1

RECTAL CARCINOMARECTAL CARCINOMA

ELSHAMI ELAMIN, MD

Central Care Cancer Center

Newton, KS-USA

NextPrevious

2

RISK FACTORSRISK FACTORS

Dietary factors• Fat• ? Fiber• ? Calcium• ? Vitamins (E, -carotene)

Aspirin/NSAIDs (Cox inhibitors)• Sulindac reduces polyps in FAP pts• Aspirin lower risk of CRC

NextPrevious

3

RISK FACTORSRISK FACTORS

Genetic Factors– FAP(APC gene = Tumor suppressor gene)

• 1-2% of CRC• Invasive cancer occurs at ~ 42Y

– HNPCC (MMR mutations)• Hx of > 3 family members involving 2

generations with one diagnosed before age 50• 4-6% incidence• Rt-sided cancer• Caused by defective DNA mismatch repair genes

NextPrevious

4

Steps for Colorectal CarcinogenesisSteps for Colorectal Carcinogenesis

1- Mutation at MCC and APC genes

2- K-ras oncogene activates adenoma to carcinoma

3- Mutation of p53 tumor suppressor gene

NextPrevious

5

SCREENINGSCREENINGPatients with average risk

• Asymptomatic• >50Y• No colorectal risk factors

FOBT (33% reduction in mortality)Flexible sig (60-80% reduction in mortality)Double-contrast BEColonoscopy (Gold standard)

NextPrevious

6

Patients with increased RiskPatients with increased Risk

First-degree relative with CRC or adenomatous polyps

FAPF.H. of HNPCCAdenomatous polypsCRCIBD

NextPrevious

7

Hereditary CRC syndromesHereditary CRC syndromesScreening and ManagementScreening and Management

FAP– Genetic counseling/gene testing

• Is cost-effective

– Genetic mutation not identified:• Flex sig at puberty and annualy

• Colonoscopy if +ve sig

– +ve FAP• Total colectomy

NextPrevious

8

HNPCC (Lynch syndrome)HNPCC (Lynch syndrome)

Lynch I:– No associated cancers

Lynch II:– Associated with ovarian, uterine cancers

Genetic testing– Difficult due to multiple mutations

• MLH1, MSH2 mutations

Screening begin at 20Y and every 1-2YGenetically +ve: Consider colectomy/TAH/BSO

NextPrevious

9

Work-upWork-upLaboratory:

– LFTs– CBC, Iron profile– CEA

Preoperative CT scan– Colon cancer: Adjacent organ invasion/Liver met– Rectal: Adjacent organ invasion/LN spread

• For preop RT

NextPrevious

10

MRIMRI

Bowel wall penetration– MRI: 64%, CT: 62%

Sensitivity for LN met: 15-40%Endorectal surface coil MRI for N1

– 72% specificity

NextPrevious

11

Transrectal USTransrectal US

Evaluation for preop cheop/RT• Only 83-88% specific in separating T-T2 from T3-T4

LN specificity• 28% for 5mm LN

• 62% for 7mm

NextPrevious

12

CEA scanCEA scan

Coupled with standard CT

• Can predict preop respectability

NextPrevious

13

PET ScanPET ScanStagingRestaging

– 91% sensitivity, ~ 100% specificity for pelvic disease (CT: 52%, 80%)

– 95% sensitivity for liver disease (CT 74%)

NextPrevious

14

StagingStagingDukes’ classification

– Based on depth of invasion and LN• A: Limited to bowel wall

• B: Extrarectal tissues

• C: LN +

Modified Dukes’ (Astler-Coller system)– C1 and C2

NextPrevious

15

TNMTNMStage I: T1 (invade submucosa) A

T2 (invade muscul propria) B1Stage II: T3 (invade through musc propria B2

into subserosa or nonperit. Tissue)

T4 (perforate ves perit or B3 invade adjacent structure)

Stage III: N1 (1-3 pericolic/rectal) N2 (> 4) C

N3 (along vascular trunk)

Stage IV: M1

NextPrevious

16

Prognostic FactorsPrognostic FactorsAdjacent tissue or vascular invasionNodal status

• Micromets (<5mm) same as enlarged LN

• 4 LN vs >4

? Cellular pathologic factors• S-phase, ploidy

Liver mets• Normal LFTs: 18 month med S

• Elevated Bil: 6 wks med S

NextPrevious

17

Prognostic FactorsPrognostic FactorsCEA

• Weak prognostic factor

• Persistant CEA elevation = Residual dz

• May increase initially during adjuvant

Not prognostic factors• Age, Sex, Tumor size

NextPrevious

18

Rectal CaRectal CaSurgical TreatmentSurgical Treatment

Abdominal Perineal Resection (APR)• Permanent Colostomy

Sphincter Preservation

NextPrevious

19

APRAPRBased on:

• Rectal cancer spread via lymphatic pathways in proximal, lateral and distal direction

