State-of-the-art of surgery for resectable primary tumors

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Early colorectal cancer State-of-the-art of surgery for resectable primary tumors (Special focus on rectal cancer surgery) Stefan Heinrich & Hauke Lang Department of General, Visceral and University Hospital of Mainz, Germany

ESMO Clinical Practice Guidelines

Staging and risk assessment for rectal cancer History & physical examination, CEA DRE, rigid rectoscopy biopsy (localization) Colonoscopy (20% synchronous cancers) CT scan of thorax & abdomen (metastases) Endorectal ultrasound (local tumor extension) MRI (local tumor extension) MDT multidisciplinary team discussion

Surgical strategy for primary rectal cancer TEM Local excision Neoadjuvant RT/CRT PME upper rectal cancer Open surgery TAMIS Multivisceral resection RECTAL CANCER Rectal resection Laparoscopic surgery Robotic surgery ISR Abdomino-perineal resection TME middle/low rectal cancer tatme

Risk adapted surgical strategy for locoregional rectal cancer ct1 (G3, V1, L1) or ct2-3 N0 or cn1 PME / TME Open Surgery Laparoscopic Surgery Robotic Surgery -- Transanal Approach (tatme and ISR)

Total Mesorectal Resection 6

In the era of TME - quality of Surgery - Department of General, Visceral and Most important pathologic outcomes 1-5 Negative circumferential resection margin (CRM) Complete TME Associated with lower local and distal recurrence rates and better long-term survival 1 Quirke et al. Lancet 2009; 373: 821828 2 Kusters et al. Eur J Surg Oncol 2010; 36: 470476 3 Nagtegaal et al. J Clin Oncol 2008; 26: 303312 4 Birbeck et al. Ann Surg 2002; 235: 449-457 5 Garcia-Granero Cancer. 2009; 115: 3400-3411 Hugen & al. Nature Reviews 2016; 13: 361-369

Circumferential Resection Margin (CRM) Cohort of 563 patients with locally advanced rectal cancer Treated with neoadjuvant CRT and surgery CRM 1mm CRM >1mm 5-year local recurrence free survival 66% 98% Trakarnsanga et al. Ann Surg Oncol 2013; 20: 1179-1184

Completeness of Mesorectal Excision Cohort of 1156 patients with locally advanced rectal cancer Treated with neoadjuvant RT or selective postoperative CRT Complete Nearly complete Incomplete 3-year local recurrence free survival 4% 7% 13% Quirke et al. Lancet 2009; 373: 821828

Laparoscopic versus open rectal resection surgical outcome oncological quality Vennix & al. Cochrane Database of Systematic Reviews 2014, Issue 4. Art. No.: CD005200 10

Laparoscopic vs. Open mesorectal excision Pathologic outcome Meta-analysis - 14 RCTs, 4034 patients LLR ORR p-value Studies Positive CRM ( 1 mm) in % 7.9 6.1 0.26 9 M.E.R.C.U.R.Y ( 2) in % 13.2 10.4 0.02 5 No significant difference - distal resection margin, lymphnodes retrieved - distance to distal and radial margins Martinez-Perez et al. JAMA Surg. 2017; 19:152:e165665.

Laparoscopic vs. Open mesorectal excision Oncologic outcome COREAN 1 non-inferiority RCT LLR (n = 170) ORR (n = 170) 3-year disease free survival rate (%) 72.5 79.2 COLOR II 2 non-inferiority RCT LLR (n = 699) ORR (n = 345) Similar rates 3-year disease free survival rate (%) 74.8 70.8 Overall survival rate (%) 86.7 83.6 1 Jeong et al. Lancet Oncol 2014; 15: 767-774 2 Bonjer et al. New Engl J Med 2015; 372: 1324-1332

Transanal vs laparoscopic TME Laparoscopic TME 13

Transanal vs laparoscopic TME Transanal TME 14

Transanal mesorectal excision Indications for tatme transanal Total Mesorectal Excision Male Gender Rectal cancer less than 12 cm from anal verge, including very low cancers Narrow and/or deep pelvis Visceral obesity and/or BMI>30 Prostatic hypertrophy Tumordiameter > 4cm Distorted tissue planes due to neoadjuvant RT Impalpable, low primary tumour requiring accurate placement of distal resection margin Motson et al. Colorectal Dis 2015

Penna & al. Ann Surg 2017; 266: 111 117 Department of General, Visceral and

Robotic vs. laparoscopic total mesorectal excision Prete & al. Ann Surg 2017; epub 17

