Healthcare Utilization, Costs, and Cost-Effectiveness of Patients Undergoing Laparoscopic and Open Hemihepatectomy: A Secondary Analysis of the ORANGE II PLUS Randomized Controlled, Phase 3, Superiority Trial

Bram Olij; Gabriela Pilz da Cunha; ORANGE II PLUS Collaborative; Merel Kimman; Francesca Ratti; Mohammad Abu Hilal; Roberto I Troisi; Robert P Sutcliffe; Marc G Besselink; Somaiah Aroori; Krishna V Menon; Bjørn Edwin; Mathieu D'Hondt; Valerio Lucidi; Tom F Ulmer; Rafael Díaz-Nieto; Zahir Soonawalla; Steve White; Gregory Sergeant; Mariëlle M E Coolsen; Christoph Kuemmerli; Vincenzo Scuderi; Frederik Berrevoet; Aude Vanlander

doi:10.1245/s10434-025-18779-4

Healthcare Utilization, Costs, and Cost-Effectiveness of Patients Undergoing Laparoscopic and Open Hemihepatectomy: A Secondary Analysis of the ORANGE II PLUS Randomized Controlled, Phase 3, Superiority Trial

Bram Olij^*
, Gabriela Pilz da Cunha
, ORANGE II PLUS Collaborative
, Merel Kimman
, Francesca Ratti
, Mohammad Abu Hilal
, Roberto I Troisi
, Robert P Sutcliffe
, Marc G Besselink
, Somaiah Aroori
, Krishna V Menon
, Bjørn Edwin
, Mathieu D'Hondt
, Valerio Lucidi
, Tom F Ulmer
, Rafael Díaz-Nieto
, Zahir Soonawalla
, Steve White
, Gregory Sergeant
, Mariëlle M E Coolsen

Christoph Kuemmerli, Vincenzo Scuderi, Frederik Berrevoet, Aude Vanlander

^*Corresponding author for this work

Maastricht University Medical Centre
IRCCS Ospedale San Raffaele
University of Jordan
Federico II University Hospital Naples
University Hospitals Birmingham NHS Foundation Trust
Amsterdam UMC, Locatie UvA/AMC
University Hospitals Plymouth NHS Trust
King's College Hospital NHS Foundation Trust
Oslo University Hospital
Department of Digestive and Hepatobiliary/Pancreatic Surgery
Digestive and Emergency Surgery Department
University Hospital Aintree
Oxford University Hospitals NHS Foundation Trust
Newcastle upon Tyne Hospitals NHS Foundation Trust
Jessa Hospital
University Hospital Southampton and University of Southampton
Ghent University Hospital
Cancer Center Amsterdam (CCA)
Amsterdam UMC
University of Southampton
Addenbrooke's Hospital

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

2 Citations (Scopus)

Abstract

BACKGROUND:

Laparoscopic hemihepatectomy (LH) has favorable short-term outcomes compared with open hemihepatectomy (OH), including shorter hospital stay. An in-depth healthcare utilization and cost-effectiveness analysis of the international multicenter ORANGE II PLUS randomized controlled trial comparing LH and OH was performed.

PATIENTS AND METHODS:

Patients were randomly assigned to LH or OH in 16 European centers from October 2013 to January 2019. Costs were determined as a product of unit costs using patient-level, clinician-reported resource utilization up to 90 days. Item-specific resource use per country was presented. The measure of effect was quality-adjusted life year (QALY). Cost and effect differences were compared between treatment arms using nonparametric bootstrapping, from a Dutch healthcare cost perspective. A cost-effectiveness analysis was performed to establish the incremental cost-effectiveness ratio (ICER), i.e., costs per QALY gained, for LH compared with OH 1 year postoperatively.

