Globally, there are 1.8 million deaths and 2.1 million new cases every year due to lung cancer, with approximately 80% of patients diagnosed with non-small cell lung cancer (NSCLC). In addition, 20‒30% have early-stage disease (T1-2N0M0, American Joint Committee on Cancer [AJCC] eighth edition stage I and IIA, AJCC seventh edition stage I) as the leading cause of cancer mortality.1 Surgical resection, scilicet video-assisted thoracic surgery lobectomy plus mediastinal lymph node dissection (VATS L-MLND) remains the standard treatment option for operable early-stage NSCLC.2 Among patients with early-stage NSCLC, 5-year survival rates were 69.7% and 55.3% for those with lesions ≤3 cm and 3.0‒5.0 cm, respectively.3 The number of elderly patients with lung cancer has increased because of aging and growth of the population, and the introduction of screening by low-dose computed tomography (CT) for early lung cancer.4,5 The median age of patients with lung cancer is 70 years. Thus, for elderly patients with early-stage NSCLC, surgery may be hampered by comorbidities, frailty, lack of access to care, or patient or physician reluctance to pursue treatment, presenting a therapeutic challenge for patients and clinicians.6
Stereotactic ablative radiotherapy (SABR) or stereotactic body radiation therapy (SBRT) is a method of external beam radiation therapy in which a fraction dose or a few fractions of radiation can be delivered with great precision to an extracranial target within the body. The target doses are high, and the dose gradients beyond the target are steep, owing to a dedicated treatment plan. Delivery of high-dose ionizing radiation in one or few fractions with an accurate targeting system and rapid dose fall-off gradients surrounding target tumors within a patient is the foundation of SBRT evolution. Stereotactic localization and radiation delivery techniques can be used in SBRT to provide noninvasive or minimally invasive treatment.7 SBRT has been used in medically inoperable T1-2N0M0 NSCLC since 1995. It has achieved good primary tumor control and better survival rates than conventionally fractionated radiotherapy. SBRT is recommended as a nonsurgical treatment alternative by the National Comprehensive Cancer Network Clinical Practice Guidelines and the European Society for Medical Oncology Consensus for stage I‒II NSCLC. Many retrospective and prospective studies have shown that SBRT has a favorable outcome in medically inoperable patients regarding overall survival (OS) and cancer-specific survival, which were similar to or even better than those reported with pulmonary resection.3,8–23
Surgery has been the standard treatment for operable diseases for a long time; the convenience, noninvasive nature, and favorable outcomes associated with medically inoperable diseases make it increasingly attractive for all patients with early-stage I NSCLC, especially elderly patients.14 Despite minimally invasive surgical techniques, elderly patients undergoing guideline-recommended lung resection have a significantly higher operative mortality rate than younger patients (6.9% vs. 3.7%).24–26 Several reports have shown that SBRT is a safe and feasible treatment for elderly patients regarding treatment complications and oncological outcomes.18,27–38 The use of SBRT as an alternative treatment modality for elderly patients has increased owing to the availability and development of various stereotactic radiotherapy techniques and equipment.
Research on SBRT is extremely limited compared with that on surgery in elderly patients with early-stage NSCLC.11,39–42 Therefore, more evidence is required to guide the choice of clinical treatment to achieve the best treatment effect in this population. We conducted a comprehensive propensity-score matching (PSM) analysis to investigate the efficacy and side-effects of VATS with SBRT treatment in patients with early-stage NSCLC aged ≥75 years at our institution.
METHODS Study design and patient selectionThe study was approved by the Ethics Committee of the Tianjin Medical University Cancer Institute and Hospital, and the tenets of the Declaration of Helsinki were strictly followed. We also obtained the committee's approval for our retrospective study, which waived the requirement for each patient's written informed consent (bc2022172). We anonymously collected all laboratory results and clinical data to protect our patients’ privacy. Patient data and medical records were not accessible to individuals aside from those in the research team.
