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International Journal of Surgery & Surgical Techniques Research Article 17 min read

Reasoning about Ilo-Mediastinal Lymphectomy during Lung Metastasectomy for Colorectal Cancer: Appropriate or Unnecessary Effort?

Ferrari PA*
* Corresponding author
ISSN: 2578-482X  10.23880/ijsst-16000193  Received: October 16, 2023  Published: November 02, 2023
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 68 references
 2 tables
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Keywords
Metastasectomy Lymph Node Lymphadenectomy Colorectal Cancer
Abstract

Abstract Lymph node dissection following lung metastasectomy is still debated, although it is considered necessary to achieve complete resection or at least gather prognostic information. When radical lymph node dissection is performed, the average rate of unexpected lymph node involvement in colorectal cancer is less than 20%. Lymph node co-involvement is an adverse prognostic factor, and preoperative mediastinal disease usually leads to patient exclusion from metastatic surgery. The authentic prognostic influence of systematic nodal dissection remains unclear. Unfortunately, many studies demonstrate no positive effect of lymphadenectomy during lung metastasectomy other than a pseudo-stage migration effect. Future studies should focus not only on survival but also on local and lymph node recurrence.

Introduction

Lung metastasectomy (LM) is a well-established local treatment for lung-limited metastases of stage IV colorectal cancer (CRC) to increase overall survival (OS) or stop the further malignant spread from the lungs to other organs.

Though lymph node (LN) dissection is essential in primary lung cancer surgery and impacts patient prognosis [1, 2], controversy exists regarding the need for lymphadenectomy during LM.

A survey among the European Society of Thoracic Surgery members revealed that only 13% perform systematic LN dissection during the removal of lung metastasis [3].

In the set of pulmonary metastatic CRC patients, the mediastinal LN positivity represents a well-documented unfavorable parameter, along with short disease-free interval, size and number of pulmonary metastases, elevated CEA, previous liver metastasis, and positive surgical margins [4].

The arguments for not performing the lymphadenectomy are partly related to the assumption that in a stage IV tumour disease, detecting any mediastinal LN positivity on pathological examination loses its significance. Even if metastatic tumour cell dissemination in regional nodes is detected, this cannot be surgically controlled. On the contrary, LN dissection affects morbidity [5] without necessarily providing survival benefits.

In contrast to the previous belief that each new lung metastasis originates from the remaining cells of the primary tumour, it is now recognised that lung metastases can spread locally via lymphatic and hematogenous invasion. Therefore, in this case, radical resection of these metastases not only produces a significant reduction in the systemic tumour burden but can also lead to a cure [6, 7].

Concurrent Thoracic Lymph Node Resection: An Overview

Approximately a half-century after the first report on the excision of two incidental lung nodules during the surgical resection of a chest wall sarcoma, Alexander and Haight in 1947 described the first series of solitary LM in 24 patients and the results of a 3-year follow-up [8, 9]. Since then, many published studies have supported pulmonary metastasectomy’s safety and oncological benefits, depending on primary tumor histology [10].

Nowadays, LM is a generally accepted treatment for selected patients with CRC-related lung metastases. In many institutions, this procedure has been considered routine practice, supported mainly by the results of retrospective studies [10, 11, 12].

Interestingly, the criteria for LM were first proposed by Thomford, et al. [13]. The basic principle of surgery is to remove all possible metastatic lesions while preserving as much lung tissue as possible. Enucleation is the ideal surgical method for lung reserve and multiple metachronous lung metastases [10]. With the development of VATS surgery, wedge resection is usually performed, while lobectomy has mainly been used for patients with central tumours, large tumours, or multiple nodules within the same lobe [14]. According to this consensus, defined eligibility criteria for metastasectomy are now mandatory to provide a standardized surgical and oncological safety approach, as summarized in Table 1 [15, 16, 17, 18].

ⅠMetastasectomy should only be performed in patients fit for lung resection
ⅡThe primary tumor must be clinically controlled, with no evidence of active disease
ⅢIf evidence of extra-thoracic disease is also suitable for resection or has already been successfully resected, the lung metastasectomy is not contraindicated
ⅣThe lung metastasis must be eligible for a guaranteed radical resection
ⅤThere should be no better option for the treatment of metastasis, than surgery.

Table 1: Criteria of eligibility for surgical lung metastasectomy.

