Survival impact of delayed treatment in patients with hepatocellular carcinoma undergoing locoregional therapy: is there a lead-time bias?
OBJECTIVE
Many reports indicate the importance of active treatment for hepatocellular carcinoma (HCC), but there are few studies available that address the impact of delayed therapy on survival or take the lead-time bias into account. The objective of this study was to investigate whether patients with delayed locoregional therapy for HCC truly have a shortened survival from the time of diagnosis.


METHODS
Survival rates were compared between 48 HCC patients with treatment delay and 96 age- and gender-matched controls without delay. All patients underwent transarterial chemoembolization or percutaneous ethanol or acetic acid injection for HCC. Treatment delay was defined as a >2 months' time interval between diagnosis and treatment.


RESULTS
Baseline comparison showed that patients with treatment delay had higher scores in the model for endstage liver disease compared with those of patients without delay (12.3+/-1.8 versus 11.1+/-2.5, p=0.01). In the Cox multivariate model, advanced cancer stage (relative risk (RR): 2.66, p=0.001), Child-Turcotte-Pugh class B (RR: 3.81, p<0.001), tumor size >5 cm (RR: 2.02, p=0.011) and treatment delay (RR: 2.91, p=0.001) were independent poor prognostic predictors. Among patients with treatment delay, disease progression was registered in 30 (63%) patients. Patients with prolonged treatment delay (>3 months) were more likely to have tumor progression (p=0.013). In the Cox model, a treatment delay of >3 months independently predicted a poor rate of survival (RR: 3.67, p=0.002).


CONCLUSIONS
Delayed HCC treatment is linked with shortened overall survival unrelated to the lead-time bias in patients undergoing locoregional therapy. Prolonged treatment delay of more than 3 months in these patients may worsen the long-term outcome.
Huo
Teh-Ia
TI
Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan. tihuo@vghtpe.gov.tw
Huang
Yi-Hsiang
YH
Chiang
Jen-Huei
JH
Wu
Jaw-Ching
JC
Lee
Pui-Ching
PC
Chi
Chin-Wen
CW
Lee
Shou-Dong
SD
D019342:Acetic Acid / Q000008:administration & dosage*; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016461:Chemoembolization, Therapeutic; D018450:Disease Progression; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D015552:Injections, Intralesional; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D015996:Survival Rate
D000431:Ethanol; D019342:Acetic Acid