Management of Colorectal Cancer for the Trainee Surgeon

This presentation includes a general workflow of managing patients with colorectal malignancies.

1. Management of Colorectal Cancer Dr. Gayanga Kottegoda June 2022

2. Objectives Epidemiology Anatomy Pathology Aetiology Clinical Features Workup Staging Management of Colon Cancer Management of Rectal Cancer

3. Epidemiology Sri Lanka 3rd Commonest cancer diagnosis when both sexes considered 4th commonest in males and 4th commonest in females 7% of total crude cancer incidence (2304 new cases) 2/3 colonoc, 1/3 rectal Global 3rd most common cancer worldwide 3rd most common cancer in men 2nd most common cancer in women There were more than 1.9 million new cases of colorectal cancer in 2020

4. Frequency of Colorectal Cancer 1/3 Rectum 2/3 Colon Men = Women

5. When is it Considered to be in the Rectum Within 15 cm from anal verge (rigid sigmoidoscopy is best at measuring) MRI – plane of sigmoid take off Introperative - identification of the plane of fusion of the two antemesenteric taenia into to an amorphous area. Importance Significant difference in management (eg – neoadjuvent RT) 3 parts of Rectum 0-6 cm lower rectum 7 – 11 cm mid rectum 12 -15 cm upper rectum

6. Tumour Pathology Morphology 4 types Annular Tubular Ulcer Cauliflower

7. WHO Histological Classification Majority are adenocarcinomas – 90 – 95% Mucinous adenocarcinoma Signet-ring cell carcinoma Squamous cell carcinoma Adenosquamous carcinoma Undifferentiated carcinoma Carcinoid tumours Non epithelial tumours Sarcoma Lymphoid neoplasm Hematopoietic neoplasm

8. Tumour Pathology - Spread Local/ Direct – longitudinally, transversely or radially to anatomicaly adjesent structures Colonic retroperitoneal colonic cancer - the ureter, duodenum and muscles of the posterior abd wall Intraperitoneal tumour - small intestine, stomach, pelvic organs, the anterior abd wall Rectal – pelvic organs, side walls Lymphatic – usually upwards to nodes along the vascular pedicle Colonic - Paracolic  nodes along main vessels  Para-aortic nodes (30% may skip) Rectum – via mesorectal nodes tumours below the peritoneal reflection may also spread laterally and downward Vascular – Liver, Lung (10%), Ovary, Adrenal, Brain, Bone, Kidney 37% have occult liver mets at Sx, 50% develop overt mets at some stage Transcoelomic – Colonic to peritoneum (by subperitoneal lymphatics/ drop mets)

9. Tumour Pathology 20% present with metastetic disease 40% develop metastesis at some time

10. Aetiology Genetic susceptibility -20% Well defined familial syndromes HNPCC (Lynch syndrome) FAP/ Gardner’s syndrome Turcot syndrome Other rarer syndromes Without well defined familial syndromes

11. Aetiology Lifestyle related Diet Western diet Red meat, poultry Obesity Smoking and alcohol Micronutrients Low folate Low vitamin D ? Lack of physical activity DM treated with Insulin

12. Aetiology Inflammatory bowel diseases Ulcerative colitis Crohns disease Past Surgery/ procedure Pelvic cancer irradiation Cholecystectomy Gastrectomy ureterosigmoidostomy

13. Protective Factors Exercise Folic acid Calcium/ Vitamin D High fibre diet Aspirin (but given only when cardiac risk is high) COX -2 Inhibitors (Celecoxib) Over expression of COX-2 seen in tumour cells

14. Familial Adenomatous Polyposis Presence of more than 100 colorectal adenomas - Diagnostic Positive family history – 80%, Remainder new mutations APC gene on the short arm of chromosome 5, autosomal dominant, Men = Female Lifetime risk of colorectal cancer is 100% Associated with benign mesodermal tumours such as desmoid tumours and osteomas. Epidermoid cysts in Gardner’s syndrome Congenital hypertrophy of the retinal pigment epithelium – screening Polyps at 15 y, almost all at 30 y Carcinoma after 10 -20y of polyps

15. Extracolonic manifestations of FAP

16. Familial Adenomatous Polyposis - Management Surgery deffered till 17y as malignancy unusual till 20y Family tree maintained, Genetic screening refferals Target of treatment – Prevent development of colorectal cancer Options Colectomy with ileorectal anastomosis – IRA Less morbidity and mortality Invasive malignancy at 30y up to 10% Restorative proctocolectomy with an ileal pouch – anal anastomosis - RPC Temporary stoma Pouch failure 10% Cancer in residual cuff of tumour - annual pouch surveillance with biopsy Total proctectomy and end ileostomy – Safest but with permanent stoma