The present single-institution retrospective study was conducted at the Tianjin Medical University Cancer Institute and Hospital (Tianjin, China). Following the eighth edition of the International Union against Cancer tumor node metastasis, the present study included all patients diagnosed with early-stage NSCLC aged ≥75 years from January 2011 to November 2018, and whose primary treatment was VATS or SBRT. Clinical staging was determined using CT scans (including the chest, upper abdomen, and brain), magnetic resonance imaging of the brain, and 18F-fluorodeoxyglucose positron emission tomography. As 18F-fluorodeoxyglucose positron emission tomography was not essential, bone scintigraphy was performed.
Overall, 310 patients participated, of whom 180 underwent VATS and 130 underwent SBRT (Table 1). Eligibility criteria were as follows: (1) all the patients were newly diagnosed with NSCLC by histopathology (surgery patients underwent postoperative pathology and SBRT patients underwent CT-guided percutaneous puncture biopsy); (2) all patients were aged ≥75 years; (3) the tumor diameter was ≤5 cm (cT1a, cT1b, cT1c, T2a, T2b, and cN0 cM0 according to the AJCC eighth edition); (4) complete clinical case and imaging follow-up data were available; and (5) no other treatment was administered before SBRT or thoracoscopic surgery. Exclusion criteria were as follows: (1) patients without histopathological diagnosis; (2) pathological examination revealed a benign tumor or small cell lung cancer (SCLC); (3) hilum, mediastinum, and distant metastases occurred before or during treatment; (4) patients who disobeyed medical advice or discontinued treatment; (5) patients who underwent both surgery and SBRT; (6) patients with a positive pathology of surgical margin; (7) previous lung or mediastinal radiotherapy; (8) previous malignancy; and (9) loss to follow-up.
TABLE 1 Baseline data of patients before and after the propensity score matching process
| Entire Cohort | Propensity | Score matching | ||||
| SBRT (n = 130) | VATS (n = 180) | p | SBRT (n = 71) | VATS (n = 71) | p | |
| Age (years) | <0.001 | <0.001 | ||||
| Median (range) | 80 (75‒88) | 77 (75‒82) | 79 (75‒88) | 77 (75‒82) | ||
| Sex | 0.652 | 0.862 | ||||
| Male | 77 (59%) | 102 (57%) | 45 (63%) | 44 (62%) | ||
| Female | 53 (41%) | 78 (43%) | 26 (37%) | 27 (38%) | ||
| KPS | <0.001 | 0.649 | ||||
| 100 | 5 (4%) | 60 (33%) | 3 (4%) | 8 (11%) | ||
| 90 | 40 (31%) | 97 (54%) | 20 (28%) | 47 (66%) | ||
| 80 | 65 (50%) | 21 (12%) | 39 (55%) | 15 (21%) | ||
| 70 | 20 (15%) | 2 (1%) | 9 (13%) | 1 (2%) | ||
| CCI (%) | <0.001 | 0.649 | ||||
| <1 | 55 (42%) | 129 (71%) | 36 (51%) | 42 (59%) | ||
| 2 | 34 (26%) | 30 (16%) | 23 (32%) | 19 (27%) | ||
| 3 | 29 (22%) | 10 (6%) | 8 (11%) | 5 (7%) | ||
| 4 | 10 (8%) | 3 (2%) | 4 (6%) | 5 (7%) | ||
| 5 | 1 (1%) | 7 (4%) | ||||
| >6 | 1 (1%) | 1 (1%) | ||||
| cT Stage | 0.022 | 0.514 | ||||
| T1a | 6 (5%) | 21 (12%) | 6 (8%) | 7 (10%) | ||
| T1b | 31 (24%) | 61 (34%) | 17 (24%) | 23 (32%) | ||
| T1c | 40 (31%) | 49 (27%) | 29 (41%) | 24 (34%) | ||
| T2a | 39 (30%) | 35 (19%) | 15 (21%) | 10 (14%) | ||
| T2b | 14 (10%) | 14 (8%) | 4 (6%) | 7 (10%) | ||
| Tumor area | <0.001 | 1.000 | ||||
| Peripheral | 106 (82%) | 172 (96%) | 67 (94%) | 67 (94%) | ||
| Central | 24 (18%) | 8 (4%) | 4 (6%) | 4 (6%) | ||
| Histology | 0.004 | 0.450 | ||||
| ADE | 67 (52%) | 128 (71%) | 42 (59%) | 46 (65%) | ||
| SCC | 54 (42%) | 44 (24%) | 27 (38%) | 21 (30%) | ||
| ADESCC | 6 (4%) | 7 (4%) | 2 (3%) | 4 (4%) | ||
| Other NSCLC | 3 (2%) | 1 (1%) |
The data are displayed as a number (%) or median (range).
