Should all patients with non-small cell lung cancer who are surgical candidates have cervical mediastinoscopy preoperatively
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《血管的通路杂志》
a Department of Thoracic Surgery, Birmingham Heartlands Hospital, Birmingham, UK
b Department of Cardiothoracic Surgery, James Cook University Hospital, Middlesbrough, UK
Abstract
A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed is whether all potential surgical candidates with non-small cell lung cancer should have cervical mediastinoscopy pre-operatively. Two hundred and forty-one papers were found using the reported search, of which 8 represented 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 were tabulated. We conclude that patients with resectable non-small cell lung cancer who have had a negative mediastinal CT scan should all undergo mediastinoscopy. The number needed to treat with mediastinoscopy to prevent an unnecessary thoracotomy is around 5–15 patients. Exceptions to this may be patients with a T1 tumour, patients with a small peripheral tumour or patients who have had a negative PET scan.
Key Words: Evidence-based medicine; Thoracic surgery; Mediastinoscopy; Non-small cell lung carcinoma; Staging
1. Introduction
A best evidence topic was constructed according to a structured protocol. This protocol is fully described in the ICVTS [1].
1.1. Clinical scenario
You are in a multidisciplinary team meeting, discussing a 76-year-old lifelong smoker who has a T2 right upper lobe adenocarcinoma. She has COPD and arthritis and is quite a frail lady and lung function testing showed that she would not tolerate a pneumonectomy. The CT scan shows a 5 cm tumour that may be resectable by lobectomy and there are no obviously enlarged mediastinal nodes although the radiologist reports that there are a few nodes there that are 0.8 cm in diameter. A consultant surgeon accepts her for lobectomy, but the anaesthetist suggests a mediastinoscopy first to reduce the likelihood of an ‘open and close’ thoracotomy. The chest physicians state that this would be contrary to current guidelines and thus you suggest that you could look up the evidence and present it at the next week's meeting.
1.2. Three-part question
In patients undergoing [lung resection for non-small cell lung cancer], would [routine cervical mediastinoscopy] reduce the incidence of [unnecessary thoracotomy].
1.3. Search strategy
Medline 1966–Oct 2005 using the Ovid interface. [exp mediastinoscopy/OR mediastinoscopy.mp] AND [exp neoplasm staging/OR staging.mp] AND [exp carcinoma, non-small-cell lung/OR non small cell lung cancer.mp] limit to humans.
1.4. Search outcome
A total of 241 papers were found from the above search. We selected four systematic reviews and meta-analyses that summarised fourteen diagnostic cohort studies on this topic. We identified three additional studies not included in the reviews and also summarised the largest cohort study in the literature. These are presented in Table 1.
2. Discussion
Accurate nodal staging, particularly N2 status is of paramount importance in the selection of patients for surgery. Studies have reported that around 20% of patients undergoing clinical staging are either overstaged or understaged when pathological staging is compared, and 20% of preoperative N0 patients may actually have pathological N1 or N2 status [2]. Thus an optimal strategy for mediastinal staging is vital.
The most important paper identified was the NICE guidance on lung cancer management and treatment, published in February 2005 [3]. They used the results from their own systematic review and that published by Toloza [2] together with a small number of additional studies to calculate the sensitivity and specificity for either CT scanning or mediastinoscopy in the diagnosis of nodal status prior to thoracotomy. The sensitivity of CT scanning across 20 studies was 57% and the specificity was 82%. Mediastinoscopy across 14 studies showed a sensitivity of 81% and a false positive rate of less than 10% (the specificity is by definition 100% as the gold standard of positive histology is obtained by mediastinoscopy). They also performed a cost-effectiveness analysis of routine mediastinoscopy and found it to be cost effective for T2 and T3 tumours. NICE however, concludes that mediastinoscopy should only be performed for patients with mediastinal lymph nodes 1 cm in the shortest axis identified on CT scanning. Finally, they also report that a negative PET scan does not need tissue confirmation but a positive PET scan should undergo confirmation with mediastinoscopy.
The Scottish Intercollegiate Guidelines Network [4] also published an update of their guidelines in 2005. They collaborated with NICE but were more liberal in their recommendation for mediastinoscopy. They state that due to the high false negative rate of CT scanning, ‘Patients with small peripheral tumours and a negative CT scan of the mediastinum require no further investigation. Otherwise it is reasonable to further investigate the mediastinum with mediastinoscopy, Grade B.’
Based on the Systematic review by Toloza et al. [2], Detterbeck et al. [5] published a guideline for the American College of Chest Physicians. They state that for patients with a negative mediastinal CT, mediastinoscopy is the invasive procedure of choice to assess the mediastinal nodes due to its low false negative rate and morbidity (Grade B). The ACCP also recommends that good practice dictates lymph node samples from high and low paratracheal nodes (2L,2R,4L,4R) pretracheal nodes (stations 1 and 3) and the anterior subcarinal nodes (station 7) when performing mediastinoscopy.
