Endoscopic Mucosal Resection May Not Be Appropriate For All T1a Gastric Cancers
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Endoscopic resection of T1a gastric cancers in a large US population: a SEER study. This data was presented at Digestive Diseases Week 2015 under the ASGE schedule.
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Endoscopic Mucosal Resection May Not Be Appropriate For All T1a Gastric Cancers
- 1. DDW/ASGE 2015 Audrey H. Choi, MD1 , Rebecca A. Nelson, PhD2 , Shaila Merchant, MD1 , Jae Y. Kim, MD1 , Joseph Chao, MD3 , Joseph Kim, MD1 1 Division of Surgical Oncology, City of Hope, Duarte, CA 2 Department of Biostatistics, City of Hope, Duarte, CA 3 Department of Medical Oncology, City of Hope, Duarte, CA Endoscopic Mucosal Resection May Not Be Appropriate For All T1A Gastric Cancers
- 2. Disclosures ď¨ The authors have no relevant disclosures
- 3. Background ď¨ Early gastric cancer (EGC) is defined as adenocarcinoma confined to the mucosa and submucosa1 ď¨ Large Asian series have reported the node-positive rate in intramucosal (T1a) EGC is very low (2-5%)2-3 ď¨ Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) were developed in Asia for minimally invasive treatment of EGC ď¤ Avoids the morbidity of gastrectomy and nodal dissection 1 Murakami. Gann Monogr Cancer Res, 1971. 2 Gotoda et al. Gastric Cancer, 2000. 3 Nam et al. Gastric Cancer, 2010.
- 4. Background ď¨ Although patients with EGC are eligible for endoscopic resection, it should be noted that EGC is not synonymous with early stage gastric cancer ď¨ The standard of care in Western countries is still formal surgical resection, but there is growing interest in expanding EMR/ESD practices ď¤ Whether these procedures can be applied to heterogenous Western populations has not been well-studied
- 5. Hypothesis ď¨ Based on our previous work examining racial/ethnic disparities in gastric cancer outcomes, we hypothesized that node-positive rates in T1a gastric cancer may vary in a heterogenous Western population
- 6. Objective ď¨ To investigate rates of node-positive disease in T1a gastric cancer patients in the US
- 7. Methods ď¨ Surveillance, Epidemiology, and End Results (SEER) database from 2002-2011 ď¨ Patients with surgically-resected, histologically- confirmed AJCC T1a gastric adenocarcinoma ď¨ Exclusion criteria: stage IV disease, multiple primaries, and receipt of neoadjuvant radiation therapy
- 8. Cohort characteristics Total N=832 N (%) Node-negative N=766 N (%) Node-positive N=66 N (%) p-value Age (Median) 68 (58-76) 68 (58-76) 68 (54-75) 0.68 Race/Ethnicity Non-Hispanic White 262 (31.5) 235 (30.7) 27 (40.9) 0.15 Black 136 (16.3) 123 (16.1) 13 (19.7) Hispanic White 149 (17.9) 138 (18.0) 11 (16.7) Asian/Pacific Islander 285 (34.3) 270 (35.2) 15 (22.7) Tumor Location Distal 390 (46.9) 364 (47.5) 26 (39.4) 0.63 Proximal 28 (3.4) 25 (3.3) 3 (4.5) Middle 288 (34.6) 262 (34.2) 26 (39.4) Whole 126 (15.1) 115 (15.0) 11 (16.7)
- 9. Total N=832 N (%) Node-negative N=766 N (%) Node-positive N=66 N (%) p-value Differentiation Well 127 (15.3) 124 (16.2) 3 (4.5) <0.01 Moderately 228 (27.4) 211 (27.5) 17 (25.8) Poorly 364 (43.8) 321 (41.9) 43 (65.2) Undifferentiated 15 (1.8) 15 (2.0) 0 (0) Unknown 98 (11.8) 95 (12.4) 3 (4.5) Tumor Size â¤2 cm 444 (53.4) 425 (55.5) 19 (28.8) <0.01 >2 cm 221 (26.6) 185 (24.2) 36 (54.5) Unknown 167 (20.1) 156 (20.4) 11 (16.7) Cohort characteristics Overall node-positive rate for T1a patients: 7.9%
- 10. Multivariate analysis of all T1A Disease-Specific Survival Overall Survival HR (95% CI) p-value HR (95% CI) p-value Age (Median) 1.05 (1.02 - 1.08) <0.01 1.07 (1.05 - 1.09) <0.01 Race/Ethnicityâ Non-Hispanic White ( reference ) - ( reference ) - Black 1.34 (0.67 - 2.65) 0.41 1.47 (0.92 - 2.35) 0.11 Hispanic White 1.03 (0.48 - 2.17) 0.95 1.09 (0.66 - 1.79) 0.74 Asian/Pacific Islander 0.48 (0.24 - 1.02) 0.06 0.64 (0.41 â 1.00) 0.05 Tumor Sizeâ â¤2 cm ( reference ) - ( reference ) - >2 cm 1.36 (0.70 - 2.66) 0.36 1.06 (0.70 - 1.61) 0.77 Unknown 2.38 (1.32 â 4.63) 0.01 1.49 (0.96 - 2.31) 0.08 Node Statusâ Negative ( reference ) - ( reference ) - Positive 4.17 (2.28 - 7.63) <0.01 2.67 (1.68 - 4.23) <0.01
