month perioperative course of chemotherapy in patients undergoing resection of either isolated liver or lung metastases from colorectal cancer. Most experts (including the NCCN [6]) would consider an oxaliplatin-based regimen, such as oxaliplatin plus leucovorin and short-term infusional fluorouracil (FOLFOX (table 1)), to be the reference regimen for this group of patients, if they are treated following resection, given the lack of benefit from an adjuvant irinotecan-containing regimen in patients with resected stage II or III colon cancer. (See "Potentially resectable colorectal cancer liver metastases: Integration of surgery and chemotherapy", section on 'Systemic chemotherapy' and "Adjuvant therapy for resected stage III (node-positive) colon cancer", section on 'Irinotecan'.)

The role of biologic agents that target the epidermal growth factor receptor (eg, cetuximab for those with RAS wild-type tumors) and tumor angiogenesis (eg, bevacizumab) after resection of pulmonary metastases from colorectal cancer is undefined. However, given the lack of activity of any of these agents in the adjuvant setting after resection of stage II or III colon cancer, most experts would not add a biologic agent to an oxaliplatin-based chemotherapy regimen after resection of pulmonary metastases. By contrast, if patients are treated in the neoadjuvant setting for liver or lung metastases, the addition of a biologic agent is reasonable. One study in patients with colorectal cancer demonstrated significant improvement in both locoregional recurrence-free survival (70 versus 24 months, p = 0.001) and overall survival (101 versus 55 months, p = 0.004) in cases with KRAS mutations (a poor prognostic factor) who were treated with perioperative bevacizumab [40]. Considerations for patients with lung metastases are similar to those in patients with liver metastases. (See "Adjuvant therapy for resected stage III (node-positive) colon cancer", section on 'Bevacizumab' and "Adjuvant therapy for resected stage III (node-positive) colon cancer", section on 'Cetuximab' and "Potentially resectable colorectal cancer liver metastases: Integration of surgery and chemotherapy", section on 'Regimen choice' and "Potentially resectable colorectal cancer liver metastases: Integration of surgery and chemotherapy", section on 'Patients with initially unresectable metastases'.)

Repeat resections — It is reasonable to consider repeated resections for appropriate patients with recurrent, isolated pulmonary metastases, as long-term overall survival can be achieved [37,44-46]. Before offering repeat resection, the patient's case should be discussed in a multidisciplinary tumor board.

Renal cell carcinoma — Complete resection of pulmonary metastases from renal cell carcinoma is associated with a significant survival benefit, with five-year survival rates that range from 20 to 74 percent [47-53]. While most of these data were derived from an era of cytokine treatment, complete metastasectomy has continued to be associated with improved survival with the availability of more recently approved systemic therapies, such as targeted therapy and immunotherapy [52]. (See "Overview of the treatment of renal cell carcinoma", section on 'Treatment options' and "Role of surgery in patients with metastatic renal cell carcinoma", section on 'Evidence for metastasectomy'.)

Larger number and size of metastatic nodules, increasing number of lymph node metastases, shorter disease-free interval, and decreased preoperative forced vital capacity are negative prognostic factors in this setting [47,54].

Data regarding the role of postresection systemic (adjuvant) therapy after metastasectomy are limited. Pazopanib and sorafenib failed to demonstrate benefit in this context, and pazopanib was associated with inferior overall survival. These patients should be discussed in a multidisciplinary tumor board. Enrollment in a clinical trial evaluating the benefit of newer approaches, such as adjuvant immunotherapy, should be encouraged. (See "Overview of the treatment of renal cell carcinoma", section on 'Adjuvant therapy after metastasectomy'.)

Germ cell cancer — The advent of effective chemotherapy has drastically changed the management of pulmonary metastases for patients with germ cell tumors. Chemotherapy is the primary treatment in this setting. (See "Initial risk-stratified treatment for advanced testicular germ cell tumors".)

Surgical resection is reserved for patients who have normalization of serum tumor markers but radiographic evidence of a residual lesion. Patients with a residual lesion on imaging and a continued elevation of tumor markers after their initial chemotherapy are generally managed with an alternative chemotherapy regimen. (See "Approach to surgery following chemotherapy for advanced testicular germ cell tumors", section on 'Lung lesions'.)

Gynecologic cancers — Encouraging results have been reported following resection of pulmonary metastases from gynecologic cancers. As an example, in a series of 133 patients, the five-year survival rates in females with squamous cell cervical carcinoma, cervical adenocarcinoma, and endometrial carcinoma were 47, 40, and 76 percent, respectively [55]. Others report a five-year overall survival rate of 69 percent in a series of 57 females with isolated pulmonary metastases from uterine malignancy [56]. There are no data addressing the benefit of postresection chemotherapy or hormone therapy in any of these settings. This subject is discussed in more detail elsewhere. (See "Management of recurrent or metastatic cervical cancer" and "Invasive cervical adenocarcinoma", section on 'Surgery for metastatic disease'.)