Abbreviations: ADE, adenocarcinoma; CCI, Charlson comorbidity index; KPS, Karnofsky Performance Status; NSCLC, non-small cell lung cancer; SBRT, stereotactic body radiotherapy; SCC, squamous cell carcinoma; VATS, video-assisted thoracic surgery.
Sex, age, Karnofsky Performance Status (KPS), Charlson Comorbidity Index (CCI), tumor histopathological characteristics, T-stage, tumor site, and other data of the two groups were provided by the Tianjin Cancer Hospital electronic file database.
SurgeryBefore making final treatment decisions, a multidisciplinary tumor board for thoracic oncology discussed patients with no contraindications to intervention and adequate pulmonary function to facilitate a consensus opinion on operability. All patients underwent VATS. The surgical procedure was as follows: the patient was placed in the healthy side position, and after general anesthesia, the surgeon made a surgical incision, which was a three-port thoracoscopic lobectomy during lung cancer treatment. One incision was made in the fourth intercostal space of the anterior axillary line as the main operating port. According to tumor location, the seventh or eighth intercostal incision in the posterior axillary line was selected as the auxiliary surgical hole. A midaxillary line incision with a sixth or seventh intercostal incision was chosen as the observation hole. With the assistance of a thoracoscope, the surgeon used surgical instruments to perform surgical operations in the thoracic cavity, separated the pulmonary blood vessels and bronchi, clamped them, removed the diseased lung lobes, and cleared the systemic nodes.
A total of 180 enrolled patients underwent VATS for resection performed by experienced oncological surgeons. They all had negative surgical margins and no lymph node metastasis at any site. A total of 39 patients underwent thoracoscopic pulmonary anatomic segmentectomies or simple tumor resection, and 141 patients underwent VATS L-MLND.
SBRTThe SBRT procedure used CyberKnife G3™ technology with a fixed cone (Accuray, Sunnyvale, CA, USA) and an image-guided robotic radiosurgical system equipped with Synchrony (Accuray Inc.) to track respiratory motion in real time on consecutive days. CyberKnife treatment included fiducial placement, CT simulation, target volume delineation, treatment planning, and normal tissue constraints.
Fiducial placementPatients received an implanted gold fiducial (gold seeds 4 0.8 mm) near or inside the treatment area for real-time targeting. In addition, patients who were contraindicated to fiducials (e.g., anticoagulant use, high-risk for pneumothorax) or locations within 5 cm of the vertebral body received treatment with a fiducial-free Xsight spindle (Accuray Inc.) spine-tracking system.
Computed tomography simulationPatient immobilization was achieved using a vacuum bag from Esform. CT scans were performed using a LightSpeed Xtra® (GE Healthcare, Chicago, IL, USA) at a thickness of 1.25 mm. Intravenous radiographic contrast was injected to highlight the tumor. We conducted a CT simulation approximately 7 days after fiducial placement to prevent fiducial migration. Four-dimensional CT (4-D CT) at 1.25 mm thickness was used to visually verify the tumor's position during Xsight.
