Rectal CancerRectal CancerRectal CancerRectal Cancer

Sophia L Fu, MD

SUNY Downstate Medical Center, Brooklyn, NY

September 10, 2009September 10, 2009

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HistoryHistoryRectal CARectal CA

40 yo female w/rectal cancer treated w/chemo-XRT

at Brookdale 11/08 who p/w rectal-vaginal fistula in

6/09 that underwent diverting ostomy. She then came g y

for an abdomino-perineal resection on 8/4/09.

PMH: depression

PSH/ FHx: Diverting OstomyPSH/ FHx: Diverting Ostomy

SocHx: 1ppd x20yrs, no ETOH, no drug abuse

Meds: Seroquel, Dilaudid, Percocet

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Physical ExaminationPhysical ExaminationRectal CARectal CA

VS 98.2 122/86 90 18

Gen: pleasant, in NAD

HEENT: anicteric no palpable nodesHEENT: anicteric, no palpable nodes

Chest: clear

Cv: nl S1 S2, RRR, no m/r/g

Abd: soft, NT, ND, +BS

Ext: no edemaExt: no edema

Rect: painful w/ulceration

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CT ScanCT ScanRectal CARectal CA

CT ScanCT Scanwww.downstatesurgery.org

Laboratory workLaboratory work--upupRectal CARectal CA

yy pp

9 6142

4.6

107

22

10

0.774 8.57

9.0

28.0603

9.6

MCH 26.8RDW16.2

TP 6.8Alb 3 9

AST 11ALT 7

12.91 0Alb 3.9

Tbili 0.3ALT 7AP 69 34.9

1.0

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Operative Report Operative Report –– 8/4/20098/4/2009Rectal CARectal CA

p pp pInsertion of Ureteral Stents

Exploratory laparotomy, extended Left Hemicolectomy,

Abdominoperineal ResectionAbdominoperineal Resection

Resection of rectovaginal fistula, TAH/BSO & partial

vulvectomy

Omental flap TRAM flap V Y flapOmental flap, TRAM flap, V-Y flap

Time IVF PRBCS EBL UO4.5 hrs 6.2 L 2 Units 500 mL 1200 mL

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Pathology Pathology –– T4, N0, M0T4, N0, M0Rectal CARectal CA

gygy , ,, ,3/0 perirectal LN neg

Lymphovascular

Colon, rectum, vagina, anus

Ad i d Lymphovascular

invasion neg by CD31 Adenocarcinoma, moderate-

poorly differentiatedstain

Uterus w/cervix6x4cm, invading pararectal fat

Post vaginal wall involved by

Atrophic endometrium

Post vaginal wall involved by

tumor

No tumor

Fallopian tubes/ovaries

Deep resection margin

involved by tumor p

No tumorPerineural invasion

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Hospital CourseHospital CourseRectal CARectal CA

Hospital CourseHospital CoursePOD#4 POD#12

Post-op fever w/u neg

POD#6

Wound Cx – MRSA &

pseudomonasPOD#6

Reg diet POD#14

POD#9

Continued fever spike

Wound debridement

POD#19Continued fever spike

CT Abd/pelvis Awaiting VAC

Perineal wound necrotic

flap – plastics consult

Absconded

Wound care

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Rectal CancerRectal Cancer

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Introduction to Colorectal CAIntroduction to Colorectal CARectal CARectal CA

Introduction to Colorectal CAIntroduction to Colorectal CA

Incidence 41 390 cases Greatest risk factor:Incidence 41,390 cases

Declined 1.8% per yr

Greatest risk factor:

Age

Improved screening & polyp

removal

Median age 71

Polyposis syndromes

Leading cancer death

2nd in men

High risk of colorectal CA

<5% of colorectal CA

3rd in womenPMH or FHx colorectal CA

Inflammatory bowel dz

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Rectal AnatomyRectal AnatomyRectal CARectal CA

Rectal AnatomyRectal AnatomyAutonomic Nerve

Preservation

Hypogastric nerve form yp g

ventral nerve roots T12 to

L3 & Sympathetic nerveL3 & Sympathetic nerve

innervation

Parasympathetic

innervation from S2 to S4

ventral nerve roots

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PresentationPresentationRectal CARectal CA

Assess phys’l condition Pelvic pain: sacral

Need for neoadjuvant

chemo

involvement

Obstipation orchemo

Need for local excision

Obstipation or

constipation: bulky

Pre-op sphincter &

sexual fxn

obstructing lesion

sexual fxn

Predisposing conditions

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DiagnosisDiagnosisRectal CARectal CA

