Interactive Cardiovascular and Thoracic Surgery 3:294-299(2004)
© 2004 European Association of Cardio-Thoracic Surgery
Best evidence topic - Thoracic general |
Is there a role for the use of radical lymph node dissection in the surgical management of resectable non-small cell lung cancer?
James Barnard,
Joel Dunning*,
Ghassan Musleh and
Nick Odom
Department of Cardiothoracic Surgery, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL, UK
jamesbbarnard{at}doctors.org.uk * Corresponding author. Tel.: +44-780-154-8122; fax: +41-161-276-8538
joeldunning{at}doctors.org.uk
Received December 18, 2003;
accepted December 22, 2003
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Abstract
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A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was whether there is any survival benefit to the employment of the technique of radical lymph node dissection in the management of operable non-small cell lung cancer (NSCLC). Altogether 305 papers were found using the reported search, of which eight presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these papers are tabulated. We conclude that extensive lymph node sampling is of benefit in accurately staging NSCLC, however, the design of studies in the literature has failed to account for the staging effect of extensive lymph node dissection on upstaging cancer patients when trying to determine a survival advantage.
Key Words: Evidence-based medicine; Thoracic surgery; Lymph node excision; Lung neoplasms
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1. Introduction
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A Best Evidence Topic was constructed according to a structured protocol. This protocol is fully described in Ref. [1].
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2. Clinical scenario
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You are a Specialist Registrar in Cardiothoracic surgery. You meet a senior trainee from Japan who is an enthusiastic proponent of radical lymph node dissection is early lung cancer. Your boss is an exponent of VATS lobectomy and you are aware that the application of radical lymph node dissection in near impossible with this technique. You wonder whether in general conducting a simpler staging technique, such as sampling, impacts on the accuracy of staging and the overall survival?
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3. Three-part question
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In [patients with Non-Small Cell Lung Cancer] can [radical lymph node dissection] improve [survival]?
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4. Search strategy
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Medline 1966–Dec 2003 using the OVID interface
[exp lymph node excision/OR lymph node dissection.af OR lymphadenectomy.af] AND [exp lung neoplasms/OR lung cancer.af OR lobectomy.af OR exp pneumonectomy/OR pneumonectomy.af] AND [exp mortality/OR exp survival/OR Survival.af] LIMIT to Human and English language.
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5. Search outcome
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Out of the 305 papers found 20 were deemed to be relevant. Eleven were out of scope and one was rejected on the basis of poor methodology. Eight papers were reviewed in full. These are listed in Table 1. A second table documenting the particular lymph node dissection strategies used in the papers is also given (Table 2).
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6. Results
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Izbicki et al. [2,3], Passlick et al. [4], Wu et al. [5] and Keller et al. [6] found a survival benefit to the use of radical lymph node dissection. Gargi et al. [7] and Sugi et al. [8] could not identify a survival benefit. Izbicki et al. [2,3] and Passlick et al. [4] describe outcomes regarding the same cohort of patients. These papers in common with Wu et al. [5] were prospective randomised controlled trials. Sugi et al.'s [8] is a randomised controlled trial, however, the findings are limited to a small subset of stage I lung cancer in which tumours are peripheral and less than 2 cm in diameter. Gargi et al. [7] conducted a retrospective case note review and acknowledged the potential for spurious down-staging of patients with inadequate sampling, a large number of patients from the original cohort were excluded due to inadequate follow-up and incomplete data.
In a number of patients in whom only a limited lymphadenectomy is performed, the true N stage remains unrecognised because the relevant lymph nodes are not removed and consequently not examined by a histopathologist. In the Izbicki cohort 5.5% of patients in the LA group had N2 disease that was detected only at lymph node levels that would not have been routinely included in the lymph node sampling group. Consequently the hypothetical benefit of LA in patients with limited mediastinal lymph node involvement might be due at least to an imbalance within the groups with respect to the number of patients with lymph node involvement at multiple levels of the N2 region. The phenomenon of stage migration as a source of misleading statistics for survival in cancer has been called the Will Rogers phenomenon [10].
Of note, the British Thoracic Society guidelines [11] with regard to lymph node management are based on the interim work of Izbicki et al. in 1994. At this juncture the results had not shown a statistical significance between their two groups of patients. According to the BTS guidelines lymph node dissection is essential at the time of lung resection to achieve accurate staging, however, extensive lymph node resection is not advised for its therapeutic value.