Delineation of the target volumeGross tumor volume was determined using simulation CT and ± positron emission tomography-computed tomography. By detecting the motion of the gold fiducial markers, planning target volume was defined as the gross tumor volume with appropriate margins on the x-, y-, and z-axes. For patients treated with the Xsight spine-tracking system, internal target volume was the gross tumor volume plus appropriate margins detected by 4-D CT and expanded by 5 mm to generate the planning target volume.
Treatment planningA treatment plan was created based on the tumor location and geometry. Then, a ray-tracing dose calculation algorithm was used to optimize plans and calculate doses. Finally, we applied heterogeneity correction using appropriate CT density models to calculate the dose.
Organs at risk, normal tissue constraints, and biologically effective dosesA soft tissue window was used in planning CT images to contour the organs at risk (trachea and main bronchus, heart and great vessels, esophagus, lung fields, brachial plexus, spinal cord, and ribs). The following dose constraints were imposed on organs at risk: volume of normal lung receiving more than 20 Gy (V20), <15%; spinal cord dose maximum (Dmax), 21.9 Gy; heart Dmax, 30 Gy; minimum dose to the most irradiated 15 cm3 of the heart, 24 Gy; great vessels Dmax, 45 Gy; bronchus Dmax, 23.1 Gy, and trachea Dmax, 30 Gy. The following formula was used to convert treated doses to biologically effective doses (BED): BEDα/β = nd [1 + d / (α/β)], where n is the number of fractions, and d is the dose/fraction (Gy); assuming α/β value of 10 for NSCLC (i.e., BED10) and α/β value of 3 for normal tissues (i.e., BED3).
Patients who refused surgery or were medically inoperable underwent SBRT. Among patients with early-stage NSCLC aged >75 years, 138 were confirmed by pathological diagnosis. In addition to loss to follow-up and other factors, the present study included 130 patients.
Follow-up and end-pointsAfter treatment completion, routine examinations (blood tests, including routine blood tests, liver and kidney function, and tumor markers; physical examination; thorax CT scans; neck and abdomen ultrasound) were conducted in the clinic at 1 month, then every 3 months for the first 2 years, and every 6 months after that for 5 years. An annual assessment of the patients was conducted after 5 years. Bone scans were performed in case of bone pain. The treating physician decided whether to perform positron emission tomography and bronchoscopy with a biopsy. Follow-up data were gathered by official contact with the patients or their relatives via the telephone or hospital records. All hospitalized patients had complete medical records.
The study had four end-points, OS, progression-free survival (PFS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS). OS was calculated from the date of initial treatment until the death date or last follow-up. PFS was defined as the time to progression, death from any cause, or last follow-up. LRFS was defined as the time to recurrence of the primary tumor or regional lymph node in the region, death from any cause, or last follow-up. DMFS was defined as the time to disease progression excluding locoregional failure, death from any cause, or last follow-up. Patients who did not show a progression or died before the last follow-up were censored. Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was used to evaluate treatment response. The Common Terminology Criteria for Adverse Events (CTCAE) 4.0 criteria were used to evaluate treatment-related toxicities. OS, PFS, LRFS, and DMFS were calculated in months.
Data analysisContinuous variables were calculated using medians with interquartile ranges, and categorical variables were calculated using proportions. Student's t-test was used for normally distributed variables, and the χ2-test or Fisher's exact test was used for categorical variables. Kaplan‒Meier method was used to plot the OS, PFS, LRFS, and DMFS curves, and log-rank tests were used for comparisons. Hazard ratios were estimated using Cox proportional hazards model (unadjusted and adjusted). All tests were two-sided, and statistical significance was set at p < 0.05. The IBM SPSS 24.0 software (IBM Corporation, Armonk, NY, USA) was used for statistical analysis, and GraphPad Prism 19.0 (GraphPad Software, San Diego, CA, USA) was used to plot the survival curve.
According to the guidelines, we used PSM to identify patient cohorts with similar baseline characteristics between the two treatment groups. With a caliper width of 0.2 of the propensity score standard deviation, PSM was conducted using a 1:1 matching protocol without replacement. The dependent variables were VATS and SBRT, and covariates were selected based on previous studies and clinical data. Covariates were selected at priority, and included sex, KPS, CCI score, tumor T-stage, and pathological type.
