Estimation of lead-time bias and its impact on the outcome of surveillance for the early diagnosis of hepatocellular carcinoma.
OBJECTIVE
Lead-time is the time by which diagnosis is anticipated by screening/surveillance with respect to the symptomatic detection of a disease. Any screening program, including surveillance for hepatocellular carcinoma (HCC), is subject to lead-time bias. Data regarding lead-time for HCC are lacking. Aims of the present study were to calculate lead-time and to assess its impact on the benefit obtainable from the surveillance of cirrhotic patients.


METHODS
One-thousand three-hundred and eighty Child-Pugh class A/B patients from the ITA.LI.CA database, in whom HCC was detected during semiannual surveillance (n = 850), annual surveillance (n = 234) or when patients came when symptomatic (n = 296), were selected. Lead-time was estimated by means of appropriate formulas and Monte Carlo simulation, including 1000 patients for each arm.


RESULTS
The 5-year overall survival after HCC diagnosis was 32.7% in semiannually surveilled patients, 25.2% in annually surveilled patients, and 12.2% in symptomatic patients (p<0.001). In a 10-year follow-up perspective, the median lead-time calculated for all surveilled patients was 6.5 months (7.2 for semiannual and 4.1 for annual surveillance). Lead-time bias accounted for most of the surveillance benefit until the third year of follow-up after HCC diagnosis. However, even after lead-time adjustment, semiannual surveillance maintained a survival benefit over symptomatic diagnosis (number of patients needed to screen = 13), as did annual surveillance (18 patients).


CONCLUSIONS
Lead-time bias is the main determinant of the short-term benefit provided by surveillance for HCC, but this benefit becomes factual in a long-term perspective, confirming the clinical utility of an anticipated diagnosis of HCC.
Dipartimento di Scienze Mediche e Chirurgiche, Policlinico S. Orsola-Malpighi, Alma Mater Studiorum - Università of Bologna, Italy. Electronic address: aleqko@libero.it.
Alessandro
A
Cucchetti
Dipartimento di Scienze Mediche e Chirurgiche, Policlinico S. Orsola-Malpighi, Alma Mater Studiorum - Università of Bologna, Italy.
Franco
F
Trevisani
Dipartimento di Scienze Mediche e Chirurgiche, Policlinico S. Orsola-Malpighi, Alma Mater Studiorum - Università of Bologna, Italy.
Anna
A
Pecorelli
Dipartimento di Scienze Mediche e Chirurgiche, Policlinico S. Orsola-Malpighi, Alma Mater Studiorum - Università of Bologna, Italy.
Virginia
V
Erroi
Dipartimento di Scienze Chirurgiche e Gastroenterologiche, Unità di Gastroenterologia, Università di Padova, Padova, Italy.
Fabio
F
Farinati
Divisione di Chirurgia, Policlinico San Marco, Zingonia, Italy.
Francesca
F
Ciccarese
Unità di Medicina Interna e Gastroenterologia, Complesso Integrato Columbus, Università Cattolica di Roma, Roma, Italy.
Gian Lodovico
GL
Rapaccini
Divisione di Medicina, Azienda Ospedaliera Bolognini, Seriate, Italy.
Mariella
M
Di Marco
Unità Operativa di Gastroenterologia, Ospedale Belcolle, Viterbo, Italy.
Eugenio
E
Caturelli
Dipartimento di Medicina Interna, Unità di Gastroenterologia, Università di Genova, Genova, Italy.
Edoardo G
EG
Giannini
Dipartimento di Scienze Mediche e Chirurgiche, Policlinico S. Orsola-Malpighi, Alma Mater Studiorum - Università of Bologna, Italy.
Marco
M
Zoli
Dipartimento di Medicina, Unità di Radiologia, Ospedale Fatebenefratelli, Milano, Italy.
Franco
F
Borzio
Dipartimento Biomedico di Medicina Interna e Specialistica, Unità di Gastroenterologia, Università di Palermo, Palermo, Italy.
Giuseppe
G
Cabibbo
Ospedale Regionale di Bolzano, Unità di Gastroenterologia, Bolzano, Italy.
Martina
M
Felder
Unità di Medicina Interna e Gastroenterologia, Policlinico Gemelli, Università Cattolica di Roma, Roma, Italy.
Antonio
A
Gasbarrini
Unità Operativa Gastroenterologia e Malattie del Ricambio, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
Rodolfo
R
Sacco
Unità di Medicina Interna, Presidio Ospedaliero di Faenza, Faenza, Italy.
Francesco Giuseppe
FG
Foschi
Unità di Malattie Infettive ed Epatologia, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
Gabriele
G
Missale
Dipartimento di Medicina Clinica e Chirurgia, Unità di Gastroenterologia, Università di Napoli "Federico II", Napoli, Italy.
Filomena
F
Morisco
Clinica di Gastroenterologia, Università Politecnica delle Marche, Ancona, Italy.
Gianluca Svegliati
GS
Baroni
Dipartimento Biomedico di Medicina Interna e Specialistica, Unità di Medicina Interna, Palermo, Italy.
Roberto
R
Virdone
Dipartimento di Scienze Mediche e Chirurgiche, Policlinico S. Orsola-Malpighi, Alma Mater Studiorum - Università of Bologna, Italy.
Mauro
M
Bernardi
Dipartimento di Scienze Mediche e Chirurgiche, Policlinico S. Orsola-Malpighi, Alma Mater Studiorum - Università of Bologna, Italy.
Antonio D
AD
Pinna
D000368:Aged; D015982:Bias; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000401:mortality; D055088:Early Detection of Cancer; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000401:mortality; D008297:Male; D013997:Time Factors
Cirrhosis; Hepatocellular carcinoma; Lead-time bias; Surveillance