Decreases local recurrenceImprove survivalPermanent colostomy

NextPrevious

20

APRAPRCandidates

• Primary sphincter dysfunction

• Tumor invading anal canal

• High risk for local recurrence• Bulky disease

• Poorly differentiated involving lower 1/3

• Direct extension into adjacent organs

NextPrevious

21

Total Mesorectal Excision Total Mesorectal Excision (TME)(TME)

Tumor spread into adjacent mesorectum>2cm distal extension from the margin carries

poor prognosisDecreases local recurrenceImprove survivalStandard for mid and lower rectal cancersPreserves pelvic autonomic nerve function

22

Surgical Options for Surgical Options for Sphincter PreservationSphincter Preservation

NextPrevious

23

Local ExcisionLocal ExcisionLower 1/3 early rectal cancer (T1)< 4 cm in diameterMobile lesionInvolve < 1/4 of circumference of bowelModerate to well differentiated

• From 2 prospective Trials• T1 : Local excision alone

• T2 : Local excision + CT/RT

NextPrevious

24

Local Excision with RTLocal Excision with RTIndications

– T2– Lymphatic/vascular invasion– Poor histology– Positive margin– Fragmented resection

NextPrevious

25

Endocavitary RTEndocavitary RTSelection criteria

• Distal lesion

• No disease beyond bowel wall

• No major extension to anal canal

• T < 3x5 cm

Local failure• 5-20%

• Salvage radical surgery

NextPrevious

26

Low Anterior Resection Low Anterior Resection (LAR)(LAR)

1- Bowel divided at 5cm above rectal tumor

2- Ligation of superior hemorrhoidal artery

3- Total Mesorectal Excision (TME) for mid/lower rectal tumors

4- 11/2 - 2cm distal margin

5- Colo-Rectal anastomosis

NextPrevious

27

Colonic J-PouchColonic J-Pouch

For low rectal cancer

To prevent incontinence/urgency

NextPrevious

28

APR vs Sphincter Sparing Resections APR vs Sphincter Sparing Resections (SSR) in Mid-rectal cancers(SSR) in Mid-rectal cancers

5 Y S %

APR SSR

Mayo et al 69 72

Patel et al 56 64

Jones/Thomson 52 67

Williams/Johnston 62 74

• Local recurrence: APR 8%, SSR 11% (not significant)

29

ADJUVANT THERAPYADJUVANT THERAPY

NextPrevious

30

Rectal CancerRectal CancerIncidence of local failure after resection

– T1, T2N0: <10%– T3N0: 15-30%– T3N1: 35-50%– T3-T4N1: 60%

• No successful salvage procedure

NextPrevious

31

Pre-Operative RTPre-Operative RTImproves local control (Several studies)

– Improves OS (Only one study)

Downside– Overtreatment of T1, T2

• Use Transrectal US

– Treatment of patient with hepatic mets• Use spiral CT

NextPrevious

32

Locally Advanced Rectal CancerLocally Advanced Rectal Cancer

PreOp external RT + IntraOp RT• 67%5Y local control, 57% DFS

PreOp RT or Chemo/RT• 70-85% resectability and sphincter sparing surgery

NextPrevious

33

Locally Recurrent DiseaseLocally Recurrent DiseaseTreatment options depend on

– Local extent• Isolated suture line recurrence after LAR

– APR + Chemo/RT if no prior RT

• Local recurrence without prior RT

– PreOp chemo/RT, Surgery + IORT

• Poor long-term DFS even with complete resection

– Symptoms– Distant mets– Prior adjuvant therapy

NextPrevious

34

CEACEA43-89% Sensitivity, 70-90% specificityPreOp elevation predicts worse prognosis

– Not useful in determining the need for adjuvant

Elevation correlates with Dukes’ stagePersistent 1-month postOp elevation predicts

metsMonitor CEA q2-3 moths during chemoModest elevation

• Fatty liver infiltration, hepatitis, pneumonia, GE

35

Systemic ChemotherapySystemic Chemotherapy

NextPrevious

36

5-FU5-FU 5 days IVP regimen:

• Mucositis, diarrhea, neutropenia

Wkly IVP regimen:• Diarrhea

CI regimen/Capecitabine:• Hand-foot syndrome, mucositis

• Diarrhea or neutropenia

High dose regimen 24-48hrs• Altered MS, angina-like chest pain

NextPrevious

Oxaliplatin = IrinotecanOxaliplatin = Irinotecan

FOLFOXFOLFIRIXELOXXELIRI

• AVASTIN/ZALTRAP• ERBITUX/VECTIBIX• REGORAFENIB

37

NextPrevious

38

Regional TherapyRegional Therapy(Liver Mets)(Liver Mets)

HAI of FUDR via an implanted pump• Addition of dexamthazone reduces sclerosing

cholangitis and enhances RR

Chemoembolization• 3mg/ml Adria + 3mg/ml MC + 10mg/ml CDDP with

bovine collagen

• Postembolization syndrome (fever, RtUQ pain, N/V, lethargy, hematologic toxicity)

Resection