Uniportal VATS lobectomy versus thoracotomy lobectomy for NSCLC larger than 5 cm: A propensity score-matched study

Study population

The records of patients with pathological T3-4N0-2M0 NSCLC that underwent curative surgery at Peking University First Hospital between January 1, 2015, and December 31, 2020 were retrospectively collected and analyzed. The ethics committee of Peking University First Hospital reviewed and approved the study, and consent was acquired for each participant.

Eligibility criteria included: (1) Patients aged 18-years or older; (2) NSCLC pathology was confirmed; (3) curative lobectomy and lymphadenectomy received; and (4) no distant metastasis was indicated before the surgery. Exclusion criteria included: (1) Small cell histological types; (2) tumor invasion to adjacent lobe; and (3) radical resection not completed.

Staging and treatment

Preoperative examination included computed tomography (CT) of the chest and upper abdomen, ultrasonography of superficial lymph nodes, cranial magnetic resonance imaging (MRI), ultrasonic cardiogram, electrocardiogram, and pulmonary function test. Positron-emission tomography (PET)-CT was routinely recommended. Whether bronchoscopy was required was at the discretion of the surgeon. Staging was carried out according to the TNM staging system of AJCC eighth edition.

Following the surgical principle that the incision design and the sequence of dissection must conform to the anatomic configuration, we, under Jian Li's guidance, developed a set of surgical plans attuned to the anatomic composition of each lobe; that is, bronchus-artery–vein posteroanteriorly of the right upper lobe (RUL), artery-bronchus-vein posteroanteriorly of the right middle (RML) and the left upper lobes (LUL), and the artery-bronchus-vein cranial-caudally of the lower lobes, to accommodate our operative maneuvers. For uVATS surgery, an incision, typically 4–6 cm, was made in the anterior third intercostal space, for the right upper, lower, and left upper lobes, and the anterior fourth intercostal space, for the lower lobes, anterior intercostal space collateral ipsilateral to the lesion. The thoracic cavity was first explored to exclude pleural metastasis. The lesion-bearing lobe was maneuvered by a gauge-protected thoracoscopic clamp to reduce the compression of the tumor to prevent iatrogenic spread of malignant cells. A one-way method was applied to dissect the tumor-bearing lobe. The basic principle was to dissect the hilar structures away from the tumor. For a tumor residing in the right upper lobe, the division and dissection were started either from the bronchus then anteriorly, or from the vein then posteriorly, and for the left upper lobe and right middle lobe, from the pulmonary arteries then anteriorly or from the vein then posteriorly. For the right and left lower lobes, from the pulmonary arteries then caudally, or from the pulmonary vein then cranially. For the thoracotomy approach, a muscle-sparing technique was routinely applied. An 8–10 cm incision was created in the anterior fourth intercostal space. The anterior serratus muscle and the latissimus dorsi muscle were dissected and protected, and through the upper edge of the fifth rib, the thoracic cavity was entered in an intercostal nerve-preserving fashion. Once the thoracic cavity was explored and metastasis was ruled out, the lobectomy was conducted in a fissure-first manner. A one-directional method would be applied if the fissure was severely undeveloped. Other maneuvers followed the same principle of the uVATS lobectomy.

The relevant station 10, 11, and 12 lymph nodes were usually completely resected with the aid of a rubber tip sheathed suction apparatus, used to bluntly pull the lobar vessels or the lymph nodes to be resected. Because the tumor burden of patients in our study was already heavy enough, we routinely dissect the ipsilateral mediastinal lymph nodes. The contralateral hilar and the pretracheal lymph nodes could also be dissected by our surgical technique if needed. The dissected lymph nodes were retrieved using the cropped finger part of rubber gloves. The specimen, that is, the tumor-bearing lobe, was loaded in the retrieving plastic bag inside the thoracic cavity, then pulled out through the incision. For tumors that did not fit the intercostal space, we would then try in-bag dimension reduction to facilitate retrievement. If dimension reduction proved ineffective, we would lengthen the incision up to 6 mm. Rib-spreading was reserved as a last resort, which, fortunately, has not yet been used for specimen retrieval in our study.

A thoracic tube was routinely placed in the pleural cavity at the end of the operation. The patient would receive postoperative treatment, typically on the first to third postoperative day, in the intensive care unit if needed, or returned to our ward if not. Routine postoperative treatments consist of prophylactic antibiotic administration, intravenous patient-controlled anesthesia, and apophlegmatic treatments. The blood routine and biochemistry tests were conducted every other day. The thoracic tube would be removed if (1) the water-sealed level remained still when the patient coughed, (2) the volume of the drainage fluid was less than 200 ml 24 h prior to removal, and (3) the color of the drainage fluid was mellow yellow colored. The patient was discharged the day after thoracic tube removal if no discomfort was reported.

