Neoadjuvant Treatment Research Articles

Reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform nonbinding recommendations that help guide the reimbursement decisions of Canada’s federal, provincial, and territorial governments, with the exception of Quebec. This review assesses pembrolizumab (Keytruda), 100 mg/4 mL vial, solution for infusion. Indication: For the treatment of adult patients with resectable stage II, IIIA, or IIIB (T3 to 4N2) non–small cell lung cancer in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment after surgery.

No validated biomarkers are available to monitor neoadjuvant treatment effects for breast cancer. Natural killer cell activity (NKA) has shown prognostic potential in other cancers. This study examined the association between NKA and treatment response. Patients had blood samples collected at baseline, before each treatment, and pre- and postoperatively. Plasma IFNγ levels were measured by ELISA as a surrogate marker of NKA, with 250 pg/mL as the cutoff for normal versus low NKA. Study endpoints were residual cancer burden (RCB) class, overall survival (OS), and invasive disease-free survival (IDFS). Seventy-eight patients were included. The five-year IDFS was 88.1% (95% confidence interval (CI) 73.7–94.9%) for patients with normal NKA versus 71.5% (95% CI 40.6–88.2%) for patients with low NKA (p = 0.049) preoperatively. At the fifth treatment cycle, the median IFNγ was 11 pg/mL (interquartile range (IQR) 0.5–124 pg/mL) in patients receiving supportive prednisolone and 753 pg/mL (IQR 192–1580 pg/mL) in patients not receiving supportive prednisolone. At the sixth treatment cycle, the corresponding values were 7 pg/mL (IQR 0–15 pg/mL) and 806 pg/mL (IQR 180–1631 pg/mL) (p < 0.0001). In conclusion, NKA may have prognostic potential as a biomarker. This study is the first to demonstrate that prednisolone impairs NKA measurement in breast cancer patients.

CHFR, which encodes an E3 ubiquitin ligase previously implicated in regulating the premitotic checkpoint and response to taxanes, is silenced in a subset of breast cancers. Here we assessed the impact of differences in CHFR expression on sensitivity to various antimitotic agents in vitro and on response to neoadjuvant taxane treatment in the clinical setting. Colony forming assays as well as live cell imaging in human breast cancer cell lines indicated that CHFR downregulation is associated with increased sensitivity to PLK1 inhibitors as well as paclitaxel in vitro that reflects premature mitotic exit and increased multinucleation. To assess the relationship between CHFR expression and neoadjuvant taxane response, we utilized immunohistochemistry to examine CHFR expression in the inter-regimen biopsy from 81 patients on the I-SPY neoadjuvant breast cancer trial (NCT01042379) who had dynamic contrast-enhanced breast MRIs before and after paclitaxel monotherapy. CHFRLow cancers had indistinguishable volumes before taxane therapy but smaller MRI tumor volumes after paclitaxel [median 0.07 cm3 (interquartile range 0–1.1) in CHFRLow versus 1.1 cm3 (0.02–5.0) in CHFRHigh cancers, p = 0.03 by rank sum test]. Moreover, there was a strong association between higher CHFR expression and lower relapse-free survival in estrogen receptor (ER) positive, HER2 negative cancers (HR 7.8, p = 0.024). These observations identify CHFR as a potential predictive marker of sensitivity in ER positive breast cancer that warrants further investigation and suggest that CHFR might also be associated with response to certain other mitotic inhibitors.

Immune checkpoint inhibitors (ICI) have transformed the management of advanced hepatocellular carcinoma (HCC), yet their integration in the perioperative setting remains insufficiently explored. This study aims to investigate the effect of hepatectomy on the tumor microenvironment and assess whether neoadjuvant or adjuvant anti-PD-1 therapy offers improved therapeutic outcomes. Using a murine orthotopic HCC model, a non-curative partial hepatectomy was performed, removing a non-tumor-bearing lobe with anti-PD-1 administered as neoadjuvant or adjuvant therapy. In a separate experiment, curative hepatectomy (resection of the tumor-bearing lobe) was performed to evaluate recurrence and survival. Anti-PD-1 therapy significantly reduced tumor growth in non-surgical settings (p=0.0094), but its efficacy was lost in the adjuvant setting. This loss correlates with reduced infiltration of effector memory CD103⁺CD8⁺ T cells, increased expression of exhaustion markers (TIM-3, LAG-3), and accumulation of myeloid-derived suppressor cells (MDSC). MDSC depletion at the time of surgery improved adjuvant efficacy (p=0.0084), and delaying adjuvant ICI partially rescued responses, indicating a temporary postoperative immunosuppressive window. By contrast, neoadjuvant anti-PD-1 therapy significantly reduced tumor burden (p=0.0005), enhanced immune cell infiltration, and increased the expression of key activation markers on CD8+ cells (Tbx21, Gzma, Cxcr6, Cd69). Moreover, neoadjuvant treatment significantly reduced recurrence rates compared to sham treatment (35% vs. 68%, p=0.0405) and improved survival (p=0.0373), which was not achieved with adjuvant therapy. Partial hepatectomy disrupts antitumor immunity and limits adjuvant ICI efficacy. Neoadjuvant anti-PD-1 immunotherapy offers a superior strategy compared to adjuvant immunotherapy in enhancing immune responses and reducing HCC recurrence.

