Survival difference between surgery and non surgery of HCC
Survival Difference between Surgery Versus Non-Surgery for the Treatment
of Hepatocellular Carcinoma Patients at Liver Centre, Malaysia
Azmawati MN 1 , Azmi MT 1
, Krishnan R 2
1Department of Community Health, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif,
Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia
2Department of Hepato-Pancreato-Bialiary, Hospital Selayang, Lebuh Raya Selayang-Kepong, Batu
Caves, 68000 Selangor Darul Ehsan, Malaysia
Abstract
Hepatic resection, the only treatment that offers long term survival for patients with Hepatocellular carcinoma
(HCC), have shown significant improvement in results over the past decades.
The aim of the study was to compare
the survival between patients receiving and not receiving surgery. A retrospective cohort study measured the survival
of newly diagnosed cases of HCC patients who underwent treatment in Selayang Hospital from 1 January 2003 till
31 December 2006.
Survival time was measured from the date of diagnosis until the subjects died or until the end of
study period (31 December 2007).
Overall survival was significantly longer in surgery group in comparison with
non-surgery group with a median survival of 43 and 20 months, respectively (p<0.001).
The following factors were
noted to have improved survival duration with surgical resection; Child Pugh Class B patients, tumor size less or
more than 4cm and number of nodules less than 3.
Subgroup analysis showed improved survival duration with
surgical resection among patients with Child Pugh Class B with tumor size less than 4cm or with nodule less than 3
and patients who had less than 3 nodules, even with tumor size of less or more than 4cm.
Multivariate Cox Regression
showed surgical intervention significantly improved survival time for overall patients (Adjusted HR: 1.5)
while non-surgery improved survival in patients with tumor size less than 4cm (Adjusted HR: 0.4).
Surgical
resection significantly improved the survival duration in overall patients while non-surgical procedure improved
survival if the tumor size was less than 4cm.
Keywords: HCC, surgery, survival, Selayang Hospital, tumor size.
Correspondence:
Dr. Azmawati Mohammed Nawi, Department of Community Health, Universiti Kebangsaan Malaysia Medical Centre, Jalan
Yaakob Latiff, 56000 Cheras, Kuala Lumpur, Malaysia. Tel: +603-91455901 Fax: +6 03-91737825 Email: atienawi@yahoo.com
Date of submission: 25th May 2011
Date of acceptance: 23rd Sept 2011
Date of publication: 03rd Oct 2011
Introduction
Most researchers have found out that Hepatocellular
Carcinoma (HCC) was increasing in trend as well as
the mortality. HCC accounts for 6% of all cancers
worldwide and the fifth commonest cancer in the
world. The estimated number of people who develop
HCC is 564,000 cases per year worldwide (1). In
Malaysia, HCC is one of the commonest malignancies
with an age-standardised annual incidence of 2.8 cases
per 100,000 populations (2). It accounts for 5.6% of all
cancers and 8.1% of all cancer related death in this
country. It is the twelfth commonest cancer in men and
ranked eighteenth amongst women in Malaysia as
reported by National Cancer Registries, 2002 (2).
Hepatic resection, the only treatment that offers longterm
survival for patients with HCC, has shown
significant improvement in results within past decade
(3-6). Although few would contest this wellOriginal
Research Article
Survival difference between surgery and non surgery of HCC Azmawati MN et al.
11
established fact, the paradox is that no randomized
study has clearly demonstrated the benefit of surgery
especially in liver centre of Malaysia, Selayang
Hospital. HCC is often associated with cirrhosis and
the remnant hepatic functional reserve is not always
preserved well and candidates for hepatic resection are
limited (7-9). Recently, HCC have been often treated
by nonsurgical therapeutic options such as transhepatic
arterial chemoembolization (TACE), percutaneous
ethanol injection treatment (PEI) (10), microwave
coagulation therapy (MCT) (11) and percutaneous
radiofrequency thermal ablation (RFA) (12).
The reported 5-year overall survival for surgery ranges
from 35% to 60%, whereas the 3-year overall survival
for non-surgery ranges from 13% to 26% (13-14). In
view of that, we opine that surgery gives better survival
for HCC patients compared to non-surgery. This study
aims to give evidence based benefit of surgery in HCC
patients at the liver centre of Malaysia with regard to
survival. It is hypothesized that surgery gives a better
survival compared to non-surgery procedures.
METHODS
Study Design
Selayang Hospital is known as liver centre of Malaysia
in which start operated on 2000. Most of hepatobiliary
disease was referred here for further management as
well as HCC. This study was a retrospective cohort to
all newly diagnosed HCC patients by CT Scan in liver
centre, Malaysia (Selayang Hospital) from 1 January
2003 till 31 December 2006. All patients were
followed up until achieving the primary endpoint
(death) or until the end of the study as on 31 December
2007. It was universal sampling with inclusion and
exclusion criteria being constructed. Inclusion criteria
were based on all newly diagnosed HCC patients with
CT Scan from 1 January 2003 till 31 December 2006
and exclusion criteria included multiple cancer.
Sample size of 210 was based on study by Verhoef et
al (15) with power of 90%. Demographic information
(age, gender, ethnic, alcohol intake, hepatitis status)
and clinical variables (tumor size, number of nodules,
Child Pugh Class, types of treatment) were obtained
from medical records. The surgeon decided on the type
of treatment that depended on findings of CT Scan in
which this study only focussed on tumor size, number
of nodules and Child Pugh Class. Small tumor, less
nodules involved with Child Pugh class A or early B
were considered as candidate for surgical resection.