Robotic and transanal total mesorectal excision Two-team approach with courtesy of Prof. W. Kneist 18

Transanal vs laparoscopic TME Positive circumferential resection margin Circumferential resection margin Macroscopic quality of tme Ma et al. BMC Cancer (2016) 16:380

Rectal resection postoperative function Low anterior resection syndrome (LARS) 5 questions regarding bowel function stool continence Jeminez-Gomez & al. Colorectal Dis 2017; doi: 10.1111/codi.13901. 20

Specific considerations - Pelvic autonomic innervation - Department of General, Visceral and CAAD technique Intraoperative electrophysiological test Bladder Internal anal sphincter Genitalia Moszkowicz et al. Dis Colon Rectum 2012 Kneist & al. Langenbecks Arch Surg 2013

Nerve sparing surgery Kauff DW, Lang H, Kneist W. Risk factor analysis for newly developed urogenital dysfunction after total mesorectal excision and impact of pelvic intraoperative neuromonitoring-a prospective 2-year follow-up study. J Gastrointest Surg 2017

Risk adapted surgical strategy for locoregional rectal cancer ct1 N0 M0 (low risk: G1/G2, L0, V0) Local excision TEM / TEO Transanal endoscopic microsurgery Transanal endoscopic operation TAMIS Transanal minimally invasive surgery Kneist W. Chirurg 2017; 88: 656-663

Minimal Surgery - Local excision TEM Originally described by Buess et al. 1984 1 Compared to Transanal Excision (TAE) 2 Less Fragmentation Higher rate of negative resection margins Lower recurrence rate 1 Buess et al. Chirurg 1984; 55: 677-680 2 Moore et al. Dis Colon Rectum 2008; 51: 1026-1030

Minimal Surgery - Local excision TAMIS Originally described by Atallah et al. 2010 Hybrid between TEM and single-site laparoscopy Designed on a readily available platform in most hospitals Atallah et al. Surg Endosc 2010; 24: 2200-2205

Overview of the quality of the local excision procedures TAE 1 TEM 1 TAMIS 2 Fragmentation rate (%) 37 0 4 Positive resection margins (%) 22 2 6 Recurrence rate (%) 24 8 2 1 Moore et al. Dis Colon Rectum 2008; 51: 1026-1030, 2 Albert et al. Dis Colon Rectum 2013; 56: 301307

TEM and TAMIS: is one technique superior? Retrospective analysis 2012 2015, Omaha, Nebraska TEM (n = 40) TAMIS (n = 29) p value Complications (%) (Urinary retention, bleeding, perforation) 13 10 0.55 Re-Operation 8 3 0.44 Positive resection margins (%) 3 10 0.19 Recurrence rate (%) 5 3 0.62 Melin et al. Am J Surg 2016; 212: 1063-1067

Minimal Surgery - Local excision - Benefits of TAMIS - Department of General, Visceral and Compared to TAE 1 Applications to lesions further away from anal verge Better oncologic outcome Compared to TEM 2,3 Reduced cost for equipment Less post-procedural sphincteric complications 1 Saclarides Clin Colon Rectal Surg 2015; 28: 165175 2 Arezzo A et al. Surg Endosc 2014; 28: 427438, 3 Albert et al. Dis Colon Rectum 2013; 56: 301307

abdomino-perineal resection (APR) Inter-spincteric resection (ISR) 29

Intersphincteric Resection (ISR) versus Abdominoperineal resection (APR) Department of General, Visceral and Low rectal cancer <5cm Local recurrence rate Tumor depth ISR APR p T1-2 T3-4 T1 0 % 0 % n.s. T2 4.9% 2.8% n.s. T3-4 13.2% 3.8% 0.039

Specific considerations - High tie vs. low tie - Department of General, Visceral and Risk of anastomotic leakage in patients with increased cardiovascular risk based on medication history Swedish colorectal cancer registry n.s. Boström P et al. Colorectal Dis 2015;17:1018-1027

Specific considerations - High tie vs. low tie - Department of General, Visceral and Impact on function HIGHLOW - randomized multicenter Trial Mari G et al. Trials 2015;16:21 212 patients sample size middle/low rectal cancer Primary end point Secondary end point urogenital function anastomotic leakage but no investigations on anorectal function

Summary Standard of care: total mesorectal excision (TME) - Minimal invasiveness - Laparoscopic resection - Robotic surgery - TaTME/TEM sufficient for early cancer (T1 G1) Anorectal/urogenital/sexual function = Quality of life 33