Lung Metastasectomy For Colorectal Cancer Research Articles

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

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.

Time to Incurable Recurrence for Patients Treated With Pulmonary Metastasectomy for Colorectal Cancer.

Probability of cure is important for patients with lung metastasis who must decide whether to undergo metastasectomy. Although progression-free survival (PFS) is thought to reflect this, it does not include curative effects by repeat metastasectomy. Thus, the authors developed a new indicator, time to incurable recurrence (TTIR), in which only incurable recurrence was set as an event that included death, with incurable recurrence defined as recurrence not treated by definitive local therapy (DLT), recurrence treated by DLT but with PFS maintained less than 2 years, or recurrence followed by re-recurrence. This multi-institutional study included 339 patients who underwent lung metastasectomy for colorectal cancer between 1990 and 2008. Among the 339 patients, 191 experienced recurrence, 77 received DLT for recurrence, 38 had a PFS of 2 years or longer after the treatment, and 33 had maintained a PFS at the last follow-up date. The patients had PFS ranging from 39 to 212 months (median, 101 months). The 5-year OS, PFS, and TTIR rates were respectively 63.4%, 42.2%, and 51.9%. The TTIR curve was similar to the OS curve 7 years after the initial metastasectomy. The difference between TTIR and PFS at 7 years was 9.7%, indicating probability of cure by repeat DLT. Multivariable analysis showed different prognostic factors among OS, PFS, and TTIR. At the initial metastasectomy, TTIR may reflect probability of a cure, including cure by repeat DLT, and can be used to analyze prognostic factors associated with cure.

Anatomical Resection Improves Disease-Free Survival After Lung Metastasectomy of Colorectal Cancer.

PurposeThis study aimed to evaluate the role of anatomical resection (AR) in lung metastasectomy (LM) of colorectal cancer (CRC) and to investigate clinically relevant prognostic factors.Patients and MethodsThe medical records of 350 consecutive patients who underwent LM of CRC from 2011 to 2019 were reviewed. The patients were designated into AR group (lobectomy and segmentectomy), and non-anatomical resection (NAR) group (wedge resection), respectively. Kaplan–Meier method was used to analyze disease-free survival (DFS), pulmonary-specific disease-free survival (PDFS) and overall survival (OS). Cox proportional hazards regression model was performed to analyze the factors associated with DFS, PDFS and OS.ResultsA total of 92 (31.2%) patients were enrolled in AR group and 203 (68.8%) in non-anatomical resection (NAR) group. AR significantly improved the 3-year DFS (64.1% vs 46.8%, HR 0.587, 95% CI 0.397–0.867, P = 0.007) and PDFS (75.0% vs 60.1%, HR 0.565, 95% CI 0.356–0.899, P = 0.016) compared with NAR. However, the extent of resection did not significantly impact the 3-year OS (AR 92.4% vs NAR 85.7%, HR 0.511, 95% CI 0.224–1.165, P = 0.110). In multivariate analysis, AR was identified as a protective factor for DFS (HR 0.576, 95% CI 0.356–0.934, P = 0.025) and PDFS (HR 0.631, 95% CI 0.409–0.973, P = 0.037). Preoperative abnormal CA19-9 was identified as the only prognostic factor for OS.ConclusionAR was superior to NAR for DFS and PDFS after LM from CRC.

P38.02 The Prognostic Role of Neutrophil to Lymphocyte Ratio (NLR) In Lung Metastasectomy for Colorectal Cancer: A Meta-Analysis

Inflammation represents a hallmark of cancer. Neutrophil to lymphocyte ratio (NLR) is correlated to patients' inflammatory status and has been proposed as a promising biomarker in different types of cancer. In the same context, prognostic markers are still limited to define good candidates for lung metastasectomy for colorectal cancer (CRC). We reviewed the available literature on patients with CRC lung metastases undergoing surgery to evaluate the potential association between preoperative NLR and long-term prognosis.

Lung metastasectomy for colorectal cancer in the PulMiCC randomised controlled trial - Authors' reply.

Lung metastasectomy for colorectal cancer in the PulMiCC randomised controlled trial - Authors' reply.

