Long-Term Quality of Life After Surgical Resection for Non-Small Cell Lung Cancer: The Role of Sublobar Resection

Abstract

Introduction: Surgical resection is the most effective therapy for patients with early non-small cell lung cancer (NSCLC). Impact on quality of life (QoL) includes a period until return to work, perioperative complications and development of physical sequelae. Lobectomy is the standard procedure. However, sublobar resections have shown similar oncological outcomes preserving healthy parenchyma. We analyze if sublobar resection is associated wiht less deterioration of QoL. Methods: We performed a retrospective analysis of patients undergoing surgical resection for NSCLC between 2017 and 2019. Cases were classified according to type of resection (sublobar vs lobectomies, bilobectomies and pneumonectomies). A survey with questions related to outcomes and QoL and occupational issues was performed. Results: A total of 169 answered the survey and were followed for 36 months. Segmentectomy was performed in 69 patients (40.9%). Lobectomy was the main type of resection (56.2%). Fatigue during walking was less common in patients undergoing sublobar resections (55.1% vs 72.7%; p = 0.02). No other differences were detected in temrs of QoL between both groups. Changes in familiar relationship after surgery were higher in patients under 70 years old. Most patients had not resume their work activities at the time of consultation. Conclusion: Feeling of fatigue while walking was lower in patients undergoing sublobar resections. Changes in familiar relationship were higher in younger patients. QoL was similar in both groups.

1. Introduction

Non-small cell lung carcinoma (NSCLC) is the most widespread oncological disease, with 1.8 million new cases every year. It is mostly diagnosed as an advanced disease, with a global five-year average survival rate of under 15% [1]. Moreover, it is the main cause of mortality related to cancer worldwide, with approximately 1.6 million deaths every year. In Spain, it is estimated that 32,768 new cases will have been diagnosed during 2024, according to the Spanish Cancer Registry Network (REDECAN) [2].

Unfortunately, due to the usually vague and non-specific symptoms during the early stages of the disease, most patients are diagnosed at stages IIIB or IV. However, early-stage or even locally advanced NSCLC shows good survival rates and a high likelihood of being cured, with surgical resection usually being the main therapeutic tool with a curative purpose when not the only option. Multidisciplinary approaches with perioperative chemotherapy (ChT), immune checkpoint inhibitors (ICIs), or radiotherapy (RT) accomplish good outcomes in selected cases, whereas advanced stages are referred for systemic treatment, with surgery considered only in exceptional cases [3].

The types of surgical resection are sublobar (wedge resection or anatomical segmentectomy), lobectomy, bilobectomy, and pneumonectomy. Lobectomy has been the standard treatment, whereas sublobar resection has been traditionally considered suboptimal from an oncological point of view. However, two randomized clinical trials have recently shown that after 10 years of follow-up, sublobar resection achieves similar disease-free survival rates in patients with localized peripheral adenocarcinomas with diameters under 2–3 cm [4]. A significant proportion of patients with a diagnosis of NSCLC show limited lung function. The loss of pulmonary capacity depending on the extension of resection has been largely investigated, with unsubstantial conclusions. The way these oncological processes involving radical and aggressive therapeutic approaches impact patients, not only physically but also in terms of psychological, social, and occupational aspects, is rarely analyzed [5,6,7,8,9]. In addition to surgical and medical complications, and frequently because of them, patients need different degrees of adaptation in their lives and changes in behaviors after the process [7,8,9,10,11,12,13]. It is worth analyzing whether resections preserving normal pulmonary parenchyma (sublobar) may be associated with easier and faster holistic recovery without jeopardizing oncological quality.

The use of instruments to assess quality of life (QOL) has become an area of interest for these patients. The methodology of this kind of study is focused on collecting information by using questionnaires that analyze patient self-perception regarding their QOL of life, including physical, psychological, and social environments. The concept of health-related quality of life (HRQOL) has evolved to encompass not only functional impairment but also broader lifestyle consequences for the patient, including their personal perceptions and interpretations. Instruments for evaluating QOL are classified as generic and specific, focusing the latter on a particular aspect or population. Despite its social and healthcare significance, the conclusions of investigations into QOL in lung cancer remain unclear [14,15,16]. The aim of our study is to analyze if sublobar resections have a less significant impact on short- and medium-term QOL than standard major resections from lobectomy onward among patients with NSCLC.

