21ST CENTURY MANAGEMENT OF

COLORECTAL CANCER – A SURGEON’S VIEW

Andrew Luck

Colorectal SurgeonNorthern Adelaide Colorectal Unit

Adelaide, South Australia

Honorary Secretary, Colorectal Surgical Society of Australia and New ZealandCSSANZ representative, National Bowel Cancer Screening Program Advisory Group

CANCER SOCIETY OF NEW ZEALAND, WELLINGTON June 2009

CRC MANAGEMENT

• Diagnosis and staging

• Surgery– Total mesorectal excision– Sphincter saving surgery– Laparoscopic colorectal surgery– Colonic stents for obstructing cancer– Local excision

• Transanal endoscopic microsurgery

• Radiotherapy– Pre op and post op– Long course and short course

• Chemotherapy

DIAGNOSIS

• Colonoscopy still the gold standard– Dye spray techniques– Narrow band imaging– SPOT marking– Markers of quality colonoscopy– Training revolution

• Barium enema• CT Colonography

DYE SPRAY

• Use of dye (indigo carmine or methylene blue) to enhance images of flat lesions at colonoscopy

• Decrease ‘miss’ rate of small and flat lesions

DYE SPRAY

NARROW BAND IMAGING

• Enhances images of capillaries in the surface layers of mucosal membranes by irradiating target areas with narrow wave bands of light– Blue (390 – 445nm) for

surface vessels– Green (530-550nm) for

deeper vessels

• Small lesions easier to see and biopsy

NARROW BAND IMAGING

‘SPOT’ MARKING

• Use of ‘SPOT’ (carbon based tattoo)

• Small cancers and large polyps requiring surgery

• Inject in the submucosal layer in 3 areas of colon just distal to lesion

• Ease of identification at surgery– Essential for laparoscopic

surgery

QUALITY COLONOSCOPY• Quality training

• Recognition of training– Conjoint Committee for the Recognition of Training in

Gastrointestinal Endoscopy• Voluntary, ?? Soon to be mandatory

• Recertification processes

• Audit– Caecal intubation rate

• >90% for all colonoscopy• >95% for screening colonoscopy

– Adenoma detection rate– Polyp retrieval rate– Complications– Withdrawal time (mean > 6 minutes)

WITHDRAWAL TIMES

TRAINING REVOLUTION

• Endoscopy curriculum (GESA)

• National Endoscopy Training Initiative workshops– Introductory– Basic– Advanced

• May be required for CCRTGE certification in time

• Train the trainer courses– UK model– Roland Valori/ John Anderson– Applies adult learning techniques to colonoscopy training

BARIUM ENEMA

CT COLONOGRAPHY

• Computerised tomography used to recreate ‘virtual’ colonoscopy– Not as accurate as conventional

colonoscopy as yet

• In Australia, only available in the event of an incomplete colonoscopy

• ? Role in screening programs in the future

STAGING

• Locoregional staging– Rectal cancer

• Endorectal ultrasound• Magnetic resonance imaging

• Distant metastases– CT chest/abdomen/pelvis

• Prognostication• Frail or elderly with asymptomatic primary• Extensive liver metastases (> 50% liver volume)• Suitable for synchronous liver resection• Primary suitable for laparoscopic resection

– PET scan

ENDORECTAL ULTRASOUND

• Intraluminal probe gives 360o image of rectum and rectal lesion– Operator dependent

• 90-95% accuracy on T stage• 70-75% accuracy on N stage

– Best for assessment of early lesions• T1 to T2 (? Local excision)• T2 to T3 (Neoadjuvant treatment)

– Less accurate at circumferential rectal margin• High frequency (10MHz) = better resolution and less

penetration• Low frequency (5MHz) = better penetration and less

resolution

ENDORECTAL ULRASOUND

MRI

• Using high resolution phased array techniques – T1 and T2 weighted images

• Most accurate measurement of involvement of circumferential rectal margin

• Decision re neoadjuvant therapy

Copyright © 2007 by the American Roentgen Ray Society

Kim, M.-J. et al. Am. J. Roentgenol. 2004;182:1469-1476

--72-year-old man with polypoid rectal carcinoma extending to submucosa

Copyright © 2007 by the American Roentgen Ray Society

Kim, M.-J. et al. Am. J. Roentgenol. 2004;182:1469-1476

--59-year-old woman with ulcerative carcinoma extending beyond proper muscle layer

ISSUES FOR THE COLORECTAL SURGEON IN THE 21ST CENTURY

• Total mesorectal excision

• Sphincter saving surgery– Colonic J pouch

• Laparoscopic colorectal surgery

• Colonic stents for obstructing cancer

• Local excision– Transanal endoscopic microsurgery

TOTAL MESORECTAL EXCISION

• High local recurrence rates– Especially low rectal lesions

• 1990s Dutch radiotherapy trial– Improvement with post op radiotherapy – Control group 28% local recurrence rate!!

