Causal Model of Survival After Pulmonary Metastasectomy of Colorectal Cancer: A Nationwide Prospective Registry

doi:10.1016/j.athoracsur.2015.12.017

The Annals of Thoracic Surgery

Volume 101, Issue 5, May 2016, Pages 1883-1890

https://doi.org/10.1016/j.athoracsur.2015.12.017 Get rights and content

Background

Although numerous existing studies have analyzed the prognostic factors of patients who have had surgical intervention for lung metastases of colorectal carcinoma (CRC), many of the results obtained until now have been contradictory. As a consequence, there is no established consensus about which group of prognostic factors could have a greater value when considered together.

Methods

This was a multicenter prospective cohort study that included all patients who underwent a first pulmonary metastasectomy of CRC, with radical intent, during a 2-year period (March 2008 to February 2010). The follow-up continued until March 2013, and an analysis of disease-specific survival (DSS), determined from the first pulmonary metastasectomy, was implemented. The selection of the best submodel was taken based on their coefficient of determination (R²) and how parsimonious they were depending on the number of variables included.

Results

The series, consisting of 522 patients, presented the following survival rates: median, 54.9 months; 3-year DSS, 69.4% (95% confidence interval [CI], 65% to 73.8%); and 5-year DSS, 46.1% (95% CI, 38.5% to 53.7%). The resulting survival model consisted of disease-free interval of 12 months or less (hazard ratio [HR], 1.76; 95% CI, 1.21 to 2.54; p = 0.003), carcinoembryonic antigen level exceeding 5 ng/mL (HR, 1.50; 95% CI, 1.04 to 2.17; p = 0.028), bilateral lung disease (HR, 1.81; 95% CI, 1.20 to 2.75; p = 0.005), and thoracic lymph node involvement (HR, 2.71; 95% CI, 1.44 to 5.12; p = 0.002).

Conclusions

According to these results from the Spanish Group of Lung Metastases of Colo-Rectal Cancer, the combination of these four variables—disease-free interval, carcinoembryonic antigen level, laterality, and thoracic lymph node involvement—constitutes the first-choice survival causal model based on the clinical and pathologic factors most frequently referenced in literature.

Section snippets

The GECMP-CCR

The Spanish Group, founded in January 2008, consists of 35 Departments of Thoracic Surgery, 32 of which actively participated in the inclusion of patients. The Research and Ethics Committees of the participating centers approved the registry.

All of the data were prospectively registered from all patients who had undergone a first colorectal pulmonary metastasectomy between March 1, 2008, and February 28, 2010. The follow-up period lasted until February 28, 2013. The criteria that were

Results

During the inclusion period, 543 patients were registered. The clinical characteristics and demographics of the cohort have been previously published 3, 4. For the analysis of the current study, 21 patients (4%) were eventually excluded because they did not comply with either of the two aforementioned inclusion criteria.

From the remaining 522 patients, several were subsequently excluded from the survival analysis: 2 patients (0.38%) died postoperatively, and no follow-up data were registered

Comment

During the last 3 decades, analyzing the clinical and pathologic prognostic factors of patients who have undergone a pulmonary metastasectomy has been the norm in literature. However, rather frequently, the results obtained can be contradictory and, at the very least, unconfirmed by other researchers [2]. A number of these inconsistencies have been dealt with previously by other authors [6].

As a previous step to the construction of our causal model of survival, we performed a bivariate analysis

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Cited by (28)

