TY - JOUR
T1 - The current status of tumor markers as biomarkers in the era of immunotherapy for hepatocellular carcinoma
T2 - alpha-fetoprotein alone is not sufficient
AU - behalf of the Real-life Practice Experts for HCC (RELPEC) Study Group and HCC 48 Group (hepatocellular carcinoma experts from 48 clinics in Japan).
AU - Hiraoka, Atsushi
AU - Kudo, Masatoshi
AU - Tada, Toshifumi
AU - Hatanaka, Takeshi
AU - Kakizaki, Satoru
AU - Kariyama, Kazuya
AU - Ohama, Hideko
AU - Tsuji, Kunihiko
AU - Ishikawa, Toru
AU - Takaguchi, Koichi
AU - Itobayashi, Ei
AU - Toyoda, Hidenori
AU - Matono, Tomomitsu
AU - Yata, Yutaka
AU - Ogawa, Chikara
AU - Naganuma, Atsushi
AU - Tani, Joji
AU - Atsukawa, Masanori
AU - Nishimura, Takashi
AU - Tajiri, Kazuto
AU - Kawata, Kazuhito
AU - Kosaka, Hisashi
AU - Kuroda, Hidekatsu
AU - Hirooka, Masashi
AU - Nishikawa, Hiroki
AU - Tada, Fujimasa
AU - Nakamura, Shinichiro
AU - Kanayama, Yuki
AU - Nouso, Kazuhiro
AU - Tanaka, Hironori
AU - Tanaka, Kazunari
AU - Imai, Michitaka
AU - Tsutsui, Akemi
AU - Nagano, Takuya
AU - Aoki, Tomoko
AU - Koshiyama, Yuichi
AU - Morishita, Asahiro
AU - Itokawa, Norio
AU - Okubo, Tomomi
AU - Arai, Taeang
AU - Fukunishi, Shinya
AU - Noritake, Hidenao
AU - Nakamura, Yoshiko
AU - Yoshida, Osamu
AU - Enomoto, Hirayuki
AU - Kaibori, Masaki
AU - Hiasa, Yoichi
AU - Kumada, Takashi
N1 - Publisher Copyright:
© 2025 S. Karger AG, Basel.
PY - 2025
Y1 - 2025
N2 - Introduction: Rapid development of systemic treatments has resulted in improved prognosis for unresectable hepatocellular carcinoma (uHCC) patients. Since immune therapy shows a favorable therapeutic efficacy, use of tumor markers as biomarkers for monitoring treatment response is necessary. This study aimed to elucidate changes in positive rates of 3 available tumor markers in Japan, including alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), and lens culinaris agglutinin-reactive AFP (AFP-L3) in uHCC patients treated with systemic therapies over time. Methods: From 2009 to 2023, 1470 uHCC patients with data of tumor markers before starting treatment were enrolled. The positivity cut-off value for AFP was 20 ng/mL, for AFP-L3 was 10%, and for DCP was 40 mAU/mL. After dividing the 15 years examined into three periods of five years each (period I, II, III), clinical features of the enrolled patients were evaluated, retrospectively. Results: The percentage of Barcelona Clinic Liver Cancer stage B patients who received systemic therapy increased from period I to III (27.7%, 38.5%, 46.6%, respectively, P<0.001), which was also seen for HCC patients with a non-viral etiology (alcohol and others) (29.9%, 39.7%, 49.6%, respectively P<0.001). Positive rates for AFP (67.8%, 62.1%, 50.8%, respectively) and DCP (84.1%, 80.5%, 72.7%, respectively) were decreased (each P<0.001), while the AFP-L3 rate did not show a significant change (54.4%, 57.7%, 51.9%, respectively P=0.390). Among the AFP-negative patients, the rate of positive for DCP or AFP-L3 was increased (24.4%, 28.1%, 35.4%, respectively, P=0.002). Conclusion: Based on introduction of systemic treatment in an early stage and increasing numbers of HCC cases with a non-viral etiology, the positive rate of AFP level has been declining. Thus, determination of DCP and AFP-L3 in addition to AFP as markers should be more actively utilized in clinical practice, as well as clinical trials for monitoring and evaluating treatment response in this era of combination immunotherapy as a powerful treatment.
AB - Introduction: Rapid development of systemic treatments has resulted in improved prognosis for unresectable hepatocellular carcinoma (uHCC) patients. Since immune therapy shows a favorable therapeutic efficacy, use of tumor markers as biomarkers for monitoring treatment response is necessary. This study aimed to elucidate changes in positive rates of 3 available tumor markers in Japan, including alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), and lens culinaris agglutinin-reactive AFP (AFP-L3) in uHCC patients treated with systemic therapies over time. Methods: From 2009 to 2023, 1470 uHCC patients with data of tumor markers before starting treatment were enrolled. The positivity cut-off value for AFP was 20 ng/mL, for AFP-L3 was 10%, and for DCP was 40 mAU/mL. After dividing the 15 years examined into three periods of five years each (period I, II, III), clinical features of the enrolled patients were evaluated, retrospectively. Results: The percentage of Barcelona Clinic Liver Cancer stage B patients who received systemic therapy increased from period I to III (27.7%, 38.5%, 46.6%, respectively, P<0.001), which was also seen for HCC patients with a non-viral etiology (alcohol and others) (29.9%, 39.7%, 49.6%, respectively P<0.001). Positive rates for AFP (67.8%, 62.1%, 50.8%, respectively) and DCP (84.1%, 80.5%, 72.7%, respectively) were decreased (each P<0.001), while the AFP-L3 rate did not show a significant change (54.4%, 57.7%, 51.9%, respectively P=0.390). Among the AFP-negative patients, the rate of positive for DCP or AFP-L3 was increased (24.4%, 28.1%, 35.4%, respectively, P=0.002). Conclusion: Based on introduction of systemic treatment in an early stage and increasing numbers of HCC cases with a non-viral etiology, the positive rate of AFP level has been declining. Thus, determination of DCP and AFP-L3 in addition to AFP as markers should be more actively utilized in clinical practice, as well as clinical trials for monitoring and evaluating treatment response in this era of combination immunotherapy as a powerful treatment.
KW - alpha-fetoprotein
KW - des-gamma-carboxy prothrombin (DCP)
KW - hepatocellular carcinoma
KW - immune-checkpoint inhibitor
KW - lens culinaris agglutinin-reactive AFP (AFP-L3)
UR - http://www.scopus.com/inward/record.url?scp=105000062369&partnerID=8YFLogxK
U2 - 10.1159/000543405
DO - 10.1159/000543405
M3 - 学術論文
C2 - 39900019
AN - SCOPUS:105000062369
SN - 0030-2414
JO - Oncology (Switzerland)
JF - Oncology (Switzerland)
ER -