However, to better contextualise these assumptions, it is helpful to point out that only one randomised controlled trial concerning the effects of LM was undertaken, the PulMiCC trial, which was prematurely closed due to recruitment difficulties [19]. The results of this study revealed that patients in the control group, who received no local treatment for limited colorectal lung metastases, had better survival than previously assumed, with a five-year survival of 29.6% (95% CI: 15.3-45.7%). Patients randomised to surgical metastasectomy had a five-year survival of 36.4% (95% CI: 21.3-53.0%) [20]. Recently, the investigators published the results of the prospective observational cohort [21]. A total of 169 patients who did not undergo lung metastasectomy had a five-year survival of 21.9% (95% CI: 16-29%). Without presenting the five-year absolute survival rate of patients undergoing pulmonary metastasectomy in this prospective cohort, the authors concluded that selection bias prevents a formal comparative analysis.According to literature screening where the OS of patients who underwent LM combined with lymphadenectomy were analyzed, the LN resection rate ranges from 12% to 100%.

As reported in Table 2, eleven studies described routine concurrent lymphadenectomy [22, 23, 24, 25, 26, 28, 29, 30, 31, 32, 33], and five specifically reserved this additional procedure only for central LM or lobectomy [27, 34, 35, 36, 37]. Other than the surgeon’s preference, no indications were described for the combined lymphadenectomy in other twenty-four studies [38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61].

Patients (n)Lymphadenectomy practice (%)Nodal involvement (%)Sub lobar resection (%)Follow-up (months)5-year survival N0 (%)5-year survival N+ (%)
Inoue, et al. [22]2510036N/S10849.514.3
Pfannschmidtet, al. [23]1671001965.55938.70
Inoue, et al. [24]8910028N/S85.950.819.3
Pfannschmidtet, et al. [25]11410028N/SN/SN/SN/S
Welter, et al. [26]1691001475.3N/S4219.2
Kim, et al., [28]27100710039.5N/SN/S
Javed, et al., [29]66100770.1N/SN/SN/S
Bolukbas ,et al.,[30]1651002273.3365923
Renaud, et al. [31]32010044N/S33N/SN/S
Balhareth, et al. [32]1110030N/S6087.512.5
Meimarakis, et al. [33]8910018N/S35.23918
Mean (95% CI)112.9 (53-1173)100%23% (15-31%)77.2% (52-102%)57 (34-78)52.3% (36-68%)15.1% (8-22%)

Table 2: A selection of clinical trials and retrospective studies assessing the impact of routinary lymphadenectomy following col

Given the criterion of regional lymphadenectomy, according to the Naruke LN map [62], it was challenging to discriminate hilar lymph node metastasis from concurrent mediastinal involvement. However, we identified twelve studies in which a mean of 11.5% (95% CI: 7.2-15.8%) of patients had N1 metastasis without mediastinal lymph node involvement [22, 51]. In comparison, in more studies, N2 involvement was described in a mean of 10.8% (95% CI: 8.3- 13.3%) of patients without N1 metastasis [22, 56].

Lung Metastasectomy and Concurrent Lymphadenectomy: 5-Year Overall Survival Rate

Twenty-seven studies Inoue M, et al. [22, 23, 24, 25, 26, 27, 61] provided details on 5-year OS rates after metastasectomy and LN dissection in lung metastatic CRC patients.

Only 18,5% of patients with lymph node metastases were alive at 5-year follow-up, while more than half (51,2%) of those without nodal disease were still alive at the same survival check.

In patients with metastatic lymph nodes, the 5-year OS of patients with N1 metastasis was 40.7% compared with

10.9% of patients with N2 lymph node metastasis.

Further fascinating insight should be made regarding the 5-year overall survival of patients without lymph node involvement after lymph node dissection (47.3%), compared with OS of patients undergoing lymph node sampling (53.2%).

Finally, the five-year OS for patients with lymph node involvement after lymph node dissection and sampling was 17.9% and 18.5%, respectively.

Prognostic Influence of Concurrent Thoracic Lymphadenectomy

Based on the data retrieved from a brief literature review, of all patients who underwent lymphadenectomy, either by sampling or lymph node dissection, 19.1% had lymph node involvement. Studies presenting the outcome of lymph node dissection had significantly more patients with lymph node involvement, and thus a higher rate of lymph node over- staging, than those that showed the outcome of lymph node sampling. However, lymph node dissection did not have a significantly different impact on the OS than lymph node sampling.

