ESD for EGC with undifferentiated histology

Transcription

1 ESD for EGC with undifferentiated histology Jun Haeng Lee, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

2 Biopsy: M/D adenocarcinoma ESD: SRC >> M/D, 1.8 cm, MM, L/V (-/-)

3 Would you ESD? - Detected during the screening endoscopy (F/60) Forcep biopsy: Tubular adenocarcinoma, poorly differentiated

4 1. Location : middle third center at body and greater curvature 2. Gross type : EGC type IIc 3. Histologic type : tubular adenocarcinoma, poorly differentiated 4. Histologic type by Lauren : diffuse 5. Size : 2x1.7x0.1 cm 6. Depth of invasion : extension to mucosa (muscularis mucosa) 7. Resection margin: free from carcinoma safety margin: distal 7.2 cm, proximal 6.8 cm 8. Lymph node: metastasis to 3 out of 52 regional LNs (pn1) 9. Lymphatic invasion : not identified 10.Venous invasion : not identified 11.Perineural invasion : not identified 12. Stage by AJCC : IB (T1a, N1, MX)

5 Outcome of endoscopic treatment of EGC with differentiated histology 1. ITT analysis (both curative and non-curative resection cases) Comparison with surgery (propensity score matched cohort) 2. PP analysis 1) Curative-resection cases: single-arm long-term data 2) Non-curative resection cases: comparison between surgery group and observation group

6 ITT analysis: comparison with surgery - Propensity score matching, differentiated type EGC Differentiated type EGC ( ) (n = 3595) EGC meeting indication treated with curative intent (n = 2563 ) Excluded 1) LNM on CT or EUS (n=6) 2) Previous gastric cancer (n=20) 3) Cancer of other origin (n=150) 4) Follow up < 2 years (n=856) Endoscopic resection (n = 1290) Surgery (n =1273) Propensity score matching Endoscopic resection (n = 611 ) Surgery (n = 611 ) Pyo JH. Am J Gastroenterol 2016

7 ITT analysis: comparison with surgery - Baseline characteristics (1) Overall Propensity score matched Variables Endoscopic resection (n=1290) Surgery (n=1273) P-value* Endoscopic resection (n=611) Surgery (n=611) P -value* Age, median (IQR), years 61 (54-68) 59 (51-65) < (53-67) 60 (53-67) Sex, n(%) Male Female 1020 (79.1) 270 (20.9) 947 (74.4) 326 (25.6) (79.4) 126 (20.6) 487 (79.7) 124 (20.3) Performance (ECOG), n(%) or above 1270 (98.5) 5 (0.4) 15 (1.2) 1261 (99.1) 4 (0.3) 8 (0.6) (99.0) 1 (0.2) 5 (0.8) 604 (98.9) 2 (0.0) 5 (0.8) F/U duration, median (IQR), month 44 (32-60) 58 (38-72) < (32-61) 58 (38-73) Criteria of indication, n(%) Absolute criterion Expanded criterion I Expanded criterion II Expanded criterion III Beyond indication 895 (69.4) 178 (13.8) 7 (0.5) 100 (7.8) 110 (8.5) 536 (42.1) 460 (36.1) 36 (2.8) 130 (10.2) 111 (8.7) < (63.2) 127 (20.8) 5 (0.8) 44 (7.2) 49 (8.0) 362 (59.2) 123 (20.1) 16 (2.6) 84 (13.7) 26 (4.3) <0.001 Pyo JH. Am J Gastroenterol 2016

