Surgery for oligometastatic non–small cell lung cancer
2023; Elsevier BV; Volume: 167; Issue: 2 Linguagem: Inglês
10.1016/j.jtcvs.2023.09.048
ISSN1097-685X
AutoresMara B. Antonoff, Nathaniel Deboever, Raphael S. Werner, Mehmet Altan, Daniel R. Gomez, Isabelle Opitz,
Tópico(s)Lung Cancer Research Studies
ResumoCentral MessageSurgery has been shown to be feasible, safe, and a valuable component of local therapy in appropriately selected patients with oligometastatic NSCLC. Surgery has been shown to be feasible, safe, and a valuable component of local therapy in appropriately selected patients with oligometastatic NSCLC. Conventionally, stage IV NSCLC has been considered incurable, with goals of therapy focused on control of disease and life prolongation. However, advances in systemic options, including targeted therapies for patients with actionable mutations and the introduction of immune checkpoint inhibitors used as single agents or as part of multidrug combinations, have contributed to significant improvements in disease control and overall survival (OS).1Altan M. Gulvin J.M. Simon G. Glisson B. Non–small cell lung cancer: general principles, management of localized disease, and treatment of metastatic disease without oncogene drivers.in: Kantarjian H.M. Wolff R.A. Rieber A.G. The MD Anderson Manual of Medical Oncology. 4th ed. McGraw Hill Education, 2022Google Scholar, 2Reck M. Rodríguez-Abreu D. Robinson A.G. Hui R. Csőszi T. Fülöp A. et al.Updated Analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non–small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater.J Clin Oncol. 2019; 37: 537-546https://doi.org/10.1200/jco.18.00149Crossref PubMed Scopus (0) Google Scholar, 3Garassino M.C. Gadgeel S.M. Gea S. KEYNOTE-189 5-year update: first-line pembrolizumab (pembro) + pemetrexed (pem) and platinum vs placebo (pbo) + pem and platinum for metastatic nonsquamous NSCLC.Ann Oncol. 2022; 33: S448-S554https://doi.org/10.1016/annonc/annonc1064Crossref Google Scholar, 4Paz-Ares L.G. Ramalingam S.S. Ciuleanu T.E. Lee J.S. Urban L. Caro R.B. et al.First-line nivolumab plus ipilimumab in advanced NSCLC: 4-year outcomes from the randomized, open-label, phase 3 CheckMate 227 part 1 trial.J Thorac Oncol. 2022; 17: 289-308https://doi.org/10.1016/j.jtho.2021.09.010Abstract Full Text Full Text PDF PubMed Scopus (176) Google Scholar, 5Novello S. Kowalski D. Baz D. et al.5-year update from KEYNOTE-407: pembrolizumab plus chemotherapy in squamous non–small cell lung cancer.ESMO Congress. 2022; (Abstract 974MO. 2022)Google Scholar Although systemic therapy remains the cornerstone of therapy in metastatic NSCLC, patients with limited burden of metastatic disease can achieve significant improvement in long-term outcomes with local consolidative therapy (LCT), which consists of surgical resection or radiotherapy to the primary tumor and metastatic sites of spread.6Gomez D.R. Tang C. Zhang J. Blumenschein G.R. Hernandez M. Lee J.J. et al.Local consolidative therapy vs. maintenance therapy or observation for patients with oligometastatic non–small-cell lung cancer: long-term results of a multi-institutional, phase II, randomized study.J Clin Oncol. 2019; 37: 1558-1565https://doi.org/10.1200/jco.19.00201Crossref PubMed Scopus (0) Google Scholar, 7Mitchell K.G. Farooqi A. Ludmir E.B. Corsini E.M. Zhang J. Sepesi B. et al.Improved overall survival with comprehensive local consolidative therapy in synchronous oligometastatic non–small-cell lung cancer.Clin Lung Cancer. 2020; 21: 37-46.e7https://doi.org/10.1016/j.cllc.2019.07.007Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar, 8Fleckenstein J. Petroff A. Schäfers H.J. Wehler T. Schöpe J. Rübe C. Long-term outcomes in radically treated synchronous versus metachronous oligometastatic non–small-cell lung cancer.BMC Cancer. 