The primary management of females with lung metastases from choriocarcinoma is chemotherapy, but surgical resection may be useful in females who are not cured by systemic therapy. The management of lung metastases in this disease is discussed elsewhere. (See "Initial management of low-risk gestational trophoblastic neoplasia".)

Melanoma — Historically, pulmonary metastases from malignant melanoma have been associated with poor survival. The largest series, based on a total of 7564 patients with melanoma, found a 12 percent incidence of lung metastases and an associated five-year survival rate of 4 percent after resection [57]. Slightly better outcomes were noted in a second report of 91 patients who underwent resection of cutaneous melanoma pulmonary metastases between 2004 and 2012; five-year overall survival was 21 percent [58]. There was worse survival with greater lesion size, particularly >2.3 cm.

However, both of these series predated the modern-day use of immune checkpoint inhibitors for metastatic melanoma. (See "Systemic treatment of metastatic melanoma lacking a BRAF mutation" and "Systemic treatment of metastatic melanoma with BRAF and other molecular alterations".)

The role of pulmonary metastasectomy in patients with melanoma is discussed in detail elsewhere. (See "Metastatic melanoma: Surgical management", section on 'Lung'.)

Head and neck cancer — A meta-analysis of resection of pulmonary metastases from head and neck squamous cell carcinoma identified 13 studies with 403 patients. The five-year survival was 29 percent [59]. Postsurgical survival following resection of pulmonary metastases from head and neck cancer varies by cell type and disease site. These issues are discussed separately. (See "Treatment of metastatic and recurrent head and neck cancer", section on 'Oligometastatic disease'.)

Osteosarcoma — Operative resection is the only potentially curative treatment for patients with thoracic metastases from osteogenic sarcoma. Following resection, adjuvant chemotherapy can improve disease-free survival and decrease the burden of metastatic pulmonary disease. Resection of pulmonary metastases should always be part of a combined modality approach. (See "Chemotherapy and radiation therapy in the management of osteosarcoma", section on 'Potentially resectable disease' and "Chemotherapy and radiation therapy in the management of osteosarcoma", section on 'Patients with metastatic disease at diagnosis'.)

Breast cancer — The management of females with metastatic breast cancer involving the lungs includes chemotherapy, hormone therapy (for hormone receptor-positive disease), and if the tumor expresses human epidermal growth factor 2 (HER2), trastuzumab. In addition to these approaches, surgical resection of isolated metastases is an important option in carefully selected patients. A meta-analysis of resected pulmonary metastases identified 16 studies with a total of 1937 patients. The resulting five-year survival was 46 percent. A disease-free interval of <3 years, incomplete resection, and a negative hormone receptor status were poor prognostic factors [60]. The role of surgery in this setting is discussed elsewhere. The role of adjuvant systemic therapy should be discussed in a multidisciplinary tumor board. (See "The role of local therapies in metastatic breast cancer", section on 'Lung'.)

Hepatocellular cancer — Following resection of hepatocellular carcinoma, intrahepatic recurrences are more common than extrahepatic recurrences. While many local ablative treatment modalities are available to address intrahepatic recurrence disease, systemic treatment for extrahepatic disease involvement remains unsatisfactory. (See "Overview of treatment approaches for hepatocellular carcinoma" and "Surgical resection of hepatocellular carcinoma" and "Localized hepatocellular carcinoma: Liver-directed therapies for nonsurgical candidates who are eligible for local ablation" and "Systemic treatment for advanced hepatocellular carcinoma".)

Selected patients with isolated pulmonary metastases might be considered for potentially curative resection. Few small case series describe long-term outcomes from pulmonary metastasectomy in such patients [61-68]. The range of reported five-year survival rates in completely resected patients is 12 to 67 percent. Among the factors associated with a favorable postresection prognosis in multivariate analysis are:

●A relapse-free interval >12 to 24 months [61-63]

●Fewer than three pulmonary metastases [63]

●Levels of serum alpha-fetoprotein <500 ng/mL before [62] or <100 ng/mL after [61] metastasectomy

●Largest size of metastases <3 cm [64]

●Whether or not the patient underwent liver transplantation [65]

Pulmonary metastasectomy should be limited to those patients who have no evidence of uncontrolled intrahepatic disease, no extrathoracic metastases, and a chest computed tomography (CT) demonstrating that complete resection is feasible [61].

Hepatoblastoma — Approximately 20 percent of newly diagnosed hepatoblastomas present with pulmonary metastasis. The current standard of care is neoadjuvant chemotherapy followed by pulmonary metastasectomy of residual disease. Adjuvant chemotherapy is generally recommended following metastasectomy [69]. (See "Overview of hepatoblastoma", section on 'Overview of treatment and outcomes'.)