Lung metastasectomy for colorectal cancer in the PulMiCC randomised controlled trial.

Lung metastasectomy for colorectal cancer in the PulMiCC randomised controlled trial.

Pulmonary metastasectomy in colorectal cancer: health utility scores by EQ-5D-3L in a randomized controlled trial show no benefit from lung metastasectomy.

AimThe aim was to assess the health utility of lung metastasectomy in the treatment of patients with colorectal cancer (CRC) using the EQ-5D-3L questionnaire.MethodsMultidisciplinary CRC teams at 14 sites recruited patients to a two-arm randomized controlled trial—Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC). Remote randomization was used, stratified by site and with minimization for seven known confounders. Participants completed the EQ-5D-3L questionnaire together with other patient reported outcome measures at randomization and then again at 3, 6, 12 and 24 months. These were returned by post to the coordinating centre.ResultsBetween December 2010 and December 2016, 93 participants were randomized, 91 of whom returned questionnaires. Survival and patient reported quality of life have been published previously, revealing no significant differences between the trial arms. Described here are patient reported data from the five dimensions of the EQ-5D-3L and the visual analogue scale (VAS) health state. No significant difference was seen at any time point. The estimated difference between control and metastasectomy patients was −0.23 (95% CI –0.113, 0.066) for the composite 0 to 1 index scale based on the descriptive system and 0.123 (95% CI –7.24, 7.49) for the 0 to 100 VAS scale.ConclusionsFollowing lung metastasectomy for CRC, no benefit was demonstrated for health utility, which alongside a lack of a survival or quality of life benefit calls into question the widespread use of the procedure.

Outcome of patients with colorectal cancer undergoing lung metastases resection: a single-institution retrospective analysis

This study was undertaken to review a single-institution cohort of patients with metastatic colorectal cancer undergoing lung resection after a multidisciplinary evaluation and to investigate the main prognostic factors for survival. Medical records of 129 patients undergoing lung metastasectomy for colorectal cancer with curative intent from 2001 to 2017 were reviewed. Tissue samples from the primary tumor were analyzed with a multiplex genotyping system for the detection of mutations in RAS and BRAF genes. Survival analyses were carried out by the Kaplan-Meier method. Univariate and multivariable analyses were performed using the log-rank test and the Cox regression model. Postoperative morbidity and mortality were 13.2% and 0%, respectively. At a median follow-up time of 62.5 months, median overall survival was 90.5 months and median relapse-free survival was 42.8 months. Multivariable analysis for overall survival identified synchronous versus metachronous metastatic presentation as the only prognostic factor, whereas relapse-free survival was independently associated with synchronous versus metachronous metastatic presentation, number of metastases, and postoperative chemotherapy. This study shows particularly favorable survival outcomes for patients undergoing lung metastasectomy. The validity of some of the main prognostic factors was confirmed and a positive effect of postoperative chemotherapy on relapse-free survival was shown. Contrary to other reports, the presence of KRAS mutations was not associated with significant survival differences. Further studies are needed in order to clarify the interactions between molecular, clinical, and pathologic characteristics and treatment-related factors.

Anatomical Resections Improve Survival Following Lung Metastasectomy of Colorectal Cancer Harboring KRAS Mutations

The aim of this study was to evaluate the benefit of anatomical resection (AR) in lung metastasectomy (LM) of colorectal cancer (CRC) harboring KRAS mutations SUMMARY BACKGROUND DATA:: KRAS mutations are related to high aggressiveness in the lung metastasis of CRC. It is unknown whether AR can lead to better outcomes than can non-AR (NAR) in KRAS patients. We retrospectively reviewed the data from 574 consecutive patients who underwent a LM for CRC. We focused on patients exhibiting 1 lung metastasis who underwent an AR (segmentectomy) or an NAR (wedge) and for whom the KRAS mutational status was known. Overall survival (OS) and time to pulmonary recurrence (TTPR) were analyzed. We included 168 patients, of whom 95 (56.5%) harbored KRAS mutations. An AR was performed in 74 patients (44%). The type of resection did not impact the median OS in wild-type (WT) patients (P = 0.67) but was significantly better following AR in KRAS patients (101 vs 45 months, P = 0.02) according to the multivariate analysis [hazard ratio (HR): 6.524; 95% confidence interval (CI), 2.312-18.405; P < 0.0001). TTPR was not affected by the type of resection in WT patients (P = 0.32) but was significantly better for AR in KRAS patients (50 vs 15 months, P = 0.01) in the multivariate analysis (HR: 5.273; 95% CI, 1.731-16.064; P = 0.003). The resection-margin recurrence rate was significantly higher for NAR in KRAS patients (4.8% vs 54.2%, P = 0.001) but not in WT patients (P = 0.97). AR seems to improve both the OS and TTPR in LM of CRC harboring KRAS mutations.