2. Patients and Methods

2.1. Patients

We conducted a retrospective study based on a prospectively collected database, including all patients with a diagnosis of NSCLC who underwent surgical resection from January 2017 to November 2019. To focus on long-term survivors, only patients with a follow-up of at least 36 months and who remained free from oncological disease were considered for the analysis. Patients who agreed to participate in the study and answered the survey signed the informed consent specifically developed for the project (Supplementary File S1).

2.2. Method

2.2.1. Variables

The database includes demographic and clinical data of the patients, the presence of other cancers, and the use of neoadjuvant or adjuvant ChT, RT, or targeted therapies. Perioperative data were also collected, with the patients being classified into two cohorts regarding the extension of surgery: group 1 represents patients who underwent sublobar resection (SR), and patients in group 2 underwent lobectomy, bilobectomy, or pneumonectomy. Postoperative data included histological subtypes, pathological staging, and the presence of postoperative complications and oncological outcomes.

Follow-up was conducted in outpatient thoracic surgery clinics according to the standard protocol, including chest-computed tomography (CT) scans every 3–6 months for the first two years and subsequently every six months until five years had been completed.

2.2.2. Survey

To assess the long-term status of each patient, a survey was developed, including dichotomous (YES/NO) questions and some open-ended responses. The survey focused on patients’ QOL, addressing their physical condition after surgery, the need for assistance, their self-perception of QOL, and their return to work (Supplementary File S2). The surgical team, either through a face-to-face interview or by telephone call, conducted the survey.

The self-designed QoL questionnaire consists of 12 questions. The first question, “On a scale of 0 to 10 (0 being no pain and 10 being the most pain), how much pain did you experience postoperatively?” refers to the Visual Analog Pain Scale (VAS). The remaining questions were independently validated and adapted to the study context and translated into QOL information for different daily activities and roles undertaken by patients during the follow-up. For the objectives of the research, we used a confidence level of 95% and a margin of error of 5%, with an estimated sample size of 167 patients answering the whole survey.

2.2.3. Statistical Methods

Qualitative variables are presented with the distribution of frequencies. Quantitative variables showing an asymmetric distribution are summarized using the median and interquartile range (IQR). The association between qualitative variables and the study groups (SR and REST) was analyzed using the χ² test or Fisher’s exact test, as required. The comparison of the Visual Analog Scale (VAS) scores between study groups was performed using the non-parametric Mann–Whitney U test. The relationship between study groups and mortality was explored through survival analysis using the Kaplan–Meier method, with the log-rank test employed to compare survival functions. A multivariate logistic regression analysis was carried out. A level of significance of 5% was accepted for all tests. Data processing and analysis were performed using IBM SPSS Statistics v.26.

For the analysis, we compared both groups regarding the type of resection. We also established a cutoff of 70 years old to analyze if age was related to the way the process affected the patients.

This study received ethical approval from the Clinical Research Ethics Committee (CEIm) of Hospital Clínico San Carlos, Madrid (Supplementary File S3). Compliance with the Declaration of Helsinki was confirmed, and informed consent was obtained.

3. Results

A total of 220 patients underwent surgery during the recruitment period. Eleven patients declined to participate, and in forty patients, the follow-up was incomplete or was not carried out by the surgical team. Thus, 169 patients completed the study and were eligible for the analysis. There were 65 women (38.4%) and 104 men (61.5%), with a median age of 66 years (range: 23–84). Demographic characteristics and analyzed variables are summarized in

Table 1. Demographic, tumoral, and surgical variables.

Variable		N	%
Previous cancer	No	98	58
	Yes	71	42
Localization	RUP	54	31.9
	ML	14	8.2
	RLL	29	18.1
	LUL	43	25.4
	LLL	27	15.9
	others	2	1.1
Hystological subtype	Squamous	47	27.8
	Adenocarcinoma	107	63.3
	NSCLC with ND	13	7.6
	Other	2	1.1
Stage	I	110	65.1
	II	31	18.3
	III	16	9.4
	IV	1	0.5
	RHC	3	0.9
Type of resection	Segmentectomy	69	40.9
	Lobectomy	95	56.2
	Bilobectomy	2	0.9
	Pneumonectomy	3	1.8
Surgical approach	VATS	52	30.8
	Thoracotomy	117	69.2
Perioperative treatments	Neoadjuvant ChT	18	10.6
	Adjuvant ChT	44	26
	Neoadjuvant RT	4	2.4
	Adjuvant RT	19	11.2
Complications	Pneumonia	23	13.6
	Bronchial Fistulae	1	0.6
	Atelectasis	11	6.5
	Hematoma	7	4.1
	Pulmonary Embolism	3	1.3
	Chylothorax	1	0.6

RUP: right-upper lobe; ML: medium lobe; RLL: right-lower lobe; LUL: left-upper lobe; LLL: left-lower lobe; NSCLC: non-small cell lung cancer; ND: neuroendocrine differentiation; VATS: video-assisted thoracic surgery; ChT: chemotherapy; RT: radiotherapy.