RESULTS Patients’ characteristicsA total of 338 elderly patients diagnosed with stage T1-2N0M0 NSCLC (AJCC eighth edition stage I and IIA) at the Tianjin Medical University Cancer Institute and Hospital (Tianjin, China) from January 2011 to November 2018 were treated as follows: 200 (59.2%) underwent VATS, and 138 (40.8%) underwent SBRT. After excluding patients lost to follow-up, 130 and 180 patients were included in the SBRT and VATS groups, respectively. Therefore, based on the aforementioned criteria, 142 patients (71 SBRT and 71 surgery) were matched with the 310 patients who underwent VATS or SBRT. The final follow-up date was July 20 2022.
The patient characteristics before and after PSM are described in Table 1. Before PSM, there was an imbalanced distribution of baseline characteristics between the two groups, including KPS, CCI, cT-stage, tumor area, and histology. Most patients who underwent SBRT chose to receive SBRT only after prudent evaluation by experienced surgeons who did not recommend VATS. Therefore, the SBRT group had higher age, higher CCI, worse lung function, and lower KPS scores. After PSM, the VATS and SBRT groups did not differ significantly, except for age. The SBRT group had older patients than the VATS group (79 years [interquartile range 75–88 years] vs. 77 years [interquartile range 75–82 years], p < 0.001).
The details of SBRT therapy, including lesion site, tracking modality type, the reason for inoperability, planning target volume, SBRT schedule, BED10, and isodose line, are shown in Table 2.
TABLE 2 A detailed description of the characteristics of the stereotactic body radiotherapy-treated matched patients
| Item | n (%) |
| Lesion site | |
| right upper lobe | 20 (28) |
| right middle lobe | 7 (10) |
| right lower lobe | 17 (24) |
| left upper lobe | 17 (24) |
| left lower lobe | 10 (14) |
| Tracking modality type | |
| Xsight | 10 (14) |
| Synchrony | 62 (86) |
| Reason for inoperability | |
| Organ dysfunction | 68 (96) |
| Refusal of surgery by patient | 3 (4) |
| PTV volume (mm3), median (range) | 28,319 (17,523.85‒47451.2) |
| SBRT schedule | |
| 60 Gy/3f | 5 (7) |
| 60 Gy/4f | 11 (16) |
| 60 Gy/5f | 18 (26) |
| 60 Gy/6f | 10 (15) |
| 56 Gy/7f | 3 (4) |
| 55 Gy/5f | 5 (7) |
| 54 Gy/3f | 5 (7) |
| 54 Gy/6f | 1 (1) |
| 51 Gy/6f | 1 (1) |
| 50 Gy/5f | 9 (13) |
| 49 Gy/7f | 1 (1) |
| 48 Gy/4f | 1 (1) |
| 45 Gy/5f | 1 (1) |
| BED10 (Gy), median (range) | 132 (115.5‒150) |
| Isodose line, median (range) | 73% (68‒76%) |
Abbreviations: BED, biologically effective doses; PTV, planning target volume; SBRT, stereotactic body radiotherapy.
Among patients undergoing VATS, 45 (63.4%) underwent VATS-MLND, 22 (31.0%) underwent thoracoscopic wedge resection, and four (5.6%) were treated with segmentectomy. In addition, 15 surgical patients (21.1%) received adjuvant chemotherapy.
OutcomesAll patients were monitored during the median follow-up period of 53.5 months. The median follow-up for the VATS group was 72 months, whereas that for the SBRT group was 53 months. The 1-, 3-, and 5-year OS rates were 90.1%, 69.0%, and 58.3% in the VATS group, and 93.0%, 63.4%, and 48.2% in the SBRT group, respectively. Statistically, the OS (p = 0.492; HR 1.167; 95% confidence interval [CI] 0.749–1.818) did not differ between the two groups. The 1-, 3-, and 5-year PFS rates were 83.6%, 70.8%, and 59% in the VATS group and 87.0%, 58.1%, and 47.7% in the SBRT group, respectively (p = 0.294; HR 1.311; 95% CI 0.790–2.174). Neither the LRFS (84 vs. 83.9% at 3 years; p = 0.866; HR 0.940; 95% CI 0.454–1.946) nor the DMFS (72.4 vs. 60.7% at 3 years; p = 0.452; HR 1.218; 95% CI 0.728–2.037) were significantly different between the two groups (Figure 1).
