Surgically Treated pT2aN0M0 (Stage IB) Non-Small Cell Lung Cancer: A 20-Year Single-Center Retrospective Study.

Introduction The suitability of adjuvant therapy (AT) in patients with stage IB non-small cell lung cancer (NSCLC) is still under debate considering the cost-benefit ratio between improvement in survival and side effects. We retrospectively evaluated survival and incidence of recurrence in radically resected stage IB NSCLC, to determine whether AT could significantly improve prognosis. Methods Between 1998 and 2020, 4692 consecutive patients underwent lobectomy and systematic lymphadenectomy for NSCLC. Two hundred nineteen patients were pathological T2aN0M0 (>3 and ≤4 cm) NSCLC 8th TNM. None received preoperative or AT. Overall survival (OS), cancer specific survival (CSS) and the cumulative incidence of relapse were plotted and log-rank or Gray's tests were used to assess the difference in outcome between groups. Results The most frequent histology was adenocarcinoma (66.7%). Median OS was 146 months. The 5-, 10-, and 15-year OS rates were 79%, 60%, and 47%, whereas the 5-, 10-, and 15-year CSS were 88%, 85%, and 83%, respectively. OS was significantly related to age (p < 0.001) and cardiovascular comorbidities (p = 0.04), whereas number of LNs removed was an independent prognostic factor of CSS (p = 0.02). Cumulative incidence of relapse at 5-, 10-, and 15-year were 23%, 31%, and 32%, respectively, and significantly related to the number of LNs removed (p = 0.01). Patients with more than 20 LNs removed and clinical stage I had a significantly lower relapse (p = 0.02). Conclusions Excellent CSS, up to 83% at 15-year, and relatively low risk of recurrence for stage IB NSCLC (8th TNM) patients suggested that AT for those patients could be reserved only for very selected high-risk cases.

An evaluation of the methodological quality of published guidelines for the surgical treatment of pleural mesothelioma.

BACKGROUND: To benchmark their quality, a project was designed to analyze the methodology of previous guidelines and recommendations for malignant pleural mesothelioma projects. METHODS: A narrative literature search was conducted, and each guideline was evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool and rated on a seven-point scale for its many items and domains. RESULTS: Six guidelines that met the inclusion requirements were evaluated. Due to greater development rigor and editorial independence, the engagement of scientific societies was associated with an improvement in methodological quality. CONCLUSION: According to the standards of AGREE II, the methodological quality of earlier guidelines was relatively low. Nonetheless, two previously published guidelines could serve as a template for the establishment of the most effective methodological quality guidelines.

Surgical Resection of Pulmonary Metastases from Melanoma in Oligometastatic Patients: Results from a Multicentric Study in the Era of Immunoncology and Targeted Therapy.

In the last decade, the emergence of effective systemic therapies (ESTs) in the form of both targeted and immuno-based therapies has revolutionized the treatment of patients with advanced stage III and stage IV melanoma. Even though lungs represent the most frequent site of melanoma metastases, only limited data are available on the role of surgery in isolated pulmonary metastases from malignant melanoma (PmMM) in the era of ESTs. The aim of this study is to describe the outcomes of patients who underwent metastasectomy of PmMM in the era of ESTs, in order to identify prognostic factors affecting survival and to provide a framework for more informed patient selection of treatmeant with lung surgery in the future. Clinical data of 183 patients who underwent metastasectomy of PmMM between June 2008 and June 2021 were collected among four Italian Thoracic Centers. The main clinical, surgical and oncological variables reviewed were: sex, comorbidities, previous oncological history, melanoma histotypes and primary site, date of primary cancer surgical treatment, melanoma growth phase, Breslow thickness, mutation pattern disease, stage at diagnosis, metastatic sites, DFI (Disease Free Interval), characteristics of lung metastases (number, side, dimension, type of resection), adjuvant therapy after lung metastasectomy, site of recurrence, disease-free survival (DFS) and cancer-specific survival (CSS; defined as the time interval between the first melanoma resection or lung metastasectomy and death from cancer). All patients underwent surgical resection of the primary melanoma before lung metastasectomy. Twenty-six (14.2%) patients already had a synchronous lung metastasis at the time of primary melanoma diagnosis. A wedge resection was performed in 95.6% of cases to radically remove the pulmonary localizations, while an anatomical resection was necessary in the remaining cases. The incidence of major post-operative complications was null, while only 21 patients (11.5%) developed minor complications (mainly air leakage followed by atrial fibrillation). The mean in-hospital stay was 4.46 ± 2.8 days. Thirty- and sixty-day mortality were null. After lung surgery, 89.6% of the population underwent adjuvant treatments (47.0% immunotherapy, 42.6% targeted therapy). During a mean FUP of 107.2 ± 82.3 months, 69 (37.7%) patients died from melanoma disease, 11 (6.0%) from other causes. Seventy-three patients (39.9%) developed a recurrence of disease. Twenty-four (13.1%) patients developed extrapulmonary metastases after pulmonary metastasectomy. The CSS from melanoma resection was: 85% at 5 years, 71% at 10 years, 54% at 15 years, 42% at 20 years and 2% at 25 years. The 5- and 10-year CSS from lung metastasectomy were 71% and 26%, respectively. Prognostic factors negatively affecting CSS from lung metastasectomy at multivariable analysis were: melanoma vertical growth (p = 0.018), previous metastatic sites other than lung (p < 0.001) and DFI < 24 months (p = 0.007). Our results support the evidence that surgical indication confirms its important role in stage IV melanoma with resectable pulmonary metastases, and selected patients can still benefit from pulmonary metastasectomy in terms of overall cancer specific survival. Furthermore, the novel systemic therapies may contribute to prolonged survival after systemic recurrence following pulmonary metastasectomy. Patients with long DFI, radial growth melanoma phase and no site of metastatization other than lung seem to be the best candidate cases for lung metastasectomy; however, to drive stronger conclusions, further studies evaluating the role of metastasectomy in patients with iPmMM are needed.