8 ITT analysis: comparison with surgery - Baseline characteristics (2) Variables Endoscopic resection (n=1290) Overall Surgery (n=1273) P-value* Propensity score matched Endoscopic resection (n=611) Surgery (n=611) P -value* Tumor size, mean (SD), cm 1.4 (0.9) 2.6 (1.7) < (1.1) 1.7 (1.1) Morphology of tumor, n(%) Elevated Flat or depressed 770 (59.7) 520 (40.3) 192 (15.1) 1081 (84.9) < (21.4) 480 (78.6) 140 (22.9) 471 (77.1) Location of tumor, n(%) Upper third Middle third Lower third Histology of tumor, n(%) Well differentiated Moderately differentiated Depth of tumor invasion, n(%) Mucosa Submucosa Lymphovascular invasion Absent Present R0 resection No Yes 78 (6.1) 357 (27.7) 855 (66.3) 511 (39.6) 779 (60.4) 1076 (83.4) 214 (16.6) 1217 (94.3) 73 (5.7) 223 (17.3) 1067 (82.7) 89 (7.0) 331 (26.0) 853 (67.0) 429 (33.7) 844 (66.3) 1054 (82.8) 219 (17.2) 1226 (96.3) 47 (3.7) 46 (3.6) 1227 (96.4) (6.6) 180 (29.5) 391 (64.0) (37.5) 382 (62.5) (84.3) 96 (15.7) (94.4) 34 (5.6) < (17.8) 502 (82.2) 45 (7.4) 170 (27.8) 396 (64.8) 224 (36.7) 387 (63.3) 504 (82.5) 107 (17.5) 588 (96.2) 23 (3.8) 23 (3.8) 588 (96.2) <0.001 Pyo JH. Am J Gastroenterol 2016

9 Overall survival Disease free survival Endoscopic resection Surgery Disease specific survival Recurrence free survival Pyo JH. Am J Gastroenterol 2016

10 PP analysis (1): single-arm follow-up - differentiated, curative (n=1,306) EGCs treated by ESD at Samsung Medical Center 1,838 patients with 1,889 differentiated-type EGCs November 2003 May 2011 Censoring date: May 2014 Differentiated-type EGC Well or moderately differentiated or papillary EGC According to the quantitatively predominant histologic type Differentiated-type EGC > 50% Min BH. Endoscopy 2015

11 PP analysis (1): single-arm follow-up - differentiated, curative (n=1,306) Median follow-up: 61 months (range ) Local recurrence: 0.08% (1/1,306) Metachronous recurrence: 3.6% (47/1,306) Definition of metachronous recurrence: at least 12 months after ER Extragastric recurrence: 0.15% (2/1,306) 5-year overall survival Absolute indication: 97.3% Expanded indication: 96.4% Min BH. Endoscopy 2015

12 Two extragastric recurrences (0.15%) Min BH. Endoscopy 2015

13 Overall-survival - 1,306 curative ESDs from December 2003 to May 2011 Min BH. Endoscopy 2015

14 PP analysis (2): non-curative resection - comparison between surgery and observation group Noncurative resection 341 Lateral margin positive 67 (19.6%) Risk of lymph node metastasis 274 (80.4%) Surgery 194 (70.8%) Lymph node 11 (5.6%) Local residual 10 (5.2%) Observation 80 (29.2%) Patients refusal : 64 High surgical risk : 8 (severe comorbidities) Concomitant advanced cancer in other organs : 8 Kim ER. Br J Surg 2015

15 Predictors of LN metastasis (5.7%) Kim ER. Br J Surg 2015

16 Progression into advanced cancer Observation group Surgery group 5 cases (6.3%) (21 to 40 months) 1 case (0.5%) (22 months) (P = 0.013) Kim ER. Br J Surg 2015

17 Overall survival - Median duration of follow-up after ER: 60.5 months (6-141) Kim ER. Br J Surg 2015

18 Evidence supporting ESD for D-type EGC is well established ITT overall PP curative PP non-curative

19 What about ESD for UD-type EGC? Jun Haeng Lee, Samsung Medical Center, SKKUSOM, Seoul

20 Issues in ESD for UD-type EGCs Are UD-type EGCs included among the expanded indications? Important point when reading the literatures about expanded indications. Representative outcome studies Limitations in the retrospective design Back to the basic: clinical simulation