Enlarge this image.FIGURE 1. Comparison of survival between stereotactic body radiotherapy (SBRT) and video-assisted thoracic surgery (VATS) in patients aged ≥75 years. (A) Overall survival. (B) Progression-free survival. (C) Locoregional-recurrence free survival. (D) Distant-metastasis free survival
Multivariate analysis showed that T-stage (p = 0.001; HR 0.389; 95% CI 0.235–0.675) was an independent factor associated with OS (Table 3).
TABLE 3 Overall survival analysis by multivariate regression
| Characteristics | HR (95% CI) | p |
| Age (≤80:>80) | 1.248 (0.654‒2.380) | 0.502 |
| Gender (women : men) | 0.638 (0.369‒1.100) | 0.106 |
| T-stage (T1 : T2) | 0.398 (0.235‒0.675) | 0.001 |
| Pathology (SCC : ADE) | 1.449 (0.875‒2.402) | 0.150 |
| Treatment mode (SBRT : VATS) | 1.250 (0.760‒2.043) | 0.379 |
| CCI (≤1:>1) | 0.683 (0.400‒1.166) | 0.162 |
| KPS (≥80:>80) | 1.011 (0.373‒2.736) | 0.983 |
| Tumor area (central : peripheral) | 0.638 (0.369‒1.100) | 0.756 |
Abbreviations: ADE, adenocarcinoma; CCI, Charlson Comorbidity Index; CI, confidence interval; HR, hazard ratio; KPS, Karnofsky Performance Status; SBRT, stereotactic body radiotherapy; SCC, squamous cell carcinoma; VATS, video-assisted thoracic surgery.
30- and 90-day mortality ratesThe 30- and 90-day mortality rates calculated from treatment start date were counted separately for the two groups to compare the short-term mortality after treatment. In each group of 71 patients, the 30- and 90-day mortality rates were 1.4% (1 case) and 4.2% (3 cases) in the VATS group, and 0 (0 cases) and 2.8% (2 cases) in the SBRT group, respectively. Patients' death within 3 months of surgical treatment were due to severe postoperative complications of pulmonary infection, leading to respiratory failure. In contrast, the two deaths recorded in the SBRT group were due to diseases other than cancer.
ToxicitiesIn the matched SBRT group, the patients were extremely old with a high level of comorbidity; however, SBRT was well tolerated. Grade 1, 2, and 3 radiation pneumonia (according to the CTCAE 5.0 scale) were observed in eight (11.3%), four (5.6%), and one (1.4%) patients, respectively, which improved significantly with glucocorticoid therapy. Symptoms, such as dyspnea, anorexia, and weakness, may occur during treatment and recover on their own without treatment or improve with symptomatic treatment. No grade 4 or 5 adverse events occurred during the first 3 months after SBRT. Severe late toxicity was also uncommon. Three patients (4.2%) had chest wall injuries, which presented as chest wall pain with no effect on daily activities.
Six patients (8.5%) in the matched VATS group developed a postoperative lung infection. Three (4.2%) developed respiratory and circulatory failure and died within 3 months of surgery. Pulmonary embolism occurred in one patient (1.4 %).
DISCUSSIONThe present results are of great importance, because none of the randomized, controlled clinical trials investigating SBRT and VATS in early-stage NSCLC have been completed. Furthermore, according to the World Health Organization scale, the average elderly patient aged ≥75 years has poor physical functions, with an increased comorbidity and frailty burden, and would easily be excluded from clinical trials because of the risk of short life expectancy. Consequently, lung SBRT in elderly patients has received very little research effort, leaving clinicians with limited data to guide their clinical decisions. Therefore, our study contributes to the literature regarding SBRT's potential role in treating elderly patients with early-stage NSCLC.