The Role of Surgery in High-Grade Neuroendocrine Cancer: Indications for Clinical Practice.

Pulmonary neuroendocrine tumors (pNET) represent a particular type of malignant lung cancers and can be divided into well-differentiated low-grade NET and poorly-differentiated high-grade NET. Typical and atypical carcinoids belong to the first group while large cell neuroendocrine carcinomas (LCNEC) and small-cell lung cancers (SCLC) belong to the second one. The aim of this mini-review is to focus on the role of surgical therapy for high grade neuroendocrine tumors. SCLC has the worst prognosis among all lung cancer neoplasms: in fact, the two-year survival rate is about 5% and median survival usually ranges between 15 and 20 months. The surgical treatment of SCLC has thus infrequently been judged as a valuable aspect of the therapeutic approach, the gold standard treatment being a combination of platinum-based chemotherapy and radiotherapy. As LCNEC are rare, there is a lack of extensive literature and randomized clinical trials, therefore the curative approach is still controversial. Current treatment guidelines suggest treating LCNEC by surgical resection in non-metastatic stages and recommend adjuvant chemotherapy according to SCLC protocol. Upfront surgery is suggested in early stages (from I to IIB), a multimodality approach is recommended in locally advanced stages (III) while surgery is not recommended in stage IV LCNEC. The rate of surgical resection is quite low, particularly for SCLC, ranging from 1 to 6% in limited diseases; lobectomy with radical lymphadenectomy is considered the gold standard surgical procedure in the case of limited disease SCLC and resectable LCNEC; pneumonectomy, although reported as an effective tool, should be avoided in the light of local and distant recurrence rates.

Unplanned Return to the Operating Room after Elective Oncologic Thoracic Surgery: A Further Quality Indicator in Surgical Oncology.

Background: An unplanned return to the operating room (UROR) is defined as a readmission to the operating room because of a complication or an untoward outcome related to the initial surgery. The aim of the present report is to evaluate the role of URORs after elective oncologic thoracic surgery. Methods: In the study, 4012 consecutive patients were enrolled; among them, 71 patients (1.76%) had an unplanned return to the operating room. Age, sex, Charlson comorbidity index, induction treatments, type of the first operation, indication to readmission to the operating room and type of second operation, length of stay, complication after reoperation and outcomes were collected. Results: The mean age was 63.3 (SD: 13.0); there were 53 male patients (74.6%); the type of the first procedure was: lower lobectomy (11.3%), middle lobectomy (1.4%), upper lobectomy (22.5%), metastasectomy (5.6%), extrapleural pneumonectomy (4.2%), pneumonectomy (40.9%), pleural biopsy (5.6%) and other procedures (8.5%). Patients presenting complications after UROR had undergone a significantly longer first procedure (p < 0.02), had a longer length of stay (p < 0.001) and had higher post-operative mortality (p < 0.001). Conclusions: The patients experiencing UROR after elective oncologic thoracic surgery have significantly higher morbidity and mortality rates when compared to standard thoracic surgery. Bronchopleural fistula remains the most lethal complication in patients undergoing UROR.

The Interdisciplinary Management of Lung Cancer in the European Community.