Digital Rectal Exam Rigid proctoscopy

Ant vs post

Mobile or fixed

Prox vs distal levels

Relation to sphincterob e o ed

Ulceration

e a o o sp c e

Vagina/prostate

Size

Extent of circumferential

Invasive CA Dx by Bx

Colonoscopyinvolvement

Relation to sphincter

py

3-5% have synchronous

l iRelation to sphincter lesions

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PrePre--operative Evaluationoperative EvaluationRectal CARectal CA

CEA levels CXRCEA levels

>5ng/mL have worse

CXR

Pulmonary mets

prognosis compared

w/stage-matched ptsCT Abd/pelvis

Distant mets (75 87% sens)Elevated pre-op levels that

do not normalize may imply

Distant mets (75-87% sens)

Tumor-related complicationsdo not normalize may imply

distant dzRegional tumor extension

Regional lymphatic metsIdentifies recurrent dz

Regional lymphatic mets

(45-73% sens)

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EndorectalEndorectal Ultrasound (ERUS)Ultrasound (ERUS)Rectal CARectal CA

EndorectalEndorectal Ultrasound (ERUS)Ultrasound (ERUS)Depth of invasion (T stage)

Accuracy 80-95%

CT: 65-75% vs MRI: 75-85%

Nodal Involvement (N)Nodal Involvement (N)

Accuracy 70-75% (>5mm)y ( )

CT:55-65% vs MRI 60-65%

FNA Bx

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AJCC Rectal Cancer StagingAJCC Rectal Cancer StagingRectal CARectal CA

g gg gPrimary tumor (T)

Tx Primary Tumor cannot be assessed

T0 No evidence of primary tumor

Tis Carcinoma in situ: intraepithelial/invasion of lamina propria

T1 T i d bT1 Tumor invades submucosa

T2 tumor invades into muscularis propria

T3 Tumor invades thru muscularis propria into subserosa or

pericolic/perirectal tissuespericolic/perirectal tissues

T4 tumor invades other organs/structures &/or visceral peritoneum

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AJCC Rectal Cancer StagingAJCC Rectal Cancer StagingR i l l h d (N) Di t t t t i (M)

Rectal CARectal CA

Regional lymph nodes (N)

Nx cannot be assessed

0 i l d i

Distant metastasis (M)

Mx cannot be assessed

0 di iN0 No regional node metastasis

N1 Regional node metastasis 1-3

N2 Regional node metastasis >4

M0 No distant metastasis

M1 Distant metastasis present

N2 Regional node metastasis >4Stage T N M % of pts

0 Tis N0 M0I T1

T2N0N0

M0M0

34

IIA T3 N0 M0 25IIB T4 N0 M0IIIA T1-2 N1 M0 26IIIB T3-4 N1 M0IIIC Any T N2 M0IV Any T Any N M1 15

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NeoadjuvantNeoadjuvant TherapyTherapyRectal CARectal CA

jj pypyDistal rectal CA

Sphincter salvage

Converts APR to LARConverts APR to LAR

Large, locally invasive or node +

Downstaging

Improved tumor resectabilityImproved tumor resectability

Higher sphincter-salvage rates

Lower toxicity w/neoadjuvant Tx

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Preoperative Radiation TherapyPreoperative Radiation TherapyRectal CARectal CA

p pyp pySwedish Rectal Cancer Trial

Randomized Ctrl’d: 1168 pts <80 yo w/resectable rectal cancer

Short-course XRT (25Gy)/surgery vs surgery alone

Local ctrl: 89% vs 73% (P<.001)

Overall survival: 58% vs 48% (P=0.008)Overall survival: 58% vs 48% (P 0.008)

GI post-op issues: 2-4x > 1x

Folkesson J et al. J Clin Oncol. 2005; 23(24): 5644-50.

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Preoperative Radiation TherapyPreoperative Radiation TherapyRectal CARectal CA

p pyp pyMed’l Research Council/Nat’l Cancer Institute of Canada

Randomized ctrl’d: 1350 Stage I to III pts

Similar design to Swedish study

Post-op chemo: positive circumferential margins &/or + nodes

Local ctrl: 5% vs 11%Local ctrl: 5% vs 11%

Dz-free survival: 80% vs 75%

O ll i l 81% 79%Overall survival: 81% vs 79%

PRE-OP XRT associated w/better local control

Sebag-Montefiore D et al. Lancet. 2009 Mar 7; 373(9666): 811-20.

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PrePre--operative operative ChemoradiationChemoradiationRectal CARectal CA

ppEuropean Organization for Research & Tx of Cancer

Randomized ctrl’d: 22921 T3 or T4 rectal cancers

4 arms

Pre-op XRT vs pre-op chemoradiation

+/- postop chemotherapy (5-FU & Leucovorin)/ postop chemotherapy (5 FU & Leucovorin)

Overall Survival: 65.2% for all groups

Local recurrence at 5yr: 8.7%, 9.6%, 7.6%

For chemo pre, post, & both (P=.002)

Worse local recurrence in no chemotherapy group: 17.1%Bosset JF et al. New Engl J Med. 2006; 355: 1114-23.

