Prognostic Significance of Recurrence and Timing of Recurrence on Survival Among Patients with Early-Stage Hepatocellular Carcinoma in U.S. Clinical Practice

Shishir K. Maithel; Rongrong Wang; Joanna Harton; Adam Yopp; Shimul A. Shah; Flavio G. Rocha; Sairy Hernandez; Spencer Cheng; Sarika Ogale; Ruoding Tan

doi:10.1245/s10434-024-16476-2

Prognostic Significance of Recurrence and Timing of Recurrence on Survival Among Patients with Early-Stage Hepatocellular Carcinoma in U.S. Clinical Practice

Shishir K. Maithel^*, Rongrong Wang, Joanna Harton, Adam Yopp, Shimul A. Shah, Flavio G. Rocha, Sairy Hernandez, Spencer Cheng, Sarika Ogale, Ruoding Tan

^*Corresponding author for this work

Surgery, Surgical Oncology Division

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Many patients with hepatocellular carcinoma (HCC) experience recurrence after curative-intent resection or ablation, with a poor prognosis. Real-world patterns of recurrence and the prognostic significance of early recurrence in U.S. clinical practice have not been well characterized. Methods: This retrospective observational study was designed to evaluate the impact of recurrence on overall survival (OS) among patients with HCC following initial curative-intent resection or ablation. We used the Surveillance, Epidemiology, and End Results cancer registry linked with Medicare claims (January 1, 2010–December 31, 2019). Eligible patients (≥66 years) diagnosed with HCC (2010–2017) had liver resection or ablation within 180 days of diagnosis. Patients were stratified by recurrence status using diagnosis- and treatment-based definitions of recurrence. Early or late recurrence was defined as within 1 year or after 1 year, respectively. Adjusted OS analyses used multivariable Cox regression models. Results: A total of 1,146 patients were included. During a median overall follow-up of 35.2 months, 736 (64%) patients had a recurrence, of whom 380 (52%) had early recurrence (within 1 year). In the adjusted analysis, patients with recurrence had a 2.24-fold higher risk of death (95% confidence interval 1.85, 2.71; P < 0.001). Patients with early recurrence had a 1.39-fold higher risk of death (95% confidence interval 1.14, 1.68; P < 0.001) than those with late recurrence. Conclusions: Recurrence and the timing of recurrence are significant predictors of increased mortality risk for patients with HCC following initial curative-intent resection or ablation, highlighting the need for effective adjuvant therapies that may delay or avoid recurrences.

Original language	English (US)
Article number	e5904
Pages (from-to)	1054-1062
Number of pages	9
Journal	Annals of surgical oncology
Volume	32
Issue number	2
DOIs	https://doi.org/10.1245/s10434-024-16476-2
State	Published - Feb 2025

Funding

This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. The authors acknowledge the efforts of the National Cancer Institute; Information Management Services (IMS), Inc.; and the Surveillance, Epidemiology, and End Results (SEER) Program tumor registries in the creation of the SEER-Medicare database. Medical writing support was provided by Jeff Frimpter, MPH, of Nucleus Global, an Inizio Company, and funded by Genentech, Inc.

Keywords

Hepatocellular carcinoma
Immunotherapy
Liver cancer
Medicare
Recurrence
Systemic therapy

ASJC Scopus subject areas

Surgery
Oncology

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10.1245/s10434-024-16476-2

Cite this

Maithel, S. K., Wang, R., Harton, J., Yopp, A., Shah, S. A., Rocha, F. G., Hernandez, S., Cheng, S., Ogale, S., & Tan, R. (2025). Prognostic Significance of Recurrence and Timing of Recurrence on Survival Among Patients with Early-Stage Hepatocellular Carcinoma in U.S. Clinical Practice. Annals of surgical oncology, 32(2), 1054-1062. Article e5904. https://doi.org/10.1245/s10434-024-16476-2

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title = "Prognostic Significance of Recurrence and Timing of Recurrence on Survival Among Patients with Early-Stage Hepatocellular Carcinoma in U.S. Clinical Practice",

abstract = "Background: Many patients with hepatocellular carcinoma (HCC) experience recurrence after curative-intent resection or ablation, with a poor prognosis. Real-world patterns of recurrence and the prognostic significance of early recurrence in U.S. clinical practice have not been well characterized. Methods: This retrospective observational study was designed to evaluate the impact of recurrence on overall survival (OS) among patients with HCC following initial curative-intent resection or ablation. We used the Surveillance, Epidemiology, and End Results cancer registry linked with Medicare claims (January 1, 2010–December 31, 2019). Eligible patients (≥66 years) diagnosed with HCC (2010–2017) had liver resection or ablation within 180 days of diagnosis. Patients were stratified by recurrence status using diagnosis- and treatment-based definitions of recurrence. Early or late recurrence was defined as within 1 year or after 1 year, respectively. Adjusted OS analyses used multivariable Cox regression models. Results: A total of 1,146 patients were included. During a median overall follow-up of 35.2 months, 736 (64%) patients had a recurrence, of whom 380 (52%) had early recurrence (within 1 year). In the adjusted analysis, patients with recurrence had a 2.24-fold higher risk of death (95% confidence interval 1.85, 2.71; P < 0.001). Patients with early recurrence had a 1.39-fold higher risk of death (95% confidence interval 1.14, 1.68; P < 0.001) than those with late recurrence. Conclusions: Recurrence and the timing of recurrence are significant predictors of increased mortality risk for patients with HCC following initial curative-intent resection or ablation, highlighting the need for effective adjuvant therapies that may delay or avoid recurrences.",

keywords = "Hepatocellular carcinoma, Immunotherapy, Liver cancer, Medicare, Recurrence, Systemic therapy",

author = "Maithel, {Shishir K.} and Rongrong Wang and Joanna Harton and Adam Yopp and Shah, {Shimul A.} and Rocha, {Flavio G.} and Sairy Hernandez and Spencer Cheng and Sarika Ogale and Ruoding Tan",