.

Regarding the presence of comorbidity, 72 patients (42.6%) suffered from arterial hypertension, 55 (32.5%) suffered from COPD, 37 (21.8%) suffered from diabetes mellitus, 22 (13%) suffered from vasculopathy, 17 (10%) suffered from cardiac ischemic disease, 18 (10.6%) suffered from prostatism and 14 (8.2) suffered from any type of arrythmia. The comorbidity variables are summarized in

Table 2. Comorbidity variables.

	Group 1		Group 2		All
	N°	%	N°	%		p
Arterial hypertension	32	18.9	40	23.6	72	0.07
COPD	28	15.5	27	15.9	55	0.3
Diabetes mellitus	20	11.8	17	10	37	0.3
Vasculopathy	10	5.9	12	7.1	22	0.27
Cardiac ischemic disease	11	6.5	6	3.5	17	0.06
Prostatism	6	3.5	12	7.1	18	0.07
Arrythmia	9	5.3	5	2.9	14	0.07

COPD: chronic obstructive pulmonary disease.

. No differences were found when comparing both groups. Other data included are the presence of neoadjuvant chemotherapy in 11 (6.5%) patients, adjuvant chemotherapy in 31 (18.3%) patients, neoadjuvant radiotherapy in 1 (0.6%) patient, and adjuvant radiotherapy in 13 patients (7.6%).

Postoperative complications were detected in 37 (21.8%) patients, with the most frequent being pneumonia in 16 (9.4%) patients and atelectasis in 6 (3.5%).

With respect to life changes after surgery, 98 patients (57.9%) reported that the surgical procedure did not result in any noticeable differences for them. Among those who responded affirmatively, the change most frequently reported was the sensation of fatigue and dyspnea. Notably, six patients reported an improvement in their quality of life (

Table 3. Changes in lifestyle, social relationships, and family environment.

Variable			N°	%
Life changes	no		98	57.9
	yes	Fatigue	39	23.0
		No same previous activities	9	5.3
		More limitations	13	7.6
		Pain	8	11.6
		Worse phycological status	5	2.9
		Limited mobility	2	1.2
		Healthier lifestye	6	3.5
		Others	8	4.7
Social changes	no		154	91.4
	yes	Friendship changes	15	8.8
		Less frequent go out	7	4.1
		Lose relationships	4	2.3
		Bad humor	4	2.3
		Changes in routines	2	1.2
Family changes	no		155	91.7
	yes	Better	4	2.3
		Lose relations	4	2.3
		Bad humor	5	2.9
		Changes in routines	1	0.5

). Regarding employment status, 18 patients were actively working, 120 were retired, 12 had taken early retirement, 3 were on disability schemes, 4 were unemployed, and 12 had never worked. Participants were also asked about their satisfaction with their work, as well as any changes resulting from their diagnosis and surgery. Notably, 84.6% expressed satisfaction with their work, with 4% reporting experiences of discrimination (

Table 4. Laboral environment.

Variable			N°	%
Laboral environment	Feels good at work	Yes	143	84.6
	Changes	Yes	5	2.9
	Discrimination	Yes	3	1.7
	Worse relationship with partners	Yes	0	0
	No answer		18	10.6

).

Regarding their physical condition after surgery, the most highly reported sequela by patients was difficulty climbing or descending stairs (69.8%), closely followed by fatigue during walking (65%). Additionally, 14.7% of patients required assistance or supervision for these activities (

Table 5. Need for assistance.

Assistance		N°	%
	No	97	57
	Familiar	11	6.5
	Psychological	56	33.1
	Economic	65	38.4
	Physical	70	41.4
	Others	68	42.2

and

Table 6. Physical limitations and need for help.

