A survival nomogram model for patients with resectable non-small cell lung cancer and lymph node metastasis (N1 or N2) based on the Surveillance, Epidemiology, and End Results Database and single-center data.

Background: The ability to predict survival in patients with lymph node metastasis has long been elusive. After surgery, the basis for decision-making on the combination treatment of patients is not clear. The purpose of this study was thus to build a survival nomogram model to effectively predict the overall survival (OS) of patients with non-small cell lung cancer (NSCLC) and lymph node metastasis. The number of dissected lymph nodes (NDLN), number of positive lymph nodes (NPLN), lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) were included in this study to determine the risk factors in patients with advanced NSCLC. Methods: The data of 5,132 patients with NSCLC and lymph node metastasis (N1 or N2) were extracted from the Surveillance, Epidemiology, and End Results (SEER) database according to inclusion and exclusion criteria and used as the training cohort. We enrolled 117 patients from the First Affiliated Hospital, Zhejiang University School of Medicine as the external validation cohort. Receiver operating characteristic (ROC) analyses were performed to determine the best cutoff values for predicting the prognosis of patients with NSCLC. Based on the risk factors affecting prognosis, a nomogram was constructed using univariate and multivariate Cox proportional hazard regression models. The discrimination ability of the nomogram was evaluated with the concordance index (C-index) and calibration curves. For the independent risk factors, survival curves were drawn using Kaplan-Meier analysis. Results: ROC curve analysis showed that the optimal NPLN cut-off value was 4, LNR was 0.26, and LODDS was -0.25, respectively. However, LNR was nonsignificant in multivariate analysis, with a P value of 0.274. The novel survival nomogram model included seven independent risk factors, among which were NPLN, LODDS, and chemotherapy. Model 4, which included N stage, NPLN, and LODDS, had a higher likelihood ratio (LR) and C-index than did the other models. The C-index was 0.648 [95% confidence interval (CI): 0.636-0.659] in the training cohort and 0.807 (95% CI: 0.751-0.863) in the external validation cohort, showing good prognostic accuracy and discrimination ability. According to the median risk score, the patients in the training cohort and external validation cohort were divided into high-risk and low-risk groups, between which significant differences in OS were found. In the training cohort, age, sex, T stage, N stage, NPLN, LODDS, and chemotherapy were significantly associated with OS (P<0.001). In the external validation cohort, T stage, NPLN, LODDS, and chemotherapy were found to be correlated with OS. Conclusions: The NPLN and LODDS nomogram is an accurate survival prediction tool for patients with N1 or N2 NSCLC. Patients with lymph node metastasis can benefit from chemotherapy, but no evidence shows that radiotherapy is necessary for patients with resectable NSCLC.

Prognostic impact of adjuvant therapy for cisplatin-unfit patients with non-small-cell lung cancer: A multicenter analysis.

INTRODUCTION: No evidence exists for postoperative adjuvant therapy in elderly or renal dysfunction patients with non-small-cell lung cancer (NSCLC) who are unfit to receive cisplatin (CDDP). Herein, we evaluated the efficacy of postoperative adjuvant therapy for CDDP-unfit patients. MATERIALS AND METHODS: We defined CDDP-unfit patients as those aged ≥75 years or with renal dysfunction based on criteria established by expert panels and from prospective studies. CDDP-fit patients comprised all others. Between 2010 and 2020, among 1,423 patients with pathological stage II-III (8th edition of the AJCC-TNM Classification) NSCLC, 454 were identified as unfit for CDDP. Following propensity score matching in CDDP-unfit patients with and without postoperative adjuvant therapy, we analyzed the overall survival (OS) and disease-free survival (DFS) of each group and assessed the impact of adjuvant therapy on survival. RESULTS: OS was significantly better in patients who received adjuvant therapy than in those who did not (5-year OS rate: 76.1 % vs. 50.0 %, p < 0.01) among 255 propensity score-matched patients. DFS was also significantly better in patients who received adjuvant therapy than in those who did not (5-year OS: 54.6 % vs. 35.1 %, p < 0.01). CONCLUSIONS: Our findings suggest that postoperative adjuvant therapy could be beneficial for CDDP-unfit patients aged ≥75 years or with renal dysfunction. Future studies for CDDP-unfit patients should be designed based on the results of this study to determine the potential benefits of adjuvant therapy.

