An evidence-based medicine review of lymphadenectomy extent for gastric cancer

doi:10.1016/j.amjsurg.2008.05.001

The American Journal of Surgery

Volume 197, Issue 2, February 2009, Pages 246-251

https://doi.org/10.1016/j.amjsurg.2008.05.001 Get rights and content

Abstract

Background

Several studies in the literature have investigated the possible role of the extent of lymphadenectomy in gastric cancer treatment failure. The current study attempted to determine the effectiveness and safety of lymphadenectomy with gastrectomy for the treatment of gastric cancer.

Methods

Randomized controlled trials (RCTs) were identified by means of MEDLINE, EMBASE, Cochrane Controlled Trials Register databases, and Chinese Biomedical Database, as well as by selecting references from relevant articles.

Results

Overall, 14 RCTs (3,432 patients) were included in the meta-analysis. Of the D1 and D2 surgery groups, the operative mortality and postoperative morbidity were higher in the D2 group than in the D1 group, but the 3- and 5-year survival rates were not statistically different. Also the operative time was shorter in D1 compared to D2. In the D2 versus the D3 surgical group, the operative mortality, percentage of postoperative complications, operative time, and hospital stay were not significantly different.

Conclusions

The results suggest that D2 and D3 surgery may not offer specific advantages for gastric cancer and instead may lead to disadvantages for patient outcomes.

Section snippets

Inclusion and exclusion criteria

Our study only considered RCTs. Studies of gastrectomy with lymphadenectomy for gastric cancer were considered for inclusion if they reported a 3- or 5-year survival, postoperative morbidity, 30-day postoperative mortality, hospital stay, and operative time (mean and SD) for a group of patients having a clearly defined type of nodal dissection. Studies without raw data available for retrieval were excluded. All patients had histologically proven adenocarcinoma of the stomach by preoperative

Study description

Thirty-one RCTs were eligible for the study. Of these, 14 trials (3,432 patients in 18 articles) were included in the meta-analysis.15, 16, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 Thirteen trials36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 were excluded for the following reasons: study design, stage of disease, histology, repetitive publication, and unavailability of the report. The characteristics of the 14 included studies (18 articles) are summarized in Table 1.

D1 versus D2

Comments

We conducted an evidence-based analysis to provide recommendations on the use of lymphadenectomy for gastric cancer with methodology from the Cochrane Collaboration and the Center of Evidence-based Medicine of Oxford.17, 49, 50 The meta-analysis showed that the operative mortality and postoperative morbidity increased in the D2 group as compared to the D1 group. The operative time was longer in the D2 group than in the D1 group. In contrast, there was no difference in the 3- or 5-year survival