Assessment of a greater number of lymph nodes correlates with improved survival in patients with colorectal, breast and bladder cancer. Wu et al. [5] found that the number of lymph node metastases was an independent predictor of survival. Vansteenkiste et al. [12] analysed 18 articles published between 1980 and 1995 and also concluded that N status is the most important prognostic factor. Hypothetically there exists a cohort of patients with metastatic disease that is truly limited to the regional lymph nodes. These are the patients who would benefit from the aggressive resection of the intrathoracic lymph nodes.
Proponents of the radical approach claim better staging of the tumour and improved prognosis. Opponents of radical lymph node dissection have claimed higher morbidity and mortality rates owing to the extent of the operation and even a negative effect on the long-term prognosis because of an impaired local immune response. Both Izbicki et al. [3] and Sugi et al. [8] found increased morbidity in the lymphadenectomy groups, however, neither found any increase in hospital or ICU stay.
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7. Clinical bottom line
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The small numbers of patients involved in these studies and the problems with study design have not yielded a clear cut answer as to the survival benefit of mediastinal lymphadenectomy. If a cohort does exist where metastatic disease is limited to the regional nodes then these are the patients who would benefit in terms of survival. This group of patients may be very small requiring a highly powered study to detect them.
doi:10.1016/j.icvts.2003.12.004
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References
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- Dunning J, Prendergast B, Kevin Mackway-Jones K. Towards evidence based medicine in cardiothoracic surgery: best BETS. Interact Cardiovasc Thorac Surg. 2003;2:416–419[Abstract/Free Full Text]
- Izbicki J, Passlick B, Pantel K, Pichlmeier U, Hosch B, Karg O, Thetter O. Effectiveness of radical systematic mediastinal lymphadenectomy in patients with resectable non-small cell lung cancer. Ann Surg. 1998;277(1):138–144
- Izbicki JR, Passlick B, Karg O, Bloechle C, Pantel K, Knoefel WT, Thetter O. Impact of radical systematic mediastinal lymphadenectomy on tumor staging in lung cancer. Ann Thorac Surg. 1995;59(1):209–214[Abstract/Free Full Text]
- Passlick B, Kubuschock B, Sienel W, Thetter O, Pantel K, Izbicki JR. Mediastinal lymphadenectomy in non-small cell lung cancer: effectiveness in patients with or without nodal micrometastases—results of a preliminary study. Eur J Cardiothorac Surg. 2002;21:520–526[Abstract/Free Full Text]
- Wu Y, Huang Z, Wang S, Yang X, Ou W. A randomized trial of systematic nodal dissection in resectable non-small cell lung cancer. Lung Cancer. 2002;36:1–6[CrossRef][Medline]
- Keller S, Adak S, Wagner H, Johnson D. Mediastinal lymph node dissection improves survival in patients with stages II and IIIa non small cell lung cancer. Ann Thorac Surg. 2000;70:358–366[Abstract/Free Full Text]
- Gajra A, Newman N, Gamble G, Kohman L, Graziano S. Effect of number of lymph nodes sampled on outcome in patients with stage I non-small-cell lung cancer. J Clin Oncol. 2003;21:1029–1034[Abstract/Free Full Text]
- Sugi K, Nawata K, Fujita N, Ueda K, Tanaka T, Matsuoka T, Kaneda Y, Esato K. Systematic lymph node dissection for clinically diagnosed peripheral non-small-cell lung cancer less than 2 cm in diameter. World J Surg. 1998;22:290–295[CrossRef][Medline]
- Wu Y, Lin C, Hsu W, Huang B, Huang M, Wang L. Long-term results of pathological stage I non-small cell lung cancer: validation of using the number of totally removed lymph nodes as a staging control. Eur J Cardiothorac Surg. 2003;24:994–1001[Abstract/Free Full Text]
- Feinstein AR, Sosin DM, Wells CK. The Will Rogers phenomenon. Stage migration and new diagnostic techniques as a source of misleading statistics for survival in cancer. N Engl J Med. 1985;312(25):1604–1608[Abstract]
- British Thoracic Society. Guidelines on the selection of patients with lung cancer for surgery. Thorax. 2001;56:89–108[Free Full Text]
- Vansteenkiste JF, De Leyn PR, Deneffe GJ, Lerut TE, Demedts MG. Clinical prognostic factors in surgically treated stage IIIA-N2 non-small cell lung cancer: analysis of the literature. Lung Cancer. 1998;19(3):219[Medline]
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Abstract
1. Introduction