De Leyn et al. [6] reported the findings of mediastinoscopy in patients with adenocarcinoma with a negative CT scan (no lymph nodes over 15 mm in long axis). Mediastinoscopy diagnosed 47 patients (20%) with N2 disease, thus avoiding unnecessary surgery. Ten percent of patients with T1 disease had mediastinoscopic N2 disease. Also of concern is the fact that despite routine CT and mediastinoscopy another 20 patients (11%) had an intraoperative diagnosis of N2 disease. The number needed to treat with mediastinoscopy to prevent an unnecessary operation was 5 in this study.
Choi et al. [7] performed routine mediastinoscopy and frozen section prior to resection in 291 patients with stage I disease after negative mediastinal CT scanning. Twenty patients had positive frozen section (7%) and had their operation cancelled. Interestingly, an additional 25 patients (9%) had N2 disease after intra-operative assessment and formal histology.
Daniels et al. [8] instituted a protocol of routine mediastinoscopy for all patients with negative mediastinal CT. Sixteen out of 66 (24%) of patients had positive mediastinoscopy, detecting N2 disease in patients previously categorized as N0.
The largest review of mediastinoscopy was by Hammound et al. [9]. They reported their experience with 2137 patients. There was a single death due to the procedure (0.05%) and 12 complications (0.5%) which included 6 arrhythmias, one oesophageal perforation and 2 bleeds, thus demonstrating that mediastinoscopy is a relatively safe procedure. Interestingly, they also had 9 patients where the mediastinoscopic frozen section was negative, but formal histology proved to be positive.
Thus, in summary, CT scanning has a high false negative rate. NICE recommends routine mediastinoscopy for patients with nodes of 1 mm on CT scanning but SIGN recommends mediastinoscopy in all but small peripheral tumours, and the ACCP recommend mediastinoscopy for all patients considered for surgery with a negative mediastinal CT scan if PET scanning cannot be performed.
3. Conclusion
Patients with resectable non-small cell lung cancer who have had a negative mediastinal CT scan should all undergo mediastinoscopy. The number needed to treat with mediastinoscopy to prevent an unnecessary thoracotomy is around 5–15 patients. Exceptions to this may be patients with a T1 tumour, patients with a small peripheral tumour or patients who have had a negative PET scan.
References
Dunning J, Prendergast B, Mackway-Jones K. Towards evidence-based medicine in cardiothoracic surgery: best BETS. Interact Cardiovasc Thorac Surg 2003; 2:405–409.
Toloza EM, Harpole L, Detterbeck F, McCrory DC. Invasive staging of non-small cell lung cancer: a review of the current evidence. Chest 2003; 123:1 Suppl157S–166S.
The diagnosis and treatment of lung cancer: Methods, evidence and guidance 2005 Commissioned by the National Institute of Clinical Excellence. Published by the National Collaborating Centre for Acute Care at The Royal College of Surgeons of England, 35–43 Lincoln's Inn Fields, London, WC2A 3PE.
Management of patients with lung cancer: a national clinical guideline, 2005 Scottish Intercollegiate Guidelines Network. Scottish Intercollegiate Guidelines Network Royal College of Physicians, 9 Queen Street Edinburgh EH2 1JQ.
Detterbeck FC, DeCamp MM Jr., Kohman LJ, Silvestri GA. American College of Chest Physicians Lung Cancer. Invasive staging: the guidelines. Chest 2003; 123:1 Suppl167S–175S.
De Leyn P, Vansteenkiste J, Cuypers P, Deneffe G, Van Raemdonck D, Coosemans W, Verschakelen J, Lerut T. Role of cervical mediastinoscopy in staging of non-small cell lung cancer without enlarged mediastinal lymph nodes on CT scan. Eur J Cardio Thorac Surg 1997; 12:5706–712.
Choi YS, Shim YM, Kim J, Kim K. Mediastinoscopy in patients with clinical stage I non-small cell lung cancer. Ann Thorac Surg 2003; 75:2364–366. [see comment].
Daniels JM, Rijna H, Postmus PE, van Mourik JC. Mediastinoscopy as a standardised procedure for mediastinal lymph node staging in non-small cell lung carcinoma. Eur J Cardio Thorac Surg 2001; 19:3377–378.