2016; 16: 348https://doi.org/10.1186/s12885-016-2379-xCrossref PubMed Scopus (61) Google Scholar, 9Khan A.J. Mehta P.S. Zusag T.W. Bonomi P.D. Penfield Faber L. Shott S. et al.Long term disease-free survival resulting from combined modality management of patients presenting with oligometastatic, non–small cell lung carcinoma (NSCLC).Radiother Oncol. 2006; 81: 163-167https://doi.org/10.1016/j.radonc.2006.09.006Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar The metastatic state, based on the 8th edition of the Joint Commission on Cancer guidelines, is defined by presence of cancer beyond regional lymph nodes.10Lim W. Ridge C.A. Nicholson A.G. Mirsadraee S. The 8(th) lung cancer TNM classification and clinical staging system: review of the changes and clinical implications.Quant Imaging Med Surg. 2018; 8: 709-718https://doi.org/10.21037/qims.2018.08.02Crossref PubMed Scopus (169) Google Scholar The term "oligometastasis" was initially introduced by Hellman and Weichselbaum11Hellman S. Weichselbaum R.R. Oligometastases.J Clin Oncol. 1995; 13: 8-10Crossref PubMed Google Scholar to describe a state of limited disease burden despite the presence of distant metastasis, referring to patients with a specific number of limited number metastases in a limited number of organs.12Na K.J. Kim Y.T. The "new" oligometastatic disease state and associated therapies in non–small cell lung cancer: a narrative review.J Surg Oncol. 2023; 127: 282-287https://doi.org/10.1002/jso.27165Crossref PubMed Scopus (3) Google Scholar The European Organisation for Research and Treatment of Cancer Lung Cancer Group has defined synchronous oligometastatic disease as one involving a maximum of 5 metastases and 3 organs.13Dingemans A.C. Hendriks L.E.L. Berghmans T. Levy A. Hasan B. Faivre-Finn C. et al.Definition of synchronous oligometastatic non–small cell lung cancer—a consensus report.J Thorac Oncol. 2019; 14: 2109-2119https://doi.org/10.1016/j.jtho.2019.07.025Abstract Full Text Full Text PDF PubMed Scopus (179) Google Scholar There is a lack of general consensus on a uniform definition of the oligometastatic NSCLC state, and no single therapeutic perspective has been adopted across institutions.14Baydoun A. Lee V.L. Biswas T. Oligometastatic non–small cell lung cancer: a practical review of prospective trials.Cancers (Basel). 2022; 14: 5339https://doi.org/10.3390/cancers14215339Crossref PubMed Scopus (5) Google Scholar As such, in order to provide the readership with the most up-to-date and relevant content in this area, the existing published literature and ongoing trials were reviewed based on expert experience and opinion15American Assoication for Thoracic SurgeryOligometastatic NSCLC: role of local consolidative therapy. AATS Global Grand Rounds Webinar: thoracic2023.https://www.aats.org/events/oligometastatic-nsclc-role-of-local-consolidative-therapyDate accessed: May 1, 2023Google Scholar and are summarized herein. An important prospective landmark trial used a definition of 3 or fewer metastases, not including the primary tumor, which has been followed by other subsequent studies.6Gomez D.R. Tang C. Zhang J. Blumenschein G.R. Hernandez M. Lee J.J. et al.Local consolidative therapy vs. maintenance therapy or observation for patients with oligometastatic non–small-cell lung cancer: long-term results of a multi-institutional, phase II, randomized study.J Clin Oncol. 2019; 37: 1558-1565https://doi.org/10.1200/jco.19.00201Crossref PubMed Scopus (0) Google Scholar,16Gomez D.R. Blumenschein Jr., G.R. Lee J.J. Hernandez M. Ye R. Camidge D.R. et al.Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non–small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study.Lancet Oncol. 