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1 Rectal Cancer Sophia L Fu, MD SUNY Downstate Medical Center, Brooklyn, NY September 10, 2009
2 History 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 for an abdomino-perineal resection on 8/4/09. PMH: depression PSH/ FHx: Diverting Ostomy SocHx: 1ppd x20yrs, no ETOH, no drug abuse Meds: Seroquel, Dilaudid, Percocet
3 Physical Examination VS / Gen: pleasant, in NAD HEENT: anicteric, no palpable nodes Chest: clear Cv: nl S1 S2, RRR, no m/r/g Abd: soft, NT, ND, +BS Ext: no edema Rect: painful w/ulceration
4 Rectal CA CT Scan
5 Laboratory work-up MCH 26.8 RDW TP 6.8 Alb 3.9 Tbili 0.3 AST 11 ALT AP
6 Operative Report 8/4/2009 Insertion of Ureteral Stents Exploratory laparotomy, extended Left Hemicolectomy, Abdominoperineal Resection Resection of rectovaginal fistula, TAH/BSO & partial vulvectomy Omental flap, TRAM flap, V-Y flap Time IVF PRBCS EBL UO 4.5 hrs 6.2 L 2 Units 500 ml 1200 ml
7 Pathology T4, N0, M0 Colon, rectum, vagina, anus 3/0 perirectal LN neg Adenocarcinoma, moderate- Lymphovascular poorly differentiated invasion neg by CD31 6x4cm, invading pararectal fat stain Post vaginal wall involved by Uterus w/cervix tumor Deep resection margin involved by tumor Perineural invasion Atrophic endometrium No tumor Fallopian tubes/ovaries No tumor
8 Hospital Course POD#4 Post-op fever w/u neg POD#6 Reg diet POD#9 Continued fever spike CT Abd/pelvis Perineal wound necrotic flap plastics consult POD#12 Wound Cx MRSA & pseudomonas POD#14 Wound debridement POD#19 Awaiting VAC Absconded Wound care
9
10 Rectal Cancer
11 Introduction to Colorectal CA Incidence 41,390 cases Declined 1.8% per yr Improved screening & polyp removal Leading cancer death 2 nd in men 3 rd in women Greatest risk factor: Age Median age 71 Polyposis syndromes High risk of colorectal CA <5% of colorectal CA PMH or FHx colorectal CA Inflammatory bowel dz
12 Rectal Anatomy Autonomic Nerve Preservation Hypogastric nerve form ventral nerve roots T12 to L3 & Sympathetic nerve innervation Parasympathetic innervation from S2 to S4 ventral nerve roots
13 Presentation Assess phys l condition Need for neoadjuvant chemo Need for local excision Pre-op sphincter & sexual fxn Pelvic pain: sacral involvement Obstipation or constipation: bulky obstructing lesion Predisposing conditions
14 Diagnosis Digital Rectal Exam Ant vs post Mobile or fixed Ulceration Size Extent of circumferential involvement Relation to sphincter Rigid proctoscopy Prox vs distal levels Relation ea to osphincter ce Vagina/prostate Invasive CA Dx by Bx Colonoscopy 3-5% have synchronous lesions
15 Pre-operative Evaluation CEA levels CXR >5ng/mL have worse Pulmonary mets prognosis compared w/stage-matched pts Elevated pre-op levels that do not normalize may imply distant dz Identifies recurrent dz CT Abd/pelvis Distant mets (75-87% sens) Tumor-related complications Regional tumor extension Regional lymphatic mets (45-73% sens)
16 Endorectal Ultrasound (ERUS) Depth of invasion (T stage) Accuracy 80-95% CT: 65-75% vs MRI: 75-85% Nodal Involvement (N) Accuracy 70-75% (>5mm) CT:55-65% vs MRI 60-65% FNA Bx
17 AJCC Rectal Cancer Staging g Primary tumor (T) Tx Primary Tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ: intraepithelial/invasion of lamina propria T1 Tumor invades submucosa T2 tumor invades into muscularis propria T3 Tumor invades thru muscularis propria into subserosa or pericolic/perirectal tissues T4 tumor invades other organs/structures &/or visceral peritoneum
18 AJCC Rectal Cancer Staging Regional llymph nodes (N) Distant tmetastasis t (M) Nx cannot be assessed N0 No regional node metastasis N1 Regional node metastasis 1-3 Mx cannot be assessed M0 No distant metastasis M1 Distant metastasis present N2 Regional node metastasis >4 Stage T N M % of pts 0 Tis N0 M0 I T1 T2 N0 N0 M0 M0 IIA T3 N0 M0 25 IIB T4 N0 M0 IIIA T1-2 N1 M0 26 IIIB T3-4 N1 M0 IIIC Any T N2 M0 IV Any T Any N M
19 Neoadjuvant Therapy Distal rectal CA Sphincter salvage Converts APR to LAR Large, locally invasive or node + Downstaging Improved tumor resectability Higher sphincter-salvage rates Lower toxicity w/neoadjuvant Tx
20 Preoperative Radiation Therapy Swedish 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) GI post-op issues: 2-4x > 1x Folkesson J et al. J Clin Oncol. 2005; 23(24):
21 Preoperative Radiation Therapy Med 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% Dz-free survival: 80% vs 75% Overall survival: 81% vs 79% PRE-OP XRT associated w/better local control Sebag-Montefiore D et al. Lancet Mar 7; 373(9666):
22 Pre-operative Chemoradiation European Organization for Research & Tx of Cancer Randomized ctrl d: T3 or T4 rectal cancers 4 arms Pre-op XRT vs pre-op chemoradiation +/- 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:
23 Pre-operative Chemoradiation German Rectal Cancer Group Randomized ctrl d: 823 T3 or T4 or node-pos dz pts Pre-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:
24 Neoadjuvant Tx Summary Surgical wks post-neoadjuvant Tx Maximal response to Tx Allow pt to recover Pre-op staging modalities unable to distinguish btwn Tx-related fibrosis vs residual tumor % pts w/complete path response to primary tumor still have lymph node involvement Therefore, pt should continue w/definitive surgical Tx