Hammound ZT, Anderson RC, Meyers BF, Guthrie TJ, Roper CL, Cooper JD, Patterson GA. The current role of mediastinoscopy in the evaluation of thoracic disease. J Thorac Cardiovasc Surg 1999; 118:894–899.(Shilajit Ghosh, Prakash N)
b Department of Cardiothoracic Surgery, James Cook University Hospital, Middlesbrough, UK
Abstract
A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed is whether all potential surgical candidates with non-small cell lung cancer should have cervical mediastinoscopy pre-operatively. Two hundred and forty-one papers were found using the reported search, of which 8 represented 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 were tabulated. We conclude that patients with resectable non-small cell lung cancer who have had a negative mediastinal CT scan should all undergo mediastinoscopy. The number needed to treat with mediastinoscopy to prevent an unnecessary thoracotomy is around 5–15 patients. Exceptions to this may be patients with a T1 tumour, patients with a small peripheral tumour or patients who have had a negative PET scan.
Key Words: Evidence-based medicine; Thoracic surgery; Mediastinoscopy; Non-small cell lung carcinoma; Staging
1. Introduction
A best evidence topic was constructed according to a structured protocol. This protocol is fully described in the ICVTS [1].
1.1. Clinical scenario
You are in a multidisciplinary team meeting, discussing a 76-year-old lifelong smoker who has a T2 right upper lobe adenocarcinoma. She has COPD and arthritis and is quite a frail lady and lung function testing showed that she would not tolerate a pneumonectomy. The CT scan shows a 5 cm tumour that may be resectable by lobectomy and there are no obviously enlarged mediastinal nodes although the radiologist reports that there are a few nodes there that are 0.8 cm in diameter. A consultant surgeon accepts her for lobectomy, but the anaesthetist suggests a mediastinoscopy first to reduce the likelihood of an ‘open and close’ thoracotomy. The chest physicians state that this would be contrary to current guidelines and thus you suggest that you could look up the evidence and present it at the next week's meeting.
1.2. Three-part question
In patients undergoing [lung resection for non-small cell lung cancer], would [routine cervical mediastinoscopy] reduce the incidence of [unnecessary thoracotomy].
1.3. Search strategy
Medline 1966–Oct 2005 using the Ovid interface. [exp mediastinoscopy/OR mediastinoscopy.mp] AND [exp neoplasm staging/OR staging.mp] AND [exp carcinoma, non-small-cell lung/OR non small cell lung cancer.mp] limit to humans.
1.4. Search outcome
A total of 241 papers were found from the above search. We selected four systematic reviews and meta-analyses that summarised fourteen diagnostic cohort studies on this topic. We identified three additional studies not included in the reviews and also summarised the largest cohort study in the literature. These are presented in Table 1.
2. Discussion
Accurate nodal staging, particularly N2 status is of paramount importance in the selection of patients for surgery. Studies have reported that around 20% of patients undergoing clinical staging are either overstaged or understaged when pathological staging is compared, and 20% of preoperative N0 patients may actually have pathological N1 or N2 status [2]. Thus an optimal strategy for mediastinal staging is vital.
The most important paper identified was the NICE guidance on lung cancer management and treatment, published in February 2005 [3]. They used the results from their own systematic review and that published by Toloza [2] together with a small number of additional studies to calculate the sensitivity and specificity for either CT scanning or mediastinoscopy in the diagnosis of nodal status prior to thoracotomy. The sensitivity of CT scanning across 20 studies was 57% and the specificity was 82%. Mediastinoscopy across 14 studies showed a sensitivity of 81% and a false positive rate of less than 10% (the specificity is by definition 100% as the gold standard of positive histology is obtained by mediastinoscopy). They also performed a cost-effectiveness analysis of routine mediastinoscopy and found it to be cost effective for T2 and T3 tumours. NICE however, concludes that mediastinoscopy should only be performed for patients with mediastinal lymph nodes 1 cm in the shortest axis identified on CT scanning. Finally, they also report that a negative PET scan does not need tissue confirmation but a positive PET scan should undergo confirmation with mediastinoscopy.
The Scottish Intercollegiate Guidelines Network [4] also published an update of their guidelines in 2005. They collaborated with NICE but were more liberal in their recommendation for mediastinoscopy. They state that due to the high false negative rate of CT scanning, ‘Patients with small peripheral tumours and a negative CT scan of the mediastinum require no further investigation. Otherwise it is reasonable to further investigate the mediastinum with mediastinoscopy, Grade B.’
Based on the Systematic review by Toloza et al. [2], Detterbeck et al. [5] published a guideline for the American College of Chest Physicians. They state that for patients with a negative mediastinal CT, mediastinoscopy is the invasive procedure of choice to assess the mediastinal nodes due to its low false negative rate and morbidity (Grade B). The ACCP also recommends that good practice dictates lymph node samples from high and low paratracheal nodes (2L,2R,4L,4R) pretracheal nodes (stations 1 and 3) and the anterior subcarinal nodes (station 7) when performing mediastinoscopy.
