The effectiveness of surgical treatment of lung cancer in Polish academic and nonacademic centers

Introduction

Of all malignancies, lung cancer is one of the leading causes of mortality. Each year, approximately 1.2 million people die from lung cancer, and the 5-year survival does not exceed 20% (1). For years, the treatment of choice for early-stage non-small-cell lung carcinoma (NSCLC) has been surgery, which includes tumor and lymph node resection (2). Not only overall survival but also factors such as shorter hospitalization, fewer postoperative complications and lower mortality are related to treatment (3-8). It has been debated for years whether these factors are affected by the volume, type of the hospital or by the experience of the surgeon (3-5,8). However, cut off values, which divide centers into higher and lower levels, have varied between studies and are not always well explained (8). Additionally, some studies in which the majority of surgeries were performed outside the United States did not confirm the impact of hospital volume on the efficacy of surgery for lung cancer (3-7).

Approximately 22,000 Poles are diagnosed with lung cancer each year, and it is the main cause of death in both sexes. Most patients with resectable lung cancer undergo surgery in high volume, accredited thoracic surgery departments. In Poland, the impact of hospital volume or academic status on lung cancer surgery efficacy has not yet been examined (9).

Most studies have examined the impact of the number of surgeries performed on treatment outcomes (10-13). In our study, we investigated the effect of academic (ACA) and nonacademic (non-ACA) status of hospitals on complications, mortality and survival. To our knowledge, this is the first sizable study that discusses this matter in our region of Europe. We present this article in accordance with the STROBE reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-752/rc).

Methods

Ethical statement

This study was approved by the ethics committee of the National Research Institute of Chest Diseases, Warsaw, Poland (No. 96/2021). Patients signed an informed consent form to be included in the database. This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).

Patients

The data were collected retrospectively from a database of the Polish Lung Cancer Study Group (PLCSG), which includes data from 30 thoracic surgery centers and contains information on every lung cancer surgery in Poland. Thoracic surgery centers are obliged to provide all information regarding patient data, advancement of the tumor, technique and extent of the surgery, complications and follow-up visits. All thoracic centers are required to collect data, which are transferred to the central register, stored and analyzed. A total of 31,777 patients who were surgically treated for NSCLC between 2007 and 2020 were included in the study. We divided the cohort based on the type of hospital. The ACA subgroup is defined as the highest referential center that participates in the training of specialists in the field of thoracic surgery or is dedicated to research activities. Additionally, ACA centers are often part of a university or medical school. Notably, the number of procedures performed each year does not correlate with the division into ACA and non-ACA subgroups. Based on these criteria, we identified 9 ACA centers with 16,345 patients and 21 non-ACA centers with 15,432 patients. The 8th edition of the TNM classification was used to define staging, whereas the lymph node stations were described using the International Association for the Study of Lung Cancer lymph node map (14,15).

Inclusion and exclusion criteria

The following patients were included in the study: operation between 2007 and 2020 with confirmed NSCLC who received radical surgery (R0) with at least 6 nodes retrieved according to the European Society of Thoracic Surgeons guidelines (2) and with complete data in the database. The following patients were excluded: non-radical resection (R1) or whose data were lost or who failed to complete follow-up.

Due to the small number of procedures or the lack of precise data on the scope of the procedure, we have excluded some specific surgical procedures (e.g., middle lobe, segment and wedge lobectomy).

Preoperative staging

Prior to the surgery, tumor staging in patients was assessed using the following tests: chest X-ray, computed tomography (CT) and magnetic resonance imaging. When the lymph nodes were enlarged more than 10 mm, the patients underwent more invasive procedures (such as endobronchial ultrasound with guided transbronchial needle aspiration (EBUS-TBNA), endoscopic ultrasound fine-needle aspiration, mediastinoscopy or mediastinotomy). Positron emission tomography-computed tomography (PET-CT) examination was not frequently performed in the first years of the study period (only 23% of patients from 2008–2010), but by the end of this period [2019–2020], the vast majority of patients (78%) had PET-CT before surgery.

Follow-up

The patients consulted with a surgeon within the first 3 weeks after surgery. Additionally, every 3–5 months for a period of 5 years, they reported for follow-up examinations, in which they had a chest X-ray, CT or PET-CT in justified cases. The pattern of failures were assessed using follow-up imaging studies and data obtained from procedures such as bronchoscopy, endobronchial ultrasound guided biopsy, endoscopic ultrasound fine-needle aspiration, transthoracic biopsy, mediastinoscopy, and mediastinotomy. Lymph node failure in the hilum or mediastinum was defined as a new or enlarging lymph node that showed excessive metabolism in PET-CT, or its short axis in CT was at least 10 mm.