Pulmonary metastasectomy with lymphadenectomy for colorectal pulmonary metastases: A systematic review
2022, European Journal of Surgical Oncology
Routine lymphadenectomy during metastasectomy for pulmonary metastases of colorectal cancer has been recommended by several recent expert consensus meetings. However, evidence supporting lymphadenectomy is limited. The aim of this study was to perform a systematic review of the literature on the impact of simultaneous lymph node metastases on patient survival during metastasectomy for colorectal pulmonary metastases (CRPM).
A systematic review was conducted according to the PRISMA guidelines of studies on lymphadenectomy during pulmonary metastasectomy for CRPM. Articles published between 2000 and 2020 were identified from Medline, Embase and the Cochrane Library without language restriction. Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to assess the risk of bias and applicability of included studies. Survival rates were assessed and compared for the presence and level of nodal involvement.
Following review of 8054 studies by paper and abstract, 27 studies comprising 3619 patients were included in the analysis. All patients included in these studies underwent lymphadenectomy during pulmonary metastasectomy for CRPM. A total of 690 patients (19.1%) had simultaneous lymph node metastases. Five-year overall survival for patients with and without lymph node metastases was 18.2% and 51.3%, respectively (p < .001). Median survival for patients with lymph node metastases was 27.9 months compared to 58.9 months in patients without lymph node metastases (p < .001). Five-year overall survival for patients with N1 and N2 lymph node metastases was 40.7% and 10.9%, respectively (p = .064).
Simultaneous lymph node metastases of CRPM have a detrimental impact on survival and this is most apparent for mediastinal lymph node metastases. Therefore, lymphadenectomy during pulmonary metastasectomy for CRPM can be advised to obtain important prognostic value.
Lung Metastases of Colorectal Cancer: Survival and Prognostic Factors after Resection
2021, Open Respiratory Archives
Prognostic value of KRAS mutation in patients undergoing pulmonary metastasectomy for colorectal cancer: A systematic review and meta-analysis
2021, Critical Reviews in Oncology/Hematology
Citation Excerpt :
The results of quality assessment of prospective studies were presented as a risk of bias graph and a risk of bias summary figure in Supplement 5. A total of 60 studies reported OS and HR with 95 % Cl data according to clinicopathological or biological parameters (Schweiger et al., 2016; Menna et al., 2018; Hachimaru et al., 2016; Bhullar et al., 2019; Corsini et al., 2019; Renaud et al., 2015a; Ghidini et al., 2016; Passot et al., 2018; Nelson et al., 2019b; Renaud et al., 2019a, b; Davini et al., 2020; Mammana et al., 2021; Shimizu et al., 2019; Jarabo et al., 2018; Rapicetta et al., 2019; Imanishi et al., 2019; Sponholz et al., 2018; Al-Ameri et al., 2018; Renaud et al., 2017; Okumura et al., 2017; Ihn et al., 2017; Murakawa et al., 2017; Fournel et al., 2009; Ampollini et al., 2017; Dudek et al., 2017; Shiono et al., 2018; Park et al., 2017; Pagès et al., 2016; Hernández et al., 2016; Guerrera et al., 2016; Embun et al., 2016; Kobayashi et al., 2016; Kim et al., 2016b; Cho et al., 2015; Suzuki et al., 2015; Nozawa et al., 2015; Renaud et al., 2015b; Yaeger et al., 2014; Salah et al., 2013; Hirosawa et al., 2013; Blackmon et al., 2012; Hwang et al., 2010; Zabaleta et al., 2011; Borasio et al., 2011; Koga et al., 2006). Twenty parameters, with the most consistency and availability, were collected to analyze their prognostic value on outcome after PM for CRC, including age, sex, Eastern Cooperative Oncology Group performance status (ECOG PS), Charlson Comorbidity Index (CCI), CEA, DFI, distribution of LM, extrapulmonary metastases, number and size of LM, T and N stage, lymph nodes invasion, KRAS and v-raf murine sarcoma b-viral oncogene homolog B1 (BRAF) mutations, type of surgery and resection, and adjuvant chemotherapy, location of CRC, total stage.
The purpose of the study was to evaluate whether KRAS mutation could be an independent prognostic biomarker in patients undergoing pulmonary metastasectomy (PM) for colorectal cancer (CRC).
A systemic review was performed by searching online databases to identify studies reporting overall survival (OS) and recurrence free survival (RFS) of CRC patients undergoing PM. Pooled HRs were calculated for OS and RFS.
A total of 15233 patients from 60 studies were included. Pooled analysis showed that KRAS mutation was associated with worse OS (HR: 1.86, 95 % Cl: 1.35–2.57) and RFS (HR: 1.68, 95 % Cl: 1.38–2.04). A significant effect on OS and/or RFS was also shown by other 18 factors.
This meta-analysis found that KRAS mutation is an important prognostic predictor for OS and RFS in CRC patients undergoing PM, supporting a comprehensive model including clinicopathological and biological factors for optimal patients selection and prognosis for surgical treatment.
Spanish Video-Assisted Thoracic Surgery Group: Method, Auditing, and Initial Results From a National Prospective Cohort of Patients Receiving Anatomical Lung Resections
2020, Archivos de Bronconeumologia
Citation Excerpt :