Optimal Treatment Strategy for Oligo-Recurrence Lung Cancer Patients with Driver Mutations.

BACKGROUND: The efficacy of local therapies for lung cancer patients with postoperative oligo-recurrence has been reported. However, whether local therapies should be chosen over molecular targeted therapies for oligo-recurrence patients with driver mutations remains controversial. Therefore, we aimed to investigate the optimal initial treatment strategy for oligo-recurrence in lung cancer patients with driver mutations. METHODS: Among 2152 patients with lung adenocarcinoma who underwent surgical resection at our institute between 2008 and 2020, 66 patients with driver mutations who experienced cancer oligo-recurrence after surgery and were treated with local or molecularly targeted therapy as an initial therapy after recurrence were evaluated. Oligo-recurrence was characterized by the presence of 1 to 3 recurrent lesions. These patients were investigated, focusing on their post-recurrence therapies and prognoses. RESULTS: The median follow-up period was 71 months. Local and molecular targeted therapies were administered to 41 and 25 patients, respectively. The number of recurrence lesions tended to be lower in the initial local therapy group than in the molecular targeted therapy group. In the initial local therapy group, 23 patients (56%) subsequently received molecular targeted therapies. The time from recurrence to the initiation of molecular targeted therapy was significantly longer in the local therapy group than in the molecular targeted therapy group (p < 0.001). There was no significant difference in post-recurrence overall survival (hazard ratio, 1.429; 95% confidence interval, 0.701-2.912; log-rank, p = 0.324) and post-recurrence progression-free survival (hazard ratio, 0.799; 95% confidence interval, 0.459-1.390; log-rank, p = 0.426) in the initial local ablative therapy group compared with the initial molecular targeted therapy group. CONCLUSIONS: Local therapies as a first-line treatment did not show statistically significant differences in post-recurrence survival or progression-free survival compared with molecular targeted therapies. However, local therapies as an initial treatment should be considered preferably, as they can cure the recurrence and can delay the start of administration of molecular targeted therapies.

Prediction of Tumor PD-L1 Expression in Resectable Non-Small Cell Lung Cancer by Machine Learning Models Based on Clinical and Radiological Features: Performance Comparison With Preoperative Biopsy.

OBJECTIVE: We investigated if PD-L1 expression can be predicted by machine learning using clinical and imaging features. METHODS: We included 117 patients with c-stage I/II non-small cell lung cancer who underwent radical resection. A total of 3951 radiomic features were extracted by defining the tumor (within tumor contour), rim (contour ±3 mm) and exterior (contour +10 mm) on preoperative contrast computed tomography. After feature selection by Boruta algorithm, prediction models of tumor PD-L1 expression (22C3: ≥1%, <1%) of resected specimens were constructed using Random Forest: radiomics, clinical, and combined models. Their performance was evaluated by 5-fold cross-validation, and AUCs were compared using Delong test. Next, study groups were categorized as patients without biopsy (training set), and those with biopsy (test set). Predictive ability of biopsy was compared to each prediction model. RESULTS: Of 117 patients (66 ± 10 years old, 48% male), 33 (28.2%) had PD-L1≥1%. Mean AUC of PD-L1≥1% for the validation set in radiomics, clinical, and combined models were 0.80, 0.80, and 0.83 (P = .32 vs. clinical model), respectively. The diagnosis of malignancy was made in 22 of 38 (58%) patients with attempted biopsies, and PD-L1 was measurable in 19 of 38 (50%) patients. Diagnostic accuracies of PD-L1≥1% from 19 determinable biopsies and 38 all attempted biopsies were 0.68 and 0.34, respectively. These were out performed by machine learning: 0.71, 0.71, and 0.74 for radiomics, clinical, and combined models, respectively. CONCLUSIONS: Our machine learning could be an adjunctive tool in estimating PD-L1 expression prior to neoadjuvant treatment, particularly when PD-L1 is indeterminable with biopsy.

Prognostication Using the Japanese Risk Calculator for Lung Cancer Surgery.

