Rectal Cancer. Madhulika G. Varma MD Associate Professor and Chief Section of Colorectal Surgery University of California, San Francisco

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1 Rectal Cancer Madhulika G. Varma MD Associate Professor and Chief Section of Colorectal Surgery University of California, San Francisco Modern Treatment for Rectal Cancer Improve Local Control Improved Imaging/Staging Optimizing surgery-tme LR 39 10% Using neoadjuvant radiation therapy less toxicity, improved compliance, downstaging Preserving the Sphincter Stapled colorectal anastomosis Hand-sewn colo-anal anastomosis Colonic Reservoir New Technologies Robotics TEM Improving Survival Better perioperative care Post-operative chemotherapy 1

2 Why is pretreatment staging important? Accurate staging based on clinical exam and radiographic imaging is critical for defining optimal treatment strategies Local Excision vs. Radical Excision Sphincter sparing operation vs. Colostomy Neoadjuvant vs. Adjuvant therapy Need at least two forms of imaging to assess tumor of distal rectum Clinical outcomes strongly influenced by pretreatment staging Tumor location (from anus, extraperitoneal) Depth of invasion Lymph node involvement Metastases %LN Met T1 T2 T3 ADVANTAGES CT Scan Assess local extrarectal spread Detect liver metastasis LIMITATIONS Does not depict layers of rectal wall Ability to diagnosis based on size criteria (LN) Relatively low resolution Cannot base decisions regarding surgery/neoadjuvant therapy on this modality alone Farouk R et al. Am J Surg

3 Endorectal Ultrasound ADVANTAGES Depict layers of the rectal wall Identifies nodal metastasis LIMITATIONS Operator dependent Distal tumors Penetration Ultrasound Staging ut1 ut3 ut2 ut3n1 3

4 MRI with Surface Coil ADVANTAGES Assess transmural spread See perirectal lymph nodes Detect abdominal metastasis Multiplane capabilities LIMITATIONS Does not depict layers of rectal wall Expensive Meta-analysis: US,CT,MRI 90 articles with at least 20 patients ERUS CT MRI Wall Invasion 94% NA 94% Perirectal Invasion 90% 79% 82% Adjacent Organ Invasion 70% 72% 74% Nodal Metastasis 67% 55% 66% Bipat S. et al Radiology

5 ADVANTAGES Images cellular metabolic changes of cancer prior to structural changes Detect primary and metastatic disease Assess tumor response to chemoradiation DISADVANTAGES Uptake in bladder,other sites Poor detection of LN Few studies to assess role PET Scan Accuracy of PET Scan Primary Tumor detection: % Lymph Node detection : 25-75% Impact on treatment plan 3 studies, change in plan in 16%,17%, and 27% included cancellation of surgery and enlargement of radiation field for LN Gearhart S. Ann Surg Onc 2006 Heriot A. DCR 2004 Kantarova I J Nuc Med

6 Why is optimizing technical aspects of surgery important? Differences in Surgical Technique Probably Explain Variation in Results Local Recurrence Rates Between Surgeons Philips et al, % McArdle et al, % Holm et al, % Its not just The distal margin. But the Circumferential Resection Margin 6

7 Circumferential Resection Margin Impact on Recurrence Circumferential Margin Negative Positive # Recurrence # Recurrence Quirke 38 3% 14 85% Adams 106 8% 35 66% Dehaus-Kock 217 8% 31 29% CRM and Local Recurrence CKVO Trial Nagtegaal et al, Am J Pathol

8 Total Mesorectal Excision Impact of TME in Local Recurrence Population Studies Local recurrence Before TME After TME Stockholm 14% 6% Norway 12% 6% Netherlands 16% 9% 8

9 Understanding the Cause of Local Recurrence Quality of the Mesorectal Excision complete excision incomplete excision Overall Recurrence-Free Interval by Completeness of Excision 9

10 Overall Recurrence-Free Interval by completeness of excision in patients with negative margins Cylindrical Abdominoperineal Excision Typical APR with coning of tissue at anal canal En bloc resection of Levators 10

11 Why is use of neoadjuvant tx important? Radiation and Radical Surgery local recurrence XRT control radiation GITSG 1885 post 25% 16% NSABP-R post 25% 16% NCCTG 1991 post 25% 13% EORTC 1888 pre 30% 15% SRCST 1990 pre 25% 11% RCG-ICRF 1996 pre 24% 17% SRCT 1997 pre 27% 11% Preoperative Radiation ADVANTAGES more dose efficient less toxicity to small bowel no radiation to neorectum better compliance reduces tumor size sphincter preservation DISADVANTAGES delays surgery operative morbidity wound healing patient selection 11

12 Neoadjuvant vs. Adjuvant Chemoradiation The CAO/ARO/AIO-94 German Trial Acute Toxicity (805 patients randomize/ 718 patients evaluable) Neoadjuvant Adjuvant Mortality 1% 1% Anastomotic Leak 12% 12% Delayed wound healing 4% 6% Bleeding 3% 3% Diarrhea (Grade 3-4) 11% 12% Leukopenia/nausea 3% 3% Sauer, Colorectal Dis Neoadjuvant vs. Adjuvant Chemoradiation The CAO/ARO/AIO-94 German Trial Oncological Results (median follow-up 46 months, range months) Neoadjuvant Adjuvant Pelvic Recurrence 6% 13% Distant Recurrence 36% 38% Disease-free Survival 68% 65% Overall Survival 76% 74% Sphincter Saving* 39% 19% Anastomotic Stricture 4% 12% Sauer, NEJM