• Bill Heald (Basingstoke)– Total Mesorectal excision

• Sharp and accurate dissection in the extrafascial plane (the plane between the fascia propria of the rectum and the presacral fascia)

• The ‘holy’ plane• 2.8% local recurrence rate (probably 6%)

THE HOLY PLANE

TOTAL MESORECTAL EXCISION

• Now the standard of care– 25-30% difference in local recurrence rates

(Havenka et al 1999)– RT now assessed in centres practising TME

• Circumferential rectal margin– Independent predictor of local recurrence rate

• CRM > 2mm 5.6% LR• CRM < 2mm 16.0% LR

– <1mm higher rate of distant metastases (37.6% vs 12.7%) and poorer survival (Nagtegaal et al 2002)

– Preservation of sexual and urinary function

SPHINCTER PRESERVATION

• 95% of rectal cancers have intramural spread of less than 1 cm– No advantage in distal margin > 2cm (Pollett and Nicholls Ann

Surg 1983)

• For mid and low rectal cancers aim for– TME– 2cm distal margin (fresh)– Sphincter preservation

• ‘Contour’ stapler– Colonic J pouch

• APR restricted to low rectal cancers with either– Inadequate distal clearance– Inadequate sphincter mechanism– Narrow male pelvis making restorative resection impossible (rare)

COLONIC J POUCH

LAPAROSCOPIC SURGERY FOR COLON CANCER

• First laparoscopic cholecystectomy 1987 (France)

• First lap right hemicolectomy 1991

• Slow to take off– Long learning curve– Unique complications– Advantages less clear– Oncological concerns

• Port site metastases

• Given away by many surgeons by late 1990’s

• Now enjoying a strong renaissance

LAP COLECTOMY RESULTS

• Meta-analysis RCT LAC vs Open• Analysis of articles published to end of 2002• 12 trials; 2512 patients.• LAC took longer to perform (32 % longer)• LAC associated with lower morbidity• LAC less wound infection (OR 0.47; 95% CI 0.28 – 0.80)• LAC reduced time to first flatus (33% less time), introduction

diet (24 % less time), reduced narcotic requirement (37% reduction), and hospital stay (21% less).

• No significant difference in perioperative mortality or oncological clearance.

Abraham, Young and Solomon. Meta-analysis of short-term outcomes after laparoscopic resection for colorectal cancer. Br J Surg 2004.

LAP COLECTOMY RESULTS

• Multicentre (48 institutions) ; 872 patients • Median follow-up was 4.4 years. • The primary end point was the time to tumor recurrence. • At three years, the rates of recurrence were similar in the two groups• 16 % LAC and 18 % Open (P=0.32; HR for recurrence, 0.86; 95 % CI,

0.63 to 1.17). • Recurrence rates in surgical wounds were less than 1 percent in both

groups (P=0.50). • Overall survival rate at 3 years was also very similar in the two groups

(86 % LAC and 85 % Open (P=0.51; HR for death in the LAC, 0.91; 95 percent confidence interval, 0.68 to 1.21)

• No significant difference between groups in the time to recurrence or overall survival for patients with any stage of cancer.

• COST Study UK

LAP COLECTOMY RESULTS

• Single institution• Analysis intention to treat• 219 patients: 111 LAC; 108 Open• LAC recovered faster with shorter return of gut activity, faster oral

intake time and reduced length of stay.• Cancer survival greater in LAC group (P=0.02)• LAC independently associated with reduced risk tumour relapse (HR

0.39, 95% CI 0.19-0.82), death from any cause (HR 0.48, 95% CI 0.23-1.01), death from cancer (HR 0.38, 95% CI 0.16-0.91)

• Stage III cancer showed the greatest benefit• CONCLUSION: LAC is more effective than open colectomy for the

treatment of colon cancer in terms of morbidity, hospital stay, tumour recurrence and cancer related survival.