2016; 17: 1672-1682https://doi.org/10.1016/s1470-2045(16)30532-0Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 17MD Anderson Cancer CenterOsimertinib, surgery, and radiation therapy in treating patients with stage IIIB or IV non–small cell lung cancer with EGFR mutations, NORTHSTAR Study. NCT03410043.https://clinicaltrials.gov/ct2/show/NCT03410043Date accessed: October 25, 2023Google Scholar, 18M.D. Anderson Cancer CenterRandomized phase III trial of local consolidation therapy (LCT) after nivolumab and ipilimumab for immunotherapy-naive patients with metastatic non–small cell lung cancer (LONESTAR). PI: John Haymach, Open Label. Est Completion Date 12/31/2022. NCT03391869.https://clinicaltrials.gov/search?term=NCT03391869Date accessed: October 25, 2023Google Scholar, 19Elamin Y. Gandhi S. Antonoff M. Mott F. Gibbons D.L. Le X. et al.BRIGHTSTAR: a pilot trial of local consolidative therapy (LCT) with brigatinib in tyrosine kinase inhibitor (TKI)-naïve ALK-rearranged advanced NSCLC.J Clin Oncol. 2020; 38: 9624https://doi.org/10.1200/JCO.2020.38.15_suppl.9624Crossref Google Scholar However, the European Society of Radiotherapy and Oncology and American Society for Radiation Oncology jointly recommended the application of this term to the presence of 1 to 5 metastatic lesions, with all sites amenable to safe local treatment.20Lievens Y. Guckenberger M. Gomez D. Hoyer M. Iyengar P. Kindts I. et al.Defining oligometastatic disease from a radiation oncology perspective: an ESTRO-ASTRO consensus document.Radiother Oncol. 2020; 148: 157-166https://doi.org/10.1016/j.radonc.2020.04.003Abstract Full Text Full Text PDF PubMed Scopus (344) Google Scholar Regardless of the exact number of sites, multidisciplinary management of this disease has rapidly evolved. Recognizing the limited disease burden, it has been hypothesized and successfully demonstrated that patients with oligometastatic NSCLC can achieve long-term survival benefits with aggressive treatment of local sites of disease sites. LCT may achieve its efficacy through multiple mechanisms. It has been postulated that initial systemic therapy leading to stable or responsive disease leaves behind treatment-resistant malignant cells that are less likely to be eliminated by subsequent maintenance therapy and may serve as a source for subsequent metastatic spread, even in the absence of radiographic progression. As such, LCT may reduce the burden of treatment-resistant cells.6Gomez D.R. Tang C. Zhang J. Blumenschein G.R. Hernandez M. Lee J.J. et al.Local consolidative therapy vs. maintenance therapy or observation for patients with oligometastatic non–small-cell lung cancer: long-term results of a multi-institutional, phase II, randomized study.J Clin Oncol. 2019; 37: 1558-1565https://doi.org/10.1200/jco.19.00201Crossref PubMed Scopus (0) Google Scholar Moreover, in addition to local effects in the tumor microenvironment of tumor cell apoptosis, ablative therapies may induce tumor antigen release, T-lymphocyte expansion, generation of tumor-specific T-cell clones, and T-lymphocyte receptor diversification that may manifest as enhanced immunosurveillance and antitumor immunity.7Mitchell K.G. Farooqi A. Ludmir E.B. Corsini E.M. Zhang J. Sepesi B. et al.Improved overall survival with comprehensive local consolidative therapy in synchronous oligometastatic non–small-cell lung cancer.Clin Lung Cancer. 2020; 21: 37-46.e7https://doi.org/10.1016/j.cllc.2019.07.007Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar,21Menon H. Ramapriyan R. Cushman T.R. Verma V. Kim H.H. Schoenhals J.E. et al.Role of radiation therapy in modulation of the tumor stroma and microenvironment.Front Immunol. 