Background/Objectives: De-escalation of axillary surgery with sentinel lymph node biopsy (SLNB) has been shown to decrease morbidity in breast cancer patients without affecting oncological outcomes. However, there are very few reports on its applicability in real-world clinical practice, especially in middle-income countries. Methods: A retrospective historical cohort study was conducted, including 787 patients with clinical stage I–IIIA breast cancer treated from 2013 to 2023 at the INC in Colombia. Two groups were analyzed based on the timing of the axillary procedure: patients undergoing SLNB as initial surgery (Upfront SLNB) and those receiving neoadjuvant chemotherapy (Post-NACT SLNB). Results: The overall sentinel lymph node (SLN) identification rate was 99.3%. SLN positivity was 32% in Upfront SLNB and 13.1% in Post-NACT SLNB. Axillary lymph node dissection (ALND) was omitted in 56% of patients with node-positive Upfront SLNB; it was avoided in 86.8% of the Post-NACT group with complete axillary response (ypN0). Regional recurrence rates were 2.33%. In multivariate analysis, the main factors linked to recurrence and mortality were triple-negative and luminal B HER2-negative biological subtypes, histological grade 2, and tumor size ≥ 2 cm. At 60 months of follow-up, 91.4% (95% CI: 88.9–93.9) of patients remained recurrence-free (time-recurrence (TR)), and overall survival (OS) was 96.1% (95% CI: 94.5–97.7), with no differences observed based on the axillary surgical strategy. Conclusions: Sentinel lymph node biopsy (SLNB) is an oncologically safe procedure for patients with early-stage and locally advanced breast cancer with an adequate response to neoadjuvant systemic treatment.

Simple SummaryThe use of neoadjuvant therapies in patients with hepatocellular carcinoma prior to liver transplantation has gained increasing relevance in recent years, yet evidence regarding their impact on post-transplant outcomes remains limited. This study aimed to assess the effect of neoadjuvant therapies on overall survival following liver transplantation in patients with hepatocellular carcinoma and to compare outcomes across treatment modalities with respect to tumor burden. A total of 107 patients were analyzed, including 90 who underwent neoadjuvant treatment. Therapeutic strategies comprised SIRT, TACE, liver resection, and combined SIRT/TACE. Neoadjuvant therapy was associated with a significant survival benefit after liver transplantation. TACE demonstrated the greatest efficacy in patients meeting established transplant criteria, typically characterized by lower tumor burden, whereas SIRT conferred superior benefit in patients with higher tumor burden or those beyond conventional listing criteria.Background: The use of neoadjuvant therapies in patients with hepatocellular carcinoma prior to liver transplantation has gained increasing popularity in recent years. To date, there are only limited data investigating the impact of neoadjuvant therapy on post-transplant survival. Methods: In this retrospective study, we evaluated patients with hepatocellular carcinoma who underwent deceased donor or living donor liver transplantation at Jena University Hospital between 2019 and 2023. Comprehensive clinical and pathological variables were systematically analyzed, including correlations between neoadjuvant therapy use, tumor burden and overall survival. Survival outcomes were estimated using the Kaplan–Meier method. Results: A total of 107 patients were included in the analysis, of whom 90 received neoadjuvant therapy prior to transplantation. Treatment modalities comprised SIRT, TACE, liver resection and combined SIRT and TACE. The 1-, 3-, and 5-year OS rates following transplantation were 93.5%, 82.2%, and 79.4%, respectively. Recurrence-free survival at 1, 3, and 5 years was 91.6%, 85.0%, and 83.2%, respectively. Among the various neoadjuvant strategies, SIRT and TACE yielded the highest OS rates. Patients listed outside the transplantation criteria (Milan, UCSF, up-to-seven) at the time of initial diagnosis who underwent SIRT had significantly better OS than those outside the criteria who underwent TACE. In contrast, among patients within the Milan, UCSF and up-to-seven criteria, TACE was associated with superior OS compared with SIRT. Conclusion: The use of neoadjuvant therapies confers a significant survival benefit following liver transplantation in patients with HCC. TACE appears to be most suitable for patients listed within established transplantation criteria, who consequently have a lower tumor burden. In contrast, SIRT is more beneficial for patients with a higher tumor burden and those beyond standard transplantation criteria. A limitation of our study, however, is that the included SIRT cohort comprised only 24 patients, and TACE was preferentially performed in patients with a lower tumor burden, which means that a selection bias cannot be fully excluded. Overall, further studies are required to define the optimal bridging strategies.

