Management of Locally Advanced Management of Locally Advanced Rectal CancerRectal Cancer

Joint Hospital Surgical Grand RoundPamela Youde Nethersole Eastern Hospital

Dr. YH Ling19 May 2007

ColorectalColorectal CancerCancer

Primary modality of treatment:

Surgical Resection

RectalRectal CancerCancer

Middle and lower rectum– Located in the confined

pelvis– Close relationship with

• urogenital tracts• anal sphincters

Goal of treatmentGoal of treatment

Achieve oncological cure– Radical resection

• Negative distal and circumferential margin

Goal of treatmentGoal of treatment

Preserve – Urinary function– Sphincter function– Sexual function

Maintain the quality of life

Radical resection

Pelvic organ functions

Locally advanced rectal cancerLocally advanced rectal cancer

Tumour and/or regional nodes have invaded the adjacent organs– Bladder, ureters– seminal vesicles, prostate– vagina– sacrum

Pre-op imaging and staging

Surgery

RadiotherapyChemotherapy

Better local disease controlImproved overall survivalGreater sphincter preservation rate

Treatment of locally advanced rectal

cancer

Multidisciplinary cancer management

Surgeons

Oncologists

Diagnostic radiologists

Locally advanced rectal cancerPre-op stagingNeoadjuvant chemoradiation therapy

Locally advanced rectal cancer

Locally advanced rectal cancerLocally advanced rectal cancer

Tumour and/or regional nodes have invaded the adjacent organs

– T3-4 or N+

– 6-10% of rectal cancer

B1AM0N0T2

D--M1Any NAny TIV

C1/C2/C3CM0N2Any TIIIC

C2/C3CM0N1T3-T4IIIB

C1CM0N1T1-T2IIIA

B3BM0N0T4IIB

B2BM0N0T3IIA

AAM0N0T1I

----M0N0Tis0

MACDukesMNTStage

B1AM0N0T2

D--M1Any NAny TIV

C1/C2/C3CM0N2Any TIIIC

C2/C3CM0N1T3-T4IIIB

C1CM0N1T1-T2IIIA

B3BM0N0T4IIB

B2BM0N0T3IIA

AAM0N0T1I

----M0N0Tis0

MACDukesMNTStage

CRM ≤ 2mm distinguishes the TNM stage III patients with high risk of local recurrence (21.4%) from patients with lower risk of local recurrence (12%), p = 0.03

Locally advanced rectal cancerLocally advanced rectal cancer

Tumour growing < 2mm from the mesorectal fascia (fascia proper)

Beyond mesorectal fasciaWith major lymph node involvement

Pre-operative staging

Imaging modalitiesImaging modalities

CT scanMRI

– With or without endorectal coilEndorectal ultrasound

CT scanCT scan

Widely used to stage colorectal cancerNot good for local staging

– Cannot delineate • layers of bowel wall

• microinvasion of perirectal fat

– Cannot detect • small lymph node metastases (<1cm)

• lymph nodes close to the tumour

Endorectal ultrasound (ERUS)Endorectal ultrasound (ERUS)

Accuracy – T staging: 83%– N staging: 65-83%

• Kim NK, et al. Ann Surg Oncol 2000;7:732–7

• Savides TJ, et al. Endosc2002;56(S4):S12–8.

Endorectal ultrasound (ERUS)Endorectal ultrasound (ERUS)

Limitations:– Bowel wall penetration (T):

• Inflammatory peritumoral changes mimic deeper invasion

Overstage T2 tumour

– Nodal status (N):• Difficult to differentiate inflammatory and

metastatic nodes• Difficult to detect small or distant lymph

nodes

Endorectal ultrasound (ERUS)Endorectal ultrasound (ERUS)

Limitations:– Stenotic lesion

• Difficult to pass the transducer

– Operator dependent– “Sampling error” for large tumour

MRIMRI

Advantage:– Visualize the

distance between the tumor and the rectal fascia proper

MRIMRI

Limitation:– Inability to distinguish tumour extension

from inflammatory changes overstage T2 lesions

• Brown G, et al.Br J Surg 2003;90:355–64

• Vliegen RFA, et al.Imaging 2003;10–6

• Williamson PR, et al. Dis Colon Rectum 1996;39:45–9

• Fleshman JW, et al. Dis ColonRectum 1992;35:823–9

Preoperative staging of rectal cancerPreoperative staging of rectal cancer

H. Kwok, LP Bissett, GL Hill et alH. Kwok, LP Bissett, GL Hill et alInt J Colorectal Dis (2000) 15:9-20Int J Colorectal Dis (2000) 15:9-20

Systemic review83 studies from 78 papers4897 patients

Bowel wall penetration Nodal status

Acc (%) Sen (%) Spe (%)

Acc (%) Sen (%) Spe (%)