17. Hereditary non-polyposis colorectal cancer HNPCC/ Lynch syndrome – most common (2-4%) Increased risk of colorectal cancer and also cancers of the endometrium, ovary, stomach and small intestine Autosomal dominant, DNA mismatch repair gene mutation (MLH1, MSH2, MSH6, PMS2) L ifetime risk of colorectal cancer is 80%, mean age at diagnosis is 45 y Proximal colon common 30 – 50 % lifetime risk of developing endometrial cancer. Diagnosis – Genetic testing or Amsterdam II criteria Management Regular endoscopic surveilance of LGI tract

18. Amsterdam II Criteria Three or more family members with an HNPCC-related cancer (colorectal, endometrial, small bowel, ureter, renal pelvis) one of whom is a first-degree relative of the other two Two successive affected generations At least one colorectal cancer diagnosed before the age of 50 years FAP excluded Tumours verified by pathological examination

19. Screening

20. Importance of Adenoma Carcinoma Sequence Average age of adenoma patients is about 5 years younger than that of the average age of carcinoma patients The distribution of adenomas in the colon is the same as that of cancers (70% left sided) Adenomas often accompany carcinoma Unusual to find carcinoma without contiguous adenomatous tissues Sporadic adenomas are histologically identical to adenomas of FAP which is unequivocally premalignant Large adenomas are more likely to display cellular atypia and genetic abnormalities than small lesions

21. Screening Good candidate for a screening program Prognosis much better in early stage compared to late stage when treated Adenoma-carcinoma sequence provides ability to treat pre-malignant lesions Stool occult blood - guaiac-based test  detects the peroxidase-like activity of haematin in faeces. Sensitivity 50-70% False negative – intermittent nature of bleeding (3 samples taken) False positive – animal haemoglobin, vegetable peroxidases Faecal immunoglobulin test minimises these Colonoscopy in stool occult blood positive patients Once only flexible sigmoidoscopy between 55-64 years – 70% coverage

22. Endoscopically Detected Polyp Variety

23. Mangement of a Endoscopically Detected Polyp Risk of malignancy increases with polyp size 1cm – 10% >3cm – 30% Colon Adenomas >5mm  Excised Snare polypectomy Large sessile – Endoscopic mucosal resection Rectal polyp – all polyps needs to be excised <2cm - EMR Lager Low lying - Transanal resection High – Transanal endoscopic microsurgery (Laparoscopic technique) Extensive villous lesion – argon beam ablation (Symptomatic but frail)

24. Management of Screening Detected Early Disease Risk catogorisation and plan management Endocopically detected malignant polyp  ? N eed of completion colectomy driven by Haggit stage Histological grade Staging CT findings Angiolymphatic invasion Positive margin within 1-2mm

25. Difficulties in Deciding on a Completion Colectomy Identifying the site of innitial polypectomy – Tattooing at initial procedure

26. Colorectal Cancer

27. Pesentation of Colorectal Cancer RS colon – Anaemia, obstruction uncommon L iquid nature of faeces Wider diameter of colon Descending or Sigmoid colon - change of bowel habit, colicky abdominal pain and blood in the stool Rectum - bleeding is predominant, mucus discharge large tumour - tenesmus Mass Incontinence, Anal pain Symptoms related to metastasis – pneumaturia, recurrent UTI, severe diarrhoea, faecal vomiting

28. Targets of Evaluation Disease and differentials Complications Due to blood loss Due to spread – Local, Metastatic Obstructive symptoms Perforation Aetiology including famaily history need of family screening Fitness for surgery Fitness for chemo/radiotherapy Dissability Plan treatment and followup

29. Evaluation Clinical History Examination Diagnosis - Sigmoidoscopy/ Colonoscopy and biopsy Radiological USS, Endorectal USS CT Colonogram Barium studies – out of practice CECT – staging in colorectal ca Pelvic MRI – staging in rectal PET-CT – limited role Blood – CEA, FBC, RFT, LFT

30. For Diagnosis Colonoscopy is Prefered Gold standard f or Diagnosis 1:1000 risk of perforation Evaluate synchronous cancer in 3-4%, Polyps in 30% 2 or more coeisting tumours at diagnosis or within 6 months, seperated by 5 cm, not submucosally connected or a satellite lesion Flat adenomas are difficult to detect without special techniques Indigo-carmine dye Narrow band imaging

31. CT Colonogram 90% sensitive for >6mm lesions Adequate alternative where colonoscopy is unfavourable Advantages No need sedation Non invasive Can do CECT at the same go with IV contrast Disadvantages Can not take biopsy Need similar bowel preperation

32. Preoperative Staging Colonic CECT (IV and Oral contrast) Chest Abdomen and Pelvis When IV contrast contraindicated – NCCT chest + MRI abdomen pelvis with contrast USS abdomen and Chest X ray as an alternative in resource poor setting Rectal in addition MRI Pelvis Assesment of circumferential resection margin (CRM) Accurate for Nodal stage EUS Accuracy better for T staging Poor accuracy for N staging In cases where CT/ MRI studies are inconclusive - PET/CT