Background: HER2-positive breast cancer accounts for 15-20% of all breast cancer cases. Neoadjuvant therapy has significantly improved treatment outcomes, particularly with HER2-targeted agents such as trastuzumab and pertuzumab. Objective: To compare pathological complete response rates in stage II and III HER2-positive breast cancer patients receiving neoadjuvant therapy with or without pertuzumab. Methods: This retrospective observational study was conducted at a tertiary care hospital in Karachi. Medical records of patients aged ≥18 years with stage II or III HER2-positive breast cancer who received neoadjuvant chemotherapy between January 2022 and December 2023 were reviewed. Patients were grouped based on HER2 blockade strategy: single-agent trastuzumab versus dual-agent trastuzumab plus pertuzumab. The primary endpoint was pathological complete response (pCR). Results: A total of 79 patients were included, with 66 (83.5%) receiving dual HER2 blockade and 13 (16.5%) receiving trastuzumab alone. The pCR rate was 60.6% in the dual blockade group and 53.8% in the trastuzumab-alone group (p=0.650). However, when assessed using a three-tier classification (no response, partial response, complete response), a significant difference was observed (p=0.040), with no absolute non-responders in the dual blockade group. On multivariate analysis, ER-negative status (OR = 7.17, p=0.026), taxane use (OR = 15.13, p=0.003), and high-grade tumors (OR = 0.185, p=0.028) were significant predictors of pCR. Dual HER2 blockade was not an independent predictor (p=0.163). Conclusion: Dual HER2 blockade did not significantly increase overall pCR rates but was associated with eliminating non-response, suggesting a potential role in reducing treatment failure. ER status, tumor grade, and taxane-based regimens were key determinants of response. These findings underscore the need for individualized treatment strategies and cost-benefit considerations in low-resource settings.

Immune checkpoint blockade (ICB) has led to paradigm shifts in the treatment of various tumour types1-4, yet limited efficacy has been observed in patients with metastatic mismatch-repair proficient (pMMR) colorectal cancer5. Here we report clinical results and in-depth analysis of patients with early-stage pMMR colon cancer from the phase II NICHE study (ClinicalTrials.gov: NCT03026140). A total of 31 patients received neoadjuvant treatment of nivolumab plus ipilimumab followed by surgery. The response rate was 26% and included six patients with a major pathological response (≤10% residual viable tumour). One patient with an ongoing clinical complete response did not undergo surgery. Circulating tumour DNA (ctDNA) was positive in 26/31 patients at baseline, and clearance was observed in 5/6 responders prior to surgery, while 19/20 non-responders remained ctDNA+. Responses were observed despite a low tumour mutational burden in all tumours, while chromosomal genomic instability scores were significantly higher in responders compared to non-responders. Furthermore, responding tumours had significantly higher baseline expression of proliferation signatures and TCF1, and imaging mass cytometry revealed a higher percentage of Ki-67+ cancer and Ki-67+ CD8+ T cells in responders compared to non-responders. These results provide a comprehensive analysis of response to neoadjuvant ICB in early-stage pMMR colon cancers and identify potential biomarkers for patient selection.

Pathologic Response to Neoadjuvant Cetuximab, Platinum, and Taxane in Locally Advanced HNSCC.

