Local recurrence after rectal cancertreatment

Danijela Scepanovic, Andrea Masarykova, Martina Lukacovicova, Andrea Hurakova,

Zuzana Dolinska, Margita Pobijakova

Department of Radiation Oncology, National Oncological Institute of Slovakia,

Bratislava, Slovakia

Background

Local recurrence is a major problem after rectalcancer surgery. Local recurrence rates historicallyvary between 15% and 45%. The introduction oftotal mesorectal excision (TME) as treatment forpatients with rectal cancer has led to an improvedlocal control and survival when compared withhistorical controls.

Purpose

To analyze local recurrence rates in ourpatients treated with preoperative

radiotherapy with/withoutchemotherapy followed by TME or non

TME surgery.

Material and methods

Two hundred fifty patients (pts) were enrolledbetween January 2004 and December 2010.

Median age was 62 years (min=26, max=83). There were 83 female and 167 male. To be eligible, patients had to have histologically

confirmed adenocarcinoma of the rectum, withoutevidence of distant metastases, and the inferiormargin of the tumor had to be located not fartherthan 15 cm from the anal verge.

Initially, 96% of patients had locally advanced stageof disease (T3/T4N0, any TN+).

Material and methodsLocation tumors in rectum

4-8cm51%

0-4cm18%

12-15cm5%

8-12cm26%

Material and methodsInitial TNM stage

T10%

T3N+55%

T2N+4%

T45%

T324%

T24%

T4N+8%

T1T2T3T4T2N+T3N+T4N+

Material and methodsRadiotherapy

All patients had preoperativeradiotherapy (RT)with a total dose of 45-50.4Gy in 25-28 fractions for5 to 5.5 weeks

020406080

100120140160180200

to 45Gy over 45Gy

No

Material and methodsChemotherapy

Chemotherapy (CT) was performed concomitantly with RT:

1. 5-fluorouracil – 168 patients

2. capecitabine – 72 patients

3. without CT – 10 patients

0

20

40

60

80

100

120

140

160

180

5-fluorouracil capecitabine without CT

No

Material and methodsSurgery

Six weeks after RT/CT patients were operated with:

1. Total mesorectal excision (TME)=118 patients

2. Non total mesorectal excision (nonTME)=132 patients

ResultsLocal recurrence rate (LRR)

Median follow-up time = 48 months(range, 12 to 96 months).

The cumulative proportion of localrecurrence was 6.8% for all group of

patients (250):1.1. TME group TME group –– 0.8%0.8%

2.2. nonTMEnonTME group group –– 6%6% p=0.0022

ResultsSites of recurrence

22

1

12

0 2 4 6 8 10 12 14

presacral

multisites

anastomosis

nonTMETME

No

ResultsInfluence of tumor distance from

the anal verge on LRR

0

1

2

3

4

5

6

7

0-4cm 4-8cm 8-12cm 12-15cm

TMEnonTME

p=0.1442

p=0.660

p=0.1604

No

Results Influence of dose irradiation on

LRR

0

2

4

6

8

10

12

to 45Gy over 45Gy

TMEnonTME

p=0.0410

p=0.0298

p=1.0000

No

Results Influence of chemotherapy type on

LRR

0

2

4

6

8

10

12

TMEnonTME

p=0.0287

p=0.2750 p=1.0000

p=0.56255-FU capecitabine without CT

p=0.1419

No

Results Influence of postoperative stage on

LRR

pT0 pT1 pT2 pT3 pT4 anyTN+0

1

2

3

4

5

6

7

TMEnonTME

p=0.3644

p=0.1341No

Results Influence of resection margins on

LRR

0

2

4

6

8

10

12

R negative R positive

TMEnonTME

p=0.0009

p=0.0196No

Results Influence of lymphovascular

invasion on LRR

0

2

4

6

8

10

12

LVI negative LVI positive

TMEnonTME

p=0.0427

p=0.0196

p=0.2550

No

Results Influence of KRAS on LRR

0

0,5

1

1,5

2

2,5

3

KRAS negative KRAS mutant

TMEnonTME

p=0.5125

p=0.0252

p=1.0000

No

ResultsTime to progression (TTP)

36

48

monthsnonTMETME

min=12; max=96

min=10; max=96

Results Distant metastases

Fifty one patients Fifty one patients had distant had distant metastases in metastases in whole group of whole group of patients:patients:

1. TME group=162. nonTME group=35

0

2

4

6

8

10

12

14

livermetastases

lungmetastases

liver/lung lung/bones bones

TMEnonTME

p=0.3451

p=0.3294

p=1

p=1 p=0.5810

p=0.0121

No

Results Influence of KRAS on distant

metastases KRAS analysis was KRAS analysis was

performed in 111 performed in 111 patients (44.4%) and patients (44.4%) and distant metastases distant metastases occurred in 24 patients occurred in 24 patients (22%):(22%):

KRAS negative:KRAS negative:1. TME group=82. nonTME group=10 KRAS mutant:1. TME group=42. nonTME=2 0

2

4

6

8

10

12

KRAS negative KRAS mutant

TMEnonTME

p=0.0194

p=0.5686

p=0.2147

No

Results5 years DFS

0

10

20

30

40

50

60

70

80

90

100

0 to 12 12 to 24 24 to 36 36 to 48 48 to 60 60 to 72 72 to 84 84 to 96

TMEnonTME

months

%

p=0.0025

Results5 years OS

0

10

20

30

40

50

60

70

80

90

100

0 to 12 12 to 24 24 to 36 36 to 48 48 to 60 60 to 72 72 to 84 84 to 96

TMEnonTME

months

%

p=0.0012

ResultsSurvival

In the group of patients with TME died 15 patients while in the group with nonTME died 39 patients

The association between groups of patients and outcome is considered to be very statistically significant (p=0.0012)

Conclusions

1. Radiotherapy followed by TME has beenshown to significantly reduce localrecurrence rates in our patients.

2. There was very statistically significant difference between TME and nonTMEgroups of pts regarding DFS and OS.

3. The strong criteria for identifying low risk group of pts for LR were:

Negative resection margins (p=0.0009) and TME (p=0.0022).