Prognostic value of neutrophil to lymphocyte ratio in lung metastasectomy for colorectal cancer.

Neutrophil to lymphocyte ratio (NLR) has been shown to be a promising biomarker in several cancers. Prognostic biomarkers are still needed to define good candidates for lung metastasectomy for colorectal cancer. We aimed to evaluate the role of NLR. Data from 574 patients who underwent lung metastasectomy for colorectal cancer in 3 departments of thoracic surgery from 2004 to 2014 were retrospectively reviewed. Overall survival (OS) and the time to pulmonary recurrence (TTPR) were the main end points. Correlations between NLR and OS (R2 = 0.53), and NLR and TTPR (R2 = 0.389) were significant (P < 0.0001 for both), with corresponding Pearson R of -0.728 (P < 0.0001) and -0.624 (P < 0.0001), respectively. A receiver operating characteristic curve analysis highlighted an NLR cut-off value of 4.05 as the best predictor of OS and TTPR. NLR ≤4.05 was observed in 238 patients (41.4%). In the univariable analysis, the median OS was 117 months for patients with NLR ≤4.05 and decreased to 40 months for patients with NLR >4.05 (P < 0.0001). The median TTPR reached 52 months in case of NLR ≤4.05 and decreased to 12 months in patients with NLR >4.05. In the multivariable analysis, NLR ≤4.05 remained an independent favourable prognostic factor on both OS [hazard ratio [HR] 0.29, 95% confidence interval (CI) 0.167-0.503; P < 0.0001] and TTPR (HR 0.346, 95% CI 0.221-0.54; P < 0.0001). Significant correlations between NLR >4.05 and KRAS (Cramer's V = 0.241, P < 0.0001) and BRAF (Cramer's V = 0.153, P = 0.003) mutations were observed. NLR is a simple and powerful predictor of outcomes in patients undergoing pulmonary metastasectomy for colorectal cancer.

Prognostic factors after pulmonary metastasectomy of colorectal cancers: a single-center experience.

Surgical resection has been widely admitted as the treatment of choice for pulmonary metastases of colorectal cancer (CRC). Nevertheless, this practice is not supported by high level of evidence and patients' eligibility remains controversial. Aim of this study was to evaluate long terms results and factors influencing survival after lung metastasectomy of CRC. A single-center retrospective analysis of patients with pathologically proven colorectal metastasis, operated from 2004 to 2013, was performed. Patients were treated with a multidisciplinary approach and selected for surgery if complete resection was considered feasible. Three hundred and six patients were considered for analysis. Mean number of lesions at CT scan was 2.6±2.3. Ratios of each largest resection type at first side surgery were: segmentectomy 20.6%, lobectomy 12.9%, bilobectomy 1.2%, pneumonectomy 1.2% and sub-lobar resection 64.1%, respectively. No in-hospital death occurred. At pathology, mean number of resected metastasis was 2.6±2.3, ranging from 1 to 12. Resection was complete in 92.5% of patients. Nodal involvement was proven in 40 (12.9%) patients. The initially planned complete resection could not be achieved in 23 (7.5%) cases. Mean follow-up was 3.06±2.36 years. Kaplan-Meier analysis revealed that recurrence-free survival (RFS) was 76.3% [95% confidence interval (95% CI), 71-80.7%], 38.9% (95% CI, 33-44.7%), 28.3% (95% CI, 22.5-34.4%) and 22.7% (95% CI, 16.5-29.5%) at 1, 3, 5 and 7 years, respectively. Overall survival (OS) estimates were 77.8% (95% CI, 72.7-82.7%), 59.0% (95% CI, 51.2-66.4%), and 56.9% (95% CI, 48.4-65.0%) at 3, 5 and 7 years, respectively. Multivariate analysis, including pT parameter of the primary tumor, number of lesions, one-sided versus bilateral lung disease, and body mass index (BMI) (all significant at univariate analysis), showed that bilateral disease (P<0.001) and pT4 primary (P=0.005) were independent pejorative predictors of OS, whereas BMI ≥25 was protective (P=0.028). Bilateralism and primary tumor local extension influence the prognosis of patients surgically treated for pulmonary colorectal metastases. Specifically designed randomized trials are necessary.

