Edited by: Alessandro Vitale, University Hospital of Padua, Italy
Reviewed by: Heshu Sulaiman Rahman, University of Sulaymaniyah, Iraq; Matteo De Pastena, University of Verona, Italy
*Correspondence: Xiaohui Wang,
This article was submitted to Surgical Oncology, a section of the journal Frontiers in Oncology
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Transarterial chemoembolization (TACE) is currently the recommended treatment for intermediate-stage hepatocellular carcinoma (HCC). Liver resection (LR) may be an effective option, although recurrences are not uncommon. TACE prior to LR has been proposed as an even better alternative.
Patients with intermediate-stage HCC who underwent curative resection were enrolled between January 2007 and December 2015. We compared overall survival (OS) and recurrence-free survival (RFS) for the 2 groups using the Kaplan-Meier method, and we determined independent risk factors for death and recurrence using multivariate regression analyses.
A total of 488 patients with HCC at BCLC B (265 patients with LR, 223 patients with TACE+LR) enrolled from our center. Mean follow-up was 40.2 (range, 3.0–128.7) months. For patients receiving TACE+LR and LR, estimated 1-, 3-, and 5-year OS rates were 90.6% and 73.3%, 61.7% and 43.5%, and 52.9% and 33.8%, respectively (all
Preoperative TACE with LR may result in better oncological outcomes than either TACE or LR alone, without a substantial increase in morbidity, and could be considered an effective combination treatment for intermediate-stage HCC.
Hepatocellular carcinoma (HCC) is one of the most common cancers in the world, ranked as the sixth most common neoplasm and the third leading cause of cancer-related mortality worldwide (
However, intermediate-stage HCC actually involves a heterogeneous group of patients, encompassing those with a wide range of tumor sizes (larger than 3 cm to over 10 cm) and numbers (2 to over 20), provided that patients have good liver function (Child-Pugh classes A or B) (
In fact, multiple recent reports have suggested that LR, when compared to TACE, might provide a survival benefit to patients with intermediate-stage HCC (
At the same time, TACE has been used successfully as a neoadjuvant therapy for large HCC prior to LR (
Over the years, our Cancer Center has treated a relatively large population of patients with intermediate-stage HCC. Provided that liver function reserve was adequate and complete resection of the tumor appeared feasible, we offered LR to these patients. For some, we also recommended preoperative TACE, with the belief that this might potentially reduce postoperative recurrences and improve long-term survival. Our hypothesis has been that some patients with BCLC stage B may benefit from not only LR but also preoperative TACE. The aim of this retrospective study was to identify patients at our Cancer Center with intermediate-stage HCC who had LR and others who had TACE prior to LR, to compare the outcomes of each approach using survival rates, and to determine the prognostic factors for recurrence and death in these patients.
This study was conducted in accordance with the principles of the Declaration of Helsinki (
We retrospectively reviewed the medical records of patients who received a diagnosis of HCC from January 2007 to December 2015 at our Cancer Center. The diagnosis of HCC was made using criteria defined by the American Association for the Study of Liver Disease and the European Association for the Study of the Liver, and was based either on positive liver biopsy or characteristic findings on imaging (multiphasic CT or dynamic contrast-enhanced MRI) combined with serum Alpha-fetoprotein (AFP) levels (
The inclusion criteria for this study included: (a) age 18 to 75 years; (b) Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; (c) HCC with 2 or more tumors, at least one of which with a diameter greater than 3 cm, confirmed on postoperative pathological examination; (d) no macrovascular invasion or extrahepatic metastasis; (e) adequate liver function (i.e., Child–Pugh class A or B liver function); (f) adequate renal function (i.e., serum creatinine concentration no higher than 1.5 times the upper limit of normal); and (g) adequate coagulation function (i.e., prothrombin activity > 40%, international normalized ratio [INR] < 1.26, and platelet count > 50 × 109/L). Patients were excluded from the analysis for any of the following reasons: (1) under 18 years or over 75 years of age; (2) recurrent HCC; (3) only a single HCC tumor of any size, or multiple HCC tumors but all with diameters of 3 cm or less; (4) received previous systematic chemotherapy, targeted (Sorafenib) therapy, or radiofrequency ablation (RFA) for HCC; (5) lost to follow-up within 90 days after LR; or (6) information about prognostic variables or follow-up could not be obtained.