Palbociclib plus letrozole versus weekly paclitaxel, both in combination with trastuzumab plus pertuzumab, as neoadjuvant treatment for patients with HR+/HER2+ early breast cancer: primary results from the randomized phase II TOUCH trial (IBCSG 55-17).

Rectal-sparing strategies for locally advanced rectal cancer are gaining interest owing to favorable oncological results and reduced impact on functional outcomes. In patients managed with watch-and-wait or local excision after neoadjuvant chemoradiotherapy (nCRT), local regrowth occurs in approximately 15-30% of cases. Total mesorectal excision (TME) is the standard treatment for regrowth; however, local excision (LE) may be considered in selected cases to preserve rectal function. This narrative review evaluates clinical and oncological outcomes of patients undergoing LE for suspected regrowth. A narrative review of the literature was conducted using databases and search terms including "rectal cancer," "rectal sparing," and "local regrowth." Five retrospective studies were identified, encompassing a total of 159 patients. Treatment protocols, neoadjuvant regimens, and follow-up strategies varied across the studies. Histopathological findings revealed ypT ≥ 2 in 45.3% of cases. Reported overall survival (OS) was consistently above 94.5%, while 2-year locoregional recurrence-free survival ranged from 74% to 85%. Systemic recurrence occurred in 9.1% of patients. LE was associated with shorter operative time, reduced blood loss, and lower rates of Clavien-Dindo ≥ 3 complications. Local excision for regrowth may represent a feasible alternative to radical surgery in selected patients, particularly within specialized centers and under strict surveillance protocols. Further prospective studies are warranted to validate its long-term oncologic safety and functional outcomes.

Esophageal cancer has a low 5-year survival rate despite treatments. scRNA-seq and MR offer insights into neoadjuvant treatment efficacy for precision medicine. Three post-neoadjuvant treatment datasets underwent QC for Seurat analysis. Marker genes identified cell subsets. MR analyzed eQTL data from GWAS cohorts for causal links. Single-cell and MR-derived genes intersected to reveal PLTP in CD4⁺T cells. Single-cell analysis of 16 samples found 40,198 genes and 120,102 cells. CD4⁺T cell numbers differed significantly between groups after therapy. Differentially expressed genes were immune-related. Pseudotime and cell-cell communication varied. PLTP, linked to esophageal cancer, co-expressed with genes involved in cell cycle processes. The study highlights CD4⁺T cells' predictive role in therapy efficacy via scRNA-seq and MR. PLTP emerges as a key gene, offering new precision medicine strategies for esophageal cancer.

