In 2010, 1 527 000 deaths1 were attributed to lung cancer (LC), one of the 10 major causes of death worldwide, and it seems very likely that this figure will increase in the coming years, given the trends observed in global tobacco consumption. In a large part of the Western world, a reduction in the specific mortality rate due to LC is being observed in men, including in Spain, although at a somewhat slower rate. Nevertheless, LC continues to be the principal cause of death from tumour disease in men and the third most common in women: 20 755 men and 3452 women in 2010, according to data from the Spanish National Institute of Statistics (INE).2

Despite advances in the knowledge of LC biology and the modest improvements in survival obtained with new drugs and new treatment regimens, LC remains a fatal disease in a high proportion of cases, and only patients diagnosed in the early stages have curative options with radical surgery or chemotherapy plus radiotherapy. Among the criteria for tumour classification, one of the most important is still the anatomical extension of the disease, expressed according to the familiar TNM classification, with its well-established and invaluable prognostic and treatment guidelines.

Since 1966, when the Union for International Cancer Control proposed the first TNM classification for LC, there have been several editions, each with its successive improvements and refinements. The 7th and latest version, drawn up and published by a committee of the International Association for the Study of Lung Cancer (IASLC) and adopted by the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) and other international societies, represented a substantial advance with respect to methodological rigour and the universality of the classification. In this project, unlike those of previous editions, not only patients undergoing surgery, but also all types of patients from all over the world, regardless of the treatment administered, were included.3,4 The SEPAR Bronchogenic Carcinoma Cooperative Group (GCCB) participated in this project with the inclusion of approximately 3000 patients, making important methodological contributions.5,6

Despite the improvements introduced in the 7th edition of the IASLC TNM, the authors recognised certain limitations, derived basically from the fact that the studies used as source data (clinical trials, institutional registries, patient series from various clinical settings) were not specifically designed for analysing the prognostic value of the degree of anatomical extension. For this reason, the IASLC Staging Committee drew up a protocol for prospective data collection, designed expressly for the validation and possible further refinement of the TNM classification. The protocol is long and detailed and is open to interested specialists around the world, who have been able to participate in the project by registering their patients in the IASCL international database which was set up and run by Cancer Research and Biostatistics7 (CRAB).

Although the data collection protocol is especially detailed with regard to anatomical staging, many other types of data are also collected (biological, laboratory and functional parameters, diagnostic procedures, tumour subtype, treatment administered and follow-up). For analysis of the prognostic value of the variables, survival time remains to be determined from the patient follow-up, which is still underway.

The aim of this article, now that the initial data collection phase has been completed, is to describe the most important findings derived from the patients included by our SEPAR (GCCB-II) group as part of the international IASLC project.

When the IASLC project was announced, a Coordinating Committee was organised by the SEPAR Oncology area, which, as of June 2007, contacted practically all the departments of our society, offering them the chance to participate in the project and help with the paperwork and authorisations required for participation. This registry project was accessible to all from the very beginning and, following the IASLC committee guidelines, allows the inclusion of any patient with a new diagnosis of histologically confirmed LC, from the date of entry in the study, regardless of the treatment given (including the option of palliative care only).

This is a prospective, observational, multicentre, data collection study of patients with LC, for participation in the international IASLC project aimed at producing the next TNM classification.

Although the number of patients included by the end of 2012 was 2615, only the data recorded up to 30 September 2011 are presented, as the date on which sufficient data for this first description were available.

In the study, 2419 patients were included in 28 centres:

• (a)

  12 hospitals registered only patients treated with surgery.

• (b)

  10 hospitals included only patients without surgical treatment.

• (c)

  6 hospitals included patients undergoing any treatment (surgical or other).

The characteristics of age, sex and smoking habit are shown in Table 1.

Table 2 shows the co-morbidity and performance status results, according to the IASLC protocol, distributed by sex. As can be observed, men had higher percentages of comorbidity for all diseases (except renal failure) and a greater incidence of weight loss and poor performance status.