We collected data about each patient’s demographic and clinical characteristics, including sex, age, body mass index (BMI), Child-Pugh grade (severity of liver disease, based on 5 clinical factors: PT or INR, albumin, bilirubin, ascites, and hepatic encephalopathy), diameter of largest HCC tumor, number of tumors, preoperative hepatitis (based on history of chronic HBV infection and/or positive hepatitis B virus RNA testing), preoperative portal hypertension (defined as esophageal varices and/or splenomegaly on imaging studies, combined with a decreased platelet count [100 × 103/μL or less]), and preoperative blood testing (including AFP, liver and renal function tests, prothrombin time [PT] and international normalized ratio [INR], and complete blood count).
We also collected data for each patient about their histopathological findings from LR (microvascular invasion and cirrhosis [of the noncancerous part of the resected specimen]), volumes of intraoperative blood loss and intraoperative blood transfusion, and postoperative complications (large pleural effusion, pneumonia, portal vein thrombosis, cholestasis, and/or ascites).
The decision to utilize TACE before LR was made by the treating physician and was based on the patient’s liver function as well as the number, size, and degree of enhancement of HCC tumors observed in imaging studies. Patients receiving TACE had it administered within 3 months of LR. TACE was carried out under the guidance of digital subtraction angiography (DSA) (Allura Xper FD 20, Philips), and it was performed through the left or right hepatic artery, and directly through a tumor-feeding artery when technically possible. Hepatic artery angiography, which was performed using a 5 Fr (RH or Yashiro) catheter, was first used to assess the location, number, size, and blood supply of the target tumors. The embolization emulsion was a mixture of Epirubicin (Farmorubicin; Pharmacia, Tokyo, Japan) 30 mg to 60 mg, Lobaplatin (Chang’an International Pharmaceutical, Hainan, China) 30 mg to 50 mg, and Lipiodol (Laboratorie Guerbet, Aulnay-sous-Bois, France) 10 mL to 30 mL, and it was infused into tumor-feeding arteries
Liver resection was performed by experienced surgeons. We developed a surgical plan based on tumor size, tumor location, and liver function. The hepatectomy method contains anatomical resection and non-anatomical resection, and the extent was defined using the Brisbane 2000 Terminology of Liver Anatomy and Resections (
A PSM method was used to balance the potential biases between two groups. The propensity score was estimated using a multivariate logistic regression by using variables of diameter of largest HCC tumor, number of tumors, serum AFP level, microvascular invasion, tumor encapsulation, resection margin, and type of hepatectomy. Patients were matched 1:1 using the nearest neighbor method with a caliber of 0.05; the matching process has been described in a previous study (
The follow-up period for this study was terminated on September 30, 2019. Patients were followed at least once every 3 months after LR; the visits involved checking serum AFP levels and performing screening abdominal imaging (e.g., abdominal CT and/or MRI and/or ultrasound scans). HCC recurrence was suspected when there was a progressive elevation of serum AFP levels, a new showing contrast enhancement in the arterial phase and washout in the venous phase on CT and/or MRI, and/or hypervascularity on hepatic angiography.
The dates of tumor recurrence, last follow-up, and death were recorded. The primary endpoint was overall survival (OS), and the secondary endpoint was recurrence-free survival (RFS). OS was defined as the time from LR to death or last follow-up, and RFS was defined as the time from LR to tumor progression, death, or last follow-up (whichever came first). Tumor progression was defined as the local tumor recurrence or the occurrence of new lesions in the liver or elsewhere, based on imaging.
