- Email: [email protected]
Surgery versus SABR for resectable non-small-cell lung cancer
Correspondence
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Tournoy KG, Keller SM, Annema JT. Mediastinal staging of lung cancer: novel concepts. Lancet Oncol 2012; 13: 221–29. Shingyoji M, Nakajima T, Yoshino M, et al. Endobronchial ultrasonography for positron emission tomography and computedt tomography-negative lymph node staging in non-small cell lung cancer. Ann Thorac Surg 2014; 98: 1762–88.
In their pooled analysis of two randomised trials that each closed early due to inadequate accrual, Joe Chang and colleagues1 compared stereotactic ablative radiotherapy (SABR) with lobectomy for stage I non-small-cell lung cancer. Their conclusion, that “SABR is better tolerated—and might lead to better overall survival—than surgery for operable clinical stage I non-small cell lung cancer”, should be interpreted with caution because it is based on an unjust comparison of modern SABR techniques to outdated surgical approaches, and due to methodological limitations of the pooled data. Although advanced SABR techniques were used in the radiotherapy group, most lobectomies were undertaken using a thoracotomy. In fact, thoracotomy was done in 19 (79%) of 24 patients who underwent lobectomy. Open lobectomy, although a time-honoured procedure, should not be thought to be a standard of care for stage I non-small cell lung cancer. Compared with open lobectomy, thoracoscopic lobectomy is associated with lower (and ever improving) postoperative morbidity2,3 and mortality,4 without impairing oncological outcomes.5 When the comparison group is best possible radiotherapy, the conclusion that lobectomy is associated with increased procedural morbidity and mortality misrepresents the evolving surgical standard for patients with stage I disease. Furthermore, the conclusions of the investigators regarding procedural mortality refers to one perioperative death in the surgical group, compared with no deaths in the SABR group. On the basis of data from large national datasets, www.thelancet.com/oncology Vol 16 August 2015
the cumulative procedure-related mortality from SABR (0·7%) is similar to the operative (30 day or hospital discharge) mortality of thoracoscopic lobectomy (0·8%).4 The methodological limitations of this study cannot be understated when considering its conclusions. Both the STARS and ROSEL trials closed early owing to poor patient accrual. The 28 sites in the STARS trial randomised only 36 patients, and the ten sites in the ROSEL study randomised only 22 patients. Owing to the obvious lack of statistical power and short follow-up (median survival was not reached in either group), conclusions pertaining to overall survival outcomes are not interpretable. Additionally, in the ROSEL study, biopsy confirmation of non-small cell lung cancer was not mandatory, and could have inflated the survival advantage of SABR. In this study, one patient in the surgical group underwent surgical resection for benign disease but the number of patients with benign disease who underwent SABR cannot be established. The report by Chang and colleagues was underpowered to study overall survival and it was also underpowered to evaluate recurrence-free survival. The rate of locoregional recurrence (lung and nodal) in this report was four times greater in patients undergoing SABR (16·1%) than in patients undergoing lobectomy (4·1%). How such data would translate into cancer-specific survival outcomes in a trial that was properly designed to examine this variable is unknown. Last, the investigators stated in the Methods section that “the analyses were exploratory in nature”, yet they made a bold conclusion that SABR is better tolerated. We agree that a multi-institutional randomised controlled trial is needed. However, future randomised trials should be designed to make fair comparisons between best radiotherapy and best surgical therapy.
The authors declare no competing interests.
Masatsugu Hamaji, Shawn S Groth, David J Sugarbaker, *Bryan M Burt [email protected] Department of Thoracic Surgery, Kyoto University Hospital, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan (MH); Division of Thoracic Surgery, Department of Surgery, Baylor College of Medicine, Houston, TX, 77030, USA (SSG, DJS, BMB) 1
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Chang JY, Senan S, Paul MA, et al. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Oncol 2015; 16: 630–37. Falcoz PE, Puyraveau M, Thomas PA, et al. Video-assisted thoracoscopic surgery versus open lobectomy for primary non-small-cell lung cancer: a propensity-matched analysis of outcome from the European Society of Thoracic Surgeon database. Eur J Cardiothorac Surg 2015; published online April 26. DOI:10.1093/ejcts/ezv154. Nwogu CE, D’Cunha J, Pang H, et al. VATS lobectomy has better perioperative outcomes than open lobectomy: CALGB 31001, an ancillary analysis of CALGB 140202 (Alliance). Ann Thorac Surg 2015; 99: 399–405. Burt BM, Kosinski AS, Shrager JB, Onaitis MW, Weigel T. Thoracoscopic lobectomy is associated with acceptable morbidity and mortality in patients with predicted postoperative forced expiratory volume in 1 second or diffusing capacity for carbon monoxide less than 40% of normal. J Thorac Cardiovasc Surg 2014; 148: 19–28. Paul S, Isaacs AJ, Treasure T, Altorki NK, Sedrakyan A. Long term survival with thoracoscopic versus open lobectomy: propensity matched comparative analysis using SEER-Medicare database. BMJ 2014; 349: g5575.
Joe Chang and colleagues1 report the combined results of two randomised trials (STARS and ROSEL) comparing stereotactic ablative radiotherapy (SABR) with surgery for early-stage non-small-cell lung cancer. Both trials were halted early because of slow recruitment. We welcome the much needed evidence from randomised controlled trials (RCTs) and agree with the Comment2 by Tom Treasure and colleagues that evidence is needed as a basis for treatment selection. Nevertheless, we believe that the evidence from these two trials should be placed in a balanced perspective and rated according to a reliable and internationally recognised grading system. For this purpose, we will e372
9
10
Tournoy KG, Keller SM, Annema JT. Mediastinal staging of lung cancer: novel concepts. Lancet Oncol 2012; 13: 221–29. Shingyoji M, Nakajima T, Yoshino M, et al. Endobronchial ultrasonography for positron emission tomography and computedt tomography-negative lymph node staging in non-small cell lung cancer. Ann Thorac Surg 2014; 98: 1762–88.