INTRODUCTION: Various calculation models to predict surgical risk have been developed globally. These have been reported to be helpful for estimating the long-term prognosis. In Japan, a similar model for lung cancer surgery was developed in 2017; however, there have been no reports investigating its association with the long-term prognosis. The objective of this study was to assess the association of the model's predictions with the long-term prognosis. PATIENTS AND METHODS: In this retrospective single-institutional study, we analyzed lung cancer patients who underwent radical lobectomy between 2010 and 2016. We calculated the predicted rates of mortality (PRM) and composite outcomes of mortality with major morbidity (PRMM) in eligible patients (N = 1054) using this model and classified them into 2 classes (class A, PRM ≥0.8% and PRMM ≥5.9%; class B, others) based on their models' predictions. We assessed the prognostic impact and clinical utility of the model's predictions. RESULTS: Class A included patients with significantly poorer postoperative overall survival than class B (log-rank, P < .001; hazard ratio, 3.160; 95% confidence interval, 2.390-4.178). Time-dependent receiver operating characteristic curve analyses revealed that the model's predictions correlated strongly with 1- and 2-year overall survival and decision curve analysis showed that they had high net benefits for prediction of those. CONCLUSION: The Japanese risk calculator could stratify the long-term prognosis for lung cancer patients after surgery. This model may be a valuable tool not only for multidisciplinary thoracic oncology teams to discuss treatment strategies for high-risk cases but also for them to share the decision-making process with patients.

Outcomes of lung oligometastasis in pancreatic cancer.

OBJECTIVE: Pancreatic cancer with lung oligometastasis may have favourable overall survival. The aim of this study was to evaluate outcomes of pancreatic cancer with lung oligometastases including both synchronous and metachronous metastases. METHODS: Consecutive pancreatic cancer patients with lung metastasis treated at our institution between February 2015 and December 2021 were identified from our prospectively maintained database. Clinical characteristics and outcomes were compared and analysed according to the extent of lung metastases. Predictors for overall survival were analysed using the Cox proportional hazards model. RESULTS: A totoal of 171 patients were included (oligometastasis/polymetastasis/multi-organ metastasis: 34/50/87). Patients with oligometastases were more likely to undergo surgical resection (41% vs. 0% vs. 2%) and showed a longer median overall survival (41.3 vs. 17.6 vs. 13.1 months) compared with those with other types of metastases. Oligometastasis (hazard ratio, 0.43; 95% confidence interval, 0.24-0.76; P = 0.004) was identified as an independent factor predicting favourable overall survival in patients with lung-only metastasis. Disease status (synchronous vs. metachronous) was not associated with survival in patients with oligometastasis (29.4 vs. 41.3 months, P = 0.527) and polymetastasis (17.9 vs. 16.7 months, P = 0.545). Selected patients who underwent surgical resection showed a median overall survival of 52.7 months. CONCLUSIONS: Patients with lung oligometastases presented a favourable prognosis. Surgical resection in selected patients was associated with a long median overall survival.

Features of anaplastic lymphoma kinase rearrangement in early-stage lung cancer: Analysis of a nationwide Japanese database.

BACKGROUND AND OBJECTIVES: Anaplastic lymphoma kinase (ALK) rearrangement is a representative driver mutation in lung cancer. However, the biology of early-stage ALK-rearranged lung cancer remains unclear. We aimed to assess the clinicopathological features, prognostic implications, and influence of ALK rearrangement on the postoperative course in surgically resected lung cancer. METHODS: We retrospectively analyzed data from the Japanese Joint Committee of Lung Cancer Registry database. Of the 12 730 patients with lung adenocarcinoma, 794 (6.2%) were tested for ALK rearrangement and were included. RESULTS: ALK rearrangements were detected in 76 patients (10%). The 5-year overall survival (OS) rate was significantly higher in the ALK rearrangement-positive group than in the ALK rearrangement-negative group (p = 0.030). Multivariable analysis revealed that ALK rearrangement was an independent prognostic factor for improved OS (hazard ratio, 0.521; 95% confidence interval, 0.298-0.911; p = 0.022). Regarding the postrecurrence state, there was no difference in the initial recurrence sites between both groups. Administration of ALK-tyrosine kinase inhibitors (TKIs) improved postrecurrence survival in any treatment lines. CONCLUSION: In one of the largest national surveys, ALK rearrangement was associated with improved long-term outcomes in surgically resected patients. ALK-TKIs may be an important treatment strategy for ALK rearrangement-positive lung adenocarcinoma in the postrecurrence state.

Risk factors for bronchopleural fistula after lobectomy for lung cancer.