2019; 10: 193https://doi.org/10.3389/fimmu.2019.00193Crossref PubMed Scopus (106) Google Scholar,22Menon H. Chen D. Ramapriyan R. Verma V. Barsoumian H.B. Cushman T.R. et al.Influence of low-dose radiation on abscopal responses in patients receiving high-dose radiation and immunotherapy.J Immunother Cancer. 2019; 7: 237https://doi.org/10.1186/s40425-019-0718-6Crossref PubMed Scopus (86) Google Scholar While further clarity on the mechanistic means of LCT merits ongoing elucidation, it is clear through completed and ongoing clinical trials that this strategy provides promise to a subset of patients with previously dismal prognosis. LCT in oligometastatic has been supported through a number of investigations, which will be discussed further in this expert review, demonstrating the feasibility and ultimate potential opportunities to help change the course of this disease through a more aggressive approach.9Khan A.J. Mehta P.S. Zusag T.W. Bonomi P.D. Penfield Faber L. Shott S. et al.Long term disease-free survival resulting from combined modality management of patients presenting with oligometastatic, non–small cell lung carcinoma (NSCLC).Radiother Oncol. 2006; 81: 163-167https://doi.org/10.1016/j.radonc.2006.09.006Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar,23Inoue T. Katoh N. Aoyama H. Onimaru R. Taguchi H. Onodera S. et al.Clinical outcomes of stereotactic brain and/or body radiotherapy for patients with oligometastatic lesions.Jpn J Clin Oncol. 2010; 40: 788-794https://doi.org/10.1093/jjco/hyq044Crossref PubMed Scopus (49) Google Scholar, 24Pfannschmidt J. Dienemann H. Surgical treatment of oligometastatic non–small cell lung cancer.Lung Cancer. 2010; 69: 251-258https://doi.org/10.1016/j.lungcan.2010.05.003Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar, 25Salama J.K. Hasselle M.D. Chmura S.J. Malik R. Mehta N. Yenice K.M. et al.Stereotactic body radiotherapy for multisite extracranial oligometastases: final report of a dose escalation trial in patients with 1 to 5 sites of metastatic disease.Cancer. 2012; 118: 2962-2970https://doi.org/10.1002/cncr.26611Crossref PubMed Scopus (282) Google Scholar This paper represents expert opinion and targeted review of recommended literature; substantial further studies are clearly in need. Although there is indisputable level 1 evidence supporting LCT for stage IV disease, many of the currently completed trials have included heterogenous patient populations and LCT strategies, causing challenges in evaluating the efficacy and safety of available modalities. The data supporting LCT for metastatic lung cancer have advanced substantially over the past decade. Since 2016, several randomized trials have been published or presented supporting its use. Gomez and colleaguesE1Gomez D.R. Tang C. Zhang J. Blumenschein G.R. Hernandez M. Lee J.J. et al.Local consolidative therapy vs. maintenance therapy or observation for patients with oligometastatic non–small-cell lung cancer: long-term results of a multi-institutional, phase II, randomized study.J Clin Oncol. 2019; 37: 1558-1565https://doi.org/10.1200/JCO.19.00201Crossref PubMed Scopus (833) Google Scholar and Iyengar and colleaguesE2Iyengar P. Wardak Z. Gerber D.E. Tumati V. Ahn C. Hughes R.S. et al.Consolidative radiotherapy for limited metastatic non–small-cell lung cancer: a phase 2 randomized clinical trial.JAMA Oncol. 