Survival after initial lung metastasectomy for metastatic colorectal cancer in the modern chemotherapeutic era

BackgroundA clear survival benefit has been reported for lung metastasectomy for colorectal cancer, and several clinicopathological prognostic factors have been proposed in the past. However, clinical advances, such as chemotherapy and radiographic imaging, should have improved patient outcome and may have altered prognosticators. This study aimed to assess patient survival and determine prognostic factors for survival and recurrence in patients who underwent initial lung metastasectomy for colorectal cancer in the modern clinical era.MethodsClinicopathological data and outcomes of 59 patients who underwent curative initial lung metastasectomy for colorectal cancer from 2004 to 2012 at a single institution in Japan were retrospectively investigated. Survival was estimated using the Kaplan - Meier method, and Cox proportional hazards regression models were used to estimate the prognostic impacts of each variable in univariate and multivariate analysis.ResultsThe 5-years overall and disease-free survival rates were 54.3 and 40.6%, respectively. A disease-free interval < 24 months after colorectal cancer resection (P = 0.004) and a serum carcinoembryonic antigen ≥ 5.0 ng/mL before initial lung metastasectomy (P = 0.015) were independent predictors for poor overall survival. Moreover, the disease-free interval after colorectal cancer resection < 24 months (P = 0.010) and a colorectal cancer with N2 stage disease (P = 0.018) were independently associated with poor disease-free survival. On the other hand, the number of lung metastasis was not identified as a poor prognostic factor for both overall and disease-free survival.ConclusionsOur findings demonstrated similar or slightly better overall survival, and substantially favorable disease-free survival as compared with past reports. Poor prognostic factors for overall survival appeared not to differ from those of past studies, although this modern series did not determine the number of lung metastasis as a poor prognostic factor, which should be investigated in future studies. Moreover, initial lung metastasectomy is not expected to be a curable treatment for patients with both a short disease-free survival after colorectal cancer resection and colorectal cancers with N2 stage disease.

Thoracoscopic surgery versus open surgery for lung metastases of colorectal cancer: a multi-institutional retrospective analysis using propensity score adjustment†.

Thoracoscopic surgery for lung metastasectomy remains controversial. The study aimed at determining the efficacy of thoracoscopic surgery for lung metastasectomy. This was a multi-institutional, retrospective study that included 1047 patients who underwent lung metastasectomy for colorectal cancer between 1999 and 2014. Prognostic factors of overall survival were compared between the thoracoscopic and open thoracotomy groups using the multivariate Cox proportional hazard model. The propensity score, calculated using the preoperative covariates, included the era of lung surgery as a covariate. A stepwise backward elimination method, with a probability level of 0.15, was used to select the most powerful sets of outcome predictors. The difference between the radiological tumour number and the resected tumour number (delta_num) was also evaluated. The c -statistics and the P -value of the Hosmer-Lemeshow Chi-square of the propensity score model were 0.7149 and 0.1579, respectively. After adjusting for the propensity score, the thoracoscopy group had a better survival rate than the open group (stratified log-rank test: P = 0.0353). After adjusting for the propensity score, the most powerful predictive model for overall survival was that which combined thoracoscopy [hazard ratio (HR): 0.468, 95% CI: 0.262-0.838, P = 0.011] and anatomical resection (HR: 1.49, 95% CI: 1.134-1.953, P = 0.004). Before adjusting for the propensity score, the delta_num was significantly greater in the open group than in the thoracoscopy group (thoracoscopy: 0.06, open: 0.33, P = 0.001); however, after adjustment, there was no difference in the delta_num (thoracoscopy: 0.04, open: 0.19, P = 0.114). Thoracoscopic metastasectomy showed better overall survival than the open approach in this analysis. The thoracoscopic approach may be an acceptable option for resection of pulmonary metastases in terms of tumour identification and survival outcome in the current era.

