What is the Preferable Treatment Option for T1/T2

Low Rectal Cancer?

What is the Preferable Treatment Option for T1/T2

Low Rectal Cancer?

Christopher H. Crane, M.D.Program Director, GI SectionProgram Director, GI Section

Department of Radiation OncologyDepartment of Radiation Oncology

Christopher H. Crane, M.D.Program Director, GI SectionProgram Director, GI Section

Department of Radiation OncologyDepartment of Radiation Oncology

No Disclosures

Complications of Radical Rectal Surgery

• Permanently altered bowel function– Often colostomy

• Urinary dysfunction from 7-68%• Impotence 15-100%• Retrograde ejaculation 3-35%

*RESPONDING PATIENTS

Chemoradiation Followed by Local Excision*

NCDB LE Special Study (1994-96)Local Recurrence – T2

5- Year

LE RR

T2 22% 15%

T2: p=0.01

You et al. Ann Surg 245(5):726-33, 2007

N=164

N=866

German Trial (CAO / ARO / AIO)Pre-operative vs Postoperative CXRT

• Significantly lower acute toxicity rate – 27% vs 40%, p=0.001

• LR improved with preoperative CXRT– 5 yr: 6% vs 13%, p=0.001

• SP higher in preoperative CXRT– 39% vs 19%, p=0.006– Subjective need for APR, not whole group

• Significantly lower late toxicity– 14% vs 24%, p=0.01

• anastamotic stricture (12% vs 4%)• Diarrhea, SBO (9% vs 15%)

Sauer, R NEJM, 351, 2004

Can Radical Surgery Be Avoided in Selected Rectal Cancer

Patients?

CXRT / Mesorectal resection- cT3 N0 ptsypN+ according to ypT stage

Crane, pESTRO 2004

ypT0 in T3 NX (including clinically node +) = 4/45 = 9%

Bedrosian, J Gastroint Surg, 2004

Pathologic T Stage

Institution 1 Institution 2 Institution 3 Total

ypT0 0/27 (0%) 0/14 (0%) 1/43 (2%) 1/84(1%) ypT1 2/29 (7%) 0/12 (0%) 4/17 (24%) 6/58 (10%) ypT2 15/95 (16%) 12/97 (12%) 4/60 (7%) 31/252 (12%) ypT3 54/166 (33%) 62/164 (38%) 15/68 (22%) 131/398 (33%) ypT4 0 5/5 (100%) 2/2 (100%) 7/7 (100%)

Local Excision of T3 tumors after Preoperative XRT

Local Excision of T2 tumors after Preoperative XRT

Study # Patients % pCR % LF

Median FU

Lezoche, Italy 2005 54 16(30%) 5 (5 yr) 55

Meadows, UF, 2006 16 T1/T2 4(25%) 9 (3 yr) 27

ypT stage

All patients -seven studies

LR

T0 0/53 (0%)

T1 1/45 (2%)

T2 6/85 (7%)

T3 7/33 (21%)

Total 17/237 (7%)

Cumulative recurrence rates based on ypT StageCXRT/LE (cT2/cT3)

Modified from Table 5, Borschitz, et al Ann Surg Onc, 2008

Randomized Trial - T2 Rectal Cancer CXRT then TAE vs Laparoscopic Resection

• 40 pts

• 50.4 Gy + PVI 5-FU (200 mg/m2)– 20 TAE– 20 LAP Resection

• One recurrence in each group (5%)

• Median FU 56 mo

Lezoche, et al Surgical Oncology, 2005

Author Wound dehiscence

Transient incontinence

Kim et al 1/26 (4%) 1/26 (4%)

Ruo et al 1/10 (10%) None

Schell et al None 2/11 (18%)

Hershman et al NS NS

Bonnen et al NS NS

Stipa et al None 1/26 (4%)

Lezoche et al 11/100 (11%) 2/100 (2%)

NS, not specified; nCRT, neoadjuvant chemoradiation; LE, local excision.

Complications, CXRT / TAE

Modified from Table 3, Borschitz, et al Ann Surg Onc, 2008

•Wound complications do not appear to be a limitation

•Diverting iliostomy could be perfomed

Non-operative Management in Complete Responders?

• University of São Paulo, Brazil• Pre-op Chemoradiation (50.4 Gy + FU/LV)• 265 pts

– Clinical CR = observation (n=71, 26%)• 2 endorectal failures, 5y OS 100%

– Incomplete CR / radical surgery, pCR (n=22%, 8.3%)• 2 DOD, 5y OS 88%

• Median follow-up 57.3 months

Habr-Gama, Ann Surg. 240(4):711-718, 2004

ACOSOG Z6041 Study Design

uT2 rectal cancer(EUS-MRI)

CXRTCape (850mg/m2 bid)oxali (50 mg/m2/wk)54 Gy

Local excision

T0-T2 R0: Observation

T3 or R+: radical resection

Follow

<8 cm fromanal verge<4 cm size

Primary Obj: 3 yr DFS in uT2N0

Chan, ASTRO 2010

ACOSOG Z6041 Study Design

uT2 rectal cancer(EUS-MRI)

CXRTCape (650mg/m2 bid)oxali (50 mg/m2/wk)50.4Gy

Local excision

T0-T2 R0: Observation

T3 or R+: radical resection

Follow

<8 cm fromanal verge<4 cm size

Primary Obj: 3 yr DFS in uT2N0

Chan, ASTRO 2010

ConclusionsNeoadjuvant CRT with CAPOX

• 44% pCR

• Only 5% of patients needed radical surgery

• Long term follow-up is needed for LC endpoint

• High GI toxicity rates

Chan, ASTRO 2010

Organ Preservation ModelLocally Advanced Rectal Ca

• Clinical selection will affect success– Tumor size, nodal status, tumor grade, others

• Neoadjuvant CXRT– Endoscopic CR

• Full thickness local excision = excisional biopsy of tumor bed– ypT0, no further surgery

• Radical surgery only for non-responders: – Gross residual disease or ypT3

• What about microscopic residual disease?

Crane, Annals of Surg Onc, (3) p288-90, 2006

Response of Primary Tumor to CXRT

• Observing response of primary key to organ preserving strategy

• Predicts Control of Microscopic Mesorectal Disease

• Could predicting response help?– Only if it leads to personalized therapy– Increase the pool of responders

• Pair agents to patients– Proteomics, genomics

• Change agents during therapy (PET)?

The Message RegardingPre-op/LE

• Promising strategy, especially in responding patients

• Better long term GI and sexual function

• Salvage rates of LR 50-70%– Close FU is critical

• Multidisciplinary team has to be on the same page