BackgroundThis study evaluates the long-term anorectal function and rectal toxicity in rectal cancer patients who achieved a clinical complete response (cCR) to total neoadjuvant treatment (TNT) and were managed with a watch-and-wait (W&W) approach. While oncological outcomes have been favorable, functional outcomes warrant further investigation. Additionally, this research identifies clinical risk factors of anorectal dysfunction post-treatment.MethodsThis was a single-center, cross-sectional study. Rectal cancer patients who underwent TNT followed by W&W between December 2014 and November 2020 were recruited. A minimum 2-year follow-up with no disease progression was required. The study took the form of semi-structured interviews. Multiple scales for evaluation were used, including the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scale, the Late Effects of Normal Tissues/Subjective Objective Management Analytic (LENT/SOMA) system, the Wexner score, the Low Anterior Resection Syndrome (LARS) score and the Memorial Sloan Kettering Cancer Center Bowel Function Instrument (MSKCC BFI). Univariate analysis and multi-factor Logistic regression were used to identify the risk factors for anorectal dysfunction.ResultsOut of 70 patients with a median follow-up of 43 months, less than half experienced grade I (28/70, 40.0%) or II (1/70, 1.4%) late rectal toxicity according to the RTOG/EORTC criteria, with no cases of more severe toxicity. The prevalence of fecal urgency was the most significant symptom reported (42/70, 60.0%). The median LARS score was 16 [interquartile ranges (IQR) 4–25]; 17.1% (12/70) of patients had minor LARS and 15.7% (11/70) had major LARS. The median Wexner score was 2 (IQR 0–3). The median MSKCC BFI total score was 82.5 (IQR 77–86). Smoking history was an independent risk factor for long-term anorectal dysfunction [odds ratio (OR) 6.562, 95% confidence interval (CI) 1.561–27.590].ConclusionMost rectal cancer patients under a W&W strategy after TNT sustain acceptable anorectal function, though fecal urgency remains a common issue. Smoking history emerged as a significant risk factor for anorectal dysfunction. Larger prospective studies focusing on bowel function are needed.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13014-025-02732-6.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and remains a leading cause of cancer-related mortality, particularly among younger men. Approximately one-third of colorectal cancers occur in the rectum. For patients with locally advanced rectal cancer, neoadjuvant therapy is considered the standard treatment approach. Despite advances in therapeutic approaches, improvements in the 5-year survival rate have been modest. Accurate assessment of tumor response to neoadjuvant therapy (NAT) is critical for guiding subsequent treatment strategies, especially when considering eligibility for non-operative management (NOM). Common evaluation methods include digital rectal examination (DRE), magnetic resonance imaging (MRI), and high-definition flexible endoscopy (HDFE). Tumor regression grading (TRG) systems-both histopathological (pTRG) and MRI-based (mrTRG)-are valuable tools for quantifying treatment response and predicting long-term outcomes. However, resistance to NAT remains a significant clinical challenge and is driven by a complex interplay of molecular mechanisms. Genetic factors, such as RAS mutations, have been linked to resistance to chemoradiotherapy (CRT), while tumors exhibiting microsatellite instability (MSI-high) tend to respond poorly to CRT but may show favorable outcomes with immune checkpoint inhibitors. Epigenetic pathways, including dysregulation of Wnt/β-catenin and PI3K/AKT signaling, along with alterations in DNA damage repair mechanisms, further influence CRT sensitivity. The tumor microenvironment also plays a pivotal role in modulating therapy response. Elements such as immune cell infiltration, hypoxia, angiogenesis, and the presence of cancer-associated fibroblasts (CAFs) contribute to a pro-resistance landscape. Moreover, emerging evidence suggests that gut microbiota composition-particularly an enrichment of Bacteroides species-is associated with diminished response to NAT. Understanding these multifaceted biological interactions is essential for developing personalized and more effective therapeutic strategies, with the goal of enhancing response to NAT and ultimately improving clinical outcomes in patients with rectal cancer.

Background: Pathological complete response (pCR) following neoadjuvant therapy (NAT) is a key surrogate marker for long-term outcomes in HER2-positive breast cancer. Identifying clinical and biological predictors of pCR, including systemic inflammatory and nutritional markers such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-albumin ratio (NAR), C-reactive protein-to-albumin ratio (CAR), systemic immune-inflammation index (SII), and prognostic nutritional index (PNI), may help refine treatment strategies and improve patient outcomes. Methods: We retrospectively analyzed 174 patients with stage II–III HER2-positive breast cancer who received neoadjuvant anti-HER2-based regimens at multiple centers between 2010 and 2025. Demographic, clinicopathological, and laboratory data were collected, and inflammatory and nutritional indices (NLR, PLR, LMR, NAR, CAR, SII, PNI) were calculated. Predictors of pCR were evaluated using univariate and multivariate logistic regression analyses. Results: Overall, 49% of patients achieved pCR. In multivariate analysis, independent predictors of pCR were hormone receptor negativity, smaller tumor size, HER2 IHC 3+ expression, dual HER2 blockade, and a higher prognostic nutritional index (PNI ≥ 55). In contrast, systemic inflammatory indices such as NLR, PLR, LMR, NAR, CAR, and SII were not significantly associated with pCR. Conclusions: This multicenter real-world study demonstrates that conventional inflammatory markers have limited predictive value, whereas the PNI emerges as a simple and practical biomarker reflecting nutritional and immune status. Integrating PNI with clinicopathological factors may enhance risk stratification and help guide individualized neoadjuvant treatment strategies in HER2-positive breast cancer.

Neoadjuvant immunotherapy for resectable stage III melanoma has demonstrated promising outcomes in recent trials, prompting a change in clinical practice in many countries. Although therapeutic lymph node dissection (TLND) remains the standard of care after neoadjuvant treatment, a less invasive index lymph node (ILN)-guided approach has been proposed. The global melanoma community's acceptance of neoadjuvant immunotherapy and the need for TLND or ILN after this remains unclear. A two-stage international survey was conducted among melanoma experts between May 2023 and January 2025. Respondents were asked about their familiarity with neoadjuvant trials, current practices, and opinions on ILN versus TLND before and after publication of the NADINA trial. The response rates were 50% (118/237) in the first survey and 62% (148/237) in the second survey. In the second survey, 74% of the respondents considered neoadjuvant therapy the standard of care, and support for ILN-guided surgery rose from 27 to 40% between the surveys. However, 54% still favored a phase 3 randomized controlled trial before changing the clinical practice guidelines, and only 27% believed the current data were sufficient for adoption of ILN as standard. Key barriers included concerns about oncologic safety, pathologic standardization, and patient selection. The current evidence supports the use of neoadjuvant immunotherapy as the standard of care for stage III melanoma. However, widespread clinical adoption of ILN-guided surgical de-escalation remains limited. A multicenter phase 3 trial (MSLT-3), launching in 2025, is expected to provide important data to guide future practice.