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Maithel, SK, Wang, R, Harton, J, Yopp, A, Shah, SA, Rocha, FG, Hernandez, S, Cheng, S, Ogale, S & Tan, R 2025, 'Prognostic Significance of Recurrence and Timing of Recurrence on Survival Among Patients with Early-Stage Hepatocellular Carcinoma in U.S. Clinical Practice', Annals of surgical oncology, vol. 32, no. 2, e5904, pp. 1054-1062. https://doi.org/10.1245/s10434-024-16476-2

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T1 - Prognostic Significance of Recurrence and Timing of Recurrence on Survival Among Patients with Early-Stage Hepatocellular Carcinoma in U.S. Clinical Practice

AU - Maithel, Shishir K.

AU - Wang, Rongrong

AU - Harton, Joanna

AU - Yopp, Adam

AU - Shah, Shimul A.

AU - Rocha, Flavio G.

AU - Hernandez, Sairy

AU - Cheng, Spencer

AU - Ogale, Sarika

AU - Tan, Ruoding

N1 - Publisher Copyright: © Society of Surgical Oncology 2024.

PY - 2025/2

Y1 - 2025/2

N2 - Background: Many patients with hepatocellular carcinoma (HCC) experience recurrence after curative-intent resection or ablation, with a poor prognosis. Real-world patterns of recurrence and the prognostic significance of early recurrence in U.S. clinical practice have not been well characterized. Methods: This retrospective observational study was designed to evaluate the impact of recurrence on overall survival (OS) among patients with HCC following initial curative-intent resection or ablation. We used the Surveillance, Epidemiology, and End Results cancer registry linked with Medicare claims (January 1, 2010–December 31, 2019). Eligible patients (≥66 years) diagnosed with HCC (2010–2017) had liver resection or ablation within 180 days of diagnosis. Patients were stratified by recurrence status using diagnosis- and treatment-based definitions of recurrence. Early or late recurrence was defined as within 1 year or after 1 year, respectively. Adjusted OS analyses used multivariable Cox regression models. Results: A total of 1,146 patients were included. During a median overall follow-up of 35.2 months, 736 (64%) patients had a recurrence, of whom 380 (52%) had early recurrence (within 1 year). In the adjusted analysis, patients with recurrence had a 2.24-fold higher risk of death (95% confidence interval 1.85, 2.71; P < 0.001). Patients with early recurrence had a 1.39-fold higher risk of death (95% confidence interval 1.14, 1.68; P < 0.001) than those with late recurrence. Conclusions: Recurrence and the timing of recurrence are significant predictors of increased mortality risk for patients with HCC following initial curative-intent resection or ablation, highlighting the need for effective adjuvant therapies that may delay or avoid recurrences.

AB - Background: Many patients with hepatocellular carcinoma (HCC) experience recurrence after curative-intent resection or ablation, with a poor prognosis. Real-world patterns of recurrence and the prognostic significance of early recurrence in U.S. clinical practice have not been well characterized. Methods: This retrospective observational study was designed to evaluate the impact of recurrence on overall survival (OS) among patients with HCC following initial curative-intent resection or ablation. We used the Surveillance, Epidemiology, and End Results cancer registry linked with Medicare claims (January 1, 2010–December 31, 2019). Eligible patients (≥66 years) diagnosed with HCC (2010–2017) had liver resection or ablation within 180 days of diagnosis. Patients were stratified by recurrence status using diagnosis- and treatment-based definitions of recurrence. Early or late recurrence was defined as within 1 year or after 1 year, respectively. Adjusted OS analyses used multivariable Cox regression models. Results: A total of 1,146 patients were included. During a median overall follow-up of 35.2 months, 736 (64%) patients had a recurrence, of whom 380 (52%) had early recurrence (within 1 year). In the adjusted analysis, patients with recurrence had a 2.24-fold higher risk of death (95% confidence interval 1.85, 2.71; P < 0.001). Patients with early recurrence had a 1.39-fold higher risk of death (95% confidence interval 1.14, 1.68; P < 0.001) than those with late recurrence. Conclusions: Recurrence and the timing of recurrence are significant predictors of increased mortality risk for patients with HCC following initial curative-intent resection or ablation, highlighting the need for effective adjuvant therapies that may delay or avoid recurrences.

KW - Hepatocellular carcinoma

KW - Immunotherapy

KW - Liver cancer

KW - Medicare

KW - Recurrence

KW - Systemic therapy

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Prognostic Significance of Recurrence and Timing of Recurrence on Survival Among Patients with Early-Stage Hepatocellular Carcinoma in U.S. Clinical Practice

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