With the development of imaging techniques, the detection rate of pulmonary nodules has increased, but many of them are benign . Therefore, PNB and BB are commonly used to diagnose pulmonary lesions when they are suspected to be malignant and difficult to differentiate from benign lesions [14,15,16]. In clinical work, however, some surgeons are concerned that invasive biopsies may lead to the spread of tumor cells, thereby increasing the risk of recurrence after radical resection . They believe that PNB or BB may lead to disruption of the tumor capsule, which may allow tumor cells to migrate and spread in the normal alveolar lumen or enter the bloodstream. Nevertheless, this study using PSM found that preoperative PNB and BB did not significantly increase the rate of STAS in patients with early-stage NSCLC or affect prognosis after radical surgery through PSM analyses.
STAS was a newly recognised mode of invasion of lung cancer cells that has not been widely considered before . It was not until 2015 when WHO formally introduced the concept in the new classification of lung cancer . Many studies have also shown that STAS is significantly associated with worse RFS and OS in lung cancer patients [6, 7]. The reason for this may be that clusters of free-floating tumor cells in the alveolar lumen are deposited in the alveolar wall to form new tumor foci, providing a biological basis for metastasis and recurrence of tumors . However, some scholars have questioned STAS, arguing that it is only the spread of tumor cell clusters caused by knife cutting during specimen processing, and called it "Spread Through a Knife Surface" . Recently, more and more studies have shown that STAS is an in vivo phenomenon rather than an artifact caused by specimen handling procedures [13, 23, 24]. However, could this in vivo phenomenon be another manipulation artifacts, caused by preoperative invasive biopsy? In the present study, neither preoperative PNB nor BB significantly increased the rate of STAS positivity in NSCLC patients either before or after PSM, further suggesting that STAS is an in vivo phenomenon and is not an artifact of preoperative or postoperative manipulation. Of course, it is also possible that tumor cell shedding or dissemination due to invasive manipulation is along the manipulation pathway, i.e., spread is more limited. STAS may not have been observed due to the limitations of pathological sampling . In addition, in this study, the STAS positivity rate was higher in the PNB group than in the non-biopsy group after matching (42.1% vs. 34.2%), but the difference was not statistically significant (P > 0.05), probably due to the smaller sample size in both groups after matching. Therefore, further prospective trials with larger sample sizes and comprehensive sampling and serial sectioning of tumor specimens are necessary.
We further analyzed the effect of preoperative biopsy on RFS and OS of patients after radical surgery. While there were significant differences in OS and RFS between the groups before PSM, there were also significant differences in the baseline characteristics of patients between the groups. BB is more suitable for the diagnosis of central lung cancer , so the BB group was mostly male patients with squamous carcinoma who smoked, which may lead to different postoperative adjuvant therapies and prognosis in these patients than in the non-biopsy group . Similarly, the selection bias exists for whether to perform PNB on patients preoperatively. Therefore, we performed PSM for the main factors of whether to choose PNB or BB preoperatively, such as the general condition of the patient and the location of the tumor, and for the main factors affecting prognosis, such as the scope of surgery, pathological stage, pathological type, and postoperative adjuvant therapy, to make the patients comparable between groups as much as possible. After PSM, the results showed that preoperative PNB or BB had no significant effect on RFS and OS after radical surgery in NSCLC patients. It is suggested that these diagnostic manipulations are safe and do not significantly affect the prognosis of patients with stage I NSCLC. Several previous studies also support our speculation. Most studies focused on preoperative PNB, as Moon et al.  found that preoperative CT-guided PNB may not affect the OS and RFS of patients with radical resection for stage I NSCLC. However, the study by Kashiwabara et al.  suggested that PNB may increase the risk of pleural metastases in patients with stage I lung cancer, especially in stage IB. However, in some other studies, no significant effect of preoperative PNB on pleural recurrence has been reported in patients with early-stage lung cancer [29, 30]. Considering that pleural invasion is an important risk factor for ipsilateral pleural recurrence and an indicator of stage IB staging, it is controversial whether patients with pleural invasion are more likely to developed pleural metastasis due to preoperative puncture biopsy. In addition, with the improvement of puncture techniques, the current use of coaxial biopsy needles has also significantly reduced the possibility of needle tract implantation ; therefore, preoperative PNB for early-stage lung cancer is still considered safe. In one of the few studies addressing preoperative BB, Hu et al.  similarly showed that preoperative BB did not increase the risk of recurrence in patients with resected stage I NSCLC, but the study only compared RFS through stratified analysis without PSM. Our study was refined in this regard and reached similar conclusions, again showing that preoperative BB for early-stage lung cancer is safe without affecting OS and RFS in patients after radical surgery.
The present study also has some limitations. First, since this study was a retrospective study, it was difficult to match the patients exactly despite PSM. Some indicators were not included, such as whether lymph node dissection, visceral pleural invasion, and genetic mutations, because too many indicators might have affected the matching of the cases. Similarly, postoperative adjuvant therapy had an effect on OS, but selection bias for whether to perform adjuvant therapy after surgery and how often to receive it after surgery was difficult to avoid. Moreover, metabolic assessment (e.g., SUVmax) can also be helpful for PSM. However, this retrospective study recruited patients with stage I lung cancer, many of whom did not have metabolic assessment before surgery, so that we did not have sufficient data to include and analyze the metabolic assessment. Second, this was a single-center study with a small number of patients and an even more limited number of patients included after PSM. Therefore, a multicenter study that includes more patients is necessary to be conducted.