For the study, the patients were divided into 2 groups, with those having TACE prior to LR placed in the TACE+LR group, and those having only LR placed in the LR group. The demographic and clinicopathological characteristics of the groups were summarized using frequencies and percentages for categorical covariates and means and standard deviation (SD) for continuous covariates. The Fisher exact test was used to compare categorical covariates, while the Wilcoxon rank-sum test was used to compare continuous covariates. The cutoffs for continuous variables were chosen to allow for easy interpretation. OS and RFS rates were calculated using the Kaplan–Meier method. Univariate and multivariate Cox regression analyses were used to determine the impact of risk factors on recurrence (using RFS) and death (using OS). Variables with
A total of 488 patients met the inclusion criteria for the study. The mean follow-up period was 40.2 (range, 3.0 to 128.7) months. Of these, 223 (45.7%) were in the TACE+LR group and 265 (54.3%) were in the LR group (
Demographic and clinicopathological characteristics of patients with BCLC stage B hepatocellular carcinoma (HCC) before and after propensity score matching (PSM), by treatment (TACE+LR vs. LR), January 2007 to December 2015.
Characteristics | Before PSM | P | After PSM | P | ||
---|---|---|---|---|---|---|
TACE+LRN (%) | LRN (%) | TACE+LRN (%) | LRN (%) | |||
Total patients | 223 (100) | 265 (100) |
|
189 | 189 | |
Sex | ||||||
|
197 (88.3) | 238 (89.8) | 0.60 | 169(89.4) | 171(90.5) | 0.73 |
|
26 (12.7) | 27 (10.2) | 20(10.6) | 18(9.5) | ||
Age, |
||||||
|
179 (80.2) | 215 (81.3) | 0.81 | 150(79.4) | 155(82) | 0.515 |
|
44 (19.8) | 50 (18.7) | 39(20.6) | 34(28) | ||
Largest HCC tumor diameter, |
||||||
|
150 (67.2) | 199 (75.1) | 0.056 | 137(72.5) | 133(70.4) | 0.65 |
|
73 (28.2) | 66 (24.9) | 52(37.5) | 56(29.6) | ||
HCC tumors, |
||||||
|
172 (77.1) | 193 (72.8) | 0.28 | 141(74.6) | 143(75.7) | 0.81 |
|
51 (22.9) | 72 (27.2) | 48(25.4) | 46(24.3) | ||
Hepatitis |
174 (78.0) | 203 (76.6) | 0.71 | 142(75.1) | 147(77.8) | 0.51 |
Portal hypertension |
18 (8.1) | 11 (4.2) | 0.07 | 12(6.3) | 8(4.2) | 0.36 |
Comorbidity |
25 (11.2) | 27 (10.2) | 0.72 | 21(11.1) | 18(9.5) | 0.61 |
Alpha-fetoprotein (AFP) level, |
||||||
|
127 (57.0) | 134 (50.6) | 0.16 | 101(53.4) | 103(54.5) | 0.84 |
|
96 (43.0) | 131 (49.4) | 88(46.6) | 86(55.5) | ||
Type of hepatectomy |
||||||
|
64 (28.7) | 79 (35.4) | 0.79 | 53(28) | 60(31.7) | 0.43 |
|
159 (71.3) | 186 (64.6) | 136(72) | 129(68.3) | ||
Resection margin |
||||||
|
200 (89.7) | 203 (76.6) |
|
166(87.8) | 164(86.8) | 0.76 |
|
23 (10.3) | 62 (24.3) | 23(12.2) | 25(13.2) | ||
Tumor encapsulation |
156 (70.0) | 161 (60.8) |
|
122(64.6) | 119(63) | 0.75 |
Microvascular invasion |
61 (27.4) | 110 (41.5) |
|
61(32.3) | 59(31.2) | 0.83 |
Cirrhosis |
117(52.5) | 147(55.5) | 0.507 | 107(56.6) | 116(61.4) | 0.347 |