Variable	N°	%
Trouble with transfers	55	32.5
Fatigue while walking	110	65
Fatigue when going upstairs or downstairs	118	69.8
Help or supervision needed during basal activities	25	14.7
Type of help (non-exclusive)
Cane for walking	12	7.1
Active personal help	6	3.5
Supervision only	7	4.1
Other	4	2.3

).

We compared the results between the groups, and we found that fatigue during walking was significantly less common in patients from group 1 (segmentary resections) compared to group 2, undergoing more extensive pulmonary resections (55.1% vs. 72.7%; p = 0.02) (

Table 7. (a) Differences in fatigue between the two groups. (b) Differences in relationships with friends and family.

(a)
Fatigue while walking	Group 1 (SR)	Group 2 (rest)
No	44.9%	27.3%	p = 0.02
Yes	55.1%	72.7%
(b)
Changes with friends	<70 y	≥70 y
No	85.3%	98.6%	p < 0.05
Yes	14.7%	1.4%
Changes with family	<70 y	≥70 y
No	86.3%	98.6%	p < 0.05
Yes	13.7%	1.4%

SR: segmentary resection.

a). Among the remaining variables analyzed, no differences were found among patients who underwent a segmentary resection; they reported the same quality of life concerning work, family, and social activities as those undergoing a more extensive pulmonary resection. Additionally, when analyzing whether age influenced these results, a significant difference was observed for the variable “changes in relationships with friends” based on age. Patients over 70 years old reported fewer changes in their friendships compared to those under 70, who showed a higher percentage of responses indicating changes in their relationships with friends. Regarding the patient’s physical condition, difficulties with transfers were reported more frequently by patients under 70 years of age. Finally, in the group of patients under 70, changes in relationships with family members following surgery were observed. In this group, eight individuals (25%) from the “S” group and five (7.9%) from the “REST” group reported such changes. However, in the group of patients aged 70 and older, no association with changes in family relationships was observed (Table 7b).

A multivariate logistic regression analysis was carried out, but it did not provide relevant results.

4. Discussion

Psychosocial problems are a natural part of the experience for individuals diagnosed with cancer. The process itself evokes fear and uncertainty, imposing significant demands on patients and their families. Almost all patients initially experience distress, stress, or emotional disturbance upon receiving a cancer diagnosis. Several studies estimate that 30–50% of patients who have cancer present psychological issues that meet the criteria for treatment by professionals. This psychological impairment affects the emotional state and QOL of patients, with depression and anxiety being the most common disorders. They are often misdiagnosed and not properly treated. Patients suffering while adapting to their condition represent a challenge for clinical teams. They experience a synchronic combination of psychological and social issues [17,18]. Cancer inherently poses a life-threatening risk, and psychological distress in patients with cancer has been widely studied. Previous studies have shown that 10–40% of patients experience psychological distress that not only causes significant suffering but also worsens QOL, reduces treatment adherence, increases the risk of suicide, places a psychological burden on families, and prolongs hospital stays [19,20,21,22]. Different therapeutic approaches are usually necessary for these patients. They all carry adverse effects. Surgical pulmonary procedures imply specific effects frequently involving respiratory function. Despite the improvement in perioperative prehabilitation, surgical techniques, and management of pain, the fact is that the resection of part of a lung leaves a chronic trace on the patient, affecting their physical, psychological, and social experiences. Some authors, such as Tobias Schulte [23], have investigated the way these processes affect patients in terms of QOL. However, most studies focus on the physical effects. Jiang et al. associated lobectomy with poorer QOL, lower survival, and more pronounced respiratory symptoms over other types of resections preserving parenchyma [22]. Our study aimed to assess the differences between segmentary resection as a conservative approach for preserving non-tumoral lung parenchyma and other types of pulmonary resections, such as lobectomy, bilobectomy, and pneumonectomy. As reported in previous studies, pneumonectomy is the surgical procedure associated with the lowest survival rates and the highest postoperative complications and sequelae. However, in our cohort, pneumonectomies were infrequent, with lobectomies being the most common procedure. Postoperatively, differences between the two groups were minimal, with no significant associations except for walking-related fatigue, which was significantly lower in the group of sublobar resections. Most surgeries in this study were performed via thoracotomy. Ohasi et al. assert that video-assisted thoracic surgery (VATS) is associated with better QOL, fewer complications, shorter hospital stays, and reduced postoperative pain. Nevertheless, they also note no significant differences between VATS and thoracotomy in terms of outcomes [24]. An important limitation when analyzing the surgical approach is that the term thoracotomy refers to a variable surgical incision in terms of size, muscle sparing, the avoidance of rib sections, etc. It would be important to specify the characteristics of such thoracotomies.

