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Pulmonary Metastasectomy

Oncology
Surgery

Authors

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Benjamin E. Haithcock, MD
Author
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Panagiotis Tasoudis, MD
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Introduction

Pulmonary metastases refer to distant tumor spread from a plethora of primary tumors to the lungs. The lung is a frequent location for metastatic tumors to establish themselves since it serves as a sieve for all of the blood that flows through the body. In fact, a total of 18 per 100,000 patients newly diagnosed with cancer present with synchronous lung metastasis, defined as the diagnosis of a distant lung metastasis together with or within a three-month interval of the diagnosis of the primary tumor.[1]
The incidence of lung metastasis fluctuates depending on the gender (20 per 100,000 in males and 16 per 100,000 in females) and the age at the time of diagnosis with the incidence ranging from 1 per 100,000 below age 40 to 116 per 100,000 in patients age 80-84.[1]
Although the traditional treatment for metastatic disease is chemotherapy and/or radiotherapy with emerging roles for chemoimmunotherapy, pulmonary metastasectomy has been historically advocated in selected patients ever since the first surgical pulmonary metastasectomy was performed in 1882.[2]
Patients with untreated metastatic disease have a 5-year survival of less than 10%, therefore pulmonary metastasectomy is credited to be the best hope for cure in patients with metastatic disease isolated to the lungs.[3] While metastasectomies account for approximately 10% of all general thoracic surgeries, what is known about these operations is based only on observational studies.[4,5]
The only randomized trial comparing metastasectomy with active monitoring was closed early due to low recruitment rates and the preliminary results demonstrated that metastasectomy offers equivalent survival outcomes to no-intervention.[6]
Due to lack of high quality studies and due to the nature of the operation per se, there are still no stringent indications, contraindications and guidelines, nevertheless, in this chapter we aim to summarize the most updated evidence revolving around pulmonary metastasectomies.

Presentation

Pulmonary metastases are typically asymptomatic. The dominant presenting symptoms are usually constitutional, including fatigue, weight loss, diffuse pain and there also might be symptoms specifically attributed to the primary tumor.
Although uncommon, patients with metastases affecting central airways could present with respiratory symptoms such as dyspnea, wheezing or even hemoptysis. Finally, peripherally located metastases could rarely progress to spontaneous pneumothorax due to tumor disruption of the visceral pleura.[7]

Evaluation

Most pulmonary metastases are detected incidentally during the initial staging workup of a primary cancer, or during the routine post-treatment surveillance radiographic studies.[1] A pulmonary metastasis is typically found in the peripheral third of the lung and usually presents as a well-circumcised nodule. Many pulmonary metastases, however, have a non-specific radiographic appearance and in order to establish a definitive diagnosis, identify the patients eligible for metastasectomy and orchestrate the operative plan further assessment with imaging is imperative.
In general, CT scans are considered the imaging modality of choice for pulmonary metastases.[8] Current evidence recommends helical chest CT scans with 3-mm to 5-mm slice thickness to diagnose lung metastases as there is no data supporting that multidetector CT and volumetric thin section scanning offer superior diagnostic results.[8] It should be noted, however, that CT scans are reported to underdiagnose pulmonary metastases.[9] Two studies reporting on patients with pulmonary metastases have reported in congruence with each other that CT scans have underestimated the number of malignant lesions in 25% of the patients.[9,10] This issue is particularly prominent in small malignant nodules (<1cm) that resemble a lot the small benign nodules that are commonly found in physiologic lungs.
Of note, incorporating 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) has not been found to facilitate more accurate diagnosis of intrapulmonary metastases.[8]
Regardless, FDG-PET is recommended in patients who are prepared for metastasectomy in combination with CT scan to diagnose or rule out occult distant metastases (unless the primary tumor is not typically PET avid).[11] The potential benefits of this policy seem to far outweigh the risks in most patients.[12]
A study examining the role of FDG-PET in preoperative assessment of potential pulmonary metastasectomy candidates reported that approximately 20% of the patients that received a PET scan were excluded from lung surgery due to the finding of concomitant extrapulmonary metastases.[12] Finally, regarding evaluation for distant metastases, brain imaging is indicated in every patient prior to resection of a pulmonary metastasis, especially for patients with cancers that have a high likelihood of metastasizing to the brain (breast cancer, melanoma, colorectal, kidney).
Prior to submitting a patient for pulmonary metastasectomy a definitive tissue diagnosis of the tumor is recommended. Preoperative CT-guided fine needle aspiration (FNA) biopsy is traditionally utilized to obtain tissue less invasively, especially if the nature of the pulmonary nodule is in doubt, the patient is a poor or borderline candidate for surgery, or the patient has a primary tumor (such as a testicular germ cell tumor or lymphoma) for which surgery may not be required.
While CT-guided FNA is the approach of choice for peripherally located tumors, bronchoscopy can be utilized for centrally located masses. Video-assisted thoracoscopic surgery (VATS) is an alternative to establish a diagnosis in small tumors that cannot be assessed via CT guided FNA or bronchoscopy. In cases where the radiographic features of the pulmonary mass and the patients’ history are indicative of pulmonary metastasis, the definitive characterization of the tumor is performed after the pulmonary resection.