With regard to the histological subtype (Table 3), epidermoid carcinoma was the most common type among men. However, adenocarcinoma is the most common tumour in women and overall. In section B of Table 3, the proportion of adenocarcinomas is compared as a function of smoking habit. It can be seen that this disease subtype is significantly more prevalent in subjects who never smoked, whether male or female.

The number and percentage of the most common diagnostic tests and staging are shown in Table 4. Chest and upper abdomen CT scans and fibrobronchoscopy were carried out in nearly all patients. Among the tests performed for detecting possible metastasis, a PET or PET/CT was carried out in over 50% of all patients (whether they underwent surgery or not).

Distribution according to TNM staging (7th edition) is shown divided into two groups (Table 5): surgical patients (cTNM and pTNM) and non-surgical patients (cTNM). As can been seen, at the time of data analysis, insufficient data were available in some cases, so the figures presented do not reflect the total number of patients included.

Finally, Table 6 provides a very brief summary of the therapeutic modality applied and, within the surgical option, the type of intervention.

We would first like to point out that the patients included in this series, whether due to the study objective (analysis of prognostic factors for validation of the TNM classification) or the design (open study with inclusion of different patients depending on the centre: some surgical; others undergoing different treatments), are not and nor are they claimed to be a representative sample of all the epidemiological aspects of the LC patient population in Spain. However, we do think it is feasible and useful to compare some features with other similar papers with a view to making some inferences, particularly with regard to trends.

As already observed in some recent studies in Spain,8,9 the proportion of women with respect to the total number of LC cases is increasing rapidly. In the SEPAR GCCB registry from 1993 to 1997, the proportion of women was 7%6; in the Spanish Epicli-CP multicentre study, in 2003, it was 10.5%8; in a registry in the Spanish regions of Castilla-León and Cantabria carried out in 2007, it was 12.9%,10 and in a multicentre series of stage i surgical patients, it was 13%.11 In our registry, the proportion of women was 16.2%. These results are fully consistent with the LC mortality trends recorded by the INE,2 which show a clear increase in LC deaths in women compared to a stabilisation in men. Despite this trend, attributable to the increase in tobacco use among women, the percentage of non-smokers among women with LC (46.1%) is very high and much greater than that among men (4.1%), although it is less than that recorded among women with LC in the Epicli-CP study (68%).8 If the smoking trends in Spain (32.5% of smokers in the male population and 22.2% of females, according to the National Health survey in 2009) are taken into account, particularly with regard to the increase in female smokers, a continued increase in the rate of LC among women in the coming years can be predicted.

Since LC usually occurs in elderly smokers and ex-smokers, the high rate of comorbidities, particularly of the cardiorespiratory type, is unsurprising. In our cases, the incidence of both cardiac-related and respiratory concomitant diseases was greater than 40% (Table 2). A large part of this comorbidity is attributable to long-term smoking. For this reason, it is understandable that men with a diagnosis of LC (96% of whom are smokers or ex-smokers) have a greater percentage of comorbidities than women (54% among smokers and ex-smokers). This higher incidence of comorbidities may also explain, at least in part, why males have a poorer performance status at the time of diagnosis. Given the differences in this respect in the data collection protocols of the different publications, it is difficult to draw comparisons.9 In a large series from the Mayo Clinic, the authors report COPD in 32.9% and heart disease in 11.1%12; in the GCCB group registry between 1993 and 1997, the authors observed that 50% of their cases had COPD,13 a somewhat higher figure, but not very different from ours.