25 How to determine which procedure?
26 Surgical Therapy Local Excision Curative intent Early-stage sage Distal rectal CA Limited to submucosa T1N0M0 Transanal Transsphincteric Transcoccygeal (Kraske) Radical Rectal Surgery High T1 rectal tumor Muscularis s propria invasion (T2N0M0) Mdi Medically fit pts Pre-op chemo Locally advanced dz T3/T4 &/or N1
27 Local Transanal Excision Full-thickness resection of primary rectal lca w/1- cm margin Reserved for those w/low risk ikof nodal dlmetastases t T1: 0% to 12% risk Highly selected T1 rectal T2: 12% to 28% CA w/min morbidity T3:36to79% 36 Criteria for Transanal Excision of Rectal Cancers (T1N0M0) Should be w/i 8-10 cm of anal verge Less than 4cm wide Involve less than 1/3 circumference rectum No lymphatic/vascular or perineural invasion Well or moderately differentiated Addition of neoadjuvant chemoxrt allows T2 resection in selected pts
28 Transanal Excision Post: lithotomy Ant: prone jackknife Lesion w/i 6-8cm Excise full thickness to perirectal fat in proper orientation for margins dentate line Circumferential block w/local anesthetic w/epi
29 Transanal Endoscopic Microsurgery (TEM) Local excision of rectal cancers in upper & middle rectum Specialized long TEM scope allows 10cm anteriorly 15cm laterally 18cm posteriorly operating 40-mm endoscope to allow fullthickness rectal resection
30 Radical Resection Circumferential margin assessed by serial slicing & evaluation of tumor & mesorectum <2mm assoc w/higher h local l recurrence, distant t mets, & death Distal margins <2cm are not associated w/higher local recurrence Distal spread >1cm of mucosal edge = 10%
31 Total Mesorectal Excision Gold standard for surgical Tx of middle & lower 1/3 rectal cancers Excising tumor en bloc w/blood & lymphatic supply
32 Total Mesorectal Excision Locoregional recurrence in rectal cancer from incomplete clearance of rectal mesentery Local recurrence: 6.5% Preservation of fxn of autonomic nerves & decrease post-op GU dysfxn
33 IMA ligation
34 Posterior Dissection in the avascular plane
35 Autonomic nerves and lateral vascular stalks
36 Anterior Anatomy
37 Anterior Dissection in Female Patient
38 Double-stapled, end-to to-end anastomosis
39 Pelvic Exenteration & Sacrectomy Indications limited by relatively high morbidity & mortality assoc w/procedure. Onocologic & palliative benefits in locally advanced or recurrent rectal cancer. 5-yr survival rates for locally ll recurrent rectal cancer: 20-30% Primary advanced rectal ca, is less often amenable to pelvic exenteration
40 Pelvic Exenteration & Sacrectomy Involve resection of anus, rectum, bladder, ureters, & pelvic reproductive organs Fecal & urinary diversion may be needed Contraindications Carcinomatosis Liver metastases Pelvic sidewall invasion Bilateral ureteral obstruction Aortic node metastases
41 Metastatic Disease Recurrence after local resection Salvage surgery if local dz only Radical surgery w/adjuvant chemo 50-88% 5-yr dz-free survival Salvage surgery in 49 pts 55% extended pelvic dissection 58% recurred or died of dz w/i 33mo Resection of isolated metastatic dz in liver or lung shows long-term survival benefit 5-yr dz-specific survival 53% Weiser MR et al. Dis Colon Rectum. 2005; 48: 1169.
42 Adjuvant Therapy Surgery remains cornerstone for curative approach Significant tendency for local failure after potentially curative 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
43 Role of Adjuvant ChemoXRT ChemoXRT 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/radiation 225 mg/m 2 per day x5wks: 53% survival (4yrs) 500 mg/m 2 days 1-3 & days 36-9: 63% survival (4yrs) Addition of Leucovorin or Levamisole does not increase efficacy of 5-FU in rectal CA as it does in colon CA
44 Surveillance & Follow-up History & Physical Examination Q3 mo x2 Years & then Q6 mo for total of 5 years 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 bc of obstruction, must be done in 3-6mo. For pts w/rectal cancer who did 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 postmetastectomy for synchronous liver disease, the recommendation for CT scans may be increased to Q3-6mo.
45 Current Recommendations Stage III (node +) Stage II (node -) Adjuvant chemo x6mo FOLFOX-4, capectibaine or IV 5- FU/LV as alternatives FOLFOX-4 most convincing Absolute benefit real but small Small power: controversial ove FOLFOX-4 or 5-FU if path has high h risk features (poor diff, lymph or vasc invasion, bowel obstruction, inadequate staging, perforation, direct extension into other organs)
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