2017; 4: e173501https://doi.org/10.1001/jamaoncol.2017.3501Crossref Scopus (720) Google Scholar published cohorts of patients with limited metastatic disease treated with ablative therapy after induction systemic therapy. In both studies, there was a progression-free survival (PFS) benefit and, with long-term follow-up, in their landmark study Gomez colleagues suggested a benefit in OS as well. It is notable that this study employed both surgery and radiation as ablative techniques. The SABR-COMET (Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastases) trial,E3Palma D.A. Olson R. Harrow S. Gaede S. Louie A.V. Haasbeek C. et al.Stereotactic ablative radiotherapy for the comprehensive treatment of oligometastatic cancers: long-term results of the SABR-COMET phase II randomized trial.J Clin Oncol. 2020; 38: 2830-2838https://doi.org/10.1200/JCO.20.00818Crossref PubMed Scopus (666) Google Scholar which included 10 centers in Canada, demonstrated a benefit of LCT in multiple histologies (18% of patients with lung cancer). Finally, a study from ChinaE4Wang X.-S. Bai Y.-F. Verma V. Yu R.L. Tian W. Ao R. et al.Randomized trial of first-line tyrosine kinase inhibitor with or without radiotherapy for synchronous oligometastatic EGFR-mutated non–small cell lung cancer.J Natl Cancer Inst. 2023; 115: 742-748https://doi.org/10.1093/jnci/djac015Crossref PubMed Scopus (96) Google Scholar demonstrated a benefit in PFS with upfront radiation therapy in the context of pathologic EGFR mutations compared with no radiation in patients receiving first-generation tyrosine kinase inhibitors. None of these initial randomized studies involved contemporary systemic therapy, such as immunotherapy or novel targeted therapy. Recently published data have begun to examine the role of LCT in this context. Investigators from the University of Pennsylvania published a single-arm phase 2 study of 51 patients receiving pembrolizumab plus radiation therapy in the context of 4 or fewer metastatic lesions.E5Bauml J.M. Mick R. Ciunci C. Aggarwal C. Davis C. Evans T. et al.Pembrolizumab after completion of locally ablative therapy for oligometastatic non–small cell lung cancer: a phase 2 trial.JAMA Oncol. 2019; 5: 1283-1290https://doi.org/10.1001/jamaoncol.2019.1449Crossref PubMed Scopus (212) Google Scholar The authors observed a median PFS of 19.1 months with an OS at 12 months of >90%, suggesting that outcomes can be improved further with this combination. The concept of comprehensive local consolidative therapy (cLCT), characterizing therapy provided to all sites of disease, also has been associated with survival benefit in patients with limited burden of thoracic disease, and nonbony metastases.7Mitchell K.G. Farooqi A. Ludmir E.B. Corsini E.M. Zhang J. Sepesi B. et al.Improved overall survival with comprehensive local consolidative therapy in synchronous oligometastatic non–small-cell lung cancer.Clin Lung Cancer. 2020; 21: 37-46.e7https://doi.org/10.1016/j.cllc.2019.07.007Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar Expanding beyond the scope of synchronous oligometastases, a randomized phase 2 study assessed the effect of LCT in the context of oligoprogression. Patients with lung or breast cancer who had progressed in up to 5 lesions were randomized to either LCT or "next-line" therapy with radiation.E6Tsai C.J. Yang J.T. Guttmann D.M. Shaverdian N. Shepherd A. Eng J. et al.Consolidative use of radiotherapy to block (CURB) oligoprogression—interim analysis of the first randomized study of stereotactic body radiotherapy in patients with oligoprogressive metastatic cancers of the lung and breast.Int J Radiat Oncol Biol Phys. 2021; 111: 1325-1326https://doi.org/10.1016/j.ijrobp.2021.09.014Abstract Full Text Full Text PDF Google Scholar The authors observed a substantial benefit to LCT in the entire cohort, which was driven by the beneficial effect in lung cancer, as the cohort of patients with breast cancer did not have a benefit with the incorporation of LCT. Considering radiotherapy-centered LCT, a phase 2 clinical trial has completed accrual of patients with stage IV NSCLC managed with