Background: Bronchopleural fistula (BPF) after lobectomy for lung cancer is a rare but serious complication. This study aimed to stratify the risk factors of BPF. Methods: Patients who underwent lobectomy without bronchoplasty and preoperative treatment for lung cancer between 2005 and 2020 were retrospectively reviewed. We examined the association between the incidence of BPF and background factors, including comorbidities, preoperative blood test results, respiratory function, surgical procedure, and extent of lymphadenectomy. Results: Among the 3,180 patients who underwent lobectomy, 14 (0.44%) developed BPF. The median interval from surgery to BPF onset was 21 days (range, 10-287). Two of the 14 patients died of BPF (mortality rate, 14%). All 14 patients who developed BPF were men and had undergone right lower lobectomy. Other factors significantly associated with the development of BPF were older age, heavy smoking, obstructive ventilatory failure, interstitial pneumonia, history of malignancy, history of gastric cancer surgery, low serum albumin levels, and histology. Multivariable analysis in the subgroup of men who underwent right lower lobectomy revealed that high level of serum C-reactive protein and a history of gastric cancer surgery were significantly associated with BPF, whereas bronchial stump coverage was inversely associated with BPF. Conclusions: Men who underwent right lower lobectomy were at increased risk of BPF. The risk was higher when the patient had high serum C-reactive protein or a history of gastric cancer surgery. Bronchial stump coverage might be effective in patients at high risk of BPF.

Detection of EGFR mutations in early-stage lung adenocarcinoma by machine learning-based radiomics.

Background: We hypothesized that epidermal growth factor receptor (EGFR) mutations could be detected in early-stage lung adenocarcinoma using radiomics. Methods: This retrospective study included consecutive patients with clinical stage I/II lung adenocarcinoma who underwent curative-intent pulmonary resection from March-December 2016. Using preoperative enhanced chest computed tomography, 3,951 radiomic features were extracted in total from the tumor (area within the tumor boundary), tumor rim (area within ±3 mm of the tumor boundary), and tumor exterior (area between +10 mm outside the tumor and tumor boundary). A machine learning-based radiomics model was constructed to detect EGFR mutations. The combined model incorporated both radiomic and clinical features (gender and smoking history). The performance was validated with five-fold cross-validation and evaluated using the mean area under the curve (AUC). Results: Of 99 patients (mean age, 66±11 years; female, 66.6%; clinical stage I/II, 89.9%/10.1%), EGFR mutations in the surgical specimen were detected in 46 (46.5%). A median of 4 (range, 2 to 8) radiomic features was selected for each validation session. The mean AUCs in the radiomics and combined models were 0.75 and 0.83, respectively. The two top-ranked features in the combined model were the radiomic features extracted from the tumor exterior and the tumor, indicating a higher impact of radiomic features over relevant clinical features. Conclusions: Radiomic features, including those in the peri-tumoral area, may help detect EGFR mutations in lung adenocarcinomas in preoperative settings. This non-invasive image-based technology could help guide future precision neoadjuvant therapy.

Initial perioperative outcomes of robot-assisted thoracoscopic lobectomy using a confronting setting.

PURPOSE: Most robot-assisted thoracoscopic surgery (RATS) is performed from the vertical view. This study evaluates the initial outcomes of our novel confronting RATS technique, in which the patient was viewed horizontally, as in open thoracotomy. METHODS: We reviewed data on patients who underwent thoracoscopic lobectomy between January, 2019 and April, 2022. Perioperative outcomes were compared between RATS and video-assisted thoracoscopic surgery (VATS), using propensity-score matching. RESULTS: RATS and VATS were performed for 83 and 571 patients, respectively. After propensity-score matching, data on 81 patients from each of the two groups were retrieved. The operative time was significantly longer for RATS than for VATS (199 ± 44 min vs. 173 ± 37 min, p < 0.001). There was no mortality or conversion to thoracotomy in either of the groups. The rates of overall complications and prolonged air leak did not differ significantly between the groups. The serum creatine phosphokinase level on postoperative day 4 was higher after RATS than after VATS. The number of resected lymph nodes and the rates of nodal upstaging did not differ significantly between the groups. CONCLUSION: The initial perioperative outcomes of RATS using the confronting settings were comparable to those of VATS.

Distinct Prognostic Impact of PET Findings Based on Radiological Appearance in Clinical Stage IA Lung Adenocarcinoma.