Postoperative complication |
13 (6.0) | 21 (8.0) | 0.37 | 11(6) | 16(8.5) | 0.32 |
|
|
|
|
|
||
|
|
|
|
|||
Body Mass Index (BMI), |
22.2 ± 3.1 | 22.4 ± 3.1 | 0.61 | 22.2 ± 3.1 | 22.1 ± 2.7 | 0.65 |
Alanine aminotransferase (ALT), |
56.1 ± 54.9 | 53.9 ± 49.4 | 0.63 | 58.7 ± 58.4 | 57.4 ± 55.2 | 0.65 |
Albumin (ALB), |
39.9 ± 6 | 40.7 ± 4.5 | 0.083 | 39.9 ± 6.5 | 40.6 ± 4.7 | 0.27 |
Total bilirubin (TBIL), |
13.8 ± 6.7 | 14.5 ± 6.5 | 0.22 | 13.9 ± 7.1 | 13.9 ± 5.4 | 0.98 |
White blood count (WBC), |
6.4 ± 2.0 | 6.8 ± 3.1 | 0.08 | 6.4 ± 1.9 | 6.8 ± 3.2 | 0.075 |
Platelet count (PLT), |
194.2 ± 85.1 | 195.9 ± 76.3 | 0.82 | 196.3 ± 84.4 | 200.3 ± 77.8 | 0.63 |
Prothrombin time (PT), |
12.1 ± 1.1 | 12.2 ± 1.1 | 0.43 | 12.1 ± 1.1 | 12.2 ± 1.1 | 0.74 |
International normalized ratio (INR) | 1.1 ± 0.1 | 1.1 ± 0.1 | 0.70 | 1.1 ± 0.1 | 1.1 ± 0.1 | 0.51 |
Intraoperative blood loss, |
651.6 ± 639.8 | 567.0 ± 794.2 | 0.20 | 673.3 ± 677.1 | 571.2 ± 637.2 | 0.13 |
Intraoperative blood transfusion, |
176.5 ± 356.2 | 148.7 ± 378.8 | 0.41 | 177 ± 359.5 | 156.6 ± 379.3 | 0.59 |
Hepatitis defined preoperatively as a history of chronic HBV infection and/or positive hepatitis C virus RNA test.
Portal hypertension defined preoperatively as esophageal varices and/or splenomegaly on imaging studies combined with a decreased platelet count [100 × 103/μL or less]).
Comorbidity defined as preoperative hypertension, diabetes, coronary disease, and/or severe anemia.
Determined by surgeon intraoperatively, anatomical approach based on the Brisbane 2000 nomenclature of liver anatomy, whereas non-anatomical approach consisted of wedge or limited resection.
Based on intraoperative surgeon estimation.
Based on intraoperative surgeon description of tumor appearing encapsulated or infiltrating (not encapsulated).
Based on postoperative histopathology report.
Postoperative large pleural effusion, pneumonia, portal vein thrombosis, and/or cholestasis.
BCLC, Barcelona Clinic Liver Cancer; TACE, transarterial chemoembolization; LR, liver resection (hepatectomy).
All bold P value were represented the significance (P < 0.05).
By the last follow-up, 107 (48%) patients in the TACE+LR group and 181 (68.3%) patients in the LR group had died. The 90-day mortality rate for patients in the TACE+LR group was 1.3% (3 patients) and for patients in the LR group was 4.2% (11 patients). Over the entire study period, patients in the TACE+LR group had significantly higher OS than patients in the LR group before PSM (
Kaplan–Meier overall survival (OS) rate curves for patients underwent TACE+LR and LR for BCLC stage B hepatocellular carcinoma (HCC) before and after PSM, January 2007 to December 2015.
Overall survival (OS) and recurrence-free survival (RFS) rates in 488 patients with BCLC stage B hepatocellular carcinoma (HCC), by treatment (TACE+LR vs. LR), January 2007 to December 2015.