Statistical analysis

In the data analysis, continuous variables were summarized using the mean and standard deviation as well as the median and range of values. Categorical variables were summarized using the frequency for each subgroup and the proportion of the considered population. Statistical significance of differences between the groups was determined using the Mann-Whitney U-test and Chi-squared test for continuous and categorical variables, respectively. Moreover, for every group and pathological N stage, the average number of lymph nodes involved and the examined lymph stations were reported. To assess the multivariable correlation between preoperative variables and the ACA and non-ACA groups, logistic regression was used. Survival curves were estimated with the Kaplan-Meier method, and the log-rank test was used to compare differences between groups. The Cox proportional hazards model was applied to univariable and multivariable analyses to determine the patients’ risk of death. The selection of predictive variables was performed based on univariable models (P value <0.05). Based on these results, the following factors were determined to be important in the univariable analysis: sex, age, stage of lung cancer, pathological T stage, pathological N stage and surgical approach, resection type, histopathological recognition, mediastinoscopy, comorbidities [cardiac infarction, chronic obstructive pulmonary disease (COPD), coronary disease, circulatory system disorders and kidney disease], statistics for examination of N1 lymph station (number of examined nodes). All tests were two-sided, and a P value <0.05 was considered statistically significant. For pairwise comparisons of more than two groups, an FDR adjustment was applied. All analyses were performed using the survival and survminer packages in R software.

Results

Population characteristics

The study analyzed a cohort of 31,777 patients including 11,460 women (36.1%) and 20,317 men (63.9%). In the non-ACA group, a significantly higher percentage of patients had insulin-dependent diabetes (4.9% vs. 2.9%, P<0.001), nervous system disorders (1.4% vs. 0.4%, P<0.001) and hypertension (47.4% vs. 45.0%, P<0.001). However, in the ACA group, there was a significantly greater percentage of patients with COPD (26.4% vs. 21.1%, P<0.001). The most frequently diagnosed histological type in both groups was adenocarcinoma [54.4% of patients in the ACA group, 52.2% of patients in the non-ACA group (P<0.001)]. In the ACA group, resection using the video-assisted thoracic surgery (VATS) was performed significantly more often than in the non-ACA group (23.6% vs. 14.2%, P<0.001). All clinical data is provided in Table 1.

Hospital characteristics

The median number of anatomical lung resection procedures performed per year for lung cancer during the period 2007–2020 was 97.5 for ACA (mean 133.98) and 54.5 for non-ACA (mean 66.5) (Table 2, Figure 1). In 3 out of 9 ACA hospitals, the number of annual resections exceeded 200 procedures during the period 2013–2019. In the non-ACA group, only 1 out of 21 hospitals, over 200 procedures were performed annually from 2015 to 2018.

Figure 1 Number of operations per year in academic and nonacademic centers.

Preoperative work-up and postoperative staging

In the ACA group, preoperative diagnostics included PET-CT and EBUS-TBNA in 49.8% and 30.5% of patients, respectively, and these values were significantly higher than those in the non-ACA group (33.1% and 16.4%, respectively, P<0.001). The pN feature analysis in the ACA group showed significantly lower proportions of pNx than those in the non-ACA group (9.2% vs. 17.1%, respectively, P<0.001).

According to results of logistic regression, patients with COPD, higher pT stage, higher pN stage, histology of squamous-cell cancer, higher number of N1 or N2 lymph nodes examined, or qualified for VATS; were more likely to be operated in ACA (P<0.01). See Table S1.

Postoperative morbidity and mortality

The rates of postoperative complications in the ACA and non-ACA groups were 30.7% and 33.8%, respectively (P<0.001). Mortality during hospitalization for the ACA and non-ACA groups was 1.1% and 1.2%, respectively (P=0.62). In the non-ACA group, the mean number of days from surgery to discharge and the entire period of hospitalization was significantly higher than those in the ACA group (9.26 and 14.0 days vs. 7.94 and 12.8 days, respectively, P<0.001). Detailed data are presented in Table 3.