chemotherapy, followed by randomization to continued maintenance chemotherapy or consolidative stereotactic body radiation therapy.E7Iyengar P. Maintenance chemotherapy versus consolidative stereotactic body radiation therapy (SBRT) plus maintenance chemotherapy for stage IV non–small cell lung cancer (NSCLC): a randomized phase II trial.https://classic.clinicaltrials.gov/ProvidedDocs/46/NCT02045446/Prot_SAP_002.pdfDate: 2023Date accessed: October 25, 2023Google Scholar Another phase 2/3 trial evaluating the effect of maintenance chemotherapy with or without LCT in patients with stage IV NSCLC also has complete accrual, and results are awaited.E8Iyengar P. Maintenance chemotherapy with or without local consolidative therapy in treating patients with stage IV non–small cell lung cancer.https://classic.clinicaltrials.gov/ct2/show/NCT03137771Date: 2022Date accessed: October 25, 2023Google Scholar The summary of the current literature surrounding LCT in the setting of metastatic lung cancer is, thus, as follows. First, the randomized data are consistent supporting a role for radiation therapy in the context of synchronous limited metastases and oligoprogressive disease.E1Gomez D.R. Tang C. Zhang J. Blumenschein G.R. Hernandez M. Lee J.J. et al.Local consolidative therapy vs. maintenance therapy or observation for patients with oligometastatic non–small-cell lung cancer: long-term results of a multi-institutional, phase II, randomized study.J Clin Oncol. 2019; 37: 1558-1565https://doi.org/10.1200/JCO.19.00201Crossref PubMed Scopus (833) Google Scholar Second, although nonrandomized data have suggested a benefit with immunotherapy in the synchronous metastases setting,E5Bauml J.M. Mick R. Ciunci C. Aggarwal C. Davis C. Evans T. et al.Pembrolizumab after completion of locally ablative therapy for oligometastatic non–small cell lung cancer: a phase 2 trial.JAMA Oncol. 2019; 5: 1283-1290https://doi.org/10.1001/jamaoncol.2019.1449Crossref PubMed Scopus (212) Google Scholar randomized trials are ongoing with respect to integrating checkpoint inhibitors and novel targeted agents.18M.D. Anderson Cancer CenterRandomized phase III trial of local consolidation therapy (LCT) after nivolumab and ipilimumab for immunotherapy-naive patients with metastatic non–small cell lung cancer (LONESTAR). PI: John Haymach, Open Label. Est Completion Date 12/31/2022. NCT03391869.https://clinicaltrials.gov/search?term=NCT03391869Date accessed: October 25, 2023Google Scholar,19Elamin Y. Gandhi S. Antonoff M. Mott F. Gibbons D.L. Le X. et al.BRIGHTSTAR: a pilot trial of local consolidative therapy (LCT) with brigatinib in tyrosine kinase inhibitor (TKI)-naïve ALK-rearranged advanced NSCLC.J Clin Oncol. 2020; 38: 9624https://doi.org/10.1200/JCO.2020.38.15_suppl.9624Crossref Google Scholar,E9Antonoff M. Deboever N. Atlan M. Swisher S. Heymach J. Sepesi B. et al.Surgical results from the NORTHSTAR trial: feasibility of pulmonary resection after osimertinib in stage IV disease.J Thorac Cardiovasc Surg. 2023; (May 6, 2023 [Epub ahead of print].)Google Scholar cLCT is associated with improved OS, and survival benefit can be characterized by histology, burden of disease, and absence of bony metastases.E10Mitchell K.G. Farooqi A. Ludmir E.B. Corsini E.M. Sepesi B. Gomez D.R. et al.Pulmonary resection is associated with long-term survival and should remain a therapeutic option in oligometastatic lung cancer.J Thorac Cardiovasc Surg. 2021; 161: 1497-1504.e2https://doi.org/10.1016/j.jtcvs.2020.02.134Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar,E11Mitchell K.G. Farooqi A. Ludmir E.B. Corsini E.M. Zhang J. Sepesi B. et al.Improved overall survival with comprehensive local consolidative therapy in synchronous oligometastatic non–small-cell lung cancer.Clin Lung Cancer. 