Management

Patient Selection
There is still scarcity of data available for pulmonary metastasectomies. The biggest report in the literature to date comes from the International Registry of Lung Metastases which incorporated 5,206 patients with lung metastases and reported that patients who underwent metastasectomies had 5-, 10-, and 15-year survival rates of 36%, 26%, and 22%, respectively.[10] Accounting for the scarcity of solid evidence, the published guidelines around this topic come mostly from expert groups that have discussed and elaborated on the indications and contraindications for pulmonary metastasectomy.[13]
A widely accepted contraindication to pulmonary metastasectomy is considered the inability to perform a complete resection of the metastatic mass. This is supported by the findings of the International Registry of Lung Metastases which reported that incomplete resection was associated with significantly worse survival rates than complete resection (median survival: 15 versus 35 months).[10]
The STS consensus group also recommends that patients with over three distinct metastatic lesions should not be offered a pulmonary metastasectomy.[13]
Once again the consensus regarding the number of lesions that contradict a lung resection is not based on strong evidence and it is vital to clarify that the most important factor that dictates the operability of a case is the feasibility of resecting all tumor sites of the disease. The study from the International Registry has outlined the favorable survival outcomes of patients with fewer lesions, however, the inverse relationship between the number of metastases and survival might be explained by the higher likelihood of incomplete disease removal in cases where multiple metastases are present.[10]
Lymph node involvement constitutes another factor that determines eligibility for metastasectomy therefore suspicious nodes should be assessed with endobronchial ultrasound biopsy/mediastinoscopy prior to attempting a resection. Presence of positive contralateral mediastinal lymph nodes (N3) is considered a contraindication for pulmonary metastasectomy.[14,15] Regarding patients with ipsilateral mediastinal lymph nodes (N2) there is no clear consensus and the final decision should be tailored according to the individual patient and tumor characteristics.[14,15]
Although the presence of positive ipsilateral intrapulmonary lymph nodes (N1) is linked with worse survival compared to N0 disease, it does not constitute a contraindication for pulmonary metastasectomy. Finally, it should be noted that in case of disease relapse following pulmonary resection a repeat metastasectomy is considered a feasible and a relatively safe option and should not be disregarded. The International Registry study reported on 1,042 patients who underwent repeat metastasectomy with 5- and 10-year survival rates of 44% and 29%, respectively.[10]
A summary of the oncological criteria for pulmonary metastasectomy according to STS consensus document and the Kondo et al. study which examined the influence of certain characteristics in the survival outcomes in patients who underwent pulmonary metastasectomies are presented in Table 1.[13,16] In addition, a summary of the positive and negative patient and tumor prognostic features is presented in Table 2.[17]
Table 1. Summary of the oncological criteria for pulmonary metastasectomy
Major Criteria
The patient is a good surgical candidate
Primary cancer is controlled or controllable
No other extrapulmonary metastasis are present, or if present it can be controlled by surgery or another treatment modality
All of the tumor is resectable, with adequate pulmonary reserve
Secondary Criteria
There are no alternative medical treatment options with lower morbidity
Effective systemic chemotherapy is available as a combined modality
Lesions that are difficult to differentiate from primary lung cancer
Symptomatic pulmonary metastases, e.g., pneumothorax, hemoptysis
Table 2. Summary of the positive and negative prognostic features
Positive features
One or few metastases
Long disease free interval
Normal CEA levels in colorectal cancers
Negative features
Active primary cancer
Extrathoracic metastases
Inability to obtain surgical radicality
Mediastinal lymphatic spread
Extent of surgical resection
The ultimate goal after a pulmonary metastasectomy is to achieve adequate margins while preserving as much normal parenchyma as possible. Wedge resections are typically sufficient to facilitate this goal and therefore are most commonly utilized to resect pulmonary metastases from various types of primary malignancies.[10,18]
The resection is usually performed using surgical devices such as staplers, electric scissors, laser scissors and coagulating tools. Regardless of the resection tool, ideally when performing a wedge resection adequate margins of >10-20mm should be achieved to prevent local disease recurrence which is reported to be as high as 30%.[19]
Segmentectomies are generally reserved for patients in whom a wedge resection cannot be performed and a ;pbectp,u is not necessary. They are usually performed for tumors located in more central areas of the lobe and in cases where there are multiple lesions in the same lobe. Lobectomies are also utilized under the same settings, however far less frequently. Of note, pneumonectomies are typically not recommended for resection of a metastatic lesion due to the aggressive nature of the operation and the high rates of peri- and post-operative complications that sequel such operations.[20]
The European Society of Thoracic Surgeons (ESTS) conducted a survey aiming to elucidate the surgeons’ preferences regarding pulmonary metastasectomies.[18] According to this survey, stapled wedge resection was the most common preferred form of resection (89%) followed by precision excision (17.8%), anatomic segmentectomy (4.8%), and lobectomy (2.1%).[18]
Finally, the role of extended pulmonary metastasectomy regarding metastatic lung lesions involving structures such as the diaphragm, the azygous vein or the chest wall is not clearly defined.[21]
Surgical approach
The goal of pulmonary metastasectomy is complete resection of all detectable disease. Accounting for the inability of helical CT scans to accurately identify all metastatic lesions, an open thoracotomy was traditionally utilized for pulmonary metastasectomies in order to facilitate intraoperative palpation and identification of masses that were initially not captured by the CT scan.[9]
Nevertheless, contemporary advancements in imaging techniques along with recently emerged evidence indicating that video-assisted thoracoscopic surgery (VATS) offers equivalent outcomes compared to open thoracotomies, have led the STS consensus to advocate for VATS compared to open thoracotomy due to the beneficial postoperative outcomes of VATS.[13] It should be noted that a bilateral approach is indicated only for those patients who present radiographically with bilateral metastases and inspection of the contralateral site is not recommended in patients with unilateral disease.