Data was collected between February to April 2009 by
review all the variables in medical record. The CT
Scan finding was noted in view of tumor size and
number of nodules involved. All the patients were
followed up for their survival status by registering
death and via telephone.
Statistical Analysis
All data were collected and analyzed with statistical
computer software (SPSS 13.0). Categorical variables
were compared using the chi-square test and overall
survival analyses were carried out using the KaplanMeier
methods. Comparisons between different groups
were carried out using log rank test. Multivariate
analyses for survival were carried out using Cox’s
Regression model. Tests were deemed to be significant
at the 0.05 levels. The survival status coded as death
(1) and censored (0).
RESULTS
Demographic
A total of 210 HCC patients were evaluated from 1
January 2003 till 31 December 2006 with 123 patients
dead and 87 being censored case. Most of HCC patients
were aged between 40-60 years, males, Chinese ethnic,
with no alcohol intake and positive hepatitis status as
shown in Table 1. Out of 210 HCC patients, 114
patients underwent surgical resection and 96 patients
received non-surgical procedure. The choice of surgery
significantly depended on age group and alcohol status.
Majority of HCC patients were Child Pugh Class A in
which 65.6% underwent surgical resection while Child
Pugh Class B and Child Pugh Class C were mostly
received non-surgery procedures. The difference was
significant as well as in number of nodules involved. As
shown in Table 2, most of HCC patients who underwent
surgical resection involved nodules less than 3(59%)
compared to only 36.4% patients with nodules more
than 3. Out of 210 patients, 128 patients presented with
tumor size more than 4cm with 59.4% were having
surgical resection. However, only 46.3% of tumor size
less than 3cm underwent surgical resection.
Survival
Overall median survival time for patients having
surgical resection was 43 months (95%CI: 31.7-54.3)
with a 3-year and 5-year survival rate of 55% and 26%,
respectively. It showed that surgery had a better survival
compared to non-surgical procedures in which overall
median survival time was only 20 months (95%CI:
15.5-24.4) with a 3-year and 5-year survival rate of only
23% and 13%, respectively (Table 3, Figure 1).
Survival difference between surgery and non surgery of HCC Azmawati MN et al.
12
Table 1: Demographic of HCC patients
Variables Total (n=210)
Had Surgery
p value
Yes (n=114) No (n=96)
Age
<40 years old 14(6.7%) 12(85.7%) 2(14.3)
40-60 years old 112(53.3%) 54(48.2%) 58(51.8%) 0.02
>60 years old 84(40.0%) 48(57.1%) 36(42.9%)
Gender
Male 166(79%) 86(51.8%) 80(48.2%)
0.16
Female 44(21%) 28(63.6%) 16(36.4%)
Ethnic
Chinese 159(75.7%) 87(54.7%) 72(45.3%)
Malay 42(20%) 23(54.8%) 19(45.2%) 0.83
Indian 9(4.3%) 4(44.4%) 5(55.6%)
Alcohol
No 124(59%) 75(60.5) 49(39.5)
0.03
Yes 86(41%) 39(45.3) 47(54.7)
Hepatitis Status
No 49(19%) 25(62.5) 15(37.5)
0.25
Yes 170(81%) 89(52.4) 81(47.6)
Table 2: Clinical variables of HCC patients
Variables Total (n=210)
Had Surgery
p value
Yes (n=114) No(n=96)
Child Pugh
Class
A 125(59.5%) 82(65.6%) 43(34.4%)
B 80(38.1%) 32(40%) 48(60%) <0.001
C 5(2.4%) 0 5(100%)
Tumor Size
<4cm 82(39%) 38(46.3%) 44(53.7%)
0.064
>4cm 128(61%) 76(59.4%) 52(40.6%)
Number of nodules
<3 166(79%) 98(59%) 68(41%)
0.007
>3 44(21%) 16(36.4%) 28(63.6%)
Table 3 summarized the differences between HCC
patients who underwent surgical resection or not with
clinical variables which played an important factor
especially before deciding the types of treatment. For
the surgery group, the median survival time was better
with Child Pugh Class B (25 months, 95% CI: 5.8-
44.2), tumor size less than 4cm (57 months, 95% CI:
44.4-69.6), tumor size more than 4cm (21 months,
Survival difference between surgery and non surgery of HCC Azmawati MN et al.
13
Table 3: Univariate Analysis of Survival
Figure 1: Kaplan-Meier survival estimates by treatment
Variables n Died Median(months) 95%CI 1
year
3
year
5
year
p value
Overall
Surgery 114 54 43 31.7-54.3 74 55 26
<0.0001
No Surgery 96 69 20 15.5-24.4 61 23 13
Child Pugh Class A
Surgery 82 34 57 39.2-74.7 75 61 35
0.22
No Surgery 43 22 26 19.9-32.0 86 37 37
Child Pugh Class B
Surgery 32 20 25 5.8-44.2 65 47 23
0.04
No Surgery 48 42 13 10.1-15.9 76 14 0.4
HCC <4cm
Surgery 37 11 57 44.4-69.6 88 84 30
0.003
No Surgery 41 24 25 17.7-32.3 73 38 25
HCC >4cm
Surgery 77 43 21 11.4-30.6 66 39 24
0.005
No Surgery 55 45 15 9.6-18.3 48 0.7 0.7
Nodule <3
Surgery 98 40 57 38.9-75.1 76 62 34
<0.005
No Surgery 68 46 21 15.1-26.8 69 27 13
Nodule >3
Surgery 16 14 12 2.5-21.5 56 19
0.632
No Surgery 28 23 12 9.5-14.5 60 15 13
Survival difference between surgery and non surgery of HCC Azmawati
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