Given that the overall recruitment of the GEVATS project was 83%, we could conclude that our sample included, approximately, 50%of the anatomical lung resections performed in our country during the study period. Since the Spanish multicentre cooperative group dealing with videothoracoscopy for minor procedures (1573 patients, registered from 1996 to 1998), different nationwide surgical cohort studies and benchmarking projects have been developed in our country.12–16 Recently, the results of the Spanish multicentre prospective cohort study of the Group of Postoperative Complications of the Spanish Society of Thoracic Surgeons (GPC-SECT), has published the first known results about VATS implementation in Spain for lung cancer.
Our study sought to know the current implementation of video-assisted thoracoscopic surgery (VATS) for anatomical lung resections in Spain. We present our initial results and describe the auditing systems developed by the Spanish VATS Group (GEVATS).
We conducted a prospective multicentre cohort study that included patients receiving anatomical lung resections between 12/20/2016 and 03/20/2018. The main quality controls consisted of determining the recruitment rate of each centre and the accuracy of the perioperative data collected based on six key variables. The implications of a low recruitment rate were analysed for “90-day mortality” and “Grade IIIb-V complications”.
The series was composed of 3533 cases (1917 VATS; 54.3%) across 33 departments. The centres’ median recruitment rate was 99% (25–75th:76–100%), with an overall recruitment rate of 83% and a data accuracy of 98%. We were unable to demonstrate a significant association between the recruitment rate and the risk of morbidity/mortality, but a trend was found in the unadjusted analysis for those centres with recruitment rates lower than 80% (centres with 95–100% rates as reference): grade IIIb-V OR = 0.61 (p = 0.081), 90-day mortality OR = 0.46 (p = 0.051).
More than half of the anatomical lung resections in Spain are performed via VATS. According to our results, the centre's recruitment rate and its potential implications due to selection bias, should deserve further attention by the main voluntary multicentre studies of our speciality. The high representativeness as well as the reliability of the GEVATS data constitute a fundamental point of departure for this nationwide cohort.
Nuestro estudio buscó conocer el grado de implementación actual de la cirugía toracoscópica asistida por video (VATS, por sus siglas en inglés) para las resecciones pulmonares anatómicas en España. Presentamos nuestros resultados iniciales y describimos los sistemas de auditoría desarrollados por el grupo español de VATS (GEVATS).
Realizamos un estudio de cohortes prospectivo multicéntrico que incluyó pacientes que fueron tratados con resecciones pulmonares anatómicas entre el 20/12/2016 y el 20/03/2018. Los controles de calidad principales consistieron en determinar la tasa de reclutamiento de cada centro y la precisión de los datos perioperatorios recolectados en base a seis variables clave. Se analizaron las implicaciones de una baja tasa de reclutamiento para “mortalidad a los 90 días” y “complicaciones de grado IIIb-V”.
La serie estaba compuesta por 3533 casos (1917 VATS; 54,3%) en 33 servicios. La mediana de la tasa de reclutamiento de los centros fue del 99% (p25-p75: 76-100%), con una tasa de reclutamiento global del 83% y una precisión de los datos del 98%. No pudimos demostrar una asociación significativa entre la tasa de reclutamiento y el riesgo de morbi-mortalidad, pero se encontró una tendencia en el análisis no ajustado para aquellos centros con tasas de reclutamiento inferiores al 80% (usando los centros con tasas de 95-100% como referencia): OR = 0,61 para el grado IIIb-V (p = 0,081), OR = 0,46 para la mortalidad a los 90 días (p = 0,051).
Más de la mitad de las resecciones pulmonares anatómicas en España se realizan a través de VATS. Según nuestros resultados, la tasa de reclutamiento del centro y sus posibles implicaciones debido al sesgo de selección, deberían recibir más atención por parte de los principales estudios multicéntricos voluntarios de nuestra especialidad. La alta representatividad y la confiabilidad de los datos de GEVATS constituyen un punto de partida fundamental para esta cohorte nacional.
Lung Metastases
2019, Abeloff’s Clinical Oncology
In this chapter, we provide a comprehensive review of the pathogenesis, features, diagnostic evaluation, management, survival, and complications from lung metastasis. Lung metastasis may arise due to a combination of dietary influences, genetic and immunologic changes using normal cellular processes to assist in metastatic spread. Computed tomography with or without positron emission tomography is most frequently used to detect lung metastases since MRI is less sensitive than these modalities. Patients with isolated or oligometastatic disease can be considered for definitive management, including radiofrequency ablation (RFA), stereotactic radiation therapy, and surgical resection with non-surgical interventions typically offered for unresectable tumors or poor surgical candidates. Primary tumor types that commonly have lung metastasis include colon carcinoma, renal cell carcinoma, sarcoma, melanoma, head and neck squamous cell carcinoma, germ cell tumors, breast cancer, and giant cell tumor of bone, and survival after treatment is highly dependent on the primary site. Common complications of metastatic disease include malignant pleural effusions, managed with indwelling catheters or sclerotic agents, and bronchial obstructions, managed with endobronchial stenting, photodynamic therapy, and radiation therapy.