33. Staging Staging is similar in colon and rectal cancer Preoperative – Clinical and Radiological  To plan manangement TNM – T componenet most important Postoperative – Pathological staging  To plan adjuvent treatment and followup

34. T1/ T2 distinction is difficult in MRI Possible in TRUSS CRM evaluation better in MRI Poorer in TRUSS

35. TNM Prognostic Groups Stage 0 – Tis, N0, M0 Stage I - T1/2, N0, M0 Stage II - T3/4 N0, M0 IIa - T3 N0 IIb - T4a N0 IIc - T4b N0 Stage III – Any T with nodes, M0 IIIa - Stage 1 with N1 IIIb - Stage II with N1 IIIc - Stage II with N2 Stage IV – Any T Any N with Metastasis

36. Management of Colorectal Cancer Surgical excision is the mainstay of treatment Surgical options - Elective Colon cancer – Complete Mesocolonic Excision (CME) Right hemicolectomy Extended right hemicolectomy L eft hemicolectomy Sigmoid colectomy (sub) Total colectomy Rectal cancer – Mesorectal excision (TME) Anterior resection Abdomino-perineal excision  Permenant colostomy But evolving area – Neoadjuvant and Adjuvant treatment options

37. Surgical Options

38. Pathological Staging Accurate, detailed and consistent pathology reporting for colorectal cancer is important for Prognostication Plan adjuvant treatment Macroscopic description Size of the tumour (greatest dimension). Site of the tumour in relation to the resection margins. Any abnormalities of the background bowel.

39. Pathological Staging - Microscopic description Histological type. Differentiation of the tumour, based on the predominant grade within the tumour Maximum extent of invasion into/through the bowel wall (submucosa, muscularis propria, extramural). Serosal involvement by tumour A statement on the completeness of excision at the cut ends (including the ‘doughnuts’ from stapling devices) and at any radial margin. The number of lymph nodes examined, the number containing metastases, and whether or not the apical node is involved. Extramural vascular invasion if present Pathological staging of the tumour according to Dukes' classification.

40. Duke’s Stages A - Tumour limited to the wall B - Tumour in extra-rectal tissues, but not LN C - Tumour in LNs C1 - Pararectal nodes C2 - Nodes along the blood vessels D – Distant Spread

41. Colon Cancer

42. Colon Cancer Elective Surgery Surgery in emergencies Adjuvent therapy

43. Preoperative Checklist for Colon Cancer Surgery Preoperative optimisation Endoscopic biopsy and confirmation of histology Synchronous cancer detected/ excluded by colonoscopy/ CT colonography Staging CECT chest abdomen and pelvis Preoperative CEA Mecahnical bowel preperation - ? VTE prophylaxis – Graduated compression stockings and SC Enoxa HB target – 7-8 in general, 8-9 in IHD, Antibiotic prophylaxis 30 – 60 mins prior to Sx

44. Mechanical Bowel Preperation No benefit in anastomotic leakage, re-operation or wound infection and recommended avoidance of MBP in elective colectomy patients Recommended in high risk emergency where anastomotic leak risk is high  creation of an upstream defunctioning stoma MBP is recommended in this setting to reduce faeces between the stoma and anastomosis

45. Enhanced Recovery After Surgery

46. Principles of Colon Cancer Surgery Colectomy with enbloc removal of lymph nodes Complete Mesocolic Excision (CME) Dissection in the embryologically defined mesocolic plane. Central ligation of the vascular pedicle (CVL). Resection of an adequate length of apparently normal colon on either side of the tumour.

47. Central Vascular Ligation (CVL) Mortality benefit of D3 resection over D2 resection in T3/ T4 disease removal of undetected micrometastatic disease within the mesentery resection of positive nodes

48. Longitudinal Resection Margin

49. Practical Guide to Resection Right hemicolectomy Caecum Right colon R ight transverse colon Transverse Colectomy Extent of longitudinal resection cannot be fulfilled by either right hemicolectomy or segmental left colectomy Segmental left colectomy Splenic flexure Left Hemicolectomy L eft colon cancer

50. Open Surgery vs Laparoscopic vs Robotic Laparoscopic surgery Advantages Equivalent oncological outcome Equevalent LN harvesting ability Encouraging postoperative recovery – shorter hospital stay wound infection rates, blood loss and postoperative pain scores are lower Disadvantages Difficulty acquiring technical competence, long learning curve High cost of laparoscopic instruments/ consumables Increased operative times Robotic – again shortest stay, least blood loss, but longest operative time and much increased cost

51. Minimally Invasive Techniques Only by experienced surgeons in minimally invasive colectomies Not utilized in Emergency Acutely obstructed Perforated Clearly locally advanced High risk prohibitive adhesions