De Leyn et al. [6] reported the findings of mediastinoscopy in patients with adenocarcinoma with a negative CT scan (no lymph nodes over 15 mm in long axis). Mediastinoscopy diagnosed 47 patients (20%) with N2 disease, thus avoiding unnecessary surgery. Ten percent of patients with T1 disease had mediastinoscopic N2 disease. Also of concern is the fact that despite routine CT and mediastinoscopy another 20 patients (11%) had an intraoperative diagnosis of N2 disease. The number needed to treat with mediastinoscopy to prevent an unnecessary operation was 5 in this study.
Choi et al. [7] performed routine mediastinoscopy and frozen section prior to resection in 291 patients with stage I disease after negative mediastinal CT scanning. Twenty patients had positive frozen section (7%) and had their operation cancelled. Interestingly, an additional 25 patients (9%) had N2 disease after intra-operative assessment and formal histology.
Daniels et al. [8] instituted a protocol of routine mediastinoscopy for all patients with negative mediastinal CT. Sixteen out of 66 (24%) of patients had positive mediastinoscopy, detecting N2 disease in patients previously categorized as N0.
The largest review of mediastinoscopy was by Hammound et al. [9]. They reported their experience with 2137 patients. There was a single death due to the procedure (0.05%) and 12 complications (0.5%) which included 6 arrhythmias, one oesophageal perforation and 2 bleeds, thus demonstrating that mediastinoscopy is a relatively safe procedure. Interestingly, they also had 9 patients where the mediastinoscopic frozen section was negative, but formal histology proved to be positive.
Thus, in summary, CT scanning has a high false negative rate. NICE recommends routine mediastinoscopy for patients with nodes of 1 mm on CT scanning but SIGN recommends mediastinoscopy in all but small peripheral tumours, and the ACCP recommend mediastinoscopy for all patients considered for surgery with a negative mediastinal CT scan if PET scanning cannot be performed.
3. Conclusion
Patients with resectable non-small cell lung cancer who have had a negative mediastinal CT scan should all undergo mediastinoscopy. The number needed to treat with mediastinoscopy to prevent an unnecessary thoracotomy is around 5–15 patients. Exceptions to this may be patients with a T1 tumour, patients with a small peripheral tumour or patients who have had a negative PET scan.
References
Dunning J, Prendergast B, Mackway-Jones K. Towards evidence-based medicine in cardiothoracic surgery: best BETS. Interact Cardiovasc Thorac Surg 2003; 2:405–409.
Toloza EM, Harpole L, Detterbeck F, McCrory DC. Invasive staging of non-small cell lung cancer: a review of the current evidence. Chest 2003; 123:1 Suppl157S–166S.
The diagnosis and treatment of lung cancer: Methods, evidence and guidance 2005 Commissioned by the National Institute of Clinical Excellence. Published by the National Collaborating Centre for Acute Care at The Royal College of Surgeons of England, 35–43 Lincoln's Inn Fields, London, WC2A 3PE.
Management of patients with lung cancer: a national clinical guideline, 2005 Scottish Intercollegiate Guidelines Network. Scottish Intercollegiate Guidelines Network Royal College of Physicians, 9 Queen Street Edinburgh EH2 1JQ.
Detterbeck FC, DeCamp MM Jr., Kohman LJ, Silvestri GA. American College of Chest Physicians Lung Cancer. Invasive staging: the guidelines. Chest 2003; 123:1 Suppl167S–175S.
De Leyn P, Vansteenkiste J, Cuypers P, Deneffe G, Van Raemdonck D, Coosemans W, Verschakelen J, Lerut T. Role of cervical mediastinoscopy in staging of non-small cell lung cancer without enlarged mediastinal lymph nodes on CT scan. Eur J Cardio Thorac Surg 1997; 12:5706–712.
Choi YS, Shim YM, Kim J, Kim K. Mediastinoscopy in patients with clinical stage I non-small cell lung cancer. Ann Thorac Surg 2003; 75:2364–366. [see comment].
Daniels JM, Rijna H, Postmus PE, van Mourik JC. Mediastinoscopy as a standardised procedure for mediastinal lymph node staging in non-small cell lung carcinoma. Eur J Cardio Thorac Surg 2001; 19:3377–378.
Hammound ZT, Anderson RC, Meyers BF, Guthrie TJ, Roper CL, Cooper JD, Patterson GA. The current role of mediastinoscopy in the evaluation of thoracic disease. J Thorac Cardiovasc Surg 1999; 118:894–899.(Shilajit Ghosh, Prakash N)