Survival analysis of Local excision versus Radical resection for Early-stage Middle and Low Rectal cancer 早期中低位直腸癌的治療： 局部切除與根治性切除之預後分析 賴以立 唐瑞平 陳進勛 游正府 江支銘 陳繹中 葉建裕 游耀東 謝寶秀 蔡文司 洪欣園 蔣昇甫 賴正洲 林耕平 林岳辰 許祐仁 林口長庚紀念醫院 大腸直腸肛門外科

Background NCCN guidelines for rectal cancer, Version 3. 2017

Background Radical resection (RR) CCRT NCCN guidelines for rectal cancer, Version 3. 2017

Background Clancy C, et al: transanal endoscopic microsurgery is oncologically superior to transanal excision for the excision of rectal neoplasms. You YN, et al: 5-year local recurrence after LE vs. Standard resection was 12.5 vs. 6.9% (P = 0.003) for T1 tumors, and 22.1 versus 15.1% (P = 0.01) for T2 tumors. Kidane B, et al: Local excision does not offer oncologic control comparable to radical surgery. Karyn B. Stitzenberg, et al: For T2N0 disease, patients treated with LE alone had significantly poorer adjusted OS than those treated with proctectomy alone or multimodality therapy. Dis Colon Rectum. 2015;58:254–261. Ann Surg. 2007 May;245(5):726-33. Dis Colon Rectum. 2015 Jan;58(1):122-40. J Clin Oncol. 2013 Dec 1; 31(34): 4276–4282.

Material and Methods - Patients Low risk Moderate risk High risk pT1: tumor < 3 cm in size No LVI or PNI Well to moderately differentiated pT1: tumor < 3 cm in size With poor differentiation and/or LVI and/or PNI pT1: tumor > 5 cm in size pT2 tumor > 3 cm in size No LVI or PNI And/or poor differentiation and/or LVI and/or PNI pT1: 3 < tumor < 5 cm in size With any other histological characteristics pT2: tumor < 3 cm in size No LVI or PNI Well to moderately differentiated The TESAR-Trial, Borstlap et al. BMC Cancer (2016) 16:513

Material and Methods - Patients Low risk Moderate risk High risk pT1: tumor < 3 cm in size No LVI or PNI Well to moderately differentiated pT1: tumor < 3 cm in size With poor differentiation and/or LVI and/or PNI pT1: tumor > 5 cm in size pT2 tumor > 3 cm in size No LVI or PNI And/or poor differentiation and/or LVI and/or PNI pT1: 3 < tumor < 5 cm in size With any other histological characteristics pT2: tumor < 3 cm in size No LVI or PNI Well to moderately differentiated CCRT Radical resection The TESAR-Trial, Borstlap et al. BMC Cancer (2016) 16:513

Material and Methods Tracing back the data from 1998 to 2016, 173 patients who matched Pathology: rectal adenocarcinoma, pT1 or pT2, Distance from anal verge (DAV) ≤ 8cm, and Moderate risk were enrolled.

Material and Methods - data Basic data, Lab data, Pathologic data, Adjuvant therapy, OP style (LAR/APR vs. LE), Intra-operative diverting ileostomy or colostomy, Post-operative morbidity (early, late, total) Outcome: Overall survival (OS), Disease-free survival (DFS), Loco-recurrence free survival (LFS). Statistics methods: Fisher's exact test, Mann-Whitney U Test, Log-rank test

Results- RR vs LE Variable RR, N = 134 (%) LE, N = 39 (%) P value Age (years), mean ± SD 63.0 ± 12.9 59.7 ± 13.9 0.178 BMI, mean ± SD 24.3 ± 3.5 25.3 ± 4.4 0.226 Sex   1.000 Male 68 (50.7) 20 (51.3) Female 66 (49.3) 19 (48.7) Family cancer history 43 (32.1) 16 (41.0) 0.339 CEA, mean ± SD 2.89 ± 3.49 2.14 ± 1.06 0.757 Albumin, mean ± SD 4.28 ± 0.42 4.43 ± 0.39 0.075 Hemoglobin, mean ± SD 13.12 ± 1.73 13.45 ± 1.71 0.350

Results- RR vs LE Variable RR, N = 134 (%) LE, N = 39 (%) P value Intra-operative ileostomy or colostomy* 59 (48.0) 0.0001 Adjuvant therapy 21 (15.7) 17 (43.6) Chemotherapy 20 (14.9) 1 (2.6)   CCRT 1 (0.7) 16 (41.0) Morbidity early 25 (18.7) 2 (5.1) 0.045 late 22 (16.4) 0.005 Total 38 (28.4) 0.002 * loss data: 11 cases

Results- RR vs LE Variable RR, N = 134 (%) LE, N = 39 (%) P value Tumor diameter, mean ± SD (cm) 2.55 ± 0.75 2.75 ± 0.98 0.193 Distance from anal verge, mean ± SD (cm) 5.93 ± 1.83 4.59 ± 1.92 0.0001 Resection margin, mean ± SD (cm) 1.54 ± 0.98 0.14 ± 0.25 Differentiation   Well 31 (23.1) 13 (33.3) 0.214 Moderate 98 (73.1) 25 (64.1) 0.317 Poor 5 (3.7) 1 (2.6) 1.000

Results- RR vs LE Variable RR, N = 134 (%) LE, N = 39 (%) P value Lymphovascular invasion 11 (8.2) 7 (17.9) 0.131 Perineural invasion 4 (3.0) 0.576 T stage   0.0001 T1 48 (35.8) 31 (79.5) T2 86 (64.2) 8 (20.5) N stage N0 (Nx) 112 (83.6) (unknown) N1 22* (16.4) *One 76-year-old male, refused adjuvant therapy due to old age.

Results- OS Overall Survival (OS) RR (N = 134) LE (N = 39) 94% 97% 89% 3-year 94% 97% 5-year 89% 88% P = 0.456 OS complete number: 24 / 9

Results- DFS Disease-Free Survival (DFS) RR (N = 134) LE (N = 39) 1-year 100% 97% 3-year 95% 5-year 92% 88% P = 0.595 DFS complete number: 10 / 4

Results- LFS Locorecurrence-Free Survival (LFS) RR (N = 134) LE 1-year 100% 97% 3-year 99% 5-year 98% 91% P = 0.104 LFS complete number: 3 / 3

Conclusion Whether RR or LE, patients with early stage mid-low rectal cancer at moderate histologic risk had similar oncological outcome. However, The RR group had higher morbidity rate (28.4% vs. 5.1%, p = 0.002), and 48% patients of this group had stomy. In this selected group, there is 16.4% positive rate of lymph node metastasis in final pathologic diagnosis.

林口長庚紀念醫院 直腸肛門科 賴以立 ryane92a5@gmail.com

Results- DFS Disease-Free Survival (DFS) LAR / APR (N = 113) No adjuvant therapy With adjuvant CCRT Disease-Free Survival (DFS) LAR / APR (N = 113) Local excision (N = 17) 1-year 100% 3-year 94% 5-year 91% P = 0.670 DFS complete number: 10 / 1