KRAS exon 2 codon 13 mutation is associated with a better prognosis than codon 12 mutation following lung metastasectomy in colorectal cancer.

IntroductionThe utilization of molecular markers as routinely used biomarkers is steadily increasing. We aimed to evaluate the potential different prognostic values of KRAS exon 2 codons 12 and 13 after lung metastasectomy in colorectal cancer (CRC).ResultsKRAS codon 12 mutations were observed in 116 patients (77%), whereas codon 13 mutations were observed in 34 patients (23%). KRAS codon 13 mutations were associated with both longer time to pulmonary recurrence (TTPR) (median TTPR: 78 months (95% CI: 50.61–82.56) vs 56 months (95% CI: 68.71–127.51), P = 0.008) and improved overall survival (OS) (median OS: 82 months vs 54 months (95% CI: 48.93–59.07), P = 0.009). Multivariate analysis confirmed that codon 13 mutations were associated with better outcomes (TTPR: HR: 0.40 (95% CI: 0.17–0.93), P = 0.033); OS: HR: 0.39 (95% CI: 0.14–1.07), P = 0.07). Otherwise, no significant difference in OS (P = 0.78) or TTPR (P = 0.72) based on the type of amino-acid substitutions was observed among KRAS codon 12 mutations.Materials and MethodsWe retrospectively reviewed data from 525 patients who underwent a lung metastasectomy for CRC in two departments of thoracic surgery from 1998 to 2015 and focused on 150 patients that had KRAS exon 2 codon 12/13 mutations.ConclusionsKRASexon 2 codon 13 mutations, compared to codon 12 mutations, seem to be associated with better outcomes following lung metastasectomy in CRC. Prospective multicenter studies are necessary to fully understand the prognostic value of KRAS mutations in the lung metastases of CRC.

Perioperative bevacizumab improves survival following lung metastasectomy for colorectal cancer in patients harbouring v-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue exon 2 codon 12 mutations†.

The role of perioperative chemotherapy (POC) and targeted therapies in lung metastasectomy for colorectal cancer (CRC) is still subject to debate. We aimed to evaluate whether POC and targeted therapies were associated with different outcomes according to the mutational status. We reviewed data from 223 patients who underwent pulmonary metastasectomy for CRC from 1998 to 2015 and for whom the V-Ki-ras2 Kirsten sarcoma viral oncogene homologue (KRAS) and V-raf Murine sarcoma viral oncogene homologue B1 (BRAF) mutational statuses were known. A total of 167 patients (74%) underwent POC: 62 (37%) received neoadjuvant therapy, 59 (35%) were in the adjuvant setting and 46 (28%) were in both the neoadjuvant and adjuvant settings. POC did not significantly influence either the loco-regional recurrence free survival (LRRFS) (P = 0.21) or the overall survival (OS) (P = 0.29). Furthermore, in cases of adjuvant chemotherapy, outcomes were not significantly different in cases of neoadjuvant chemotherapy or both neoadjuvant and adjuvant treatment (P = 0.26 for OS, P = 0.14 for LRRFS). For patients with KRAS mutation, perioperative bevacizumab was associated with a significant improvement in both LRRFS [70 months (41.58–98.42) vs 24 months (1.15–46.86), P = 0.001] and OS [101 vs 55 months (49.77–60.23), P = 0.004]. However, this benefit was only significant in cases of KRAS exon 2 codon 12 mutations [median OS: 101 months (83.97–118.02) vs 60 months (53–66.99), P < 0.001; median LRRFS: 76 months (64.62–87.38) vs 44 months (35.27–52.73), P < 0.001]. Perioperative bevacizumab appears to be beneficial in patients with exon 2 codon 12 KRAS mutations who have undergone lung metastasectomy for CRC.

