Is Adjuvant Radiochemotherapy Always Mandatory in Patients with Resected N2 Non-Small Cell Lung Cancer?

Abstract

Background In patients with non-small cell lung cancer (NSCLC), the pathologic union for international cancer control (UICC) stage IIIA is a heterogeneous entity, with different forms of N2-lymph node involvement representing different prognoses. Although a multimodality treatment approach, including surgery, systemic therapy, and/or radiotherapy, is almost always recommended, in this retrospective observational study, we sought to determine whether long-term survival might be possible in selected patients who are treated with complete surgical resection alone.

Methods Between 2013 and 2018, we retrospectively identified 24 patients with NSCLC (16 men and 8 women), who were found to have pathologic N2-lymph node involvement, and were treated with complete surgical lung resection and systematic mediastinal and hilar lymph node dissection but no neoadjuvant or adjuvant treatment.

Results The most frequent reason (n = 14) for forgoing adjuvant treatment was patient refusal. The mean overall survival (OS) was 34.5 months (interquartile range [IQR]: 15.5–53.5 months). The mean disease-free survival (DFS) was 18 months (IQR: 4.75–46.75 months). We identified five patients who survived at least 5 years without recurrence (21%). In each of these cases, the nodal metastases were restricted to a single level and no extracapsular lymph node involvement were detected. Additionally, worse DFS was associated with pT3/4 (vs. a lower T-stage), as well as microscopic lymphovascular invasion.

Conclusion Although the small sample size precludes any definitive conclusions, it was possible to demonstrate that long-term survival without neoadjuvant and adjuvant treatment is possible in some patients if complete tumor and nodal resection is performed.

Keyword

lung cancer treatment (surgery - medical) - practice guidelines - pathology

Publikationsverlauf

Eingereicht: 04. Oktober 2020

Angenommen: 21. Dezember 2020

Artikel online veröffentlicht:
18. Februar 2021

• References

• 1 Rosell R, Gómez-Codina J, Camps C. et al. A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer. N Engl J Med 1994; 330 (03) 153-158
• 2 van Meerbeeck JP, Kramer GWPM, Van Schil PEY. et al; European Organisation for Research and Treatment of Cancer-Lung Cancer Group. Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small-cell lung cancer. J Natl Cancer Inst 2007; 99 (06) 442-450
• 3 Pignon J-P, Tribodet H, Scagliotti GV. et al; LACE Collaborative Group. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol 2008; 26 (21) 3552-3559
• 4 Bezjak A, Temin S, Franklin G. et al. Definitive and adjuvant radiotherapy in locally advanced non-small-cell lung cancer: American Society of Clinical Oncology Clinical Practice Guideline Endorsement of the American Society for Radiation Oncology Evidence-Based Clinical Practice Guideline. J Clin Oncol 2015; 33 (18) 2100-2105
• 5 Kris MG, Gaspar LE, Chaft JE. et al. Adjuvant systemic therapy and adjuvant radiation therapy for stage I to IIIA completely resected non-small-cell lung cancers: American Society of Clinical Oncology/Cancer Care Ontario Clinical Practice guideline update. J Clin Oncol 2017; 35 (25) 2960-2974
• 6 S3-Leitlinie Prävention, Diagnostik, Therapie und Nachsorge des Lungenkarzinoms. Accessed December 4, 2020 at: https://www.awmf.org/uploads/tx_szleitlinien/020-007OL_l_S3_Lungenkarzinom_2018-03.pdf
• 7 Verstappen CCP, Heimans JJ, Hoekman K, Postma TJ. Neurotoxic complications of chemotherapy in patients with cancer: clinical signs and optimal management. Drugs 2003; 63 (15) 1549-1563
• 8 Morishima Y, Ogura M, Yoneda S. et al; Japan Erythropoietin Study Group. Once-weekly epoetin-beta improves hemoglobin levels in cancer patients with chemotherapy-induced anemia: a randomized, double-blind, dose-finding study. Jpn J Clin Oncol 2006; 36 (10) 655-661
• 9 Anders JC, Grigsby PW, Singh AK. Cisplatin chemotherapy (without erythropoietin) and risk of life-threatening thromboembolic events in carcinoma of the uterine cervix: the tip of the iceberg? A review of the literature. Radiat Oncol 2006; 1: 14
• 10 Dienemann H, Hoffmann H, Koebe H-G. Technik und Rationale der Lymphknotendissektion bei Bronchialcarcinom. Chirurg 1998; 69 (04) 412-417
• 11 Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457-481
• 12 Mountain CF. Revisions in the international system for staging lung cancer. Chest 1997; 111 (06) 1710-1717
• 13 Kassis ES, Vaporciyan AA. Defining N2 disease in non-small cell lung cancer. Thorac Surg Clin 2008; 18 (04) 333-337
• 14 Wang J, Chen J, Chen X, Wang B, Li K, Bi J. Blood vessel invasion as a strong independent prognostic indicator in non-small cell lung cancer: a systematic review and meta-analysis. PLoS One 2011; 6 (12) e28844
• 15 Okiror L, Harling L, Toufektzian L. et al. Prognostic factors including lymphovascular invasion on survival for resected non-small cell lung cancer. J Thorac Cardiovasc Surg 2018; 156 (02) 785-793
• 16 Gabor S, Renner H, Popper H. et al. Invasion of blood vessels as significant prognostic factor in radically resected T1-3N0M0 non-small-cell lung cancer. Eur J Cardiothorac Surg 2004; 25 (03) 439-442
• 17 Tabatabaei SV, Nitche C, Michel M, Rasche K, Hekmat K. Prognostic impact of extracapsular lymph node invasion on survival in non-small-cell lung cancer: a systematic review and meta-analysis. Adv Exp Med Biol 2018; 1116: 27-36
• 18 Luchini C, Veronese N, Nottegar A. et al. Extranodal extension of nodal metastases is a poor prognostic moderator in non-small cell lung cancer: a meta-analysis. Virchows Arch 2018; 472 (06) 939-947
• 19 Riquet M, Assouad J, Bagan P. et al. Skip mediastinal lymph node metastasis and lung cancer: a particular N2 subgroup with a better prognosis. Ann Thorac Surg 2005; 79 (01) 225-233
• 20 Saji H, Tsuboi M, Shimada Y. et al. A proposal for combination of total number and anatomical location of involved lymph nodes for nodal classification in non-small cell lung cancer. Chest 2013; 143 (06) 1618-1625
• 21 Nakanishi R, Osaki T, Nakanishi K. et al. Treatment strategy for patients with surgically discovered N2 stage IIIA non-small cell lung cancer. Ann Thorac Surg 1997; 64 (02) 342-348
• 22 Andre F, Grunenwald D, Pignon JP. et al. Survival of patients with resected N2 non-small-cell lung cancer: evidence for a subclassification and implications. J Clin Oncol 2000; 18 (16) 2981-2989
• 23 Vansteenkiste JF, De Leyn PR, Deneffe GJ. et al; Leuven Lung Cancer Group. Survival and prognostic factors in resected N2 non-small cell lung cancer: a study of 140 cases. Ann Thorac Surg 1997; 63 (05) 1441-1450
• 24 David EA, Cooke DT, Chen Y, Nijar K, Canter RJ, Cress RD. Does lymph node count influence survival in surgically resected non-small cell lung cancer?. Ann Thorac Surg 2017; 103 (01) 226-235
• 25 Sigurdson ER. Lymph node dissection: is it diagnostic or therapeutic?. J Clin Oncol 2003; 21 (06) 965-967