52. Surgical Complications Anastomotic leak – Most devastating – 4 – 8% Wound infections - 10%

53. Surgical Complications - Anastomotic Leak Causes Technical problems – around 1-2 days Ischaemia – around day 5 Diagnosis Poor progression Persistant tachycardia, pyrexia, arrhythmia Respiratory problems Abdominal pain or distension Sudden r ise of CRP >200 (daily CRP)

54. Surgical Complications Anastomotic Leak Evaluation CECT – Chest abdomen pelvis without rectal contrast Subtle changes – bubbles adjacent to the anastomosis Also, to exclude other problems Followed by water soluble contrast enema Management Conservative in well patients – Not well established Antibiotics Operative when deteriorating Preserving anastomosis  Defunctioning stoma, Drain at site Anastomosis can not be preserved  Hartmann's procedure

55. Risk Factors for Anastomotic Leak Male sex Renal disease Comorbidities History of radiotherapy Tumour >3cm Advanced tumour stage Emergency surgery Metastatic disease Smoking Obesity Poor nutrition Alcohol intake in excess Immunosuppr essants Bevacizumab Blood loss/transfusion Duration of surgery (> 4 H)

56. Emergency Surgical Options for Colorectal Cancer Resuscitation Evaluation Main presentations requiring emergency surgery (20% in total) Obstruction (16% present like this) Perforation Significant haemorrhage Increased post op complications Increased mortality Principles of emergency surgical procedure Oncological clearance when appropraite Releive obstruction Remove contamination – control of sepsis

57. Obstruction Evaluation CT preffered over X ray Endoscopy/ contrast enema study to exclude psedo-obstruction Expedited management Evidence of sepsis Caecal region tenderness/ >12cm Caecal diameter Options Stenting (left colon lesion) – allows elective resection after stabilisation and evaluation Emergency Surgery – depending on the stability Resect and anastomose Resect and defunct – Hartmann’s procedure Defunct only (without resection) Systemic therapy with chemo I n medically unfit or unresectable lesion G oal – Conversion to a resectable lesion or with palliative intent

58. Stenting for Left Colonic Lesions Relief of abstruction  Stabilisation  Evaluation  Definitive Sx No evidence over definitive emergency surgery without stenting Less stomas with this stratergy May be the definitive treatment in the pallitive setup Problems F ailure to releive obstruction Perforation Technical difficulty

59. Right Hemicolectomy Hartmann’s Procedure

60. Perforation At the site of the tumour At a distant site due to dilatation/ diverticuli Primary may be missed Management Resection Control of sepsis Reconstruction where appropriate Generally leads to a defunctioning stoma

61. Adjuvent Therapy – Resectable Colon Cancer Mainly as a postoperative adjuvant Not indicated T1/ T2 (Stage I) Some Stage II Indicated Some stage II T4 benefit in node positive disease poorly differentiated / undifferentiated tumours lymphovascular invasion perineural invasion Poor LN sampling Treatment Based on fluoropyrimidines (IV 5-fluorouracil Oral capcitabine ) Combinations with oxaliplatin

62. TNM Prognostic Groups Stage 0 – Tis, N0, M0 Stage I - T1/2, N0, M0 Stage II - T3/4 N0, M0 IIa - T3 N0 IIb - T4a N0 IIc - T4b N0 Stage III – Any T with nodes, M0 IIIa - Stage I with N1 IIIb - Stage II with N1 IIIc - Stage II with N2 Stage IV – Any T Any N with Metastasis

63. Radiotherapy has no role in primary disease in most cases Risk of radiation enetritis to adjacent small bowel Mobile nature of large bowel where directed therapy is difficult Limited role of radiotherapy for ablative radiotherapy for liver and lung mets highly selected cases/ clinical trial. should not be used in place of surgical resection highly conformal delivery required - 3-D conformal radiation therapy, intensity-modulated radiation therapy (IMRT), or stereotactic body radiation therapy (SBRT). Adjuvent Therapy – Resectable Colon Cancer

64. Neoadjuvent Treatment Options –Colon Cancer Preoperative chemoradiation used selectively in T4 tumours penetrating to a fixed structure for patients with recurrent disease L ocally unresectable tumours Neoadjuvant chemotherapy For bulky nodal disease or clinical T4b

65. Management of Locally Advanced Colon Cancer Target Where possible treatment with curative intent Or appropriate palliation Operative options Bypass surgery may be appropriate Multi-organ en bloc resection may be curative Neoadjuvant Intent of downgrading – improving resectability Palliative intent