Surveillance

There is no definitive imaging surveillance protocol after pulmonary metastasectomy. A follow-up baseline scan 4 to 6 weeks after completion of the surgery. Additional CT scans are recommended every 4-6 months for 2 years and then yearly for at least 5 years. Since there are no controlled studies examining the optimal follow-up scheme, surveillance imaging should be tailored according to the tumor’s characteristics in each individual case.

Controversies

Much debate remains on the optimal timing for surgery. Some claim that once pulmonary metastasis(es) is discovered, there does not seem to be a benefit in delaying the time to pulmonary metastasectomy because pulmonary metastases can further metastasize.[22]
Others maintain that a surgical intervention should be delayed for six to eight weeks from the time of diagnosis to avoid the need for an unnecessary procedure and its subsequent implications in the patients’ quality of life. Although the six-to-eight-week interval is to some extent arbitrary, the notion behind delaying the procedure is to ensure that the already present lesions will not increase dramatically in size and number. Especially small lesions have been found to have a fast growth rate, meaning that delaying the surgery offers a better understanding of the metastatic masses to the surgeon.[23] Delaying surgery may also allow previously hidden metastases to become clinically evident, allowing for a more thorough resection and better long-term results.[24]
The optimal timing for surgery also depends on the surgical approach that is planned for each individual patient. If a patient’s treatment plan involves a VATS metastasectomy for an isolated lung lesion waiting is typically deferred because even in the case of recurrent disease, a repeat VATS would be feasible. On the other hand, open thoracotomy is linked with long recovery periods and extensive adhesions formation. Therefore, waiting for the full extent of the disease to be revealed might offer decreased disease recurrence rates and therefore lower risk for a very challenging reoperation.

Summary

  • Pulmonary metastases are a common entity and are typically asymptomatic at presentation with the majority of them being detected during the initial staging workup of a primary cancer, or during the routine post-treatment surveillance.
  • Helical chest CT scans with 3-mm to 5-mm slice thickness to diagnose lung metastases. FDG-PET is recommended in patients who are prepared for metastasectomy in combination with CT scan to diagnose or rule out occult distant metastases. Brain imaging is indicated for patients with cancers that have a high likelihood of metastasizing to the brain.
  • A definitive tissue diagnosis of the tumor is recommended in cases in which the nature of lesion is in doubt via CT-guided FNA for peripherally located lesions, bronchoscopy for centrally located lesions and VATS for lesions that cannot be assessed otherwise.
  • A patient should
    1. be a good surgical candidate,
    2. have the primary cancer controlled or controllable,
    3. have no other extrapulmonary metastasis,
    4. have a metastatic tumor that is resectable with adequate pulmonary reserve to be considered eligible for pulmonary metastasectomy.
  • Stapled wedge resection is the most common preferred form of resection followed by precision excision, anatomic segmentectomy, and lobectomy. Pneumonectomies are typically avoided for pulmonary metastasectomies.
  • Even though open thoracotomies are credited to facilitate better palpation and more accurate diagnosis of initially uncaptured small metastases, VATS is the preferred surgical approach as it was shown to offer equivalent oncological outcomes with lower postoperative morbidity.
  • After the resection, a follow-up baseline scan at 4 to 6 weeks is recommended with additional CT scans every 4-6 months for 2 years and then yearly for at least 5 years.
  • There is still no consensus on whether the pulmonary metastasectomy should be delayed following the initial diagnosis or not. Delaying the resection six to eight weeks following the diagnosis should be tailored to each individual case.

References

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