- 11. T1a Cohort by Race/Ethnicity White N=262 Black N=136 Hispanic N=149 API N=285 p-value Age* 71 (59-79) 61 (53.5-73) 68 (58-74) 69 (60-76) <0.01 Differentiation Well 40 (15.3%) 20 (14.7%) 25 (16.8%) 42 (14.7%) 0.48 Moderately 61 (23.3%) 42 (30.9%) 43 (28.9%) 82 (28.8%) Poorly 115 (43.9%) 61 (44.9%) 63 (42.3%) 125 (43.9%) Undifferentiated 7 (2.7%) 0 (0%) 1 (0.7%) 7 (2.5%) Unknown 39 (14.9%) 13 (9.6%) 17 (11.4%) 29 (10.2%) Tumor Size â¤2cm 124 (47.3%) 63 (46.3%) 82 (55.0%) 175 (61.4%) <0.01 >2cm 72 (27.5%) 38 (27.9%) 46 (30.9%) 65 (22.8%) Unknown 66 (25.2%) 35 (25.7%) 21 (14.1%) 45 (15.8%)
- 12. White N=262 Black N=136 Hispanic N=149 API N=285 p-value Tumor Location Distal 114 (43.5%) 72 (52.9%) 69 (46.3%) 135 (47.4%) 0.08 Proximal 12 (4.6%) 4 (2.9%) 6 (4.0%) 6 (2.1%) Middle 85 (32.4%) 37 (27.2%) 54 (36.2%) 112 (39.3%) Whole 51 (19.5%) 23 (16.9%) 20 (13.4%) 32 (11.2%) Surgery Type Total/Near Total 54 (20.6%) 17 (12.5%) 23 (15.4%) 31 (10.9%) 0.01 Partial 208 (79.4%) 119 (87.5%) 126 (84.6%) 254 (89.1%) # of Examined Nodes 1-14 179 (68.3%) 92 (67.6%) 106 (71.1%) 168 (58.9%) 0.03 âĽ15 83 (31.7%) 44 (32.4%) 43 (28.9%) 117 (41.1%) T1a Cohort by Race/Ethnicity
- 13. Node-Positive Rates by Race/Ethnicity 10.3% 9.6% 7.4% 27/235 13/123 11/138 15/270N p=0.15
- 14. AJCC Stage by Race/Ethnicity p=0.07
- 17. How many patients would have met EMR/ESD criteria? Total T1a cohort N=832 Non-intestinal N=115 Intestinal N=717 ⤠2 cm N=386 > 2 cm N=187 Unknown N=144 White N=104 Black N=56 Hispanic N=71 API N=155 46.4% 44.3% 45.5% 51.4% 54.4%
- 18. Limitations of SEER ď¨ SEER does not provide data on chemotherapy ď¤ Examination of node-positive rates before and after publication of MAGIC (2006) shows number of node-positive patients decreased for the entire cohort in the 2007-2011 period ďŽ No significance difference in node-positive rate by race/ethnicity after 2006 ď¤ MAGIC does not report downstaging rate ď¨ SEER does not provide data on lymphovascular invasion or tumor ulceration ď¨ Limitations in histology codes
- 19. Conclusions ď¨ Overall lymph node metastasis rate for T1a gastric adenocarcinoma in the US was 7.9% ď¤ Higher than published historical Asian data of 2- 5% for T1a gastric cancers ď¨ Lymph node metastasis rates and AJCC stages varied by race/ethnicity ď¤ API had lowest rate of lymph node metastases and highest rate of stage IA disease
- 20. Conclusions ď¨ Our data suggests definitive endoscopic treatment should be considered carefully in heterogeneous Western populations, as it may not be appropriate for all patients ď¤ If EMR/ESD are considered, strict adherence to endoscopic treatment guidelines is paramount in order to minimize the risk of lymph node metastases, particularly in non-Asian patients
- 21. Thank you
Hinweis der Redaktion
- Early gastric cancer is defined as adenocarcinoma confined to the mucosa or submucosa of the gastric wall. Large retrospective Asian series have reported the node-positive rate for intramucosal EGC is very low, in the 2-5% range, which makes patients with EGC eligible for endoscopic resection. Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) were developed in Asia for the minimally invasive treatment of EGC. These procedures have the potential to be curative, thereby avoiding the morbidity associated with gastrectomy and nodal dissection in appropriately selected patients.
- Although patients with EGC are eligible for endoscopic resection, it should be noted that EGC is not synonymous with early stage gastric cancer. Therefore the rate of lymph node positivity associated with EGC is essential to the curative success of EMR/ESD. The standard of care in Western countries is still formal surgical resection, but there is growing interest in expanding EMR/ESD practices in countries such as the US. Whether EMR/ESD can be applied to heterogeneous Western populations has not been well-studied.