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Complete mesogastric excision for locally advanced gastric cancer: short-term outcomes of a randomized clinical trial
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Citation Excerpt :
Currently, the standard operation for advanced gastric cancer (AGC) is gastrectomy with D2 lymphadenectomy.3 However, 38% to 50% of patients develop recurrent disease after curative surgery.4,5 In the past three decades, implementation of the complete mesocolic excision (CME)/total mesorectal excision (TME) technique in colorectal cancer surgery has successfully reduced local relapse and improved tumor survival.6–11
Implementation of complete mesogastric excision in gastric cancer surgery, named D2 lymphadenectomy plus complete mesogastric excision (D2+CME), has recently been proposed as an optimal procedure. However, the safety and efficacy of D2+CME remain uncertain. In this randomized controlled trial, patients receiving D2+CME exhibit less intraoperative blood loss, more lymph node harvesting, and earlier postoperative flatus than patients receiving conventional D2 radical surgery. Univariate Cox regression analysis reveals that the risk ratio for postoperative flatus in D2+CME group is 1.247 (p = 0.044). Overall postoperative complications are comparable between the two groups, but complications are significantly less severe in the D2+CME group than the D2 group (Clavien-Dindo classification grade ≥ IIIa: 4 D2+CME patients [11.8%] versus 9 D2 patients [33.3%]; p = 0.041). In conclusion, our work shows that D2+CME is associated with better short-term outcomes and surgical safety than conventional D2 dissection for patients with advanced gastric cancer.
Lymph node ratio as a prognostic factor in gastric cancer patients following D1 resection. Comparison with the current TNM staging system
2017, European Journal of Surgical Oncology
Nodal ratio (NR) has been demonstrated to be an independent prognostic factor in patients with gastric cancer. We evaluated the prognostic role of NR comparing it with the current TNM (2010) classification in gastric cancer patients treated with curative (R0) D1 resection.
We retrospectively reviewed 110 patients who underwent R0 resection for gastric cancer at University Hospital of Larissa between 2002 and 2011. All patients had a D1 lymphadenectomy plus the nodes along the left gastric artery. Factors affecting survival as well as correlations between the N status, NR status and resected nodes were investigated.
In univariate analysis the N and NR status but not the numbers of retrieved nodes were significant prognostic factors. Inside N1 and N2 categories, patients with different NR groups were present and survival of some of these subpopulations was statistically different at long-rank test. There was a correlation between the nodes retrieved and N status but not with the NR category. In multivariate analysis both N status (HR = 1.45; 95% C.I. = 1.19–1.89) and NR (HR = 4.53; 95% C.I. = 1.86–11.03) found to be independent prognostic factors of survival.
Prognostic significance of N status and NR status was comparable. Unlike N status, NR is independent by the number of resected nodes, and therefore it is particularly useful in case of conventional lymphadenectomy.
Lymphadenectomy extent and survival of patients with gastric carcinoma: A systematic review and meta-analysis of time-to-event data from randomized trials
2015, Cancer Treatment Reviews
Citation Excerpt :
This is the first time that a meta-analysis supports a survival benefit for gastric cancer patients undergoing a more extended lymph node dissection. In fact, none of the meta-analyses published so far could demonstrate such a benefit [30–36]. However, it should be pointed out that all previous meta-analyses suffer from some limitations.
The extent of lymph node dissection in patients with resectable non-metastatic primary carcinoma of the stomach is still a controversial matter of debate, with special regard to its effect on survival.
We conducted a systematic review and meta-analysis of time-to-event data from randomized controlled trials (RCTs) comparing the three main types of lymphadenectomy (D1, D2, and D3) for gastric cancer. Hazard ratio (HR) was considered the effect measure for both overall (OS), disease-specific (DSS) and disease-free survival (DFS). The quality of the available evidence was assessed using the GRADE system.
Eight RCTs enrolling 2515 patients were eligible. The meta-analysis of four RCTs (n = 1599) showed a significant impact of D2 versus D1 lymphadenectomy on DSS (summary HR = 0.807, CI: 0.705–0.924, P = 0.002), the corresponding number-to-treat being equal to ten. This effect remained clinically valuable even after adjustment for postoperative mortality. However, the quality of evidence was graded as moderate due to inconsistency issues.
When OS and DFS were considered, the meta-analysis of respectively five (n = 1653) and three RCTs (n = 1332) found no significant difference between D2 and D1 lymph node dissection (summary HR = 0.911, CI: 0.708–1.172, P = 0.471, and summary HR = 0.946, CI: 0.840–1.066, P = 0.366, respectively). However, at subgroup analysis D2 type resulted superior to D1 type lymphadenectomy in terms of OS considering the two RCTs carried out in Eastern countries (summary HR = 0.627, CI: 0.396–0.994, P = 0.047).
As regards the D3 vs D2 comparison, the meta-analysis of the three available RCTs (n = 862) showed no significant impact of more extended lymphadenectomy on OS (summary HR = 0.990, CI: 0.814–1.205, P = 0.924).
Our findings support the superiority of D2 versus D1 lymphadenectomy in terms of survival benefit. However, this advantage is mainly limited to DSS, the level of evidence is moderate, and the interaction with other factors affecting patient survival (such as complementary medical therapy) remains to be elucidated.
Lymph node dissection: What for? From esophagus to rectum: Surgical and lymph node related prognostic factors
2014, Bulletin du Cancer
La chirurgie reste le pilier du traitement curatif des cancers digestifs et le statut ganglionnaire de ces cancers est, pour presque toutes les localisations, un facteur pronostique majeur. Pour le cancer de l’œsophage comme pour le cancer de l’estomac, aucune attitude standardisée ne s’est encore imposée au niveau international. Si les équipes occidentales prônent actuellement pour ces deux cancers des curages plus limités que les équipes asiatiques afin d’en limiter la morbidité, les recommandations imposent malgré tout des curages relativement importants : 23 ganglions au moins pour le cancer de l’œsophage et 25 ganglions pour le curage D2 ou D1,5 du cancer de l’estomac. La généralisation des traitements néo-adjuvants et adjuvants n’a pour l’instant pas modifié cette attitude. La chirurgie du cancer du rectum est quant à elle bien standardisée avec notamment le concept d’exérèse totale du mésorectum (TME) apparu à la fin des années 1980. Le développement de techniques mini-invasives (cœlioscopie puis robot) a permis de diminuer la morbidité et d’accélérer la récupération après ces interventions qui restent malgré tout lourdes et grevées d’une morbidité non négligeable. Le développement de la radio-chimiothérapie néo-adjuvante et la bonne connaissance des facteurs de risque d’envahissement ganglionnaire ont ouvert la voie à la chirurgie transanale consistant en l’exérèse de la tumeur avec toute l’épaisseur de la paroi rectale sans curage ganglionnaire. Le but est d’épargner la morbidité de la TME tout en maintenant au minimum le risque de récidive loco-régionale. Cette technique ne met donc pas à l’abri d’une proctectomie de rattrapage si les critères histologiques ne sont pas favorables.
Surgery has still a key role in curative treatment of digestive carcinomas, and for almost all localisations, lymph node status is a major prognostic factor. As far as oesophageal and gastric cancer are concerned, there is not yet any internationally standardized approach. Occidental guidelines recommend more limited lymph node dissections than Asiatic ones. Lymph node numbers requested during surgery of such cancers remain high, at least 23 lymph nodes for oesophageal cancer, and 25 for a D2 or D1.5 lymphadenectomy for gastric cancer. Generalisation of neo-adjuvant and adjuvant treatments has not yet modified these standards. On the other hand, rectal cancer surgery is well standardized since the global adoption of Total Mesorectal Excision (TME) for the late eighties. Development of mini-invasive techniques (laparoscopy and robot-assisted surgery) enabled an important decrease of surgery related morbidity as well as an enhanced post-operative recovery. However, rectal cancer surgery still has an important morbidity. Development of neo-adjuvant chemo-radiotherapy as well as in-depth knowledge of risk factor of lymph node invasion opened up the path for transanal full thickness resection without lymphadenectomy. The goal of such an approach is to avoid TME's morbidity without risking local recurrence rate increase. As a consequence, this technique might need to be completed with a TME case histological factors are not favorable.
Systematic review of risk factors for metastasis to para-aortic lymph nodes in gastric cancer
2013, Surgical Oncology
A meta-analysis was performed to evaluate the possible predictors of the positive PALN(para-aortic lymph nodes) for identifing specific patients who are at high risk of PALN metastases and for whom super-extended lymphadenectomy or pre-operative DCS therapy could be recommended.
Five databases (PUBMED, EMBASE, the Cochrane Library and the China Biological Medicine Database, CNKI) were searched that finally identified 11 candidate studies. Original data were abstracted from each study and used to calculate odds ratios. The random effects or fixed-effect model was used to combine odds ratios to determine the strength of the associations.
In this study, we eventually found 6 risk factors in the clinicopathologic characteristics including tumour located in the upper third(P < 0.01, OR = 2.19), tumour size exceeding 5 cm(P < 0.01, OR = 3.42), tumour infiltrating deeper than T2 (P < 0.01, OR = 2.07), tumour in the stage N2 and N3(P < 0.01, OR = 12.03), and tumour regarded as the poorly differentiated type by the histologic classification (P < 0.01, OR = 2.49)and the Borrman 3,4 type by the macroscopic classification(P < 0.01, OR = 2.58). Moreover, the metastasis of lower lymph nodal stations may be the predictors of the positive PALN especially NO.1, NO.3, NO.7 and NO.9 stations which had evidently higher odd ratios (OR>7) over others.
Although we cannot conduct a multivariate logistic regression to assess all risk factors together because of the limited information extracted from the studies, the risk factors above-mentioned may also have some indications especially when they have strong relationships with the positive PALN(OR>3). D2 Plus Para-Aortic Lymphadenectomy or pre-operative chemotherapy may be required for those patients who have a high risk for metastasis to PALN so that they may get better prognosis.