KRAS and BRAF mutations are prognostic biomarkers in patients undergoing lung metastasectomy of colorectal cancer.

Background:We evaluated KRAS (mKRAS (mutant KRAS)) and BRAF (mBRAF (mutant BRAF)) mutations to determine their prognostic potential in assessing patients with colorectal cancer (CRC) for lung metastasectomy.Methods:Data were reviewed from 180 patients with a diagnosis of CRC who underwent a lung metastasectomy between January 1998 and December 2011.Results:Molecular analysis revealed mKRAS in 93 patients (51.7%), mBRAF in 19 patients (10.6%). In univariate analyses, overall survival (OS) was influenced by thoracic nodal status (median OS: 98 months for pN−, 27 months for pN+, P<0.0001), multiple thoracic metastases (75 months vs 101 months, P=0.008) or a history of liver metastases (94 months vs 101 months, P=0.04). mBRAF had a significantly worse OS than mKRAS and wild type (WT) (P<0.0001). The 5-year OS was 0% for mBRAF, 44% for mKRAS and 100% for WT, with corresponding median OS of 15, 55 and 98 months, respectively (P<0.0001). In multivariate analysis, WT BRAF (HR: 0.005 (95% CI: 0.001–0.02), P<0.0001) and WT KRAS (HR: 0.04 (95% CI: 0.02–0.1), P<0.0001) had a significant impact on OS.Conclusions:mKRAS and mBRAF seem to be prognostic factors in patients with CRC who undergo lung metastasectomy. Further studies are necessary.

EComment. Lymph node dissection in pulmonary metastasectomy for colorectal cancer

We read with great interest the article by Renaud et al. [1] regarding the effect of lymph node status on survival after lung metastasectomy of colorectal cancer. This is a retrospective study, which reports data on an impressive 320 patients over 20 years, 140 of whom had positive lymph nodes. The authors confirm that lymph node involvement is correlated with decreased survival. However, since the presence of lung metastases is synonymous with systemic disease, adjuvant therapy is mandatory irrespective of lymph node status and, thus, prognostic factors are not very important in that sense. The real questions are whether lymph node status is a contraindication to resection and, if not, whether radical mediastinal lymphadenectomy can offer a reasonable chance for cure. The authors state that neither lymph node positivity, nor the number of metastases were considered a contraindication for resection. Further, they managed to achieve a complete resection in all patients, and they suggest that the reported rather satisfactory overall survival (37 months in patients with mediastinal disease) should be interpreted as a confirmation that their strategy is successful. It is important to remember that this is a major operation performed with curative intent [2]. We can already see from the report that 35% of N0 and 33% of N+ patients were re-operated for recurrence [1]. To justify the certain detrimental effect of a thoracotomy and the loss of lung parenchyma - as well as the psychological impact of offering false hope to a patient - [2] we must be able to offer a reasonable chance for cure. Although this question may only be answered when data from randomized trials are available [3], it would be very interesting if the authors could show that they managed to prevent recurrence in a significant number of N+ patients by presenting relapse-free survival alongside overall survival. Conflict of interest: none declared

Does nodal status influence survival? Results of a 19-year systematic lymphadenectomy experience during lung metastasectomy of colorectal cancer