With regard to tumour subtype, adenocarcinoma is the most common form in most countries and its incidence appears to increase in younger cohorts.14–16 In Spain and in some other countries in the south of Europe, perhaps due to the smaller proportion of women with LC compared to other regions, epidermoid carcinoma has been reported as the most common.9 In our study, we found for the first time, in a multiregional study in Spain, a higher rate of adenocarcinomas in the overall patient set. This trend is influenced without doubt by the growing proportion of women. As can been seen in Table 3, up to 69% of the women with LC who never smoked had adenocarcinoma, but even among smokers and ex-smokers this percentage was over 50%. Epidermoid carcinoma is still predominant among men, but when the small group of non-smokers is examined, adenocarcinoma, with 51.2%, represents the majority. In Castilla-León and Cantabria, although the percentage of this tumour subtype was lower among women, the same difference in histological distribution depending on smoking habit was observed.10

With regard to staging, the 7th edition of the TNM classification3,4 was used for this study. The distribution of stages is presented separately for patients undergoing surgery and those receiving other treatments, since, as mentioned above, our overall patient set is not representative of the Spanish LC population. Indeed, given the proportion of hospitals that provided only surgical patients, it was to be expected that the complete set would show marked over-representation of surgical cases, as has happened (Table 6). Moreover, comparison of the results with other papers, even if analysed by subgroups (surgical patients versus non-surgical patients), is difficult, since many of the publications used the previous TNM classification (6th edition, Mountain).

Even with these limitations and the necessary reservations, grouping stages into 3 categories (local, locoregional and metastatic), in the same way as the US epidemiological cancer surveillance group (SEER) distributed their data,17 it is worth pointing out that local LCs (stage ia-iib) in our series account for 77% of those undergoing surgery, a higher percentage than that recorded by the GCCB group between 1993 and 1997 (around 60%)6 and very similar to that obtained by the Icelandic national registry of patients undergoing interventions between 1994 and 2008 (78.7%).16 It appears, at least in Spain, that among operated patients, there is a growing proportion of patients presenting with early stages, compared to locally advanced stages (iiia and iiib). In accordance with this, the percentage of pneumonectomies with respect to the total number of surgical procedures has fallen: 29.5% in the GCCB registry of 1993-199718 and 12% in the current series (Table 6). However, in the above-mentioned Icelandic study, when the period under study (1994–2008) was divided into three stages, with the aim of detecting trends, the authors did not detect any changes either in the proportion of early stages or in the number of pneumonectomies performed: 12.9% in 1994–1998 and 16.1% in 2004–2008. Although this difference in trends may be due to other reasons, it should be pointed out that PET was not performed in any of the cases during the period examined by these authors.16

With regard to patients who received other treatments (chemotherapy, radiotherapy or palliative care only), the proportion of cases with stage iv disease (61.6%) is higher than in the majority of studies of series around the world: 27% in Slovenia in 199619; 41% in Spain (Epicli-CP study, 2003)8; 34.2% in the Mayo Clinic experience 1997–200312; and 56% in the US epidemiological surveillance registry.17 The higher percentage observed in our series may be explained in part by the fact that we excluded surgical patients from this group. Moreover, the criteria for participation and inclusion in our registry limited comparability with other global LC studies, but we would like to point out that, unlike most large series, in ours, given the central objectives of the study (a precise TNM evaluation), special emphasis has been placed on more exact staging tests, as can be seen in Table 5. In fact, PET and PET/CT were performed in more than half of the patients. It is quite possible that this has contributed to the detection of a not insignificant subgroup of cases with stage IV disease and silent metastases which would have gone unnoticed with less exhaustive staging procedures.

We hope that the detailed analysis of the data recorded by our group, together with those from other countries which have contributed and continue to contribute to the international IASLC project, allows us, once the patients’ survival time has been determined, to continue our advances towards the common objective of achieving an even more robust and precise TNM classification. Nevertheless, without in any way taking away from the importance of this classification of anatomical disease extension, we are aware that this is only one more aspect of the tumour disease and a consequence of its biological properties, the molecular substrate of which is only just beginning to be revealed. For this reason, we have reached agreements with other Spanish research groups, which have the necessary resources for participating in projects for the genomic and molecular analysis of resected tumour samples. We hope that, in this way, the molecular information can be combined with the detailed clinical and anatomical extension data collected from our patients.

The authors declare no conflict of interests.