Lung cancer continues to be the largest cause of cancer-related mortality among men and women globally, accounting for around 27% of all cancer-related deaths. Recent advances in lung cancer medicines, particularly for non-small-cell lung cancer (NSCLC), have increased the need for multidisciplinary disease care, thereby enhancing patient outcomes and quality of life. Different studies in the European community have evaluated the impact of multidisciplinary care on outcomes for lung cancer patients, including its impact on survival, adherence to guideline treatment, utilization of all treatment modalities, timeliness of treatment, patient satisfaction, quality of life, and referral to palliative care. This publication will examine the roles and duties of all multidisciplinary members and the influence of multidisciplinary care on lung cancer outcomes in Europe. Multidisciplinary treatment is the foundation of lung cancer treatment. The optimal setting for interdisciplinary collaboration between specialists with complementary functions is multidisciplinary meetings. Multidisciplinary care in lung cancer facilitates the delivery of a high-quality service, which may improve lung cancer patients' survival, utilization of all treatment modalities, adherence to guideline management, and quality of life, despite the fact that only limited observational data have demonstrated these results. To confirm the relationship between multidisciplinary treatment and improved lung cancer patient outcomes, however, further research is required.

State of the art and new perspectives in surgical treatment of lung cancer: a narrative review.

Background and Objective: Lung cancer is the leading cause of cancer-related deaths worldwide, and its incidence has increased over the past two decades. The standard care for stage I, stage II, and selected cases of stage IIIA non-small cell lung cancer (NSCLC) is surgical resection; in some cases, patients may be offered adjuvant systemic therapy after surgical resection. Patients with lung cancer presenting with distant metastases belong to stage IV: in this setting, some carefully selected patients may benefit from surgery within a multimodality approach. Methods: We performed a comprehensive, non-systematic review of the latest literature to define the present role of surgery in lung cancer treatment. Key Content and Findings: The literature review disclosed a pivotal role of surgery in early stage lung cancer and a complimentary role in locally advanced lung cancer; in very selected cases, surgery might be considered in oligometastatic disease. Conclusions: Surgical treatment of lung cancer still plays a pivotal role in early stages of the disease while, in locally advanced stages, it may contribute to improve overall survival in combination with medical treatments and radiotherapy. More recently, an effective role of surgery has been advocated in carefully selected oligometastatic patients with encouraging initial results.

Minimally Invasive Anatomical Segmentectomy versus Lobectomy in Stage IA Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVE: A systematic review and meta-analysis was performed to assess potential differences in perioperative outcomes and disease-free survival (DFS) and overall survival (OS) of patients with pathological stage IA non-small cell lung cancer (NSCLC) who underwent minimally invasive anatomical segmentectomy or lobectomy. METHODS: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search of EMBASE (through Ovid), MEDLINE (via PubMed), and Cochrane CENTRAL was conducted. Two researchers independently reviewed each eligible study that included patients with stage IA NSCLC who underwent minimally invasive anatomical segmentectomy and lobectomy and compared perioperative and/or survival outcomes of patients. RESULTS: A total of 887 publications were identified. Of these, 10 articles met our eligibility criteria. A significantly higher number of lymph nodes were harvested in lobectomies. The two groups did not significantly differ in postoperative complication rates, DFS, and OS. Patients who underwent segmentectomy had shorter postoperative hospital stays. CONCLUSIONS: Minimally invasive lobectomy and segmentectomy showed comparable short-term and long-term outcomes in stage IA NSCLC patients. Postoperative complication rates were similar. Minimally invasive lobectomies are associated with a higher number of harvested lymph nodes, although this did not affect the final staging or the survival outcomes.

CT-Derived Body Composition Values and Complications After Pneumonectomy in Lung Cancer Patients: Time for a Sex-Related Analysis?

Purpose: This study aimed to assess if CT-derived body composition values and clinical characteristics are associated with the risk of postsurgical complications in men and women who underwent pneumonectomy for lung cancer. Materials and Methods: Patients who underwent pneumonectomy between 2004 and 2008 were selected. The ethics committee approved this retrospective study with waiver of informed content. Main clinical data collected were sex, age, weight and height to calculate body mass index (BMI), albumin, C-reactive protein, smoking status, side, sarcopenia, presurgical treatments, reoperation, and complications within 30 days after pneumonectomy, classified as: lung complications, cardiac complications, other complications, and any complication. From an axial CT image at the level of L3, automatic segmentations were performed to calculate skeletal muscle area (SMA), skeletal muscle density, subcutaneous adipose tissue, and visceral adipose tissue. Skeletal muscle index was calculated as SMA/square height. Univariate and multivariate logistic regression analyses were performed to estimate the risk of any complication, both on the total population and in a by sex subgroup analysis. All tests were two tailed and considered significant at 5% level. Results: A total of 107 patients (84 men and 23 women) were included. Despite no significant differences in BMI, there were significant differences of body composition values in muscle and adipose tissue parameters between men and women, with women being significantly more sarcopenic than men (p = 0.002). Separate analyses for men and women showed that age and SMA were significantly associated with postoperative complications in men (p = 0.03 and 0.02, respectively). Conclusions: Body composition measurements extracted from routine CT may help in predicting complications after pneumonectomy, with men and women being different in quantity and distribution of muscle and fat, and men significantly more prone to postpneumonectomy complications with the increase of age and the decrease of skeletal muscle area.