Rates |
Treatment |
|
|
---|---|---|---|
TACE+LR (n = 223) % | LR (n = 265) % | ||
1-year OS | 90.6 | 73.3 |
|
3-year OS | 61.7 | 43.5 |
|
5-year OS | 52.9 | 33.8 |
|
1-year RFS | 54.6 | 39.4 |
|
2-year RFS | 41.4 | 29.4 |
|
3-year RFS | 36.3 | 26.3 |
|
BCLC, Barcelona Clinic Liver Cancer; TACE, transarterial chemoembolization; LR, liver resection (hepatectomy).
Bold values provided in this table was that P value < 0.05, there was significant difference between the two groups.
Based on multivariate analysis, LR (vs. TACE+LR) as treatment (HR=1.94, 95% CI 1.52–2.48,
Univariate and multivariate analyses of demographic and clinicopathological prognostic factors for overall survival (OS) in 488 patients with BCLC stage B hepatocellular carcinoma (HCC), January 2007 to December 2015.
Characteristics | Variables | Univariate Analysis | Multivariate Analysis | ||
---|---|---|---|---|---|
Hazard Ratio (95% CI) |
|
Hazard Ratio (95% CI) |
|
||
Type of treatment | LR vs. TACE+LR | 1.80 (1.42–2.29) |
|
1.94 (1.52–2.48) |
|
Age, |
>60 vs. ≤60 | 1.00 (0.75–1.34) | 0.99 | – | – |
Sex | Male vs. female | 0.94 (0.64–1.37) | 0.73 | – | – |
Largest HCC tumor diameter, |
≥10 vs. < 10 | 1.32 (1.03–1.7) | 0.03 | NS | 0.30 |
HCC tumors, |
>3 vs. ≤3 | 2.52 (1.97–3.23) |
|
2.19 (1.69–2.84) |
|
Portal hypertension |
Yes vs. no | 0.97 (0.60–1.59) | 0.91 | – | – |
Alpha-fetoprotein (AFP), |
>400 vs. ≤400 | 1.46 (1.16–1.84) |
|
NS | 0.15 |
Type of hepatectomy |
Non-anatomical vs. anatomical | 1.35 (1.05–1.73) |
|
1.29 (1.01–1.66) |
|
Resection margin |
>1 vs. ≤1 | 1.09 (0.81–1.47) | 0.56 | – | – |
Tumor encapsulation |
Yes vs. no | 0.84 (0.66–1.06) | 0.15 | – | – |
Microscopic vascular |
Yes vs. no | 1.94 (1.53–2.45) |
|
1.48 (1.15–1.90) |
|
Cirrhosis |
Yes vs. no | 2.67 (2.09–3.41) |
|
2.41 (1.88–3.01) |
|
Intraoperative blood transfusion | Yes vs. no | 1.71 (1.33–2.20) |
|
1.45 (1.13–1.93) |
|
Portal hypertension defined preoperatively as esophageal varices and/or splenomegaly on imaging studies combined with a decreased platelet count [100 × 103/μL or less]).
Determined by surgeon intraoperatively, anatomical approach based on the Brisbane 2000 nomenclature of liver anatomy, whereas non-anatomical approach consisted of wedge or limited resection.
Based on intraoperative surgeon estimation.
Based on intraoperative surgeon description of tumor appearing encapsulated or infiltrating (not encapsulated).
Based on postoperative histopathology report.
BCLC, Barcelona Clinic Liver Cancer; CI, confidence interval; TACE, transarterial chemoembolization; LR, liver resection (hepatectomy); NS, not significant.
Bold values provided in this table was that P value < 0.05, there was significant difference between the two groups.
By the last follow-up, 158 (70.9%) patients in the TACE+LR group and 213 (80.4%) patients in the LR group had experienced recurrence. Over the entire study period, patients in the TACE+LR group had significantly higher RFS than patients in the LR group (
Kaplan–Meier recurrence-free survival (RFS) rate curves for patients underwent TACE+LR and LR for BCLC stage B hepatocellular carcinoma (HCC) before and after PSM, January 2007 to December 2015.