66. Advanced Disease – Recurrence of Colon Cancer Local recurrence  Resection attempted, if not palliative bypass

67. Metastesis in Colon Cancer Usually metachronously after locoregional treatment (50– 60%) Synchronously 20 – 34% in liver (worse than metachronous) Operable Hepatic resection (No RCT, Generally for 1-3 mets in one lobe of liver, preoperative chemo may have a role in improving operability, 30% 5 year survival Don’t biopsy potentially resectable hepatic mets  risk of dissemination Pulmonary – rarely possible as only 10% pulmonary mets and only 10% of them have disease confined to lung, 20% 5 year survival Peritoneal spread alone, or with easily operable liver metastases, peritonectomy combined with heated intraperitoneal chemotherapy (HIPEC) Inoperable Chemotherapy containing fluoropyrimidines is the only established treatment Palliative surgery mainly to relieve obstruction – Stoma/ Stenting

68. Surveilance is Based on Prognostic Stage Stage I - Imaging is not routinely indicated and should only be based on symptoms and clinical concern for recurrent/metastatic disease. Stage II & III - Chest, abdomen, and pelvic CT every 6 to 12 months for a total of 5 years. PET/CT is not indicated. Stage IV – Chest, abdomen, and pelvic CT every 3 to 6 months 2 years then every 6 to 12 months for a total of 5 years PET/CT can be considered for assessment of response and liver recurrence after image-guided liver-directed therapies ( ie , ablation, radioembolization) or serial CEA elevation during follow-up

69. Intensive Follow Up History and physical examination in every 3 months for 2 years and then in every 6 months for total of 5 years CEA in every 3 months for 2 years and then in every 6 months for total of 5 years Annual CECT of chest, abdomen and pelvis for 5 years Colonoscopy in 1, 3 and 5 years, (Then 5 yearly up to 80 years)

70. Rectal Cancer

71. Preoperative Checklist for Rectal Cancer Preoperative optimisation Endoscopic biopsy and confirmation of histology MMR/ MSI testing Synchronous cancer detected/ excluded by colonoscopy/ CT colonography Staging CECT chest abdomen and pelvis Pelvic MRI/ Endoscopic USS Preoperative CEA Mecahnical bowel preperation done for low anterior resection Siting of stoma and councelling preoperatively Fertility risk discussion/ counselling VTE prophylaxis – Graduated compression stockings and SC Enoxa HB target – 7-8 in general, 8-9 in IHD, Antibiotic prophylaxis 30 – 60 mins prior to Sx

72. Rectal cancer Surgery - Objectives Oncological cure Most cases  Radical excision of the rectum, together with the mesorectum and associated lymph nodes (TME) High proximal ligation of the inferior mesenteric lymphovascular pedicle Margin distally minimum 1 cm, Proximally > 5cm Preserve function Restore GI continuity Preserve anal sphincter – lower margin of tumour >2cm from anaorectal junction Stratergies in low rectal tumours - Stapled anastomosis Chemoradiotherapy down-staging Bladder function Sexual function

73. Management Options in Rectal Cancer Surgical Local excision - Difficult in higher lesions Trans anal excision Excision of the t umour by TEMS (transanal endoscopic microsurgery) Transabdominal resection + TME Higher - anterior resection Lower - abdominoperineal excision – smaller group Neoadjuvant LCCT SCRT Adjuvant CT/ RT/ CRT

74. Management Stratergies

75. Management Stratergies Localised Disease - <T2, N0, M0 Upfront surgery Locoregional rectal cancer - >T2 or ≥ N1 Neoadjuvant therapy

76. Circumferential Resection Margin CRM is the surface of the nonperitonealised part of the rectum that is resected during surgery MRI is the most reliable imaging modality to determine potential CRM CRM is the shortest distance between the outermost part of the rectal tumour and the MRF Positive < 1 mm Threatened - between 1 and 2 mm Not threatened - >2 mm CRM status is not applicable if the tumour is situated in a peritonealised aspect of the rectal wall.

77. Circumferential Resection Margin Need to achieve a negative surgical margin as risk of local recurrence is 40% if margins positive Reasons for this recurrence risk Close proximity of rectum to adjacent pelvic organs Absence of a serosa surrounding the rectum Technical difficulties obtaining a wide surgical margin at resection To achieve a negative margin, mesorectal fascia should be free of tumour at the time of TME Radiotherapy enables an R0 resection by making the MRF free of tumour Radiotherapy is feasible to pelvis compared to abdomen where sensitive small bowel is located

78. Neo-adjuvent for Rectal Cancer Neoadjuvant strategies – preoperative radiotherapy produces better disease control and less morbidity than postoperative treatment Short course radiotherapy (SCRT) Long course chemoradiotherapy (LCRT) Total neoadjuvant therapy (TNT)

79. SCRT - Short Course Radiotherapy Indications T3 with uninvolved CRM in upper and mid rectal cancers T2 lower rectal cancer in which muscularis propria preserved < 1mm N1 Modality - 25Gy over 5 days (Monday to Friday) Surgery in next week before acute mucosal side effects occur Surgery after 6 weeks if downstaging is needed