Follow-up and outcome

After discharge, the patient would receive follow-up every 3 months in the first 2 years, then every 6 months in the 3–5 years. Chest CT, ultrasonography of the abdomen and superficial lymph nodes, head MRI and serum tumor marker test were performed at each follow-up. The primary outcomes of our study were OS and RFS. The OS rate was calculated from the date of the surgery to the date of death of any cause, and the RFS rate was calculated from the date of the surgery to the date of disease recurrence. The event-free patient at the last available follow-up date was right-censored at this date in the survival analysis.

Propensity score matching

Propensity score matching (PSM) analysis, a method that could limit the bias caused by an existing dataset for nonrandom assignment analysis,⁸ was utilized to minimize the inherent bias in the retrospective study. Propensity scores were calculated using logistic regression based on the patient's preoperative characteristics, including age, sex, body mass index, smoking index, forced expiration volume, and diffusion capacity of the carbon monoxide. A 1:1 matched cohort was generated by matching patients who underwent the uVATS and the thoracotomy approach using a caliper width equal to 20% of the standard deviation of propensity scores without replacement. The post-matching balance was tested by student's t-test or Wilcoxon rank-sum test for continuous variable and the chi-square test or Fisher's exact test for categorical variables.

Statistical analysis

The OS and RFS of patients who underwent uVATS and the thoracotomy approach were calculated and compared via the Kaplan–Meier method in the overall study population and the PS-matched cohort. A variable would be included in multivariable Cox regression if univariable Cox regression suggested significance.

The normality of continuous variables was tested by the Shapiro-Wilk test. Student's t-test and Wilcoxon rank-sum test were applied to compare the normal and skewed distributed continuous variables between groups, respectively. The chi-square test or Fisher's exact test was performed for categorical variables. For all analyses, a p-value <0.05 in a two-tailed test was considered statistically significant. All analyses were performed with STATA/MP 15.1 software (StataCorp LLC), the R Project for Statistical Computing,⁹ and the R studio.

Patient characteristics

A total of 110 NSCLC patients who underwent either uVATS or thoracotomy approach lobectomy were identified, including 72 patients who underwent uVATS and 38 patients who underwent thoracotomy. The patients who received uVATS were younger, had a higher BMI, and fewer underwent preoperative bronchoscopy. There were more patients with squamous cell cancer in the thoracotomy group. PSM generated 23 pairs of patients, whose preoperative characteristics were well-balanced (Table 1).

Perioperative outcomes

Perioperative outcomes of the whole and the PS-matched cohorts are presented in Table 2. The uVATS groups showed a significantly less thoracic drainage tube placement time compared to the thoracotomy groups (p = 0.013), which did not persist in the PS-matched cohort. The operative time and bleeding of uVATS groups were less compared to the thoracotomy group without statistical significance nonetheless (p = 0.496 and p = 0.110, respectively). The amount of lymph nodes dissected in N1, and N2 stations and the amount of N2 stations dissected were also comparable in both the whole and the PS-matched cohorts (Table 2). In the PS-matched cohort, the number of N1 lymph nodes dissected in the uVATS group was even greater than that in the thoracotomy groups (Figure 1).

Survival outcomes

The median follow-up period was 35 months (range 6–89 months), the 5-year OS was 55.64%, and the 5-year RFS was 53.72%. In the whole cohort, the 5-year OS rate of the uVATS group was 54.39%, and the right approach group was 58.29% (p = 0.775) (Figure 2a). The 5-year RFS rate of the left and right approach groups were 51.62% and 58.05% (p = 0.352), respectively (Figure 2b). After PS matching, the 5-year OS rates of the left and right approach groups were 39.09% and 50.78% (p = 0.501, respectively (Figure 2c), the 5-year RFS rates were 35.51% and 50.47% (p = 0.316), respectively (Figure 2d).

We investigated the pattern of recurrence in the groups using competing risk analyses. No statistical difference in the local recurrence rate was found in the analysis between the uVATS and thoracotomy groups (Figure 3). In the multivariate Cox regression analysis, a higher diffusion capacity for carbon monoxide, more intraoperative bleeding, and the presence of pathological nerve invasion were independently associated with worse OS and RFS (Table 3).