Based on multivariate analysis, LR (vs. TACE+LR) as treatment (HR=1.55, 95% CI 1.26–1.91,
Univariate and multivariate analyses of demographic and clinicopathological prognostic factors for recurrence-free survival in 488 patients with BCLC stage B hepatocellular carcinoma (HCC), January 2007 to December 2015.
Characteristics | Variables | Univariate Analysis | Multivariate Analysis | ||
---|---|---|---|---|---|
Hazard Ratio (95% CI) |
|
Hazard Ratio (95% CI) |
|
||
Type of treatment | LR vs TACE+LR | 1.44 (1.17–1.76) |
|
1.55 (1.26–1.91) |
|
Age, |
>60 vs. ≤60 | 0.97 (0.75–1.25) | 0.80 | – | – |
Sex | Male vs. female | 0.85 (0.60–1.20) | 0.85 | – | – |
Largest HCC tumor diameter, |
≥10 vs. < 10 | 1.51 (1.21–1.88) |
|
1.39 (1.11–1.75) |
|
HCC tumors, |
>3 vs. ≤3 | 3.43 (2.73–4.32) |
|
2.98 (2.35–3.79) |
|
Portal hypertensiona | Yes vs. no | 1.00 (0.66–1.53) | 0.99 | – | – |
Alpha-fetoprotein (AFP), |
>400 vs. ≤400 | 1.35 (1.10–1.65) |
|
NS | 0.12 |
Type of hepatectomyb | Non-anatomical vs. anatomical | 1.31 (1.05–1.64) |
|
NS | 0.09 |
Resection marginc, |
>1 vs. ≤1 | 0.97 (0.74–1.27) | 0.83 | – | – |
Tumor encapsulationd | Yes vs. no | 0.86 (0.70–1.07) | 0.18 | – | – |
Microscopic vascular |
Yes vs. no | 1.79 (1.45–2.21) |
|
1.45 (1.16–1.81) |
|
Cirrhosise | Yes vs. no | 1.91 (1.55–2.36) |
|
1.74 (1.41–2.15) |
|
Intraoperative blood transfusion | Yes vs. no | 0.92 (0.74–1.27) | 0.83 | – | – |
aPortal hypertension defined preoperatively as esophageal varices and/or splenomegaly on imaging studies combined with a decreased platelet count [100 × 103/μL or less]).
bDetermined by surgeon intraoperatively, anatomical approach based on the Brisbane 2000 nomenclature of liver anatomy, whereas non-anatomical approach consisted of wedge or limited resection.
cBased on intraoperative surgeon estimation.
dBased on intraoperative surgeon description of tumor appearing encapsulated or infiltrating (not encapsulated).
eBased on postoperative histopathology report.
BCLC, Barcelona Clinic Liver Cancer; CI, confidence interval; TACE, transarterial chemoembolization; LR, liver resection (hepatectomy); NS, not significant.
Bold values provided in this table was that P value < 0.05, there was significant difference between the two groups.
Patients with intermediate-stage HCC have large and multifocal HCCs and do not have evidence of intrahepatic macrovascular invasion or extrahepatic metastases (
Some researchers suggest that the evidence supporting TACE as first-line treatment for intermediate-stage HCC may not be strong enough, and they suggest that because LR may result in better outcomes than TACE, it should be considered first-line treatment for most patients with intermediate-stage disease (
In this retrospective clinical study, we looked not only at 256 patients who had received LR for intermediate-stage HCC but also at 223 patients who underwent LR preceded by TACE, over a 9-year period, with a mean duration of follow-up of 40.2 months. When we compared the 2 groups in the study, we found them to be well-matched, with no significant differences in demographic or preoperative clinical characteristics (including tumor size or number, as well as baseline hepatitis, comorbidity, or AFP levels), or in type of hepatectomy performed, histopathological evidence of cirrhosis, or postoperative complications.
