Multimodality therapy for rectal cancer

Multimodality therapy for rectal cancer

Carlo AscheleOncologia Medica B

Istituto Nazionale per la Ricerca sul Cancro - Genova

Carlo AscheleOncologia Medica B

Istituto Nazionale per la Ricerca sul Cancro - Genova

Highlights in the management of gastrointestinal cancerRoma - May 21-22, 2010

LOCAL FAILURE AND SITE OF RECTAL CANCER

tumor odds 95%site ratio c.i.

upper 0.43 0.24-0.77third

middle/lower 1.0third

p=0.004

Hermanek, 1995

EFFECT OF RT ON LOCAL FAILURE AND SITE OF RECTAL CANCER

Dutch TME trial

cm from 2-y LR, % anal verge RT+TME TME p

0-5 5.8 10 0.05

5-10 1.0 10.1 <0.001

10-15 1.3 3.8 0.17

NEJM, 2001

• SOTTO LA RIFLESSIONE PERITONEALE

• ENTRO 12 CM DALLA RIMA ANALE

età-sesso-altezza-peso-condizioni ginecologiche ed ostetriche

(nord vs sud europa)anteriore vs posteriore

INTERVENTO- RETTOSCOPIA (STR RIGIDO)-RMN

CHI?

Locally advanced rectal cancerLocally advanced rectal cancer

• perirectal fat penetration

• adjacent organ invasion

• lymphnode infiltration

• mesorectal fascia (CRM) involvement

TRUS - CT scan - MRI

Tx neoadiuvante del carcinoma del rettoTx neoadiuvante del carcinoma del retto

Patient selection- tumor location- tumor stageStandard treatmentChemotherapy– role (concomitant and adjuvant)– simplification / potentiationSurgery / pathologyStandard vs selective approach

Patient selection- tumor location- tumor stageStandard treatmentChemotherapy– role (concomitant and adjuvant)– simplification / potentiationSurgery / pathologyStandard vs selective approach

Tx neoadiuvante del carcinoma del rettoTx neoadiuvante del carcinoma del retto

Patient selection- tumor location- tumor stageStandard treatmentChemotherapy– role (concomitant and adjuvant)– simplification / potentiationSurgery / pathologyStandard vs selective approach

Patient selection- tumor location- tumor stageStandard treatmentChemotherapy– role (concomitant and adjuvant)– simplification / potentiationSurgery / pathologyStandard vs selective approach

IMPACT OF POST-OP CMTT3 and/or N+

IMPACT OF POST-OP CMTT3 and/or N+

local failure, % 5-y survival, %

GITSG 7175 11 54

Mayo/NCCTG 79-47-51 14 5386-47-51 9-11 60-70 (4-y)

INT 0114 14 64

NSABP R-02 9 62-65

Compared to surgery alone: ~ 50 ~ 15-25

Copyright © American Society of Clinical Oncology

Gunderson, L. L. et al. J Clin Oncol; 22:1785-1796 2004

(NCCTG 794751, 864751; NSABP R01, R02; INT 0114. N=3791)

LOCALLY ADVANCED RECTAL CANCER. IMPACT OF ADJUVANT CMT ON

SURVIVAL

Post-op chemoradiationPost-op chemoradiation

Compliance 46-76 %

Acute toxicity 26-53 %

(grade III-IV)

Long-term toxicity 46-56 %

NCCTG 79-4751 / 86-4751; GITSG 7175 ; NSABP R02; CAO/ARO/AIO 94

CAO/ARO/AIO-94

R

50.4 GyCI FU TME FU x 4 cy

TME FU x 4 cy50.4 GyCI FU

Post-op Pre-op p5-y outcome (n=394) (n=405)

Survival % 74 76 0.80 LF % 13 6 0.006

acute toxicity 40 27 0.001chronic toxicity 24 14 0.01

NEJM 2004

CAO/ARO/AIO-94CAO/ARO/AIO-94

TME SURGERY

CAO/ARO/AIO-94

declared to sphincter-saving require APR surgery

Post 78 19 % (15/78)

Pre 116 39 % (45/116)

p 0.004

NEJM 2004

PRE-OP CHEMORADIATION: IMPACT ON SPHINCTER SAVING

Standard treatment of locally advanced rectal cancer

Standard treatment of locally advanced rectal cancer

TME

45-50.4 Gy

CT

RT

T3-4 and/or N+

Pre-op RT vs. surgery alone:Risk of local recurrence in phase III trials

Role of chemotherapyPRE-OP RT +/- CONCOMITANT CT

Role of chemotherapyPRE-OP RT +/- CONCOMITANT CT

pCR, %

RT RT + CT

EORTC 5 14

FFCD 3 10

Bosset, NEJM 2006; Gerard, JCO 2006

Role of chemotherapyPRE-OP RT +/- CONCOMITANT CT

Role of chemotherapyPRE-OP RT +/- CONCOMITANT CT

5-y LR, %

RT RT + CT

EORTC 17 8

FFCD 16 8

Bosset, NEJM 2006; Gerard, JCO 2006

NSABP R-04

RT + Capecitabine +/- oxaliplatin

S

RT + CI 5-FU +/- oxaliplatin

R

N=1460

R

RT 50.4 GyFU 225 mg/m2/day PVI OXA 60 mg/m2 weekly x 6

RT 50.4 GyFU 225 mg/m2/day PVI

TME

6-8wks

n=747

n=598

STAR-01

ACCORD

ypT0(N0)