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ReviewAn evidence-based medicine review of lymphadenectomy extent for gastric cancer

Abstract

Background

Methods

Results

Conclusions

Section snippets

Inclusion and exclusion criteria

Study description

D1 versus D2

Comments

J Thorac Cardiovasc Surg

Surgery

Lancet

Lancet

Eur J Surg Oncol

Lancet Oncol

Surgery

Am J Surg

Eur J Surg Oncol

J Surg Res

Am J Surg

Cancer statistics, 2006

CA Cancer J Clin

Lymph node metastases: indicators, but not governors of survival

Arch Surg

The general rules for the gastric cancer study in surgery and pathologyPart I. Clinical classification

Jpn J Surg

Significance of para-aortic lymph node dissection in advanced gastric cancer

Hepatogastroenterology

Study of para-aortic lymph node metastasis of gastric cancer subjected to superextensive lymph node dissection

Nippon Geka Gakkai Zasshi

Clinico-pathological studies and problems on para-aortic lymph node dissection—D4 dissection

Nippon Geka Gakkai Zasshi

Effectiveness of paraaortic lymph node dissection for advanced gastric cancer

Hepatogastroenterology

Paraaortic lymphadenectomy in patients with advanced carcinoma of the upper-third of the stomach

Hepatogastroenterology

Japanese Classification of Gastric Carcinoma

Japanese Classification of Gastric Carcinoma—2nd English Edition

Gastric Cancer

Indications for paraaortic lymph node dissection in gastric cancer patients with paraaortic lymph node involvement

Hepatogastroenterology

Extended versus limited lymph nodes dissection technique for adenocarcinoma of the stomach

Cochrane Database Syst Rev

Review
An evidence-based medicine review of lymphadenectomy extent for gastric cancer