80. LCRT - Long Course Chemoradiotherapy CT given concurrently with RT to increase RT sensitization and enhances tumoricidal effect Does not improve overall survival or disease free survival Indications - high risk features CRM threatened Presence of EMVI T4 N2 In lower rectal cancers T3 with >1mm from CRM Modality - 45-50.4Gy in 5 weeks RT + 5-FU in first 5 days and last 5 days Surgery is done in 12 weeks Recovery from CRT associated toxicities Time for pathological tumour response to occur before tumour starts repopulating

81. Primary Surgery without Neoadjuvant vs LCRT vs SCRT Swedish trial, Dutch TME trial – local control is better compared to surgery alone, but no improvement in overall survival Studies comparing LCRT and SCRT e.g. Polish trial No difference in LR, OS, R0 resection rates LCRT is associated with serious side effects SCRT patients would likely to have a permanent stoma

82. Assesment of Response to Neoadjuvant Clinically, repeat MRI and colonoscopy 50-60% are down sized 20% shows complete clinical response (normal 2 layered rectal wall) Long term outcome of the patient directly correlates to response to neoadjuvant - Mercury trial

83. Watch and Wait Stratergy Complete clinical response to long-course chemoradiotherapy (20%). Whitish fibrosis in previous site of tumour No residual cancer (clinical, biopsy or imaging  intense surveillance ? Cure No morbidity of resectional surgery. NCCN doesn’t recommend watch and wait, recommends to perform resectional surgery to confirm complete response pathologically 30% will recur  but can be salvaged by surgical resection.

84. Downstaging Rectal Cancer with Preoperative Radiotherapy T3 above or mid rectal tumour – High risk local recurrence Surgery (TME with inact cover of fat and fascia) Lower T3 – by definition gone through bowel wall, may involve sphincter complex

85. Complications of Preoperative Radiotherapy for Rectal Cancer Perineal wound breakdown Diarrhoea Proctitis Urinary tract infection Small bowel obstruction Leukopenia Venous thrombosis Adverse effects on anal function Adverse effects on anastomosis

86. Trans Anal Excision/ TEMS  TEMS has better oncological outcomes compared to trans anal excision, same principles apply. Criteria T1, N0 cancers <3cm, well to moderately differentiated tumours within 8cm of the anal verge limited to <30% of the rectal circumference Procedure Full thickness excision of bowel wall in to perirectal fat should be done >3mm negative deep and mucosal margins should be achieved Tumour fragmentation should not happen Locally excised specimen should be oriented and pinned before fixation to be sent to pathologist

87. Trans Anal Excision/ TEMS …  If pathologic evaluation shows following Positive margins LVI Poor differentiation Invasion in to lower third of the submucosa → radical resection is needed Studies show CRT followed by TAE could be a safe alternative to transabdominal resection for T2N0 lesions Good option for patients who refuse or are unfit for transabdominal surgery

88. Trans Anal Excision / TEMS - Advantages  Minimal morbidity (sphincter sparing) Minimal mortality Rapid post-operative recovery Limitations and disadvantages Pathologic staging of nodal involvement is not possible → probably why patients have more local recurrences (LN micro metastases are common in early rectal lesions and cannot be detected by endorectal US) More local recurrences and less OS compared to radical resection

89. Transabdominal Surgery Options Anterior resection Abdominoperineal resection Options Open Laparoscopic Always with TME (Total mesorectal excision)

90. Total Mesorectal Excision (TME) En -bloc removal of the mesorectum including vascular and lymphatic structures, fatty tissue and mesorectal fascia as a " tumor package"  Through sharp dissection Autonomic nerves are spared Mesorectal excision should extend 4-5cm below the distal edge of the tumour If CRM + ve → LR is 0% If CRM - ve → LR is 6-8% Unless other nodes are clinically suspicious, NCCN does not recommend extension of nodal dissection beyond the TME (i.e. in to iliac nodes etc.)

91. Anterior Resection (AR) Removal of part or the complete rectum for a rectal tumour can be performed if about 3cm is there from anorectal angle to the tumour (limitation is application of the stapler to the pelvis) Procedure En bloc removal of rectosigmoid and surrounding mesentery Rectum with a 4-5cm distal clearance leaving a cuff of rectum for upper and middle rectal cancer if lower rectal tumour 0.9mm pathological distal margin is enough TME followed by colorectal anastomosis Extended AR – Coloanal anaestomosis

92. Abdominoperineal Resection (APR) Indications Tumour directly involves anal sphincters Tumour directly involves levator muscles margin-negative resection of the tumour results in loss of sphincter function Procedure En bloc removal of Rectosigmoid and surrounding mesentery, rectum and TME, anus and perianal soft tissue Creation of an end colostomy APR has worse local control and overall survival than AR Reasons unclear Due to surgical procedure? Tumour related factors as in APR offered for more malignant lesions?

