Comparison of the Outcome of Primary and Secondary

Surgical Treatment for Recurrent Colorectal Liver Metastases

Lee H 1, Heo JS 1, Jung KU 2, Park YA 1, Cho YB 1, Yun SH 1,

Kim HC 1, Lee WY 1, Choi SH 1, Choi DW 1, Chun HK 2

1 Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea 2 Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

Introduction

NR: not reported

Year Journal Author

1° hepatic

resection

(n)

2° hepatic

resection

(n)

Overall survival of

repeat hepatectomy (%)

1 year 3 year 5 year

2012 J Visc Surg Lopez et al. Review of 29

studies NR 24–74 16–49

2007 Ann Surg Oncol Yan et al. Review of 17

studies NR 24–68 21–49

2013 Br J Surg Wicherts et al. 1036 288 NR 76 54

2012 Ann Surg Oncol Jones et al. 405 52 Median survival : 19 months

2012 Br J Surg Adair et al. NR 195 91.2 44.3 29.4

2011 HPB Andreou et al. NR 43 NR NR 73

2009 Dis Colon Rectum Brachet et al. NR 62 NR NR 40

2009 J Gastrointest Surg de Jong et al. 1706 246 NR 69.9 47.1

Survival after repeat hepatic resection in recurrent colorectal liver

metastases (CLM) (published during last 5 years)

Introduction

Repeat hepatectomy for recurrent CLM

• Five year survival after repeat hepatectomy : 16 – 49%

• Morbidity of repeat hepatectomy : 0 – 44%

• Prognostic factors after repeat hepatectomy

Number of lesion (single lesion, ≤ 3 lesions, ≤ 4 lesions)

Size ≤ 5 cm

Location (single hemi-liver)

Metachronous

CEA

Extrahepatic metastasis

Introduction

Clinical question

Is there a difference between the outcomes of

1° and 2° hepatic resection ?

Comparative studies are rare

Clinical question

What is the risk factor of repeat hepatectomy for recurrent

CLM ?

Many studies

Purpose

To investigate the outcomes of

secondary surgical treatment

(hepatectomy and RFA)

for recurrent CLM

compared with primary surgical treatment

for primary CLM.

Patients and Methods

Study period

January 2000 - December 2007 (retrospective study)

Inclusion criteria

Patients with synchronous or metachronous CLM

− Who underwent hepatectomy or RFA:

R0 or R1 operation

No viable tumor on radiologic examination after RFA

Curative intent (R0 or R1) surgical treatment for recurrent CLM

Exclusion criteria

Extrahepatic metastases

Double primary carcinoma

R2 operation (grossly remnant tumor)

Patients and Methods

Divided into 2 groups

Group 1:

Primary CLM patients who underwent R0 or R1 surgical treatment

Group 2:

Recurrent CLM patients who underwent curative intent surgical

treatment

Survival analysis

Disease free survival (DFS)

Overall survival (OS)

1st operation 2nd operation Death

1st recurrence 2nd recurrence

DFS of Group 1

OS of Group 1

DFS of Group 2

OS of Group 2

Definitions of DFS and OS period in Group 1 and 2

Results – patients selection algorithm

Metachronous

CLM

489

R2 or no

Surgical

treatment

465

Primary hepatic

resection

(R0 or R1)

349

Recurrent CLM

218

Secondary hepatic

resection

(R0 or R1)

44

Colorectal cancer with

surgical treatment

6998

R2 or no

Surgical

treatment

43

Synchronous

CLM

699

R2 or no

Surgical

treatment

367

Extrahepatic

recurrence

131

Results – demographics

* Chi square test, Fisher’s exact test or Mann Whitney U test

Variables

Primary CLM

(Group 1)

(n = 349) (%)

Recurrent CLM

(Group 2)

(n = 44) (%)

P value*

Sex Female 120 (34) 14 (32)

0.735 Male 229 (66) 30 (68)

Median age (years) 59 (26 - 79) 61 (36 - 85) 0.140

Number of CLM (n) (mean ± SD) 1.6 ± 1.0 1.3 ± 0.7 0.013

CLM size (mean ± SD) 2.8 ± 1.7 2.7 ± 1.3 0.914

Number of CLM (n) (mean ± SD) 1.6 ± 0.8 1.9 ± 1.0 0.058

Liver metastases Synchronous 227 (65) 31 (70)

0.476 Metachronous 122 (35) 13 (30)

CLM number Single 209 (60) 35 (80)

0.011 Multiple 140 (40) 9 (20)

CLM treatment

Resection 263 (75) 19 (43)

< 0.001 RFA 66 (19) 25 (57)

Both 20 (6) 0 (0)

T stage T1 or T2 30 (9) 1 (2)

0.231 T3 or T4 319 (91) 43 (98)

N stage N0 113 (32) 11 (25)

0.321 N1 or N2 236 (68) 33 (75)

Results – perioperative outcomes

* Patients who underwent RFA were excluded

† Fisher’s exact test or Mann Whitney U test

Perioperative outcomes

Primary CLM with

1° hepatectomy*

(n = 263) (%)

Recurrent CLM with

2° hepatectomy*

(n = 19) (%)

P value†

Complications Yes 34 (13) 0 (0)

0.143 No 229 (87) 19 (100)

Hospital day (days) 10 ≥ 132 (50) 14 (74)

0.058 10 < 131 (50) 5 (26)

Operation time (minutes)

(mean ± SD) 276.4 ± 101.3 263.5 ± 58.7 0.875

Results – survival analysis

Comparisons of survival curves between 1°and 2° surgical treatment

A. DFS (N = 393) B. OS (N = 393)

Median follow up: 39.7 months (range, 1 to 195)

Results – survival analysis

Comparisons of DFS curves between 1°and 2° surgical treatment in

single or multiple CLM

A. Single CLM (N = 244) B. Multiple CLM (N = 149)

Results – risk factors of repeat hepatectomy

* Cox regression test (not performed multivariate analysis)

Variables Univariate analysis of DFS Univariate analysis of OS

HR 95% CI P value* HR 95% CI P value*

Female 1.528 0.702 – 3.326 0.286 1.609 0.742 – 3.491 0.229

Age 0.991 0.959 – 1.023 0.577 1.011 0.979 – 1.043 0.511

Metachronous

origin 1.223 0.537 – 2.788 0.632 1.148 0.515 – 2.556 0.736

Number of CLM 1.605 1.029 – 2.502 0.037 1.272 0.796 – 2.033 0.313

Size of CLM 1.352 0.984 – 1.858 0.063 1.254 0.875 – 1.796 0.217

3rd or 4th

hepatectomy 1.063 0.429 – 2.635 0.895 0.549 0.191 – 1.583 0.267

RFA 1.488 0.686 – 3.230 0.314 1.417 0.657 – 3.059 0.374

T4 0.880 0.209 – 3.173 0.862 1.236 0.290 – 5.263 0.774

N1 or N2 1.608 0.651 – 3.973 0.303 2.337 0.865 – 6.317 0.094

Limitations

Not a randomized controlled trial

→ Random error

Retrospective study

→ Random error, selection bias

Different surgical time

→ Length time bias

→ Might be minimized with long term follow up

Conclusion

Secondary surgical treatment for recurrent CLM is

as effective as

primary surgical treatment for primary CLM

Multiple metastatic lesion is a poor prognostic factor

in the treatment of recurrent CLM

Thank you for your attention