- Based on our previous work examining racial and ethnic disparities in gastric cancer outcomes, we hypothesized that node-positive rates in T1a gastric cancer may vary in a heterogenous Western population
- Thus the objective of this study was to investigate the rates of node-positive disease in T1a gastric cancer in the US
- To do this, we utilized SEER data from the years 2002-2011. Patients with surgically-resected, histologically confirmed T1a gastric adenocarcinoma were included. Patients with stage IV disease and multiple primaries were excluded, as were patients who had received neoadjuvant radiation therapy or whose radiation status was unknown.
- There were 832 patients in our cohort of T1a gastric adenocarcinoma patients. First we divided them into node-negative and node-positive patients. No significant differences were found in age, race/ethnic group, tumor location, surgery type, or # LN examined.
- The overall node-positive rate for the T1a cohort was 7.9%. As one might expect, node-positive patients tended to have higher frequency of poorly differentiated tumors and tumors greater than &gt; 2 cm.
- We then performed a MVA for disease-specific and overall survival for the T1a cohort that was controlled for age, race, tumor location, tumor grade, tumor size, # of LN examined, and presence of node-positive disease. Both increasing age and presence of node-positive disease were independent predictors of poorer DSS and OS. Interestingly, with respect to the racial/ethnic groups, we see that black patients tended to have worse survival compared to white patients, Hispanic patients had similar survival to white patients, but API patients demonstrated significantly improved OS compared to white patients
- To further investigate this difference in outcomes by race/ethnicity, we divided the cohort into white, black, Hispanic and API. Black patients tended to be younger. There was no difference in the tumor differentiation across the 4 groups. With respect to tumor size, Hispanic and API patients had higher frequencies of tumors &lt; 2 cm
- There was no difference in the tumor location. For the # of LN examined, API had the highest frequency of 15 or more LNs examined (# of LN examined was not statistically significant on the MVA)
- Given that the overall node-positive rate of 7.9% for the cohort, we also wanted to examine this figure by race/ethnic group. The node-positive rate for white patients with T1a gastric adenocarcinoma was 10.3%, for black patients it was 9.6%, for Hispanic patients 7.4% and for API it was 5.3%. In addition to having the lowest node-positive rate, API patients were the only group to have a node-positive rate similar to historical Asian data on which the EMR/ESD criteria are based. Strikingly, white and black patients demonstrated nearly double the node-positive rate compared to API patients.
- Because EGC is not necessarily the same as early stage gastric cancer, we also looked at the AJCC staging by race and ethnic groups. API patients had the highest rate of stage IA disease, at nearly 94%, with low rates of IB, IIA and IIB disease.
- Looking at the survival rates for patients with T1a gastric adenocarcinoma by race/ethnicity, we found that there were significant differences in disease-specific survival. API patients, represented by the yellow line, had the best DSS with 97% of patients surviving at 3 years and 96% surviving at 5 years.
- A similar trend was observed for the overall survival with significant differences seen among racial and ethnic groups. Again, API patients demonstrated the best overall survival, with 93% and 87% 3- and 5-year rates. White, black and hispanic patients had similar 3-year survival rates around 85% with Hispanics doing slightly better at the 5-year mark (represented by the green line).
- Finally, we wanted to see how many patients in the original T1a cohort would have potentially fit standard EMR/ESD criteria, which is comprised of 4 components: (1) intestinal subtype histology, (2) tumor size &lt;= 2 cm, (3) absence of tumor ulceration, (4) absence of lymphovascular invasion. Of 832 patients in the T1a cohort, 717 had intestinal histologies. Of those patients, 386 patients had tumors &lt;= 2 cm, which is 46.4% of the original T1a cohort. So of patients fitting the histology and tumor size criteria, we see 104 were white, 56 were black, 71 were hispanic and 155 were API. The percentages shown at the bottom are out of the total number of patients from that race/ethnicity. So for instance, 54.4% of all the API patients in the cohort would have fit these two endoscopic resection criteria, which is the highest rate of the four racial and ethnic groups.
- As this is a SEER study, there are a few important limitations to be noted. Firstly, SEER does not provide data on the receipt of chemotherapy. Since the MAGIC study was published in 2006 providing level 1 evidence of the efficacy of perioperative chemotherapy administration for gastric cancer, we decided to examine the node-positive rates before and after 2006. We found that although node-positive rates for the entire T1a cohort declined significantly after the publication of MAGIC, this occurred equally over the racial/ethnic groups, as there was no significant difference in node-positive rates by race/ethnicity after 2006 that could have explained our findings. Additionally, MAGIC does not report the rate of downstaging associated with giving perioperative chemotherapy. SEER does not provide data on lymphovascular invasion or tumor ulceration. It also has limitations in the specificity of the histology codes. While these last few factors limit our ability to fully classify the cohort into those who fit all 4 EMR/ESD criteria, they do not impact the node-positive rates we have reported.
- What are some reasons for this observed N+ rate difference in API? Was it related to API having smaller tumors? Less aggressive biology? No differences in the tumor location or tumor differentiation