Analysis of Molecular Biomarkers in Resected Early-Stage Non-Small Cells Lung Cancer: A Narrative Review.

Next-generation sequencing has become a cornerstone in clinical oncology practice and is recommended for the appropriate use of tailored therapies in NSCLC. While NGS has already been standardised in advanced-stage NSCLC, its use is still uncommon in the early stages. The recent approval of Osimertinib for resected EGFR-mutated NSCLC in an adjuvant setting has launched the hypothesis that other targeted therapies used in metastatic patients can also lead to improved early-stage outcomes of NSCLC. The impact of molecular biomarkers on the prognosis of patients undergoing radical surgery for NSCLC is still unclear. Notably, the heterogeneous populations included in the studies that analysed surgical patients could be the main reason for these results. In this review, we report the most important studies that analysed the impact of principal molecular biomarkers on the survival outcomes of patients who underwent radical surgery for NSCLC.

Surgical management of superior sulcus tumors: A twenty-year experience of an oncological high volume referral centre.

Objectives: Superior sulcus tumour, which affects the lung's apex, is an uncommon subtype of non-small cell lung cancer (NSCLC). The current study examined the clinical characteristics and management of superior sulcus NSCLC patients in a high-volume referral oncological centre over 22 years. Methods: Retrospective review of 100 surgeries with curative intent for superior sulcus NSCLC over 22 years (July 1998 - December 2020). The surgical approach was defined according to the lesion site and the anatomy of the thoracic inlet. Survival curves, including non-cancer-related deaths, were drawn using the Kaplan-Meier methods, and the log-rank test was used to evaluate differences in survival across groups of patients. Cox proportional hazards regression was used to assess the association between selected clinical and pathologic characteristics on OS. Results: 54 patients received induction treatments. The surgical approach was anterior thoracotomy in 53 patients, Paulson incision in 30, and a combined in 8. The median postoperative length of stay was 11 days (range: 5 - 27 days). Overall 90-day mortality was 6.93%. The median OS was 24.3 months. After a median follow-up of 3 years, 5-year and 10-year OS rates were 33.9% and 26.4%, respectively. A significantly lower 5-year OS was observed in patients with the nodal disease (46.6% in pN0 vs 13.2% in pN+; p = 0.024), without preoperative treatments (41.0% in patients without preoperative treatments versus 17.4%; p = 0.09) and anteriorly located tumour (anterior vs posterior: 17.4% vs 49.1%; p = 0.032). Cox proportional hazards regression showed better survival in the pT1 stage (HR = 4.6; 95% CI: 1.9 - 11.2; p = 0.00076) and in R0 (HR = 4.2; 95% CI: 1.4 - 12.5; p = 0.010). Conclusions: Superior sulcus tumours still represent a life-threatening condition that, while curable in a significant proportion of cases, requires complex procedures with high surgical risks and a multimodality treatment setting. An optimal surgical approach should be planned to maximise resection completeness and survival. Other factors affecting survival are related to tumour staging, emphasising the importance of a meticulous preoperative workup and candidate selection to identify those expected to benefit from a survival benefit.

Intraoperative Extra Corporeal Membrane Oxygenator for Lung Cancer Resections Does Not Impact Circulating Tumor Cells.

BACKGROUND: The diagnosis of active neoplastic disease was traditionally judged an absolute contraindication for extracorporeal membrane oxygenator (ECMO) because of the fear of tumor cells being scattered or seeded. The aim of this study is to compare the number of circulating tumor cells (CTCs) before and after surgery in patients receiving lung cancer resection with and without intraoperative ECMO support. METHODS: This is a prospective, non-randomized, two-arms observational study comparing the number of CTCs before and after surgery in patients receiving lung cancer resection with and without intraoperative ECMO support. The ECMO arm includes patients suffering from lung cancer undergoing pulmonary resection with planned intraoperative ECMO support. The non-ECMO arm includes patients suffering from non-early-stage lung cancer undergoing pulmonary resection without planned intraoperative ECMO support. RESULTS: Twenty patients entered the study, eight in the ECMO arm and twelve in the non-ECMO arm. We did not observe any significant difference between the ECMO and non-ECMO groups in terms of postoperative complications (p = 1.00), ICU stay (p = 0.30), hospital stay (p = 0.23), circulating tumor cells' increase or decrease after surgery (p = 0.24), and postoperative C-reactive protein and C-reactive protein increase (p = 0.80). The procedures in the non-ECMO arm were significantly longer than those in the ECMO arm (p = 0.043). CONCLUSIONS: Intraoperative ECMO for lung cancer resections did not impact CTC increase or decrease after the procedure.