INTRODUCTION: Although solid appearance on computed tomography and positive findings on positron emission tomography (PET) have been both associated with poor outcome in lung adenocarcinoma, the extent to which these findings overlap is unknown. This study aimed to determine the differences in prognostic significance of PET findings in part-solid nodules (PSNs) and solid nodules. MATERIALS AND METHODS: We retrospectively investigated 417 patients with clinical stage IA adenocarcinoma who underwent curative resection between 2010 and 2017. We compared disease-free survival (DFS), cumulative incidence of disease recurrence (CIR) and clinicopathological characters between PET-positive and negative groups among PSNs and solid nodules, respectively. We used 2.5 as a cut-off value of maximum standardized uptake value (SUV max). RESULTS: In PSNs (n = 235), PET-positive group (n = 59) showed more aggressive features in several clinicopathological variables, poorer DFS (P < .001) and higher CIR (P < .001) than PET-negative group (n = 176). In contrast, in solid nodules (n = 182), DFS (P = .521) and CIR (P = .311) were not significantly different between PET-positive (n = 128) and negative groups (n = 54). SUV max was proved to be the independent prognostic factor of DFS by multivariate analysis (HR, 1.155; 95% CI, 1.036-1.287) only in PSNs. CONCLUSION: These findings showed distinct impact on prognosis of PET findings between PSNs and solid nodules. PET-positive finding was more important prognostic factor in PSNs than in solid nodules among clinical stage IA lung adenocarcinoma.

Advances in the treatment of postoperative recurrence of non-small cell lung cancer and their impact on survival in Asian patients.

OBJECTIVES: We investigated the effect of tyrosine kinase inhibitors (TKIs) and immunotherapy on survival after postoperative recurrence of non-small cell lung cancer (NSCLC). METHODS: This single-center retrospective study included patients with NSCLC who underwent lobectomy or more with complete pathological resection between 2008 and 2018 (N = 2254). Median follow-up was 5.1 years. Survival trends and the effect of TKIs/immunotherapy were analyzed using Joinpoint (National Cancer Institute) and Cox regression. RESULTS: In 443 (19.7%) postoperative recurrences, median time to recurrence was 1.1 years; epidermal growth factor receptor mutation (EGFR+), 191 (43.1%); anaplastic lymphoma kinase rearrangement (ALK+), 13 (2.9%); not detected or unknown (ND), 239 (54.0%). In multivariable analysis, age, time to recurrence, adenocarcinoma, symptomatic recurrence, any treatment for recurrence, use of the epidermal growth factor receptor TKI, use of the anaplastic lymphoma kinase TKI, and use of immunotherapy were significant prognostic factors. Survival was significantly better in the EGFR+/ALK+ group than in the ND group (median, 4.7 vs 2.1 years; P < .01). Between 2010 and 2018, 2-year postrecurrence survival improved significantly (annual percentage change [APC], 4.2; 95% CI, 1.5-7.0). In subset analyses, neither change in 2-year survival nor TKI use was significant over time in the EGFR+/ALK+ group, but the ND group experienced significant improvement in 2-year survival (APC, 13.5; 95% CI, 5.4-22.2) and increasing trend in immunotherapy use (APC, 23.0; 95% CI, -5.9 to 60) after 2013. CONCLUSIONS: Survival after postoperative recurrence of NSCLC has improved significantly since 2010. Use of immunotherapy in patients without driver mutations may have contributed to that improvement. Prognosis in patients with driver mutations remains favorable with the TKIs introduced before the study period.

Branching patterns and variations of the bronchus and blood vessels in the superior segment of the right lower lobe: a three-dimensional computed tomographic bronchography and angiography study.