2020; 21: 37-46.e7https://doi.org/10.1016/j.cllc.2019.07.007Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar Finally, the current data do not suggest that one modality is superior to another in the setting of LCT. These findings thus suggest that treatment should be individualized based on the approach that can best balance toxicity and efficacy, whether that is surgery, radiation, or interventional-guided ablation. Moreover, further investigations to best elucidate the best strategies for various stratified patient cohorts remain in strong need. We have entered an exciting time in which we have shown that LCT, consisting of surgery and/or radiation, can be associated with favorable outcomes, and that patients can be optimally selected for LCT based on tumor- and disease-related features. However, it remains highly relevant to clarify the distinct and specific role of surgical resection. Retrospective review of nearly 200 patients who underwent LCT at MD Anderson Cancer Center over a span of 2 decades identified a group of 88 patients who underwent cLCT, among whom nearly one-third had surgical resection of their primary lung tumor.E10Mitchell K.G. Farooqi A. Ludmir E.B. Corsini E.M. Sepesi B. Gomez D.R. et al.Pulmonary resection is associated with long-term survival and should remain a therapeutic option in oligometastatic lung cancer.J Thorac Cardiovasc Surg. 2021; 161: 1497-1504.e2https://doi.org/10.1016/j.jtcvs.2020.02.134Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar Among these patients, 80% underwent lobectomy, with 12% having pneumonectomy and 8% sublobar resections, at a median time from diagnosis to surgery of 3.7 months. The 90-day postoperative mortality was 0, and, excitingly, after a median follow-up of 57 months, the median OS after lung resection was 55.2 months, highlighting an important change in expectations and dogma in treating stage IV NSCLC. These findings importantly emphasized that surgical resection of the primary tumor is feasible and associated with promising oncologic outcomes in selected patients with synchronous oligometastatic NSCLC, and that surgery should remain a component of LCT for operable oligometastatic patients. A subsequent evaluation of long-term outcomes from the same institution followed 52 patients who underwent lung resection for oligometastatic disease, the majority of whom (>90%) had cLCT and achieved R0 resection.E12Deboever N. Mitchell K.G. Farooqi A. Ludmir E.B. Hofstetter W.L. Mehran R.J. et al.Perioperative and oncologic outcomes of pulmonary resection for synchronous oligometastatic NSCLC: evidence for surgery in advanced disease.J Thorac Cardiovasc Surg. August 22, 2023; ([Epub ahead of print])Abstract Full Text Full Text PDF Scopus (1) Google Scholar After a median follow-up of 95 months, mean OS was 51.7 months and median PFS was 9.4 months. Although difficult,E13Antonoff M. Deboever N. Swisher S. Sepesi B. Atlan M. Vaporciyan A.A. et al.Surgical resection after targeted therapy in stage IV NSCLC: nuances and considerations.J Thorac Oncol. 2023; 18: e18https://doi.org/10.1016/j.jtho.2022.09.044Abstract Full Text Full Text PDF Google Scholar these operations are safe and feasible, with median operative duration and blood loss of 234 minutes, and 175 mL, respectively. Common postoperative events of prolonged air leak and atrial arrhythmias occurred infrequently at rates of 5% and 10% respectively.E9Antonoff M. Deboever N. Atlan M. Swisher S. Heymach J. Sepesi B. et al.Surgical results from the NORTHSTAR trial: feasibility of pulmonary resection after osimertinib in stage IV disease.J Thorac Cardiovasc Surg. 2023; (May 6, 2023 [Epub ahead of print].)Google Scholar In a Swiss