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PrePre--operative operative ChemoradiationChemoradiationRectal CARectal CA

ppGerman Rectal Cancer Group

Randomized ctrl’d: 823 T3 or T4 or node-pos dz pts

P t h di tiPre-op vs post-op chemoradiation

Overall 5yr survival: 75% vs 74% (P=0.80)

Local recurrence: 6% vs 13% (P=0.006)

Acute toxic effects: 27% vs 40% (P=0.001)

Long-term toxic effects: 14% vs 24% (P=0.01)

Sauer R et al. New Engl J Med. 2004; 351: 1731-40.

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NeoadjuvantNeoadjuvant TxTx SummarySummaryRectal CARectal CA

jj yySurgical resection @6-8 wks post-neoadjuvant Tx

Maximal response to Tx

All t tAllow pt to recover

Pre-op staging modalities unable to distinguish btwn

Tx-related fibrosis vs residual tumor

1.8-16% pts w/complete path response to primary

tumor still have lymph node involvement

Therefore, pt should continue w/definitive surgical Tx

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How to determine which How to determine which d ?d ?procedure?procedure?

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Surgical TherapySurgical TherapyRectal CARectal CA

Local Excision Radical Rectal Surgery

Curative intent

Early-stage

High T1 rectal tumor

Muscularis propria a y s age

Distal rectal CA

uscu a s p op a

invasion (T2N0M0)

M di ll fiLimited to submucosa

T1N0M0

Medically fit pts

Pre-op chemoTransanal

TranssphinctericLocally advanced dz

T3/T4 &/ N1Transsphincteric

Transcoccygeal (Kraske)T3/T4 &/or N1

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Local Local TransanalTransanal ExcisionExcisionRectal CARectal CA

Full-thickness resection

f i t l CA /1

Reserved for those w/low

i k f d l t tof primary rectal CA w/1-

cm margin

risk of nodal metastases

T1: 0% to 12% risk

Highly selected T1 rectal

/ i bidi

T2: 12% to 28%

T3: 36 to 79%CA w/min morbidity T3: 36 to 79%

Addition of neoadjuvant Criteria for Transanal Excision of Rectal Cancers (T1N0M0)

chemoXRT allows T2

resection in selected pts

Should be w/i 8-10 cm of anal vergeLess than 4cm wideInvolve less than 1/3 circumference rectum resection in selected ptsInvolve less than 1/3 circumference rectumNo lymphatic/vascular or perineural invasionWell or moderately differentiated

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TransanalTransanal ExcisionExcisionRectal CARectal CA

Post: lithotomy Excise full thickness to

Ant: prone jackknife perirectal fat in proper

orientation for marginsLesion w/i 6-8cm

dentate line

orientation for margins

dentate line

Circumferential block

w/local anesthetic

w/epi

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TransanalTransanal Endoscopic Endoscopic Mi (TEM)Mi (TEM)

Rectal CARectal CA

Microsurgery (TEM)Microsurgery (TEM)Local excision of rectal TEM scope allowsLocal excision of rectal

cancers in upper &

TEM scope allows

10cm anteriorly

middle rectum 15cm laterally

Specialized long

operating 40-mm

18cm posteriorly

operating 40-mm

endoscope to allow full-

thickness rectal resection

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Radical ResectionRadical ResectionRectal CARectal CA

Circumferential margin assessed by serial

slicing & evaluation of tumor & mesorectum

<2 /hi h l l di t t<2mm assoc w/higher local recurrence, distant

mets, & death

Distal margins <2cm are not associated

w/higher local recurrence

Di t l d >1 f l d 10%Distal spread >1cm of mucosal edge = 10%

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TotalTotal MesorectalMesorectal ExcisionExcisionRectal CARectal CA

Total Total MesorectalMesorectal ExcisionExcisionGold standard for

surgical Tx of middle &

lo er 1/3 rectal cancerslower 1/3 rectal cancers

Excising tumor en bloc

w/blood & lymphatic

lsupply

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TotalTotal MesorectalMesorectal ExcisionExcisionRectal CARectal CA

Total Total MesorectalMesorectal ExcisionExcisionLocoregional recurrence in

rectal cancer from

incomplete clearance ofincomplete clearance of

rectal mesentery

Local recurrence: 6.5%

Preservation of fxn of

autonomic nerves &

decrease post-op GU dysfxn

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IMA ligationIMA ligationRectal CARectal CA

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Posterior Dissection in the Posterior Dissection in the avascularavascularRectal CARectal CA

planeplane

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Autonomic nerves and lateral Autonomic nerves and lateral Rectal CARectal CA

vascular stalksvascular stalks

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Anterior AnatomyAnterior AnatomyRectal CARectal CA

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Anterior Dissection in Female Anterior Dissection in Female Rectal CARectal CA

PatientPatient

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DoubleDouble--stapled, endstapled, end--toto--end end Rectal CARectal CA

anastomosisanastomosis

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Pelvic Pelvic ExenterationExenteration & & SacrectomySacrectomyRectal CARectal CA

yyIndications limited by relatively high morbidity &

mortality assoc w/procedure.

