Randomized clinical trial comparing survival after D1 or D2 gastrectomy for gastric cancer
31
Commentary
Randomized clinical trial comparing survival after D1 or D2 gastrectomy for gastric cancer (Br J Surg 2014; 101: 23–31) The extent of lymph node dissection has been the subject of debate and clinical trials over the past decades. After a number of underpowered studies, the UK Medical Research Council1 and Dutch Gastric Cancer2 trials indicated clearly that extended lymphadenectomy was associated with higher morbidity and mortality rates compared with standard limited lymphadenectomy. The unfavourable outcomes were associated mostly with pancreatosplenectomy, which was an integral part of the D2 dissection in both trials; the mortality rate ranged between 10 and 13 per cent1,2 . In 2010, a multicentre phase II study in Italy3 , randomizing for D1 or D2 gastrectomy with pancreas-preserving D2 dissection, demonstrated similar and low operative mortality for the two procedures when surgery was performed in high-volume centres with strict quality control. The present trial by the Italian Gastric Cancer Study Group indicates no overall 5-year survival benefit from D2 dissection. Importantly, the trial shows that D2 dissection in experienced hands can be performed adequately with a low risk of operative mortality. Unfortunately, the sample size was calculated at 320 patients, but enrolment was stopped after 267 patients because of slow accrual. Therefore, the impression is that this is an underpowered trial. Equally, despite quality control, high rates of contamination in D1 and non-compliance in D2 occurred. The 5-year survival rate of approximately 65 per cent is impressive, but may be related also to the unexpectedly high proportion (33 per cent) of patients with pathological tumour (pT) category 1 tumours, who have a good prognosis and probably would not benefit from a D2 procedure. What lesson can be learned from this paper? The long-term results after 15 years of the Dutch Gastric Cancer trial2 indicated a significant decrease in the risk of dying from gastric cancer after D2 dissection (37 per cent versus 48 per cent for D1 resection) and better locoregional control. In a subgroup analysis of the present Italian study, with all its limitations, survival appeared to be improved after D2 resection for patients with tumours in a category higher than T1 and who were node-positive. As a result of clinical trial experience worldwide, European guidelines now recommend D2 lymphadenectomy without pancreatectomy or splenectomy for stage II and III gastric cancers in patients without severe co-morbidities. The Italian study contributes to the view that D2 lymphadenectomy can be performed safely and adequately, producing 5-year survival results that help to close the gap between survival results reported from Asia and those from Europe. There are still major differences between Asia and the West in disease stage classification, types of tumour and types of patient, and the usually high-volume centres of the East. A recent overview of outcomes in gastric cancer surgery across Europe4 demonstrated the relationship between volume and operative mortality, but also indicated that this was not the only factor responsible 2013 BJS Society Ltd Published by John Wiley & Sons Ltd
www.bjs.co.uk
BJS 2014; 101: 31–32
M. Degiuli, M. Sasako, A. Ponti, A. Vendrame, M. Tomatis, C. Mazza et al.
32
for better outcomes. The Japanese guidelines for gastric cancer5 witness the development of a more individualized approach dependent on tumour node metastasis (TNM) stage. In Europe there is a clear need for surgical quality assurance and audit to provide further insight into differences between hospitals and countries, with the ultimate aim of improving outcome for patients with gastric cancer throughout Europe, and of closing the gap in survival results between East and West. C. J. H. van de Velde Department of Surgery, Leiden University Medical Centre, Albinusdreef 2, 2333, ZA Leiden, The Netherlands
(e-mail: [email protected]) DOI: 10.1002/bjs.9380
Disclosure
The author declares no conflict of interest. References 1 Cuschieri A, Fayers P, Fielding J, Craven J, Bancewicz J, Joypaul V et al. Postoperative morbidity and mortality after D1 and D2 resections for gastric cancer: preliminary results of the MRC randomised controlled surgical trial. The Surgical Cooperative Group. Lancet 1996; 347: 995–999. 2 Songun I, Putter H, Kranenbarg ME, Sasako M, van de Velde CJ. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Lancet Oncol 2010; 11: 439–449. 3 Degiuli M, Sasako M, Ponti A; Italian Gastric Cancer Study Group. Morbidity and mortality in the Italian Gastric Cancer Study Group randomized clinical trial of D1 versus D2 resection for gastric cancer. Br J Surg 2010; 97: 643–649. 4 Dikken JL, van Sandick JW, Allum WH, Johansson J, Jensen LS, Putter H et al. Differences in outcomes of oesophageal and gastric cancer surgery across Europe. Br J Surg 2013; 100: 83–94. 5 Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2010 (ver. 3). Gastric Cancer 2011; 14: 113–123.