In their pooled analysis of two randomised trials that each closed early due to inadequate accrual, Joe Chang and colleagues1 compared stereotactic ablative radiotherapy (SABR) with lobectomy for stage I non-small-cell lung cancer. Their conclusion, that “SABR is better tolerated—and might lead to better overall survival—than surgery for operable clinical stage I non-small cell lung cancer”, should be interpreted with caution because it is based on an unjust comparison of modern SABR techniques to outdated surgical approaches, and due to methodological limitations of the pooled data. Although advanced SABR techniques were used in the radiotherapy group, most lobectomies were undertaken using a thoracotomy. In fact, thoracotomy was done in 19 (79%) of 24 patients who underwent lobectomy. Open lobectomy, although a time-honoured procedure, should not be thought to be a standard of care for stage I non-small cell lung cancer. Compared with open lobectomy, thoracoscopic lobectomy is associated with lower (and ever improving) postoperative morbidity2,3 and mortality,4 without impairing oncological outcomes.5 When the comparison group is best possible radiotherapy, the conclusion that lobectomy is associated with increased procedural morbidity and mortality misrepresents the evolving surgical standard for patients with stage I disease. Furthermore, the conclusions of the investigators regarding procedural mortality refers to one perioperative death in the surgical group, compared with no deaths in the SABR group. On the basis of data from large national datasets, www.thelancet.com/oncology Vol 16 August 2015
the cumulative procedure-related mortality from SABR (0·7%) is similar to the operative (30 day or hospital discharge) mortality of thoracoscopic lobectomy (0·8%).4 The methodological limitations of this study cannot be understated when considering its conclusions. Both the STARS and ROSEL trials closed early owing to poor patient accrual. The 28 sites in the STARS trial randomised only 36 patients, and the ten sites in the ROSEL study randomised only 22 patients. Owing to the obvious lack of statistical power and short follow-up (median survival was not reached in either group), conclusions pertaining to overall survival outcomes are not interpretable. Additionally, in the ROSEL study, biopsy confirmation of non-small cell lung cancer was not mandatory, and could have inflated the survival advantage of SABR. In this study, one patient in the surgical group underwent surgical resection for benign disease but the number of patients with benign disease who underwent SABR cannot be established. The report by Chang and colleagues was underpowered to study overall survival and it was also underpowered to evaluate recurrence-free survival. The rate of locoregional recurrence (lung and nodal) in this report was four times greater in patients undergoing SABR (16·1%) than in patients undergoing lobectomy (4·1%). How such data would translate into cancer-specific survival outcomes in a trial that was properly designed to examine this variable is unknown. Last, the investigators stated in the Methods section that “the analyses were exploratory in nature”, yet they made a bold conclusion that SABR is better tolerated. We agree that a multi-institutional randomised controlled trial is needed. However, future randomised trials should be designed to make fair comparisons between best radiotherapy and best surgical therapy.
The authors declare no competing interests.
Masatsugu Hamaji, Shawn S Groth, David J Sugarbaker, *Bryan M Burt [email protected] Department of Thoracic Surgery, Kyoto University Hospital, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan (MH); Division of Thoracic Surgery, Department of Surgery, Baylor College of Medicine, Houston, TX, 77030, USA (SSG, DJS, BMB) 1
2
3
4
5
Chang JY, Senan S, Paul MA, et al. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Oncol 2015; 16: 630–37. Falcoz PE, Puyraveau M, Thomas PA, et al. Video-assisted thoracoscopic surgery versus open lobectomy for primary non-small-cell lung cancer: a propensity-matched analysis of outcome from the European Society of Thoracic Surgeon database. Eur J Cardiothorac Surg 2015; published online April 26. DOI:10.1093/ejcts/ezv154. Nwogu CE, D’Cunha J, Pang H, et al. VATS lobectomy has better perioperative outcomes than open lobectomy: CALGB 31001, an ancillary analysis of CALGB 140202 (Alliance). Ann Thorac Surg 2015; 99: 399–405. Burt BM, Kosinski AS, Shrager JB, Onaitis MW, Weigel T. Thoracoscopic lobectomy is associated with acceptable morbidity and mortality in patients with predicted postoperative forced expiratory volume in 1 second or diffusing capacity for carbon monoxide less than 40% of normal. J Thorac Cardiovasc Surg 2014; 148: 19–28. Paul S, Isaacs AJ, Treasure T, Altorki NK, Sedrakyan A. Long term survival with thoracoscopic versus open lobectomy: propensity matched comparative analysis using SEER-Medicare database. BMJ 2014; 349: g5575.
Joe Chang and colleagues1 report the combined results of two randomised trials (STARS and ROSEL) comparing stereotactic ablative radiotherapy (SABR) with surgery for early-stage non-small-cell lung cancer. Both trials were halted early because of slow recruitment. We welcome the much needed evidence from randomised controlled trials (RCTs) and agree with the Comment2 by Tom Treasure and colleagues that evidence is needed as a basis for treatment selection. Nevertheless, we believe that the evidence from these two trials should be placed in a balanced perspective and rated according to a reliable and internationally recognised grading system. For this purpose, we will e372