Resection of pulmonary metastases originating from colorectal cancer is increasingly considered. While several adverse risk factors for long-term outcome are known, the selection of patients who may benefit from surgery remains unclear. In particular, few studies have addressed the impact of lymph node involvement, and signification of the hilar or mediastinal level of extent. We retrospectively reviewed the data of 320 patients operated in two thoracic departments between 1992 and 2011. Appropriate statistical tests were used to compare groups at risk. There were 105 women and 215 men with a mean age of 63.3 years (range: 27-86) at the time of metastasectomy. Lymph node involvement appeared as a significant prognostic factor in both the univariate and multivariate analyses [median survival: 94 months N0 vs 42 months N+, P < 0.0001; OR = 0.573 (0.329-1), P = 0.05]. Survival was similar for hilar and mediastinal locations (median survival: 47 months vs 37 months, respectively, P = 0.14). Associated hepatic metastases had a negative impact on survival in both univariate and multivariate analyses [median survival: 74 months vs 47 months, P < 0.01; OR = 0.387 (0.218-0.686), P = 0.001]. Multiple lung metastases significantly decreased survival in univariate analysis only (median survival: 81 months vs 55 months, P < 0.01). Disease-free survival and preoperative carcinoembryonic antigen had no impact on survival. While lymph node involvement was associated with decreased survival, the impact of mediastinal location on survival did not differ from that of hilar location. Consequently, these patients should not be excluded from surgical treatment.

Risk Factors for Survival after Lung Metastasectomy in Colorectal Cancer Patients: A Systematic Review and Meta-Analysis

Resection of lung metastases (LM) from colorectal cancer (CRC) is increasingly performed with a curative intent. It is currently not possible to identify those CRC patients who may benefit the most from this surgical strategy. The aim of this study was to perform a systematic review of risk factors for survival after lung metastasectomy for CRC. We performed a meta-analysis of series published between 2000 and 2011, which focused on surgical management of LM from CRC and included more than 40 patients each. Pooled hazard ratios (HR) were calculated by using random effects model for parameters considered as potential prognostic factors. Twenty-five studies including a total of 2925 patients were considered in this analysis. Four parameters were associated with poor survival: (1) a short disease-free interval between primary tumor resection and development of LM (HR 1.59, 95 % confidence interval [CI] 1.27-1.98); (2) multiple LM (HR 2.04, 95 % CI 1.72-2.41); (3) positive hilar and/or mediastinal lymph nodes (HR 1.65, 95 % CI 1.35-2.02); and (4) elevated prethoracotomy carcinoembryonic antigen (HR 1.91, 95 % CI 1.57-2.32). By comparison, a history of resected liver metastases (HR 1.22, 95 % CI 0.91-1.64) did not achieve statistical significance. Clinical variables associated with prolonged survival after surgery for LM in CRC patients include prolonged disease-free interval between primary tumor and metastatic spread, normal prethoracotomy carcinoembryonic antigen, absence of thoracic node involvement, and a single pulmonary lesion.

Survival after lung metastasectomy for colorectal cancer: Importance of previous liver metastasis as a prognostic factor

Aims To analyse patient survival after the resection of lung metastases from colorectal carcinoma and specifically to verify whether presence of liver metastasis prior to lung metastasectomy affects survival. Methods All patients who, between 1998 and 2008, underwent lung metastasectomy due to colorectal cancer were included in the study. Kaplan–Meier survival analysis was performed with the log-rank test and Cox regression multivariate analysis. Results During this period, 101 metastasectomies were performed on 84 patients. The median age of patients was 65.4 years, and 60% of patients were male. The 30-day mortality rate was 2%, and incidence of complications was 7%. The overall survival was 72 months, with 3-and 5-year survival rates of 70% and 54%, respectively. A total of 17 patients (20%) had previously undergone resection of liver metastasis. No significant differences were found in the distribution of what were supposed to be the main variables between patients with and without previous hepatic metastases. Multivariate analysis identified the following statistically significant factors affecting survival: previous liver metastasectomy ( p = 0.03), tumour-infiltrated pulmonary lymph nodes ( p = 0.04), disease-free interval ≥ 48 months ( p = 0.03), and presence of more than one lung metastasis ( p < 0.01). In patients with previous liver metastasis, the shorter the time between primary colorectal surgery and the hepatectomy, the lower the survival rate after pulmonary metastasectomy ( p = 0.048). Conclusions A previous history of liver metastasis shortens survival after lung metastasectomy. The time between hepatic resection and lung metastasectomy does not affect survival; however, patients with synchronous liver metastasis and colorectal neoplasia have poorer survival rates than those with metachronous disease.