Lacy et al. Laparoscopy-assisted colectomy versus open colectomy of non-metastatic colon cancer: a randomised trial. Lancet 2002

AlCCAS TRIAL

• 602 patients (321 RHC; 223 HAR)• 294 LAP; 298 Open; 9 Exclusions• 43 conversions (14.6%)• 6 deaths (2 open; 4 lap)• Length of Stay 7 vs 8 days (P<0.001)• Wound infection no difference• Medical complication 37% vs 56% (P=0.042)• Node resection no difference

LAP COLECTOMY SUMMARY

• Short term post operative advantages

• At least equivalent oncologically to open colectomy

• Long learning curve

• Increasing role in colon cancer surgery

• Jury still out for rectal cancer

COLONIC STENTS

• Treatment of malignant large bowel obstruction – Inserted by colonoscopy under endoscopic or fluoroscopic

control (or both)– Avoid emergency laparotomy with colostomy

• Best for left sided cancers – Right and transverse colon cancers can have resection and

anastomosis– Rectal cancers rarely obstruct (and stent migrates out)

• Two situations– Palliative – ‘Bridge’ to definitive surgery

COLONIC STENTS

COLONIC STENTS

COLONIC STENTS

COLONIC STENTS

COLONIC STENTSNo. patients

Guidance Technical success (%)

Clinical success (%)

Spinelli (1993) 13 E 92 85

Rey (1995) 12 E 92 92

Saida (1996) 15 E+F 80 80

Baron (1996) 25 E+F 92 84

Choo (1998) 20 E+F 90 75

DeGregorio (1998) 24 F 100 96

Diaz (1998) 12 F 100 100

Wholey (1998) 10 F 100 90

Mainar (1999) 71 F 90 90

Camunez (2000) 80 F 88 84

Long term results

• DeGregorio (1998)– 24 patients (Rectosigmoid tumours)– Stent occlusion in 1 (at 7/12) – new stent)– Stent migration in 2 (1 surgery, 1 new stent)– Faecal impaction in 2 (enemas)– 14 died unobstructed before 12 months– 7 had occlusive ingrowth of tumour at 1 year

• As palliative chemotherapy increases lifespan, palliative stenting may have a reduced role

TRANSANAL ENDOSCOPIC MICROSURGERY

TRANSANAL ENDOSCOPIC MICROSURGERY

TEM RESULTS

• Excellent results for benign disease– Low recurrence rate– Avoidance of major resection and

permanent or temporary stoma– Probably gold standard of care

• ? Role in malignant disease

TEM RESULTS

• Recurrence rate (A stage T1 and T2)– Mellegren 2000 28%– Floyd 2006 7.5% (T1 only)– Bregahol 2007 15%– Whithouse 2008 26%– Winde 1996 4.1% (T1 only)

• Options– Not for cancer– ? T1 only (or even sm1 only)– ? Immediate radical resection for T1 (sm2 or 3) and T2– ? Add radiotherapy

RADIOTHERAPY FOR RECTAL CANCER

• RT decreases local recurrence rates in advanced cases of rectal cancer (many RCT and meta-analyses)

• Pre operative vs post operative– Clear advantage in post op function to preop RT– Preop now thought to decrease local recurrence rate cf post op– 13% vs 22% (Frykholm et al DCR 1993)– 6% vs 13% (Sauer et al German Rectal Cancer Trial NEJM 2004)

• Short course– 25Gy over 5 days– Surgery soon afterwards

• Long course– 45Gy over 25 treatments and 5 weeks– Combined with 5FU based chemotherapy via bolus or infusion– Delay of 6-8 weeks before surgery

RADIOTHERAPY

• Indications– T3, T4 or N1– Low rectal cancers– Threatened margin (CRM)

• Short course as effective as long course, but less down sizing and less complete pathological response– Long course for large tumours requiring

shrinkage– May need defunctioning prior to treatment

CHEMOTHERAPY

• Not that long ago– Only one option– 5FU/folinic acid 6 cycles– 5 days on then 3 weeks off

• Now many more options– Significant improvement in prognosis– Colorectal cancer mortality/incidence ratio

• 1992 0.55 2005 0.32

• Complex and occasionally bewildering to the non-oncologist

CHEMOTHERAPY

• Massive subject

• No discussion of modern CRC management complete without

• Beyond the scope of this presentation

• Adjuvant therapy– All Stage C patients– High risk stage B patients

• Poorly differentiated• Large tumours• Perforated tumours• Extramural venous invasion• Young patients

• Neoadjuvant therapy (as part of long course radiotherapy)• Palliative chemotherapy for Stage D

CHEMOTHERAPY

• 5 fluorouracil/folinic acid– Bolus– Infusional

• Oxaliplatin• Irinotecan• Capecitabine (oral prodrug to 5FU)• Monoclonal antibodies

– Bevacizumab (anti angiogenesis)– Cetuximab (anti EGFR)