93. IMA High Ligation or Low Ligation No evidence to say and difference in overall survival If patient is an elderly with possible atherosclerotic disease, high ligation should not be done and instead low ligation of IMA should be done to preserve blood supply to left colon

94. Diversion with Ileostomy Reduces but not prevent clinical anastomotic leak Mainly reduces clinical manifestation of a leak Considered in Anastomosis below the peritoneal reflection Leakage risk for overall colon is 4%, for below the peritoneal reflection is 17% (Approx. 4 times higher) Neoadjuvant RT (20% increased risk) Low nutritional status Anaemia Patients with atherosclerotic disease (likely to have poor blood supply) If spillage/perforation of the tumour/bowel wall occurs during surgery

95. Adjuvant Therapy Chemotherapy Sate II and III rectal cancer who received neoadjuvent CRT a nd surgery Chemoradiotherapy Sate I without neoadjuvant radiotherapy which are upstaged to II/III after pathology Regimens  FOLFOX = 5-FU, Folinic acid, oxaliplatin CapeOx = Capecitabine, Oxaliplatin FOLFIRI = 5-FU, Folinic acid, irinotecan Timing Should be started as soon as patient is medically able to withstand chemo following surgery → if waited for longer times, results in reduction in overall survival Should be given to complete 6 months of chemotherapy altogether (4 months adjuvant if neoadjuvant CRT given)

96. Management of Locally Advanced Disease Target Where possible treatment with curative intent Or appropriate palliation Threatened circumferential resection margin/ spread to neighbouring structures  Neoadjuvant radiotherapy/ chemotherapy Long-course chemoradiotherapy is given as 5 fractions of radiotherapy combined with chemotherapy over a 6-week period.  Aim is to downstage Resection margins are not threatened but the cancer is still at high risk for local recurrence (e.g. peri-rectal lymph node involvement) Preoperative ‘short-course’ (5 days) radiotherapy Palliative radiotherapy with or without a defunctioning stoma

97. Management of Locally Advanced Disease Endoluminal Stenting Palliative intent Releive obstruction and plan curative procedure Colostomy – Intestinal obstruction Palliative intent Before downstaging treatment Extensive surgery Pelvic evisceration Pelvic exenteration (in younger, fitter patients) Perineal reconstruction Ileal conduit Palliative radiotherapy – Pain, obstruction, bleeding

98. Management of Metastetic Disease 50% will develop mets, 30% synchronously Prognosis worse with synchronous mets vs metachronous mets Resectable metastesis – Liver, Lung, Hilar nodes, Spleen, Adrenal Rationale – improves overall and disease free survival Unresectable mets – Coeliac axis, Paraaortic nodes, Peritoneal carcinomatosis Assesment Possibility of R0 resection of primary R0 resection of mets should be possible (adequate residual organ etc) Healthy liver 20%, Unhealthy liver 40% No other unresectable mets

99. Management of Metastetic Disease Liver/ Lung resection in carefully selected patients offers the best chance of cure for single or well-localised liver metastases Synchronous with primary surgery (Classical) or as a delayed procedure (Staged) Complete resection should be feasible Adequate hepatic/ lung function should be expected Re-resection in some very rare cases Unresectable Conformal external beam radiotherapy – highly selected cases to liver Chemotherapy  Conversion to resectable  Resection If not still resectable treatment with palliative intent Local chemotherapy – Hepatic arterial infusions, TACE, DEB-TACE Directed radiation – Arterial radioembolization, EBRT Tumour ablation – RFA, Microwave, Cryo , Perc ethanol, electrocoagulation

100. Management of Metastetic Disease Peritoneal Carcinomatosis 17% of metastatic colorectal cancer patients have this Only metastatic site in 2% Overall shorter survival Goal is palliative Primarily managed with systemic therapy Palliative surgery for primary or stenting if obstruction/impending obstruction But if R0 resection is possible for the peritoneal met - experienced centres can attempt to do surgical resection Complete cytoreductive surgery and HIPEC (hyperthermic intraperitoneal chemotherapy)

101. Follow-up Depends on the Initial Findings Transanal local excision only Proctoscopy (with endoscopic ultrasound [EUS] or MRI with contrast) every 3–6 months for the first 2 y, then every 6 months for a total of 5 y Colonoscopy at 1 y after surgery If advanced adenoma, repeat in 1 y If no advanced adenoma, repeat in 3 y, then every 5 y Stage I with full surgical staging Colonoscopy at 1 y after surgery If advanced adenoma, repeat in 1 y If no advanced adenoma, repeat in 3 y, then every 5 y Stage II-IV Most intense surveillance