Février et al. have shown that sublobar resections are associated with faster recovery and return to baseline physical functioning one year after surgery [25]. Stamatis also suggests an improved clinical status and faster return to normal activities with enhanced mental health outcomes, overall experience, and QOL among patients undergoing sublobar resection [26].

Support networks around the patient play a critical role in managing both the disease and post-surgical life. No differences were observed in the influence of support networks based on surgical type, which is consistent with Jiang et al., who showed similar psychosocial and social quality of life scores regardless of the type of resection performed [22]. Six patients reported an improvement in their QOL after surgery, probably due to adopting healthier lifestyle habits, which highlights the importance of continuous prehabilitation during the process. Different tools have been developed to optimize the clinical and psychological conditions of patients undergoing surgical resection for lung cancer [27].

Survivors of chronic illnesses must learn to face new vital challenges, adapt to their new lifestyles, and reorganize their lives with a short- or long-term perspective. Both the tumor and its treatment result in physical and psychological sequelae that require resilience and behavioral changes [8]. Employment, as an indirect tool for the measure of QOL and social reintegration, remains underexplored in patients undergoing oncological processes. Return to work is a crucial goal for many patients with cancer. However, the American Society of Clinical Oncology estimates that 90% of patients suffer from forms of discrimination upon returning to work [8].

In our study, most participants were retired. Among those who returned to work, most individuals reported no issues or discrimination, regardless of the type of surgical resection. Employment contributes to personal independence and autonomy, with significant repercussions on quality of life, highlighting the importance of further research on this topic.

Another crucial aspect of quality of life is mental health at all stages of the disease. As noted by Jiang, patient education about their illness is essential to maintain realistic expectations [22]. Psychological support and cognitive-behavioral stress management are critical for addressing anxiety and depression, which are common among cancer patients. Detecting and addressing these disorders is imperative to ensure optimal care and quality of life. Our study found no significant differences in psychological outcomes based on the type of resection, although Jiang et al. reported poorer psychological profiles in patients undergoing lobectomies [22].

Exploring patients’ physical profiles is also important. Assessing their ability to perform daily activities, transfer independently, and navigate fatigue or dyspnea is essential to identify problems and provide targeted solutions. Encouraging independence and maximizing quality of life should be the goal of all interventions.

The follow-up of patients undergoing surgery is important to obtain an evaluation of the patient’s perceived quality of life through different tools. An increasing interest in this approach in patients after surgical resection for lung cancer can be detected in the literature [28].

An important limitation of these kinds of studies is that they are based on the subjective feelings of the patients. The answers to a survey are potentially influenced by different factors that are difficult to control. The use of standardized measuring tools is important for unified methodological issues. In conclusion, our findings indicate that patients undergoing segmentary resections have a comparable long-term QOL regarding work, family relationships, and social activities compared to those undergoing more extensive pulmonary resections. We only found differences in walking-related fatigue, which was higher in the latter group. Specifically, patients aged 70 and older reported fewer changes in social relationships with friends and family and fewer transfer-related difficulties compared to younger patients.

A multidisciplinary approach to patients with lung cancer should include tools to achieve the best possible quality of life. It must include interventions aimed at preventing complications, maintaining or improving physical and psychological well-being, and reducing symptoms such as fatigue and dyspnea.

Our study has limitations such as its retrospective nature. Furthermore, regarding the level of pain, the thoracoscopic approach was not considered separately. Finally, the psychometric validation of the personalized QOL questionnaire was not performed. There is a lack of validated tools to properly evaluate the holistic recovery of cancer patients, along with the combination of objective and subjective variables, which favors the presence of biases, and, thus, requires caution with the conclusions drawn in this type of study.

5. Conclusions

Among patients undergoing resection for lung cancer with a curative purpose, feelings of fatigue while walking were lower in patients undergoing sublobar resections when compared to lobectomies, bilobectomies, or pneumonectomies. Patients over 70 years old reported fewer changes in social relationships with friends and family as well as fewer transfer-related difficulties compared to younger patients.

QoL was similar in both groups. The type of surgical resection did not significantly affect the occupational or social environments of the patients.