However, we did find that relative to the group that underwent LR alone, a significantly higher proportion of patients in the group that received TACE+LR had intraoperative findings of narrow resection margins, and a significantly lower proportion in that group had postoperative histopathological evidence of microvascular invasion. These observations suggest that by exposing the disease to cytotoxic agents and then blocking tumor vessels, TACE may have created a strong cytotoxic effect and caused substantial tumor necrosis prior to surgery, resulting in tumor contraction, narrower margins, and eradication of some of the microvascular invasion. These findings and potential mechanisms are consistent with those reported by others (
When we compared survival outcomes, patients having TACE+LR showed significantly longer OS and RFS than those having only LR. For example, the 5-year OS rate for the TACE+LR group was 52.9%, whereas that for the LR group was 33.8%. Likewise, the 3-year RFS rate for the TACE+LR group was 36.3%, whereas that for the LR group was 26.3%. Our OS and RFS results for patients having TACE+LR were markedly better than those reported by Zhao et al. for patients with intermediate-stage HCC having TACE alone. The 5-year OS rate was 12% and the 3-year RFS rate was 25% for the patients treated with only TACE, despite the vast majority of their patients having only a solitary tumor (
As noted above, some authors in the past have suggested that doing TACE before LR may increase the risk of perioperative morbidity. However, in our study there was no significant difference in the proportion of patients having postoperative complications, when comparing those having LR with those having TACE before LR. Similarly, Li et al. showed not only that the addition of preoperative TACE to LR for huge HCC (10 cm or larger) was associated with an improved OS and RFS, but also that this combination therapy did not increase perioperative morbidity or mortality (
Compared to the group of patients in our study who had LR alone, those who received TACE before LR exhibited higher numerical mean volumes of intraoperative blood loss (652 mL vs. 567 mL) and intraoperative blood transfusion (177 mL vs. 149 mL), but these differences were not statistically significant. Some have suggested that patients with hepatitis who undergo preoperative TACE before LR might suffer more intraoperative bleeding and present more operative challenges than those who do not have TACE before LR (
On multivariate analyses, confirming our results based on Kaplan-Meier estimates, we observed that LR alone was independently associated with HCC recurrence and death. Furthermore, we observed that more than 3 HCC tumors, non-anatomical hepatectomy, microscopic vascular invasion, cirrhosis, and intraoperative blood transfusion were all independent predictors of poor OS. Most of these results echo the findings from several other studies of patients who have had LR for intermediate-stage HCC (
This study has several limitations. First, this was a retrospective, single-center study that lacked randomization. The fact that the choice of treatment was made at the discretion of the treating physician may have introduced selection bias. Second, this study does not address which patients might benefit most from the addition of TACE prior to LR. It would be worthwhile to conduct an additional study to develop clinical prediction models (including with the possible use of radiomics) to identify the population that would be best served by the addition of TACE to LR for intermediate-stage HCC.
In this large retrospective study of patients with intermediate-stage HCC, the addition of TACE 1 to 3 months prior to LR resulted in significantly longer OS and RFS compared to LR alone. These results and comparisons with findings from other studies suggest that preoperative TACE with LR may result in better oncological outcomes than either TACE or LR alone, without a substantial increase in morbidity, and that this approach could be considered an effective combination treatment for intermediate-stage HCC.
All datasets presented in this study are included in the article/supplementary material.
The studies involving human participants were reviewed and approved by Ethics Committee of the Sun Yat-sen University Cancer Center. The patients/participants provided their written informed consent to participate in this study.
Conceptualization: MC, JH. Data curation: QZ, JW, ZH, FT. Formal analysis: QZ, XW, RL. Data analysis: RL, QZ. Funding acquisition: JH, QZ. Investigation: QZ, JW, ZH. Methodology: QZ, XW, ZH. Project administration: QZ, XW, JH, MC. Resources: QZ, MC, JH. Original draft: QZ, XW. Writing—review and editing: QZ, MC, JH. All authors contributed to the article and approved the submitted version.
This research was funded by the Chinese Postdoctoral Science Foundation (No. 2019M653203); National Natural Science Foundation of China (No. 81771955).
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.