Combined Hepatic and Pulmonary Metastasectomies From Colorectal Carcinoma. Data From the Prospective Spanish Registry 2008–2010
2018, Archivos de Bronconeumologia
Citation Excerpt :
As far as we know it is the greatest surgical series of patients with liver and lung metastasectomy ever published. Some results referring different topics from the whole series area available.9–13 From our whole series, 24.4% of patients underwent liver metastasectomy (95.7% before lung surgery).
Resection of both liver and lung metastases from colorectal carcinoma (CRC) is a standard of care in selected patients with oligometastatic disease. We present here the analysis of the subgroup of patients undergoing combined surgery from the Spanish Group of Surgery of Pulmonary Metastases (PM) from Colorectal Carcinoma (GECMP-CCR-SEPAR).
We analyze characteristics, survival and prognostic factors of patients undergoing combined resection from March-2008 to February-2010 and followed-up during at least 3 years, from the prospective multicenter Spanish Registry.
A total of 138 patients from a whole series of 543 cases from 32 thoracic surgery units underwent both procedures. Seventy-seven (43.8%) resected liver metastases were synchronic with colorectal tumor. Median disease specific survival (DSS) from first pulmonary metastasectomy was 48.9 months, being three and 5-year DSS 65.1% and 41.7%, respectively. From CRC-surgery median DSS was 97.2 months, with 3 and 5-year DSS rates of 96.7% and 77%, respectively. Five-year DSS from pulmonary metastasectomy was 41.7% for patients with combined resection and 52.4% for those without hepatic involvement (P = .04). Differences disappeared when considering DSS from colorectal surgery. Carcinoembrionary antigen (CEA) before lung surgery over 10 mg/dl and bilateral PM were independent prognostic factors for survival (hazard ratio 2.4 and 2.5, respectively).
Patients with resection of PM of CRC with history of resected hepatic metastases presented significantly lower disease specific survival rates than those undergoing pulmonary metastasectomy alone. CEA before lung surgery and bilateral PM associated worse prognosis.
La resección de metástasis hepáticas y pulmonares del carcinoma colorrectal (CCR) es un tratamiento estándar para determinados pacientes con enfermedad oligometastásica. Presentamos el análisis del subgrupo de pacientes sometidos a cirugía combinada del Grupo Español de Cirugía de Metástasis Pulmonares (MP) de Carcinoma Colorrectal (GECMP-CCR-SEPAR).
Analizamos las características, la supervivencia y los factores pronósticos de los pacientes sometidos a resección combinada desde marzo de 2008 a febrero de 2010, con seguimiento durante al menos 3 años en el Registro Español, prospectivo y multicéntrico.
Se sometieron a ambos procedimientos 138 pacientes de una serie completa de 543 casos, procedentes de 32 unidades de cirugía torácica. Setenta y siete (43,8%) de las metástasis hepáticas resecadas eran sincrónicas al tumor colorrectal. La mediana de la supervivencia específica para la enfermedad (SEE) desde la primera metastasectomía pulmonar fue de 48,9 meses; las SEE a 3 y 5 años fueron del 65,1 y 41,7%, respectivamente. La mediana de la SEE desde la cirugía del CCR fue de 97,2 meses, con tasas de la SEE a 3 y 5 años del 96,7 y 77%, respectivamente. Las SEE a 5 años de la metastasectomía pulmonar fueron del 41,7% para los pacientes con resección combinada y del 52,4% para aquellos sin afectación hepática (p = 0,04). Las diferencias desaparecieron cuando se tenía en cuenta la SEE desde la cirugía colorrectal. Tener un nivel de antígeno carcinoembrionario (ACE) por encima de 10 mg/dl antes de la cirugía pulmonar y la presencia bilateral de MP fueron factores pronósticos independientes para la supervivencia (odds ratio: 2,4 y 2,5, respectivamente).
Los pacientes con resección de MP de CCR con antecedentes de metástasis hepáticas resecadas presentaron tasas de SEE significativamente más bajas que aquellos sometidos a metastasectomía pulmonar sola. El ACE antes de la cirugía pulmonar y la presencia de MP bilaterales se asociaron a peor pronóstico.

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Original articleGeneral thoracicCausal Model of Survival After Pulmonary Metastasectomy of Colorectal Cancer: A Nationwide Prospective Registry

Background

Methods

Results

Conclusions

Section snippets

The GECMP-CCR

Results

Comment

Ann Thorac Surg

J Thorac Oncol

Ann Thorac Surg

Ann Thorac Surg

J Thorac Oncol

Colon cancer, version 3.2014

J Natl Compr Canc Netw

Pulmonary metastasectomy in colorectal cancer: a prospective study of demography and clinical characteristics of 543 patients in the Spanish colorectal metastasectomy registry (GECMP-CCR)

BMJ Open

Morbidity and mortality in a large series of surgical patients with pulmonary metastases of colorectal carcinoma: a prospective multicentre Spanish study (GECMP-CCR-SEPAR)

Eur J Cardiothorac Surg

A note on the generalized information criterion for choice of a model

Biometrika

Original article
General thoracic
Causal Model of Survival After Pulmonary Metastasectomy of Colorectal Cancer: A Nationwide Prospective Registry