2013 BJS Society Ltd Published by John Wiley & Sons Ltd
www.bjs.co.uk
BJS 2014; 101: 31–32
31
Commentary
Randomized clinical trial comparing survival after D1 or D2 gastrectomy for gastric cancer (Br J Surg 2014; 101: 23–31) The extent of lymph node dissection has been the subject of debate and clinical trials over the past decades. After a number of underpowered studies, the UK Medical Research Council1 and Dutch Gastric Cancer2 trials indicated clearly that extended lymphadenectomy was associated with higher morbidity and mortality rates compared with standard limited lymphadenectomy. The unfavourable outcomes were associated mostly with pancreatosplenectomy, which was an integral part of the D2 dissection in both trials; the mortality rate ranged between 10 and 13 per cent1,2 . In 2010, a multicentre phase II study in Italy3 , randomizing for D1 or D2 gastrectomy with pancreas-preserving D2 dissection, demonstrated similar and low operative mortality for the two procedures when surgery was performed in high-volume centres with strict quality control. The present trial by the Italian Gastric Cancer Study Group indicates no overall 5-year survival benefit from D2 dissection. Importantly, the trial shows that D2 dissection in experienced hands can be performed adequately with a low risk of operative mortality. Unfortunately, the sample size was calculated at 320 patients, but enrolment was stopped after 267 patients because of slow accrual. Therefore, the impression is that this is an underpowered trial. Equally, despite quality control, high rates of contamination in D1 and non-compliance in D2 occurred. The 5-year survival rate of approximately 65 per cent is impressive, but may be related also to the unexpectedly high proportion (33 per cent) of patients with pathological tumour (pT) category 1 tumours, who have a good prognosis and probably would not benefit from a D2 procedure. What lesson can be learned from this paper? The long-term results after 15 years of the Dutch Gastric Cancer trial2 indicated a significant decrease in the risk of dying from gastric cancer after D2 dissection (37 per cent versus 48 per cent for D1 resection) and better locoregional control. In a subgroup analysis of the present Italian study, with all its limitations, survival appeared to be improved after D2 resection for patients with tumours in a category higher than T1 and who were node-positive. As a result of clinical trial experience worldwide, European guidelines now recommend D2 lymphadenectomy without pancreatectomy or splenectomy for stage II and III gastric cancers in patients without severe co-morbidities. The Italian study contributes to the view that D2 lymphadenectomy can be performed safely and adequately, producing 5-year survival results that help to close the gap between survival results reported from Asia and those from Europe. There are still major differences between Asia and the West in disease stage classification, types of tumour and types of patient, and the usually high-volume centres of the East. A recent overview of outcomes in gastric cancer surgery across Europe4 demonstrated the relationship between volume and operative mortality, but also indicated that this was not the only factor responsible 2013 BJS Society Ltd Published by John Wiley & Sons Ltd
www.bjs.co.uk
BJS 2014; 101: 31–32
M. Degiuli, M. Sasako, A. Ponti, A. Vendrame, M. Tomatis, C. Mazza et al.
32
for better outcomes. The Japanese guidelines for gastric cancer5 witness the development of a more individualized approach dependent on tumour node metastasis (TNM) stage. In Europe there is a clear need for surgical quality assurance and audit to provide further insight into differences between hospitals and countries, with the ultimate aim of improving outcome for patients with gastric cancer throughout Europe, and of closing the gap in survival results between East and West. C. J. H. van de Velde Department of Surgery, Leiden University Medical Centre, Albinusdreef 2, 2333, ZA Leiden, The Netherlands
(e-mail: [email protected]) DOI: 10.1002/bjs.9380
Disclosure
The author declares no conflict of interest. References 1 Cuschieri A, Fayers P, Fielding J, Craven J, Bancewicz J, Joypaul V et al. Postoperative morbidity and mortality after D1 and D2 resections for gastric cancer: preliminary results of the MRC randomised controlled surgical trial. The Surgical Cooperative Group. Lancet 1996; 347: 995–999. 2 Songun I, Putter H, Kranenbarg ME, Sasako M, van de Velde CJ. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Lancet Oncol 2010; 11: 439–449. 3 Degiuli M, Sasako M, Ponti A; Italian Gastric Cancer Study Group. Morbidity and mortality in the Italian Gastric Cancer Study Group randomized clinical trial of D1 versus D2 resection for gastric cancer. Br J Surg 2010; 97: 643–649. 4 Dikken JL, van Sandick JW, Allum WH, Johansson J, Jensen LS, Putter H et al. Differences in outcomes of oesophageal and gastric cancer surgery across Europe. Br J Surg 2013; 100: 83–94. 5 Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2010 (ver. 3). Gastric Cancer 2011; 14: 113–123.
2013 BJS Society Ltd Published by John Wiley & Sons Ltd
www.bjs.co.uk
BJS 2014; 101: 31–32