multicenter retrospective cohort study analyzing 124 patients with oligometastases (defined as ≤5 synchronous metastases in ≤2 organs) who underwent resection of primary tumor at 4 centers (August 2001 to February 2018), the 5-year OS rate was 36%.E14Opitz I. Patella M. Payrard L. Perentes J.Y. Inderbitzi R. Gelpke H. et al.Prognostic factors of oligometastatic non–small-cell lung cancer following radical therapy: a multicentre analysis.Eur J Cardiothorac Surg. 2020; 57: 1166-1172https://doi.org/10.1093/ejcts/ezz384Crossref PubMed Scopus (28) Google Scholar The brain was the most common metastatic site (61.3%), followed by the adrenal glands (10.4%); 77.4% of all patients only presented with a single distant metastasis. Cox regression analysis showed that patients younger than 60 years (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.24-0.69, P = .001) and patients with no nodal metastases (pN0) (HR, 0.38; 95% CI, 0.21-0.69, P = .002) had a significant survival benefit. In the highly selected subgroup of patients who were both younger than 60 years and presented a pN0 status, a 5-year OS of 83% was reached.E14Opitz I. Patella M. Payrard L. Perentes J.Y. Inderbitzi R. Gelpke H. et al.Prognostic factors of oligometastatic non–small-cell lung cancer following radical therapy: a multicentre analysis.Eur J Cardiothorac Surg. 2020; 57: 1166-1172https://doi.org/10.1093/ejcts/ezz384Crossref PubMed Scopus (28) Google Scholar The presence of bone metastasis negatively affected survival (HR, 2.53; 95% CI, 1.05-6.09, P = .04). Median PFS time was 11 months (95% CI, 8-13). PFS at 1, 2, 3, and 5 years was 41%, 29%, 25%, and 23%, respectively. The resection of the primary tumor was safely performed with a 30- and 90-day mortality of 0% and 2.4%, respectively. These results support previous results of local ablative treatment including surgical resection of the primary tumor in oligometastatic NSCLC with a curative strategy with 5-year OS of 36% for the entire cohort, and 83% for younger patients in absence of lymph node involvement.E14Opitz I. Patella M. Payrard L. Perentes J.Y. Inderbitzi R. Gelpke H. et al.Prognostic factors of oligometastatic non–small-cell lung cancer following radical therapy: a multicentre analysis.Eur J Cardiothorac Surg. 2020; 57: 1166-1172https://doi.org/10.1093/ejcts/ezz384Crossref PubMed Scopus (28) Google Scholar In a French multicenter retrospective analysis of 59 patients with oligometastatic NSCLC and adrenal metastases who underwent LCT including a surgical resection of the primary tumor and the adrenal metastases, the 5-year OS was as high as 59%.E15De Wolf J. Bellier J. Lepimpec-Barthes F. Tronc F. Peillon C. Bernard A. et al.Exhaustive preoperative staging increases survival in resected adrenal oligometastatic non–small-cell lung cancer: a multicentre study.Eur J Cardiothorac Surg. 2017; 52: 698-703https://doi.org/10.1093/ejcts/ezx193Crossref PubMed Scopus (12) Google Scholar In line with the Swiss analysis, mediastinal lymph node involvement was a detrimental prognostic factor for OS with a 5-year OS rate of 27% in the N2 population versus 68% in the N0 and N1 population. The authors concluded that bifocal resection of adrenal oligometastatic NSCLC is feasible with favorable short- and long-term results.E15De Wolf J. Bellier J. Lepimpec-Barthes F. Tronc F. Peillon C. Bernard A. et al.Exhaustive preoperative staging increases survival in resected adrenal oligometastatic non–small-cell lung cancer: a multicentre study.Eur J Cardiothorac Surg. 2017; 52: 698-703https://doi.org/10.1093/ejcts/ezx193Crossref PubMed Scopus (12) Google Scholar However, the results from both abovementioned multicenter European stud
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