16%

16%

p=0.94

R

RT 50 GyCAPE 1600 mg/m2/day

OXA 50 mg/m2 weekly x 5

RT 45 GyCAPE 1600 mg/m2/day

TME

6-8wks

14%

19%

p=0.11

ASCO ‘09

Standard treatment of locally advanced rectal cancer

Standard treatment of locally advanced rectal cancer

TME

45-50.4 Gy

CT

RT

T3-4 and/or N+

5–10%5–10%

Blunt dissection Blunt dissection TME TME

LR 20–40%LR 20–40%

Fascial plane In mesorectum In/on muscularis

Dataset for colorectal cancer (2° edition), RCOP, 2007

SURGERY QUALITY:EFFECT OF THE PLANE OF SURGERY ON

LOCAL RECURRENCE

Circumferential resection margin

Copyright © American Society of Clinical Oncology

Nagtegaal, I. D. et al. J Clin Oncol; 26:303-312 2008

LOCAL RECURRENCE AND CRM

Standard treatment of locally advanced rectal cancer

Standard treatment of locally advanced rectal cancer

TME

45-50.4 Gy

CT

RT

T3-4 and/or N+

FU-based adjuvant chemotherapy in rectal cancer patients. QUASAR

study (n=948). survival

n = 3239

Effect of FU-based adjuvant chemotherapy in colon and rectal cancer patients. QUASAR studyRecurrence

Effect of adjuvant FU-based chemotherapy in rectal cancer

patients included in the QUASAR studyRecurrence at any timen = 948

Lancet 2008; 371: 1503

CAO/ARO/AIO-94

R

50.4 GyCI FU TME FU x 4 cy

TME FU x 4 cy50.4 GyCI FU

Gunderson, L. L. et al. J Clin Oncol; 22:1785-1796 2004

(NCCTG 794751, 864751; NSABP R01, R02; INT 0114. N=3791)

LOCALLY ADVANCED RECTAL CANCER. IMPACT OF ADJUVANT CMT ON

SURVIVAL

Surg +/- RT

+ Adj Chemo

ECOG 5204

* RT + bolus or CI FU ± LV, or Cape

or NSABPR 04

JCO, 2007

Effect of adjuvant chemotherapy in pts with good and poor response to pre-op treatment

DF

S

Tx neoadiuvante del carcinoma del rettoTx neoadiuvante del carcinoma del retto

Patient selection- tumor location- tumor stageStandard treatmentChemotherapy– role (concomitant and adjuvant)– simplification / potentiationSurgery / pathologyStandard vs selective approach

Patient selection- tumor location- tumor stageStandard treatmentChemotherapy– role (concomitant and adjuvant)– simplification / potentiationSurgery / pathologyStandard vs selective approach

Standard treatment of locally advanced rectal cancer

Standard treatment of locally advanced rectal cancer

TME

45-50.4 Gy

CT

RT

Optimal for every LARC patient?

n=188 (TRUS 130 / MRI 58)

22 % node + after pre-op CRT

n 3-y LR 5-y LR

routine pre 674 4% 5%

selective post 676 11% 12 %

HR=0.39 (95% CI 0.27-0.58); p<0.0001

MERKEL et al 2001

• pT3<5mm, N any

T2 and early T3 tumours <5mm have 85-90% 5 year cancer specific survival.

STANDARD vs SELECTIVE APPROACH STANDARD vs SELECTIVE APPROACH

• almeno 7-8 cm dalla rima anale• infiltrazione grasso < 5 mm (MERCURY)• non evidenza di linfonodi patologici• margine radiale atteso di almeno 2 mm• chirurgo dedicato

• TME con mesoretto integro e CRM -• pT3a-bN0 (almeno 12 linfonodi negativi) • G1-G2

patients’ preference

Rectal cancer:adjuvant / neoadjuvant treatment

Rectal cancer:adjuvant / neoadjuvant treatment

SURGEON

MEDICAL ONCOLOGIST

RADIOTHERAPIST

CUREQOL

PATHOLOGIST

STOMA THERAPIST NURSE

RADIOLOGIST