Onocologic & palliative benefits in locally advancedOnocologic & palliative benefits in locally advanced

or recurrent rectal cancer.

5-yr survival rates for

l ll t t l

Primary advanced rectal

i l flocally recurrent rectal

cancer: 20-30%

ca, is less often

amenable to pelvic

exenteration

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Pelvic Pelvic ExenterationExenteration & & SacrectomySacrectomyRectal CARectal CA

yyInvolve resection of anus, rectum, bladder, ureters, &

pelvic reproductive organs

Fecal & urinary diversion may be neededFecal & urinary diversion may be needed

Contraindications

Carcinomatosis Bilateral ureteral

b iLiver metastases

Pelvic sidewall invasion

obstruction

Aortic node metastasesPelvic sidewall invasion

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Metastatic DiseaseMetastatic DiseaseRectal CARectal CA

Recurrence after local resection Resection of Salvage surgery if local dz only

Radical surgery w/adjuvant chemoisolated

metastatic d inad ca su ge y w/adjuva c e o

50-88% 5-yr dz-free survivalmetastatic dz in

liver or lung Salvage surgery in 49 pts

55% extended pelvic dissection

shows long-term

survival benefit55% extended pelvic dissection

58% recurred or died of dz w/i 33mo

survival benefit

5-yr dz-specific survival 53%Weiser MR et al. Dis Colon Rectum. 2005; 48: 1169.

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Adjuvant TherapyAdjuvant TherapyRectal CARectal CA

j pyj pySurgery remains cornerstone for curative approach

Significant tendency for local failure after potentially

ti ticurative resection

Salvage surgical procedures are technically difficult &

often unsuccessful

Improve locoregional ctrl

Lower risk of systemic dz

5-FU based Tx to all pts who received neoadjuvant Tx

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Role of AdjuvantRole of Adjuvant ChemoXRTChemoXRTRectal CARectal CA

Role of Adjuvant Role of Adjuvant ChemoXRTChemoXRTChemoXRT superior to surgery alone or XRT

postop: Recommended for ≥ T3 or node positive

Reduced risk of local failure, distant failure, & death

Continuous infusion of 5 FU w/radiationContinuous infusion of 5-FU w/radiation

225 mg/m2 per day x5wks: 53% survival (4yrs)

500 mg/m2 days 1-3 & days 36-9: 63% survival (4yrs)

Addition of Leucovorin or Levamisole does not increaseAddition of Leucovorin or Levamisole does not increase

efficacy of 5-FU in rectal CA as it does in colon CA

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Surveillance & FollowSurveillance & Follow--upupRectal CARectal CA

Surveillance & FollowSurveillance & Follow upupHistory & Physical E amination

Q3 mo x2 Years & then Q6 mo for total of 5 yearsExamination

CEA Q3mo x2yrs & then Q6mo for 5 yrs for lesions >T2

Colonoscopy Perform in 1 yr. If abnormal, repeat in 1 yr. If no polyps found, repeat Q2-3yrs. If a pre-op colonoscopy could not be performed bcof obstruction, must be done in 3-6mo. For pts w/rectal cancer who did not receive pelvic radiation alt4ernatives may include adid not receive pelvic radiation, alt4ernatives may include a flexible sigmoidoscopy Q6mo x5yrs.

CT scan May be considered annually for people at high risk of recurrence as defined by poorly differentiated histologic grade & tumors w/perineural or venous invasion. If the patient is postmetastectomyfor synchronous liver disease the recommendation for CT scansfor synchronous liver disease, the recommendation for CT scans may be increased to Q3-6mo.

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Current RecommendationsCurrent RecommendationsRectal CARectal CA

Current RecommendationsCurrent RecommendationsStage III (node +) Stage II (node -)

Adjuvant chemo x6mo

FOLFOX-4

Absolute benefit real but small

Small power: controversialFOLFOX-4,

capectibaine or IV 5-

FU/LV l i

S a powe : co ove s a

FOLFOX-4 or 5-FU if path has

hi h i k f ( diffFU/LV as alternatives

FOLFOX-4 most

high risk features (poor diff,

lymph or vasc invasion, bowel

convincing obstruction, inadequate staging,

perforation, direct extension

into other organs)

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