In this study, SBRT and VATS did not result in different survival (OS, PFS, LRFS, and DMFS) for elderly patients diagnosed with early-stage NSCLC by pathological and radiographic examination using population-based data. The survival data shown are compelling for several reasons. First, multidisciplinary tumor boards deemed approximately 96% of patients undergoing SBRT unfit for surgery. Also, SBRT patients (median age 79 years) who may have inferior outcomes than younger patients were older than the VATS group (median age 77years)6. However, with SBRT, the LRFS was 83.9% at 3 years. Therefore, SBRT OS may be superior in medically operable patients.
Additionally, SBRT is a minimally invasive outpatient treatment with a low 30-day mortality rate (0 in this study) despite the treatment of a high-risk patient population. This finding is important for patients' decision-making, because patients are unwilling to take short-term risks that cause death. Coincidentally, it corresponds to a recent discovery made by Syed et al., in which postoperative mortality was lower for patients with early-stage NSCLC undergoing surgery at medical institutions using SBRT more frequently. This implies that SBRT can improve the selection of surgery candidates anticipated to have high postoperative mortality rates.43
The outcomes of the present study for SBRT patients are in correspondence with previous studies,11,18,19,27,30,32–35,39–42,44,45 such as the first comparison of SBRT and surgery among matched pairs of elderly patients with clinical early-stage I NSCLC conducted by Palma et al.; the 3-year OS was 42% and 60% for the SBRT and surgery groups, respectively (p = 0.22), and the 30-day mortality rate was 8.3% and 1.7% for the surgery and SBRT groups, respectively.11 The matched-paired SBRT and surgery groups showed no significant differences, with a 5-year OS of 40.4% in the SBRT group and 55.6% in the surgery group (p = 0.124) in a Japanese elderly patients' study(≥80 years).40 In addition, Shirvani et al. retrospectively analyzed a database of 10,923 elderly patients aged ≥66 years based on the Surveillance, Epidemiology, and End Results database, divided them into SBRT and surgery groups, and found that OS (p = 0.38) and cancer-specific survival (p = 0.10) did not differ significantly between the two groups. According to a recent study conducted by Dong et al., the researchers included 205 patients aged ≥70 years diagnosed with stage I NSCLC who underwent SBRT or surgery at the Zhejiang Cancer Hospital (Hangzhou) from January 2012 to December 2017; the 3- and 5-year LRFS rates were 90.0% and 80.0% for the surgery group, and 91.1% and 84.1% for the SBRT group, respectively.42 However, a matched analysis from the Netherlands Comprehensive Cancer Organization compared SBRT with VATS lobectomy in patients with early-stage I NSCLC aged ≥65 years, and found that VATS lobectomy significantly improved long-term survival, which is important when deciding whether to perform surgery on elderly patients who can tolerate it. After VATS lobectomy, the OS rates at 1, 3, and 5 years were 91%, 68%, and 58%, respectively, and the rates were 87%, 46%, and 29% after SBRT (p < 0.001).41 The treatment approach in that study was very similar to the present study, but the age was limited to ≥65 years (median age 74 years), which is much lower than our study population (≥75 years, median age, 77 years). Elderly patients usually have poor physical functions, more comorbidities, longer trauma recovery time, and more treatment difficulties. Therefore, that study is not comparable with the present study.