Overall survival

The median follow-up time for the entire group was 2,369 days. Overall, the 5-year survival was not significantly different (P=0.2) between the ACA (56%) and the non-ACA group (56%) (Figure 2). Regarding the type of surgery, significantly worse long-term results were found for pneumonectomy than for upper and lower lobectomies (41%, 60% and 56%, P<0.001, respectively). The survival rates for pN0, pN1 and pN2 in the ACA vs. non-ACA groups were 64% vs. 63% (P=0.02), 45% vs. 47% (P=0.08), and 33% vs. 31%, respectively (P=0.36). With regard to the pT feature, no significant differences were found between the groups at any stage except pT2a. All survival data are presented in Table 4. Detailed data on 5-year survival regarding clinical and pathological stage are presented in Table S2 and Figure S1.

Figure 2 Impact of the type of hospital on overall survival.

Discussion

The indicators determining the results of the treatment are the percentage of postoperative complications, mortality and long-term survival depending on the stage of advancement (3-8). Theoretically, academic hospitals have an advantage over nonacademic hospitals in that they have a more highly qualified staff of surgeons and appropriate diagnostic facilities and infrastructure, including intensive care units. In the literature, the most common division is between high-volume and low-volume hospitals, but the appropriate number of treatments per year has not been established thus far (3-5). The division into high-volume and low-volume hospitals does not correspond to the division into ACA and non-ACA groups, as shown in our results. The study by Bernard et al. showed that a statistically significant threshold for the number of procedures is 70 resections per year, where the risk of death within 30 days decreases by 31% compared with centers performing <10 operations. Of these, 60% of university hospitals were classified as high volume (<70), whereas only 5.6% of nonacademic hospitals were included in this group (10). However, the work of Lüchtenborg et al. showed that in centers with a volume ≥150 resections per year, the risk of survival was significantly decreased compared with centers with <70 resections per year, particularly in the early postoperative period (11). Similar results were presented by Møller et al., who found that mortality statistically significantly decreased in centers with >190 procedures per year compared with those performing 77–112 resections (12). A different view was presented by Schillemans et al., which stated that the significant risk of death within 2 months of surgery increases by 13% with <10 resections, but showed no difference above 10 procedures. Similarly, 3-year survival with <10 treatments is significantly worse, whereas >10 treatments showed no significant improvement (13). In the meta-analysis by von Meyenfeldt et al. covering 19 studies, centers performing <5 and even <60 resections qualified as low-volume centers. The cut-off value for high-volume hospitals varied from >20 to >129.4 procedures per year (8). In this study, it was shown that survival is better in high-volume hospitals; however, it did not reach statistical significance.

The data cited above still do not answer the question of what impact teaching facilities (TF) have on the results of surgical treatment of lung cancer. In a study by Cheung et al., the results of treatment in centers with TF and nonteaching facilities (NTF) were analyzed. In the TF centers, a higher percentage of patients were treated for arterial hypertension, congestive heart failure, cardiac arrhythmias, rheumatoid arthritis, and chronic pulmonary disorders (16). In the current study, in the non-ACA group corresponding to NTF, a higher percentage of patients had insulin-dependent diabetes, nervous system disorders and arterial hypertension. However, the ACA group showed a higher percentage of COPD patients. Similarly, differences in nicotine consumption were shown with a predominance in the non-ACA group.

As in the previously cited study, more patients were operated on in ACA centers with locally advanced lung cancer, but the rate of pneumonectomy was lower than that in non-ACA centers (11.6% vs. 15.4%, P<0.001). In the study by Cheung et al., the rates of pneumonectomy in TF and NTF were 10.9% and 14.1%, respectively (P<0.001) (16). However, in the work of Sioris et al., in both groups, the rate of pneumonectomy was similar, although it occurred at an unexpectedly high level (27.7% vs. 27.2%) (7). In the present study, a significantly higher percentage of patients treated at ACA centers underwent VATS surgery. There were statistically significant differences with a predominance in the percentage of patients who underwent PET-CT and EBUS-TBNA in the ACA group. The demonstrated differences undoubtedly influenced the higher percentage of pNx in the non-ACA group.

The present study showed a significantly higher complication rate in the non-ACA group than in the ACA group, but without significant differences in mortality. However, in the ACA group, a reduction in hospitalization time and postoperative stay was found. In the study by Meguid et al., the percentage of fatal complications during hospitalization was significantly higher in teaching hospitals than in nonteaching hospitals (9.9% vs. 8.1%, respectively, P<0.001) and was highest in the group of patients who underwent pneumonectomy (7.6% vs. 9.5%, P=0.025) with the rate of pneumonectomy being lower than in the present study (9.9% and 8.1%) (17).