Background: Superior segmentectomy is classified as simple due to the single intersegmental plane between the superior and basal segments. However, oncological outcomes in patients undergoing superior segmentectomy tend to be worse compared to those receiving other segmentectomy. The aim of this study is to determine the branching patterns and variations of the bronchus and blood vessels of the superior segment of the right lower lobe (RS6). Methods: Three-dimensional computed tomographic bronchography and angiography (3D-CTBA) was reconstructed in 316 patients who underwent enhanced chest computed tomography (CT) and subsequent surgery in our center from November 2018 to March 2021. Results: The bronchus in RS6 consisted of a single stem in 96.5% cases (305/316), and 2 separate stems in the remaining 3.5% cases (11/316). The artery in RS6 consisted of a single stem in 59.5% cases (188/316), 2 separate stems in 37.0% cases (117/316), and 3 separate stems in the remaining 3.5% cases (11/316). The vein in RS6 consisted of a single stem in 94.3% cases (298/316) and 2 separate stems in the remaining 5.7% cases (18/316). B6 variation was noted in 1.6% cases (5/316). A6 variation was noted in 18.0% cases (57/316), including the following: (I) coexistence of A6 and A2 (n=25); (II) A6b originating from A9+10/A10 alone (n=20); (III) A6c originating from A9+10 (n=10); and (IV) co-draining of A6 and A7 (n=2). V6 variation was noted in 11.7% cases (37/316), including the following: (I) co-draining of V6 and V2 (n=20); (II) co-draining of V6 and V4 (n=5); (III) V6 and V8+9 co-draining (n=3); (IV) V6 draining into the superior pulmonary vein (n=4); and (V) direct V6 draining into the left atrium (n=5). Conclusions: Variation of A6 and V6 in RS6 is much more common than previously reported. 3D-CTBA reconstruction is useful for pre-surgery planning.

Impact of previous upper gastrointestinal cancer surgery on complications after lobectomy for lung cancer.

Background: The number of lung cancer patients with a history of other malignancies is increasing. Previous upper gastrointestinal cancer (UGIC) surgery may increase the risk of complications after lung cancer surgery due to malnutrition and susceptibility in patients; therefore, we investigated its short-term outcomes. Methods: We retrospectively examined patients with lung cancer who underwent thoracoscopic lobectomy between 2011 and 2021 and collected data regarding postoperative complications and postoperative pulmonary complications ≥ grade II of the Clavien-Dindo classification that developed within 3 months post-surgery. The effect of UGIC surgery on the postoperative complications was evaluated by multivariable analysis using logistic regression. Results: Among the 1,385 included patients, 377 patients had a history of cancer surgery and 65 (4.7%) of them had undergone UGIC surgery. Postoperative and pulmonary complications were observed in 155 (11.2%) and 39 (2.9%) patients, respectively. The frequency of pulmonary complications was significantly higher in patients with previous UGIC surgery (9.2% vs. 2.5%, P=0.003) with no significant difference in all complications (16.9% vs. 10.9%, P=0.137). Multivariable analysis showed that previous UGIC surgery is an independent factor associated with postoperative pulmonary complications (odds ratio =2.923, P=0.029). In contrast, previous surgery for cancer other than UGIC was not associated with postoperative pulmonary complications (the rate was 1.2% after lower gastrointestinal cancer surgery and 3.0% after non-gastrointestinal cancer surgery). Conclusions: Previous UGIC surgery was an independent factor associated with postoperative pulmonary complications after lung cancer surgery.

Optimal timing for lung metastasectomy in patients with colorectal cancer.

OBJECTIVES: The possibility of occult metastasis remains a concern when deciding on lung metastasectomy. This study aimed to evaluate the utility of our two-step determination, which required confirmation that no new metastases had occurred over 3 months before surgery. METHODS: Patients who were referred for colorectal lung metastases between 2007 and 2015 were reviewed. Immediate wedge resection was performed for cases with a single peripheral metastasis, whereas surgical indications for others were determined by the two-step determination. Early increase was defined as the emergence of new metastases within 4 months after the diagnosis of lung metastases. RESULTS: Among 369 patients included, 92 were unresectable upon initial diagnosis, and 74 with single peripheral metastasis underwent immediate wedge resection. Surgical indications for the remaining 203 patients were ascertained based on the two-step determination. Surgery was not indicated in 48 patients (24%) due to new metastases or a favourable response to chemotherapy, with a median waiting duration of 4.8 months. Those who did not receive surgery had a worse prognosis than those who did (5-year overall survival: 21% vs 69%, P < 0.001) and were comparable to the initially unresectable group (5-year overall survival: 23%). Thirty-eight patients with early increase had lower surgical resection rates and worse prognoses than those without. Multivariable analysis identified early increase as an independent prognostic factor (hazard ratio: 4.49, P < 0.001). CONCLUSIONS: Patients with colorectal lung metastasis who developed new metastasis during the waiting period exhibited poor prognosis, suggesting the utility of the two-step determination of surgical indications.