Choosing SBRT or surgery in patients with early-stage NSCLC who are medically operable is a long-standing challenge. SBRT is not equivalent to lobectomy; however, some prospective studies have reported similar overall outcomes. Three randomized trials (STARS, ROSEL, and ACOSOGZ4032) attempted to compare the two treatment modalities that have been initiated for a long time, but poor accruals resulted in premature termination.14,46,47 The STARS and ROSEL trials showed that SABR provided higher survival than surgery for operable early-stage NSCLC in a pooled analysis; however, the analysis had notable limitations.22 Recently, Chang et al. updated the revised STARS trial's long-term results, in which increased sample size was reacquired for the SABR group, together with a PSM comparison with a contemporary institutional cohort of prospectively registered VATS L-MLND patients. The study concluded that SABR for operable stage IA NSCLC was not inferior to VATS L-MLND regarding long-term survival. However, this conclusion has provoked a heated debate among researchers. Our outcomes were significantly worse than those from these clinical trials because of the stringent entry requirements, in which the patient population consists of selected, relatively fit individuals. In a retrospective analysis, there was no uniform conclusion, considering that it may be influenced by age, stage, operation mode, and other factors.
The present study analyzed the survival of 310 elderly patients (≥75 years) who underwent VATS or SBRT for early-stage NSCLC from January 2011 to November 2018. This study is the first to compare the outcomes between the two therapeutic approaches in individuals aged ≥75 years who had pathologically proven early-stage NSCLC. Future trials comparing SBRT with a minimally invasive surgical procedure can be based on it. According to our analysis, SBRT and VATS were not significantly different in terms of survival in this patient population (p > 0.05). However, after observing the patients' survival rate data within 3 years, we found that SBRT may have a better survival trend. Nevertheless, as the present study targeted elderly patients whose survival rates are affected by age, more studies are required to confirm this. One of the advantages of this study is that the match between the two patient groups pretreatment physical status and tumor-related factors is comprehensive, with no significant individual difference. All patients were treated at the same hospital, and there was little difference in radiation technology and operative conditions. Additionally, the patient population reflected clinical practice meaningfully, and the long follow-up time after treatment was also one of our advantages.
According to the present results, there appeared to be no significant difference in the long-term efficacy between these two therapies in treating early-stage NSCLC; however, the SBRT group has certain advantages in comparing the long-term quality of life. Because of the small radiation response and radiation damage of SBRT, the radiation dose to normal tissue is within the allowable range, and lung function is slightly impaired. However, surgical trauma can cause bleeding and systemic inflammatory reactions, resulting in postoperative anorexia, fatigue, cough, shortness of breath, pain, and other adverse reactions, which can affect cardiopulmonary function. Therefore, the long-term efficacy of VATS and SBRT for treating early NSCLC in elderly patients is similar; however, the long-term quality of life after SBRT is higher than that of surgical treatment, which can result in better clinical application prospects.
There were several limitations to the present study. First, there were inherent biases that could be controlled, but never eliminated completely, as this was not a randomized controlled trial. We performed data matching analysis for all basic conditions; however, the effects of factors other than matching data remained in the surgical and SBRT groups. This difference also contributed to the deviation in the treatment choice between the two groups. Second, the study was limited by the lack of pulmonary function data, which is important for assessing the patient's physical condition. Finally, the small sample size and single-center design were limitations. Therefore, a large, multicenter, randomized controlled clinical trial comparing VATS and SBRT is required to avoid imbalance and selection bias.
Early-stage NSCLC treatment in elderly patients is quite challenging. Outcomes of VATS and SBRT were almost identical in the present study. Owing to its lower risk of perioperative mortality and the potential to promote long-term survival, SBRT may be effective in elderly patients. Large, multicenter, randomized controlled trials are required to accurately compare outcomes between the two therapeutic approaches.
ACKNOWLEDGMENTSThis study was funded by the National Natural Science Foundation of China (No. 82172674) and the Natural Science Foundation of Tianjin Municipal Science and Technology Bureau (Grant No. 20JCYBJC00090) to Zhiyong Yuan.
CONFLICT OF INTERESTThe authors declare that they have read the article and there are no competing interests.
ETHICS STATEMENTThe study was approved by the Ethics Committee of the Tianjin Medical University Cancer Institute and Hospital, and the tenets of the Declaration of Helsinki were strictly followed.
© 2022. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.