Metastatic disease traditionally classifies gastric cancer as stage M1, precluding surgical intervention and enrolling patients in palliative treatment protocols. This principle holds regardless of the number, the location, and the quantity of metastatic sites. "Oligometastatic disease" is an intermediate state between localized and widely spread gastric cancer. Locoregional treatments may offer long survival or even cure in highly selected cases. There are no evidence-based guidelines for the appropriate management of this clinical entity. Tailored strategic techniques are required to incorporate surgical treatment, when applicable, into the management protocols of these patients. The surgical approach (following neoadjuvant treatment) aiming at R0 resection of neoplasms that are technically or oncologically unresectable, or only borderline resectable at initial evaluation is defined as "conversion therapy". The surgical approach aims at locoregional control of the disease, radical resection of all cancer sites, adequate lymph node cleansing and uncomplicated anastomosis. Disease progression is a clear indication of palliative treatment. In this article, we aim to provide an extensive literature search about current status of oligometastatic gastric disease multimodal treatment. Given the malignancy potential of gastric cancer, the decision for an operative approach should be made with strict criteria by experienced surgeons and rational oncologists.

Outcomes with neoadjuvant osimertinib and/or chemotherapy in patients with EGFR-mutant resectable non-small cell lung cancers.

Intraductal Carcinoma Predicts Poor Response to Neoadjuvant Therapy in High-risk Prostate Cancer: A Retrospective Analysis of a Prospective Trial

Aim of this study is to evaluate the prognostic role of nodal parameter in early stage pathologically patients with N0 who underwent lobectomy and lymphadenectomy. Clinical and pathological characteristics of patients who underwent anatomical lung resection from 1/01/2010 to 31/12/2019 were reviewed and retrospectively analyzed. GGO and part-solid tumors, MIA, AIS, more than 5cm in size, with nodal and/or distant metastases, or receiving neoadjuvant treatment were excluded. Operatory and pathological report were reviewed to collect data on lymphadenectomy. The primary end-point was disease-free survival (DFS), calculated from surgery to recurrence appearance. Clinical/pathological characteristics and nodal parameters were associate to DFS using Kaplan-Meier curves. The log-rank test was used to assess differences between subgroups. A multivariable model was built using Cox-regression analysis, including variable resulting significant (p value<0.05), at univariable analysis. The final analysis was conducted on 487 patients. Most patients presented stage I tumor (82.4%). The mean number of resected nodes (#RN), resected N1 (#RN1) nodes, and resected N2 nodes (#RN2) resulted 9.5±8.0, 3.4±4.3, and 5.9±4.4. The mean number of total resected stations (#RS), N1 resected stations (#RSN1), and N2 resected stations (#RSN2) resulted 2.5±1.6, 1±0.8, and 1.5±1.2, respectively. During a mean follow-up of 43±28months, a recurrence occurred in 137 (28.1%) patients. At univariable analysis, age<70years (p=0.025), N1 lymphadenectomy (p=0.019), #RSN1≥3 (p=0.001), #RN≥10 (p=0.019), #RN1≥3 (p<0.001), node sampling with more than 3 resected nodes (p=0.049), at least 3 stations with 3 N1 nodes resected (p=0.013), at least 3 stations resected with 10 lymphnodes, and 3N1 lymphnodes (p=0.020) significantly correlated with improved DFS. Multivariable analysis confirmed as independent prognostic factor #RN1≥3 (p=0.017; HR 1.782; and 95% CI: 1.107-2.867). Patients with #RN1≥3 presented a 5-years DFS of 76.3% versus 57.8% of patients with #RN1<3 (p=0.001). Hilar lymphadenectomy seems to significantly correlate with disease-free survival in patients with pN0NSCLC and should be better defined in lymphadenectomy guidelines.