Author, date and country | Patient group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
---|---|---|---|---|---|
Izbicki J et al, 1995, Germany | 201 patients with operable NSCLC 100 patients with radical systematic mediastinal lymph node dissection (LA) 82 patients with mediastinal lymph node exploration and removal of suspicious nodes only (LS) After randomisation 19 patients (LS n=1, LA n=18) were excluded from analysis due to residual tumour or classification as small cell lung cancer | Controlled prospective RCT (level 2b) | Effect of redical lymphadenectomy on nodal staging of NSCLC | Procedure: LS n=1 wef00 N0 55%, N1 20%, N2 23%, N3 2% LA n=82, N0 58.5%, N1 10.9%, N2 26.8%, N3 3.7% No significant difference | Disproportionately high number excluded from the LA group Small patient numbers in each subgroup Median follow-up period was only 26.8 months LS involved extensive sampling Nodes from stations 4,5 and 7 were excised from all patients, nodes in regions 2-9 were explored and removed if suspicious |
Survival/local recurrence | Type of lymphadectomy did not influence the risk of local tumour recurrence, distant mediastasis or survival | ||||
Izbicki JR et al, 1998, Germany | 201 patients with operable NSCLC 32 patients excluded from analysis LA n = 76 LS n = 93 Same patient population as Izbicki et al 1995 Median follow up 47.5 months (range 25-67) | Controlled prospective randomized clinical trial (level 2b) | Survival | LA 5 yr survival 70.6%* LS 5 yr survival 47.9%* LA prolonged relapse free survival p=0.037 with a borderline effect on overall survival (p = 0.058) in patients with limited lymph node involvement (*pN1 disease or pN2 disease with involvement of only one lymph node level); In patients with pN0 disease, no survival benefit was observed | Median follow up 47.5 months (25-67 months) Small numbers within subgroups reducing statistical power More squamous cell carcinomas in the LA group than in the LS group (52.7 vs. 31.6%) Study was powered to detect a 20% survival benefit of LA over LS only if there were 100 patients in each group Stage migration |
Morbidity | Post operative course was more or less the same in the 2 groups Higher need for post op transfusion and higher incidence of prolonged air leakage in patients with systematic lymph node dissection No difference in Hospital or ICU stay | ||||
Passlick B et al, 2002, Germany | 94 patients with pathological stage I-IIIA NSCLC Stage I NSCLC n = 73 Radical systematic en-bloc-mediastinal lymphadencetomy (LA) n = 42 Mediastinal Lymph node sampling (LS) n = 31 Samples were screened by immunohistochemistry for disseminated tumour cells using antibody Ber-Ep4 | Prospective Randomized Trial (level 2b) | Survival | Overall survival was 54.7% 5 year survival in the LA group and 41% in the LS group p=0.27 Stage I LA 62% 5 yr survival, LS 42% 5 year survival p=0.044 Stage II to IV LA 27% 5 yr survival, LS 30% 5 yr survival, p=0.39 | Small numbers involved in the stage II to IV group (only 21 patients in total) |
Immuno-histochemistry evidence of micrometastases | In patients without nodal micrometastases LA was associated with significantly improved long-term outcome p = 0.0044 In patients with nodal micrometastases the prognosis was not influenced by the type of lymphadenectomy | ||||
Wu Y et al, 2002, China | Resectable clinical stage I-IIIA NSCLC 268 patients assigned to lung cancer resection combined with systematic lymph node dissection (SND) 264 patients were assigned to lung cancer combined with mediastinal lymph node sampling (MLS) 471 patients were eligible for follow up | Prospective Randomized Trial (level 1b) | Survival | Stage I n=156, SND 82.2% 5 yr survival, MLS 57.5% 5 yr survival p=0.0104 Stage II n=136, SND 50% 5 yr survival, MLS 34.1% 5 year survival p=0.052 Stage III n=179, SND 27% 5 yr survival, MLS 6.2% 5 yr survival p=0.284 | More stage I and less stage IIIA patients in those undergoing MLS, suggesting that MLS is less accurate in staging the disease and that stage migration may influence survival in this trial Unequal follow up between groups |
Post operative recurrence | SND 7 (2.9%) MLS 11 (4.8%) No statistical significance specified | ||||
Metastases | SND 54 (22.5%) MLS 71 (30.7%) No statistical significance specified | ||||
Keller SM et al, 2000, USA | 373 patients with non small cell lung cancer 186 patients underwent systematic sampling (SS) of the mediastinal lymph nodes 187 patients underwent complete mediastinal lymph node dissection (MLND) | Non randomized controlled study (level 2b) | Survival | N1 disease SS 5 yr survival 57%, MLND 5 year survival 48%, p=0.04. N2 disease SS 5 yr survival 41%, MLND 5 yr survival 35%, p=0.035. | Not randomized 192 surgeons involved in the study, some exclusively performed one technique or the other 131 surgeons entered only one patient |
Garja A et al, 2003, USA | 442 patients with stage I NSCLC 246 patients had random sampling. 115 patients had systematic sampling (SS) 81 patients had complete mediastinal lymphadenectomy (MLND) | Retrospectve Cohort Study (level 4) | Overall survival | 56%, 83% and 86% (p<0.0001) for random sampling, SS and MLND respectively | Retrospective data Spurious downstaging of patients with inadequate sampling Large number of patients excluded from the original cohort due to inadequate follow up and incomplete data |
Disease free survival | 51%, 80% and 80% (p<0.0001) for random sampling, SS and MLND respectively | ||||
Sugi K et al, 1998, Japan | 115 patients with peripheral non small cell lung cancers < 2cm diameter 59 patients had lymph node sampling 56 patients had radical lymph node dissection | Randomized Controlled Trial (level 2b) | Survival | Lymph Node Sampling Group 83.9% 5 yr survival Lymph Node Dissection Group 81.4% 5 year survival No statistically significant difference | Small numbers in each group Study limited to 2cm diameter tumours, therefore excluding some stage I tumours |
Morbidity | Morbidity was significantly higher in the dissection group 26.8% vs. 3.4% p value not stated Comparable ICU and hospital stay | ||||
Wu YC et al, 2003 Taiwan | 321 patients undergoing surgery for Stage I NSCLC | Retrospective Cohort Study (level 2b) | Survival | Removed no. of lymph nodes > 15 5 yr survival 57.1% 10 yr survival 46.3% Removed no. of lymph nodes < 15 5 yr survival 45.5% 10 yr survival 31.5% p<0.01 | 13 patients with inadequate pulmonary reserve had sub lobar resections 18 patients lost to follow up Retrospective study Spurious downstaging of patients with inadequate sampling |