Outcome data following surgical resection of pulmonary metastases in hepatoblastoma are limited but promising, provided that the liver tumor could be completely resected:

●In the prospective JPLT-2 study of 60 hepatoblastoma cases with pulmonary metastasis at time of diagnosis, following neoadjuvant chemotherapy 33 had residual lung nodules [70]. Among those who underwent complete pulmonary metastasectomy and complete liver resection (n = 9), three-year event-free survival (EFS) was 56 percent. In patients who had complete liver resection but residual lung disease (n = 13), the three-year EFS was only 37 percent.

●In another series of 10 hepatoblastoma patients with isolated pulmonary relapse managed through pulmonary metastasectomy, eight patients were alive at a follow-up of 18.5 months [71].

If orthotopic liver transplantation is needed because of the extent of liver disease, pulmonary metastasectomy should be performed prior to transplantation [69,72,73].

Gastric cancer — Isolated pulmonary metastases from gastric cancer are rare, as most pulmonary metastases represent lymphangitic spread or pleural metastases. Pulmonary metastasectomy for metastatic gastric cancer can potentially result in long-term survival in a highly selected group of patients [74,75]. A review of 21 studies from 1975 to 2008 included 48 pulmonary resections among 43 patients (82 percent solitary lesions) [74]. At a median follow-up of 23 months, the median survival time was 29 months, and the five-year survival was 33 percent. The median overall survival was numerically higher among patients with a disease-free interval of at least 24 months (65 versus 19 months, p = 0.12).

The rarity of attempted pulmonary metastasectomy for this disease can be illustrated by a case series of 2590 patients who underwent gastrectomy for gastric cancer over an eight-year period; only 10 patients (0.4 percent) had a pulmonary metastasectomy for isolated pulmonary metastases [75].

This approach should be reserved for those patients who present with small isolated lesions after a prolonged disease-free interval.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Colorectal cancer".)

SUMMARY AND RECOMMENDATIONS

●Role of resection

•Aggressive surgical resection of lung metastases in appropriately selected patients offers a chance for extended disease-free survival that would not be possible with systemic therapy. (See "Surgical resection of pulmonary metastases: Benefits, indications, preoperative evaluation, and techniques".)

•The survival rate is influenced by the disease-free interval, number of metastases, and extent of resection. The potential benefits of resection and the approach to the patient are also dependent upon the histology of the tumor. (See 'Outcomes by histology' above.)

•However, with the exception of oligometastatic non-small cell lung cancer, there are no randomized trials proving benefit, and questions remain as whether surgical results are better than those that can be achieved using modern ablative techniques, such as stereotactic body radiation therapy or radiofrequency ablation. Thus, nonsurgical therapy is also an option. A multidisciplinary tumor board discussion for decision-making is preferred in these patients.

●Contribution of systemic therapy

•Following resection of colorectal cancer lung metastases, we suggest a course of adjuvant systemic chemotherapy (Grade 2C). We prefer an oxaliplatin-based regimen, such as oxaliplatin plus leucovorin and short-term infusional fluorouracil (FOLFOX (table 1)) or capecitabine plus oxaliplatin (CAPOX/XELOX (table 2)), as is used following resection of colorectal cancer liver metastases. (See 'Benefit of postresection adjuvant therapy' above and "Potentially resectable colorectal cancer liver metastases: Integration of surgery and chemotherapy", section on 'Systemic chemotherapy'.)

•Systemic therapy is an important component of multimodality treatment of pulmonary metastases in other histologic types as well, including primary lung cancer, osteosarcoma, breast cancer, germ cell tumors, and choriocarcinoma. (See "Chemotherapy and radiation therapy in the management of osteosarcoma", section on 'Patients with metastatic disease at diagnosis' and "The role of local therapies in metastatic breast cancer", section on 'Lung' and "Approach to surgery following chemotherapy for advanced testicular germ cell tumors", section on 'Lung lesions' and "Initial management of low-risk gestational trophoblastic neoplasia".)

For other histologic tumor types, there are few, if any, data addressing the benefit of adjuvant systemic therapy, and decisions regarding its use must be individualized and discussed in a multidisciplinary tumor board.

●Post-treatment surveillance – For most patients, following treatment, we suggest regular radiographic surveillance with chest computed tomography (CT) scans every four months. Radiographic evidence of recurrence mandates a full evaluation of disease extent and cardiorespiratory reserve.

●Repeat resection – Most of the data on repeat resection are in patients with metastatic colorectal cancer. If the indications for pulmonary metastasectomy are still met, a repeat surgical procedure may be considered as an alternative to systemic therapy or other locally ablative options. A chest CT scan should be repeated six weeks after the initial observation of suspected recurrence and prior to repeat surgery, as this may reveal additional deposits of recurrence that may preclude surgery. (See 'Repeat resections' above.)