102. Follow Up Stage II-IV History and physical examination in every 3 months for 2 years and then in every 6 months for total of 5 years CEA in every 3 months for 2 years and then in every 6 months for total of 5 years Annual CECT of chest, abdomen and pelvis for 5 years Colonoscopy in 1, 3 and 5 years, (Then 5 yearly up to 80 years) PET CT not recommended

103. CEA – Carcinoembryonic Antigen An oncofoetal antigen Produced by foetal gut tissue and epithelial tumours, especially those of the large bowel Normal value <2.5 ng/ml Smokers up to 5 ng/ml Low sensitivity and specificity Mucin-producing and poorly differentiated adenocarcinomas which do not often present with a raised CEA Importance prognostic value - good prognosis is associated with lower levels tumour burden for follow up - levels raised 2-6mon before recurrent lesion becomes visible

104. CEA – Carcinoembryonic Antigen Other conditions with elevated CEA Malignant Pancreatic adenocarcinoma Medullary thyroid cancer Benign Smoking COPD IBD Pancreatitis liver disease OJ

105. CEA – Carcinoembryonic Antigen In favour of CEA CEA rises 1.5 - 6 months prior to macroscopic recurrence Helps in finding early liver mets - helps in resecting liver mets completely - long term relapse free survival is possible up to 40% of patients Even if the mets are unresectable - still good overall survival can be achieved with chemo (irinotecan, oxaliplatin and 5-FU based chemo) compared to only supportive care for metastatic CRC Argument against CEA 30-40% of patients with CRC recurrence, CEA wouldn't rise Not a cost effective method (but this is controversial, as some studies have shown it's the best cost effective test for detecting potentially curable disease) There are no data showing that it was CEA that improves survival or quality of life

106. Management of Advanced Disease - Recurrence in Rectal Cancer Local Recurrance Disease of pelvis, site of anastomosis of perineum Mostly incurable Debilitating symptoms - pelvic pain, ureteric obstruction, intestinal and urinary tract fistulation, and poor bowel and urinary function Mainly due to failure in complete excision of tumour in primary surgery Risk Factors Size of the primary Involvement of CRM Distal tumour/ near the verge Extramural vascular invasion Poor differentiation of tumour Nodal status Extent of extramural spread Peritoneal involvement

107. Specific Management of Rectal Cancer Recurrence

108. Considered Unresectable/ Inoperable if Distant metastasis Sacral invasion above S2-S3 Extensive pelvic side wall involvement resulting in bilateral hydronephrosis Encasement of external iliac vessels (>180 degrees) Invasion to anterior pubic bone Extension through sciatic notch

109. Prognosis Disease Stage 5 Year Survival Early Stages (Localised Stage I/ II) – Colon 91% Early Stages (Localised Stage I/ II) – Rectal 88% Regional disease (Stage III) – Colon/ Rectal 70% Metastetic Disease (Stage IV) < 12%

110. Summary

111. Important Points - Basics Colonoscopy is the gold standard in diagnosis – Colorectal cancer Screening is helpful in detecting early lesions with better prognosis CECT chest abdomen and pelvis is mandatory for preoperative colorectal cancer screening MRI pelvis is standard for preoperative staging of rectal cancer T o assess mesorectal fascia (potential CRM) Aids selection for neoadjuvant treatment ERAS – Reducing hospital stay Laparoscopic surgery – reduces hospital stay Evidence supports intense follow-up for colorectal cancer

112. Important Points – Colon Cancer Complete mesocolic excision is associated with improved oncological outcomes. Colorectal surgeons must be aware of the variable vascular anatomy of the colon. Improved imaging will allow planning of surgery for individual patients. Anastomotic leak should be suspected and diagnosed early. Stenting provides an attractive alternative to emergency surgery for obstruction when appropriate facilities are available.

113. Important Points – Rectal Cancer Optimal outcome for rectal cancer requres TME Low anterior resection  Defunctioning stoma is important Low rectal cancer involving sphicters  Extralevator APE

114. Important Points – Chemoradiotherapy Oxaliplatin-fluoropyrimidine adjuvant chemotherapy improves survival and is standard for stage III colon cancer and is commonly used for high-risk stage II colon cancer. Adjuvant chemotherapy is used in rectal cancer by extrapolation from colon cancer but the evidence to support its use following high-quality TME surgery and preoperative (chemo)radiotherapy is weak. There is a strong evidence base demonstrating that preoperative radiotherapy reduces the risk of local recurrence after resection of rectal cancer, although it does not improve overall survival. The addition of concurrent 5FU to long-course radiotherapy reduces the risk of local recurrence. Earlier stage tumours have a greater chance of achieving a complete response to pelvic chemoradiation, thereby potentially avoiding radical surgery. Neoadjuvant preoperative chemotherapy in rectal cancer are attractive because micrometastatic disease (the main cause of rectal cancer death), is treated earlier than with current standard postoperative chemotherapy. (Needs further evidence)