13 Neoadjuvant vs. Adjuvant Radiation Functional Outcomes (Low Anterior Resection and Straight Coloanal Anastomosis) Radiation Pre Post None Number Follow-up (years) Frequency 41% 91% 41% Clustering 46% 82% 36% Continence >75% >75% >75% Satisfaction >70% <55% >70% Nathanson, DCR 2003 Preop XRT + TME: Local Recurrence 13

14 Postoperative Chemo? All T stage Stratified by T 0-2 vs. T 3-4 Collete, L et al JCO 2007 So if you can do a TME How low can you go? Anterior Resection Low Anterior Resection 14

15 Liberalization of SPS 15

16 Colo-anal Anastomosis Transanal Intersphincteric Oncological outcomes of CAA after ultra-lar Study Year N Local recurrence Survival Enker et al % at 31 mo - Hautefeuille et al % at 5 yrs 64% at 5 yrs Paty et al % at 5 yrs 73% at 5 yrs Nagamatsu et al % at 5 yrs 79% at 5 yrs Allal et al % at 3 yrs 83% at 3 yrs Nakagoe et al % at 5 yrs 78% at 5 yrs 16

17 Radical Proctectomy with TME Complications Anastomotic leak 17% LAR Syndrome 13-80% Urgency Frequency Clustering Defecatory problems 38% Urinary incontinence 39% Impairment of sexual function 29% of women 45% of men Peeters et al, JCO 2006 Hendren et al, Ann Surg 2005 Paty Am J Surg 1994 Improve Function Increase reservoir capacity Disperse peristaltic waves 17

18 Functional results Kirwan classification for grading fecal incontinence: 32% at 6 mo, 14% at 1 yr Frequency: 36% at 6 mo, 21% at 1 yr No differences between straight(19) and J-pouch (25) anastomoses Is the J-pouch superior? Compiled 35 studies over 20 yrs comparing straight CAA to reservoirs (J-pouch and coloplasty) 2240 pts (1055 straight CAA, 1050 J-pouch, 124 coloplasty) Endpoints: post-op complications, functional/physiological outcomes Timepoints: 6 mo, 1 yr, >2 yr 18

19 J Pouch vs. Coloplasty J pouch vs. Straight CAA Functional Outcomes: Slight advantage to colonic J pouch over straight CAA that diminished with time No advantage of coloplasty over J pouch 19

20 Why Robotic Surgery? Enhanced visualization Improved ergonomics More precision Articulating instruments Better retraction More surgeon control Suturing - improved anastomosis? Robot Setup Quality of life: Lower conversion rate Faster recovery Oncological Improved mesorectal excision Less positive CRM Functional Sparing pelvic nerves Prevent sexual and urinary dysfunction 20

21 Oncologic Resection Baik et al Ann Surg Oncol 2009 Park et al Surg Endosc 2011 Robotic Rectal Cancer Surgery No long term data comparing robot,lap,and open TME Mean FU 20 months Baek et al Ann Surg

22 Transanal Endoscopic Microsurgery (TEM) Results with TEM Alone Series Stage Recurrence Survival Buess T1 T1 2% T2 T2 12% Smith T1 15 T2 6 T3 40% -- Steele 96 7 T1 14 T2 14% 100% Mentges T1 13 T2 4 T3 6% -- Heintz T1 10% 62-79% Saclarides T1 8 T2 25% -- Lezoche T1 19 T2 3 T3 6% 71% Lee T1 T1 4% T1 100% 17 T2 T2 19% T2 95% Neary 03 5 T1 8T2 1 T3 0% 100% Platell T1 7 T2 4 T3 0% 100% Ganai 06 Stipa T1 4 T2 5 T3 15% 83% 23 T1 21 T2 T1 8% T2 9% T1 100% T2 70% 22

23 TEM & Rectal Cancer Christoforidis et al. U Minn Rectal cancer Higher tumor in TEM group Positive Margin* Fragmented specimen TEMs N=42 2% 0% TAEs N=129 16% 9% Local recurrence 12% T1 22% T1 Ann Surg 2009; 249: TEM & Rectal Masses Moore et al. U Vermont Rectal masses Combined benign and malignant Clear Margin* TEMs N=82 90% TAEs N=89 71% Non Fragmented specimen* 94% 65% Complication 15% 17% Local recurrence* 5% 27% Dis Colon Rectum 2008; 51:

24 Summary Rectal cancer patients should be adequately staged before deciding the treatment plan Total mesorectal excision remains the primary treatment of rectal cancer regardless of distal margin Most patients with locally advanced rectal cancer should receive neoadjuvant chemoradiation Sphincter sparing techniques are more common in large volume centers but patients must be apprised of functional outcomes New techniques for rectal cancer surgery are emerging and may provide advantages for oncologic resection, long term results are needed 24