CR07 results and informed patient consent

David Sebag-Montefiore Leeds Cancer Centre

N=1350

Clinically operable adenocarcinoma of the rectum <15cm from anal verge; no metastases

Adjuvant chemotherapy given as per local policy

POST

Post-op CRT45Gy / 25F

+ concurrent5FU

PRE

Pre-operative RT25Gy / 5F

Surgery

Pathology

Surgery

Pathology

CRM-ve CRM+ve

No RT

Trial Design

LR by treatment (ITT)

100

676 594 457 333 214 115POST

0

10

20

30

40

50

60

70

80

90

0 1 2 3 4 5

Time (years)

LR

rat

e (%

)

At risk:

674 587 475 338 236 134PRE

N Events 3yr LR 5yr LRPRE 674 27 4% 5%POST 676 71 10% 15%

HR(95%CI)=2.50(1.66, 3.72) p<0.0001

676 557 414 309 196 109POST

DF

S R

ate

(%)

0

10

20

30

40

50

60

70

80

90

100

Time (years)

0 1 2 3 4 5

At risk:

674 556 436 312 219 126PRE

N Events 3yr 5yrPRE 674 147 77% 73%POST 676 188 73% 65%

HR(95%CI)=1.30 (1.05, 1.61) p=0.0154

DFS by treatment (ITT)

100

676 608 484 359 232 121POST

0

10

20

30

40

50

60

70

80

90

0 1 2 3 4 5

Time (years)

Su

rviv

al (

%)

674 593 484 343 239 136PRE

N Events 3yr OS 5yr OSPRE 674 153 81% 71%POST 676 173 80% 66%

HR(95%CI)=1.12(0.90, 1.40) p=0.2886

Survival by treatment arm (ITT)

Subset analyses

• Treatment effect for:-

• Low mid and upper rectum

• Anterior resection and APER

• By stage (increased difference with higher stage

• Irrespective of plane of surgery achieved

Bowel problems

02

55

07

51

00

Pro

po

rtio

n 'q

uite

a b

it' o

r 'v

ery

mu

ch'

0 6 12 18 24Assessments (months)

Pre-op RT

Selective post-op RT

25. Frequent bowel movementsduring day?

02

55

07

51

00

Pro

po

rtio

n 'q

uite

a b

it' o

r 'v

ery

mu

ch'

0 6 12 18 24Assessments (months)

Pre-op RT

Selective post-op RT

26. Frequent bowel movementsduring night?

02

55

07

51

00

Pro

po

rtio

n 'q

uite

a b

it' o

r 'v

ery

mu

ch'

0 6 12 18 24Assessments (months)

Pre-op RT

Selective post-op RT

27. Urge to move bowels withoutproducing stool?

02

55

07

51

00

Pro

po

rtio

n 'q

uite

a b

it' o

r 'v

ery

mu

ch'

0 6 12 18 24Assessments (months)

Pre-op RT

Selective post-op RT

28. Unintentional release of stools?

Worse

Better

Sexual problems

02

55

07

51

00

Pro

po

rtio

n 'q

uite

a b

it' o

r 'v

ery

mu

ch'

0 6 12 18 24Assessments (months)

Pre-op RT

Selective post-op RT

20. Difficultly getting an erection?

02

55

07

51

00

Pro

po

rtio

n 'q

uite

a b

it' o

r 'v

ery

mu

ch'

0 6 12 18 24Assessments (months)

Pre-op RT

Selective post-op RT

21. Problems with ejaculation?

02

55

07

51

00

Pro

po

rtio

n 'q

uite

a b

it' o

r 'v

ery

mu

ch'

0 6 12 18 24Assessments (months)

Pre-op RT

Selective post-op RT

22. Dry vagina during intercourse?

02

55

07

51

00

Pro

po

rtio

n 'q

uite

a b

it' o

r 'v

ery

mu

ch'

0 6 12 18 24Assessments (months)

Pre-op RT

Selective post-op RT

23. Pain during intercourse?

Worse

Better

Informed patient consent

• Clinical oncologist required!

• Planned operation important• Perineal wound re APER• Bowel funnction re AR

• Erectile dysfunction• Sterility• Small bowel stricture• Pelvic insufficiency fractures

Three key issues

• Pre-operative radiotherapy works – the question is where to define the threshold where radiotherapy is considered

• If surgery first and node positive (irrespective of margin status), post-operative chemoradiation should be considered

• Radiation causes late toxicity

LR by stage III

0

10

20

30

40

50

60

70

80

90

100

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5Time (years)

LR

ra

te (

%)

N 3 yr 5 yr

PRE 252 9.0% 10.2%

POST 271 17.4% 25.6%

p=0.008

LR for node +ve CRM -ve

0

10

20

30

40

50

60

70

80

90

100

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5

Time (years)

LR

rate

(%

)

N 3 yr 5 yr

PRE 214 6.7% 8.2%

POST 221 17.1% 24.5%

p=0.0039

Which patients not to treat?

T1/2 N0

CRM -ve

T3++/T4

CRM +ve

NNT= 18X

Which patients to treat?

T1/2 N0

CRM -ve

T3++/T4

CRM +ve

T3/4 Tany N0 N+

CRM -ve

NNT= 9

Which patients to treat?

T1/2 N0

CRM -ve

T3++/T4

CRM +ve

Tany N+ve

CRM -ve

NNT= 6

Different scenarios

T1/2 N0

CRM -ve

T3++/T4

CRM +ve

CRT S

SCPRT

>2mm T3/N+ CRM-ve>5mm T3/N+ CRM-ve

LN+ rate by extramural spread of T 3 tumours (YCN data) n=4731

0

20

40

60

80

100

<=2mm >2-5mm >5-10mm >10mmN=1948 N=1279 N=786 N=718

41% 59%

32%68%

Use of radiotherapy according to selection criteria used for T3 tumours

>2mm cut off >5mm cut off

Pre Post Pre Post

SCPRT 59 32

Receive SCPRT 56 30

Use of radiotherapy according to selection criteria used for T3 tumours

>2mm cut off >5mm cut off

Pre Post Pre Post

SCPRT 59 32

Receive SCPRT 56 30

Surgery first 41 68

LN+ve 13 23

Receive post-op CRT 9 16

Use of radiotherapy according to selection criteria used for T3 tumours

>2mm cut off >5mm cut off

Pre Post Pre Post

SCPRT 59 32

Receive SCPRT 56 30

Surgery first 41 68

LN+ve 13 23

Receive post-op CRT 9 16

RT courses 65 48

RT fractions 505 400

Yorkshire audit

• Network agreed MRI reporting proforma• Includes the MRI T stage and N stage

• SCPRT criteria to agree (predicted CRM-ve)• >2mm or 5mm (unit policy)• N+

• Document if SCPRT given or reasons why not given

• Histopathology

Conclusion

• Identify patients without threatened margins at significant risk of LR

• There is not a definitive answer!

• Share practice

• Prospective audit

Some need 5x5 in the middle!

Its chemorads or nothing!