CT 73 78 63 66 52 78

ERUS 87 93 78 74 71 76

MRI 82 86 77 74 65 80

MRI with endorectal coil

84 89 79 82 82 83

MRI with endorectal coilMRI with endorectal coil

Most useful technique for preoperative staging of rectal cancer

Limited availability

Limits its routine use

Limited use in stenotic lesions

Neoadjuvant chemoradiation therapy

Potential AdvantagesPotential Advantages

Reduction in tumour size – improve resectability– increase sphincter preservation

Decrease risk of local failure– Improve tumour response in the pre-

operative setting

Potential AdvantagesPotential Advantages

Decrease risk of toxicity– Small bowel more readily excluded from

the radiation field in preoperative setting

Less bowel dysfunction– Colon used for reconstruction is not in

the radiation fieldNo delay of therapy in patients with

operative morbidity

Disadvantage:Disadvantage:

Over-treat patient with pre-op overstaged disease

Preoperative staging of rectal cancerPreoperative staging of rectal cancerH. Kwok, LP Bissett, GL Hill et alH. Kwok, LP Bissett, GL Hill et al

Int J Colorectal Dis (2000) 15:9-20Int J Colorectal Dis (2000) 15:9-20

Staging modality

Accuracy (%)

Over-staged (%)

Under-staged (%)

CT 80 13 7

ERUS 84 11 5

MRI 74 13 13

MRI with endorectal coil

81 12 6

Prospective randomized clinical trials that Prospective randomized clinical trials that analyzed neoadjuvant therapy for rectal canceranalyzed neoadjuvant therapy for rectal cancer

Study Year N Main resultsSwedish rectal cancer trial

1997 908 High-dose pre-op radiation therapy reduced local recurrence and improved survival

Dutch colorectal cancer group

2001 1805 Pre-op radiation therapy decreased local recurrence following total mesorectal excision

German rectal cancer study group

2004 823 Pre-op chemoradiation therapy improved local control but did not improve overall survival compared to post-op chemoradiatoin therapy

Rectal cancerT3 or T4 or N +

Long course radiation+

Infusional 5-FUTME

TMERadiation therapy

+Infusional 5-FU

n = 415 n = 384

6 weeks

5-year cumulative risk of local failure:– Pre-op chemoradiation group: 6%– Post-op chemoradiation group: 13%

• P = 0.006

Survival:– No difference in two groups

Improved sphincter preservation rates in pre-op chemoradiation therapy group

20% of patients randomized to the post-op chemoradiotherapy group actually have stage I disease on evaluation of resection specimen

These patients will be over-treated if they were treated preoperatively

Chemotherapy with preoperative radiotherapy in rectal cancer

N Engl J Med 2006;355(11):1114-23

Bosset JF, Collette L, Calais G, et al

Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD

9203 J ClinOncol 2006;24(28):4620-5

Gerard JP, Conroy T, Bonnetain F, et al

1011 patients with clinical stage T3 or T4 resectable rectal cancer

Randomized to 4 groups:

Pre-op Post-op

1 RT -

2 Chemo-RT -

3 RT chemotherapy

4 Chemo-RT chemotherapy

The cumulative incidences The cumulative incidences of local recurrences as a of local recurrences as a first event at 5 yearsfirst event at 5 years

Pre-op Post-op Cummulative incidence of local

recurrence (%)

1 RT - 17.1

2 Chemo-RT - 8.7

3 RT chemotherapy 9.6

4 Chemo-RT chemotherapy 7.6

p=0.002 for the comparison between the group receiving preoperative radiotherapy alone and the other three groups

733 patients with T3-4 Nx M0 rectal cancer

Randomized to 2 groups– Pre-op radiotherapy group– Pre-op chemoradiotherapy group

The 5-year incidence of local recurrence – Pre-op radiotherapy 16.5%– Pre-op chemoradiotherapy 8.1%

• p < 0.05

Overall 5-year survival:

– No difference

Neoadjuvant therapy with combined chemoradiation is becoming

standard of care in locally advanced rectal cancer

Surgical resectionSurgical resection

Resection of the primary tumourWith en bloc resection of adjacent

involved structuresObtain negative margins

Neoadjuvant therapy cannot compensate for irradical resection

ConclusionsConclusions

Locally advanced rectal cancer– TNM staging: T3-T4 or N+– Circumferential resection margin:

• Tumour < 2mm from the mesorectal fascia• Tumour beyond mesorectal fascia• Tumour with major lymph node involvement

ConclusionsConclusions

MRI with endorectal coil is the best diagnostic tool but not widely available

Endorectal ultrasound (ERUS) is widely used with good accuracy

Neoadjuvant therapy:– Pre-op radiation therapy combined with

chemotherapy better local control– No survival benefits shown

ConclusionsConclusions

Management of locally advanced rectal cancer is a multidisciplinary cancer management involving diagnostic radiologists, oncologists and surgeons

ThankThank YouYou