In the meta-analysis by Attaar et al. the main reasons for prolonged air leak are decreased spirometric values and smoking (18). Patients operated on in ACA centers had statistically more pronounced prolonged air leak than in non-ACA centers. Moreover, lower spirometric values were noted in ACA compared to non-ACA group, and the number of COPD patients was greater in the ACA group. On the other hand, the number of smokers was statistically higher in the case of patients operated on in nonacademic centers.

Long-term survival is undoubtedly the key parameter for assessing the influence of the type of center on the quality of surgical treatment of lung cancer. In a study by Bach et al., significantly higher 5-year survival was found in teaching hospitals (42% vs. 34%, P<0.001) (19). Similar conclusions have been reached in most studies devoted to this topic (8,10). Most studies show a rather strong correlation between long-term survival and the volume of operations performed in a given center (13). However, in our study, 5-year survival was not significantly different in ACA and non-ACA centers, despite significant differences in postoperative staging between the groups.

Despite the differences in perioperative care in both types of centers, the long-term results were similar. There are undoubtedly visible shortcomings in preoperative diagnostics in non-ACA centers, manifested as limited access to PET-CT and EBUS-TBNA. There are also visible shortcomings in the training of surgeons, resulting in a much lower rate of VATS surgery. This, in turn, translates into a higher percentage of postoperative complications and longer hospitalizations.

The present work has several important limitations. First, it is a retrospective study based on data from the PLCSG surveys, which entails the possibility of errors in the analyzed data. The study also did not consider the volume in individual centers, and as we showed, the division into ACA and non-ACA centers did not correspond to the division into high-volume and low-volume hospitals. Moreover, the analysis conducted in our study is based on the Polish system of organizing chest surgery centers, in which lung cancer surgery is performed only by specialists in the field of thoracic surgery. Therefore, the conclusions resulting from this analysis cannot be generalized to organizational systems in other countries, although a high degree of similarity is certainly visible.

Conclusions

In summary, the present study showed that ACA centers are characterized by better preoperative diagnostics, a higher rate of VATS, a lower percentage of postoperative complications and a shorter hospitalization than non-ACA centers. However, there were no statistically significant differences in 5-year survival.

Acknowledgments

Principal investigators of institutions participating in this study include Piotr Gabryel (Poznan University of Medical Sciences, Poznan, Poland), Piotr Rudzinski (National Research Institute of Chest Diseases, Warsaw, Poland), Robert Wlodarczyk (National Cancer Center, Warsaw, Poland), Wojciech Laudanski (Bialystok University of Medical Sciences, Bialystok, Poland), Tomasz Marjanski (Medical University of Gdansk, Gdansk, Poland), Krzysztof Buczynski (Lublin University of Medical Science, Lublin, Poland), Konrad Pawelczyk (Lower Silesia Center of Lung Diseases, Wroclaw, Poland), Roman Lewandowski (Zabrze Medical University of Silesia, Katowice, Poland), Marcin Wawrzycki (Lodz University of Medical Science, Lodz, Poland), Andrzej Bala (Department of Thoracic Surgery, Bydgoszcz, Poland), Krzysztof Brulinski (Center of Pulmonology and Thoracic Surgery, Bystra Slaska, Poland), Arkadiusz Gebski (Department of Thoracic Surgery, Czerwona Gora, Poland), Piotr Talar (Krakow University of Medical Sciences, Krakow, Poland), Mariusz Lochowski (Department of Thoracic Surgery, Lodz, Poland), Janusz Golota (Olsztyn University of Medical Science, Olsztyn, Poland), Anna Zel (Center of Lung Diseases, Otwock, Poland), Dariusz Preis (Department of Thoracic Surgery, Prabuty, Poland), Kazimierz Wojtun, Janusz Rybka, Adam Lis, Grzegorz Kobak (Center of Lung Diseases, Rzeszow, Poland), Michal Bielewicz (Szczecin University of Medical Sciences, Szczecin, Poland), Pawel Pryszczek (Department of Thoracic Surgery, Zielona Gora, Poland), Michal Wilkojc (Department of Thoracic Surgery, Zakopane, Poland), Mariusz Bella (Bydgoszcz University of Medical Sciences, Bydgoszcz, Poland), Mariusz Chabowski (Military Clinical Hospital with Polyclinic, Wroclaw, Poland), and Joanna Nogaj (Kielce University of Medical Science, Kielce, Poland).

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-752/rc

Data Sharing Statement: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-752/dss

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-752/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-752/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the ethics committee of the National Research Institute of Chest Diseases, Warsaw, Poland (No. 96/2021), and patients signed an informed consent form to be included in the database.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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