21 Are UD-type EGCs included among expanded indications? Depth Histology M cancer SM cancer No ulceration Ulcerated SM1 SM2 20 mm > 20 mm 30 mm > 30 mm 30 mm Any size Differentiated Undifferentiated Modified from Soetikno. J Clin Oncol 2005

22 UD-type EGCs in the guidelines. Small UD-type mucosal cancers are included among the expanded indications in the Korean, the Japanese, and the European guidelines. J Gastric Cancer 2015 Gastric Cancer 2011 Endoscopy 2015

23 Many literatures about expanded indications do not include UD-type EGCs. Goto. Endoscopy 2009

24 ER for UD-type EGC - Early experience at Yonsei University Kim. Gastrointest Endosc 2009

25 Kim JH. Surg Endosc 2014

26 ER for UD-type EGCs (n=125) - curative resection 64.8% (n=81), noncurative resection 35.2% (n=44) Oka. Surg Endosc 2014;28:639

27 ER for UD-type EGCs (n=125) - curative resection 64.8% (n=81), noncurative resection 35.2% (n=44) - follow up data analysis in 84 (67.2%) Expanded criteria 52 (61.9%) Curative resection 41 Incomplete resection 11 Beyond expanded criteria 32 (38.1%) Complete resection 18 Incomplete resection 14 Surgery required 43 Surgery done 17 (39.5%) Surgery not done 26 (60.5%) Oka. Surg Endosc 2014;28:639

28 ESD for UD-type EGCs at SMC - October 2002 to June 2011 ESD for undifferentiated type by ESD pathology PD: 42 SRC: 17 Gastrectomy 44 No gasterctomy 15 No LN mets No recur : 12 F/U loss : 3

29 Dig Dis Sci 2014:59:

30 In many cases with UD-type histology in the ESD specimen, the initial biopsy was differentiated-type histology. No discrepancy: only 15.3% (9/59) Dig Dis Sci 2014:59:

31 Indications are different from criteria Indication Pre-treatment Selection of ESD candidates Criteria Post-treatment Additional surgery after ESD

32 Endoscopic resection of EGCs with undifferentiated-type histology in the forceps biopsy : a clinical simulation with unselected surgical cohort Jun Haeng Lee, Dong Shin Kwak, Jae J. Kim, Kyoung-Mee Kim, Tae Sung Sohn, Sung Kim Departments of Medicine, Pathology and Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

33 Surgery for gastric cancer in 2014 (n=1,336) ESD candidate selection by EGD and CT findings (1) Suspected M cancer (2) No ulcer (3) 2 cm or less (4) No LN in CT PD (n=104, 37.1%) in forceps biopsy UD-type histolology in forceps biopsy (n=802) Suspected as EGC in EGD (n=537) ESD candidates Beyond ESD indication (n=280, 52.1%) (n=257) SRC (n=176, 62.8%) in forceps biopsy Curative Non-curative Curative Non-curative resection resection resection resection

34 Rate of curative resection for expanded indications in undifferentiated type EGCs P< % 31% 48% 20 0 Total PD SRC

35 Reasons of non-curative resection

36 Three cases with lymph node metastasis in the curative resection group F/46 Biopsy: PD Final pathology - PD with SRCs cm - mucosal F/64 Biopsy: PD Final pathology - PD with SRCs cm - mucosal F/58 Biopsy: SRC Final pathology - PD with SRCs cm - mucosal

37 Outcomes of simulated ESD for smaller EGCs SRC-type less than 1 cm in diameter is the best candidate for ESD

38 Proposed indications based on pathology database of surgery patients Shim. World J Gastroenterol 2014

39 Be careful about undifferentiated! ITT overall Only small studies PP curative PP non-curative Evidence ESD for EGC with undifferentiated histology is NOT sufficient.

40 Conclusion Evidence supporting ESD for UD-type EGC is not enough. Data from surgical pathology is inconsistent. Long-term outcome data is not enough. Most importantly, selection bias makes the interpretation difficult. I propose to start with safer indications such as tumor size < 1 cm with histology of SRC to achieve better outcomes.

41 Thank you for your attention.