Nevertheless, according to the selection criteria of each study, many patients with lymph node metastasis had unsuspected lymph node involvement. Patients with suspected or established mediastinal lymph node metastases in the preoperative workup are likely to have a poorer outcome. The results of this review highlight the worse oncologic outcome of patients with lung metastasis from CRC and simultaneous lymph node metastasis.

From the analysis of survival based on the anatomical location of the involved lymph node stations, differences were found: a five-year overall survival rate of 10.9% and a median survival of 23.2 months for N2 lymph node metastases, significantly lower than those found in patients with N1 lymph node metastases [11]. The next step will be to identify patients with mediastinal lymph node metastases better to select those most suitable for lung metastasectomy. Several studies have reported preoperative invasive mediastinal staging in CRC patients with LM by mediastinoscopy [63] or endobronchial-endoscopic ultrasound [64, 65, 66], the application of which, however, is limited. To date, there is no consensus on the contraindication for local radical therapy in cases of lymph node metastasis. Recently, Guerra, et al. [67] demonstrated the low sensitivity of both computed tomography (CT) and positron emission tomography (PET) in detecting lymph node metastasis in patients with lung metastasis from CRC (11% and 34%, respectively), concluding that PET-CT cannot adequately define an optimal treatment strategy. The main limitations of this review were the lack of detailed data description from individual studies and the lack of dispersion on the obtained survival data.

Currently, the retrospective studies available in the literature do not allow us to determine the potential therapeutic effect of lymphadenectomy in CRC lung metastasis. Despite attempts to objectify the impact of lymphadenectomy on survival [68], selection bias rules out generalizability.

Recommendations

Based on these assumptions, it is mandatory to exclude common confounders in order to identify the real benefit of lymphadenectomy during CRC lung metastasectomy. A prospective, randomized study of pulmonary metastasectomy has been unfeasible in the past and will be challenging to apply in the future for more detailed issues such as lymphadenectomy. Therefore, a multicenter or national enrollment of patients undergoing metastasectomy into a registry with prospectively collected data might be valuable. Based on a histologic entity with a single lesion, analysis of OS, disease-specific survival, and recurrence rate (local, mediastinal, distant) can be stratified with or without systematic lymphadenectomy [33]. The type of resection (anatomic vs. nonanatomic), laser use, and lymph node metastatic involvement are other essential variables that must be considered.

Because of the suboptimal sensitivity of PET-CT in detecting thoracic lymph node metastases from CRC, a role should be defined for preoperative endosonographic staging of the mediastinum in selected patients or when extensive surgery may be indicated as radical intent.

Conclusion

In several retrospective studies, thoracic and mediastinal LN metastases are a significant and independent negative prognostic factor for survival after pulmonary metastasectomy for metastatic CRC. Either lymph node sampling or dissection (no significant difference in terms of detection) should be recommended to provide useful information on the presence of nodal metastasis for determining postoperative treatment.

However, because of the need for more evidence, its impact should be studied properly in further studies, possibly multicenter and with prospective data collection.

Conflict of Interest

Authors have no conflict of interest to declare.

Funding

No funding has been received for this study.

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@article{ferrari2023,
  title   = {Reasoning about Ilo-Mediastinal Lymphectomy during
Lung Metastasectomy for Colorectal Cancer: Appropriate or
Unnecessary Effort?},
  author  = {Ferrari PA},
  journal = {International Journal of Surgery & Surgical Techniques},
  year    = {2023},
  volume  = {7},
  number  = {2},
  doi     = {10.23880/ijsst-16000193}
}
Ferrari PA (2023). Reasoning about Ilo-Mediastinal Lymphectomy during
Lung Metastasectomy for Colorectal Cancer: Appropriate or
Unnecessary Effort?. International Journal of Surgery & Surgical Techniques, 7(2). https://doi.org/10.23880/ijsst-16000193
TY  - JOUR
TI  - Reasoning about Ilo-Mediastinal Lymphectomy during
Lung Metastasectomy for Colorectal Cancer: Appropriate or
Unnecessary Effort?
AU  - Ferrari PA
JO  - International Journal of Surgery & Surgical Techniques
PY  - 2023
VL  - 7
IS  - 2
DO  - 10.23880/ijsst-16000193
ER  -