RESULTS:

Among 332 patients randomized to LH (n = 166) and OH (n = 166), intraoperative costs were higher for LH (LH 13,208 € versus OH 9437 €), while postoperative costs were lower for LH (LH 5774 € versus OH 7703 €). Longer operative time and greater instrument use contributed to higher intraoperative costs, while shorter hospital stays contributed to lower postoperative costs. Mean overall costs per patient were higher in LH (LH 18,982 € versus OH 17,141 €). The QALYs gained over 1 year postoperative were mean (standard deviation [SD]) 0.834 (0.218) for LH and mean 0.795 (0.237) for OH. The ICER was 36,677 € per additional QALY gained, and uncertainty analyses showed that LH had a 77% probability of being cost-effective compared with OH at a willingness-to-pay (WTP) threshold of 80,000 €.

CONCLUSIONS:

Although LH was more costly than OH, in a multicenter randomized trial, its clinical advantages translated into more QALYs gained over the first postoperative year and high probability of cost-effectiveness. These findings suggest that, where resources allow, LH may be preferred over OH for selected patients, offering both clinical benefits and acceptable economic value.

Original language	English
Journal	Annals of Surgical Oncology
Early online date	12 Dec 2025
DOIs	https://doi.org/10.1245/s10434-025-18779-4
Publication status	Published - Apr 2026
Externally published	Yes

Bibliographical note

Publisher Copyright:
© The Author(s) 2025.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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Olij, B., Pilz da Cunha, G., ORANGE II PLUS Collaborative, Kimman, M., Ratti, F., Abu Hilal, M., Troisi, R. I., Sutcliffe, R. P., Besselink, M. G., Aroori, S., Menon, K. V., Edwin, B., D'Hondt, M., Lucidi, V., Ulmer, T. F., Díaz-Nieto, R., Soonawalla, Z., White, S., Sergeant, G., ... Vanlander, A. (2026). Healthcare Utilization, Costs, and Cost-Effectiveness of Patients Undergoing Laparoscopic and Open Hemihepatectomy: A Secondary Analysis of the ORANGE II PLUS Randomized Controlled, Phase 3, Superiority Trial. Annals of Surgical Oncology. https://doi.org/10.1245/s10434-025-18779-4

@article{4a3223205f2e4ce181540685e32d08fe,

title = "Healthcare Utilization, Costs, and Cost-Effectiveness of Patients Undergoing Laparoscopic and Open Hemihepatectomy: A Secondary Analysis of the ORANGE II PLUS Randomized Controlled, Phase 3, Superiority Trial",

abstract = "BACKGROUND: Laparoscopic hemihepatectomy (LH) has favorable short-term outcomes compared with open hemihepatectomy (OH), including shorter hospital stay. An in-depth healthcare utilization and cost-effectiveness analysis of the international multicenter ORANGE II PLUS randomized controlled trial comparing LH and OH was performed.PATIENTS AND METHODS: Patients were randomly assigned to LH or OH in 16 European centers from October 2013 to January 2019. Costs were determined as a product of unit costs using patient-level, clinician-reported resource utilization up to 90 days. Item-specific resource use per country was presented. The measure of effect was quality-adjusted life year (QALY). Cost and effect differences were compared between treatment arms using nonparametric bootstrapping, from a Dutch healthcare cost perspective. A cost-effectiveness analysis was performed to establish the incremental cost-effectiveness ratio (ICER), i.e., costs per QALY gained, for LH compared with OH 1 year postoperatively.RESULTS: Among 332 patients randomized to LH (n = 166) and OH (n = 166), intraoperative costs were higher for LH (LH 13,208 € versus OH 9437 €), while postoperative costs were lower for LH (LH 5774 € versus OH 7703 €). Longer operative time and greater instrument use contributed to higher intraoperative costs, while shorter hospital stays contributed to lower postoperative costs. Mean overall costs per patient were higher in LH (LH 18,982 € versus OH 17,141 €). The QALYs gained over 1 year postoperative were mean (standard deviation [SD]) 0.834 (0.218) for LH and mean 0.795 (0.237) for OH. The ICER was 36,677 € per additional QALY gained, and uncertainty analyses showed that LH had a 77\% probability of being cost-effective compared with OH at a willingness-to-pay (WTP) threshold of 80,000 €.CONCLUSIONS: Although LH was more costly than OH, in a multicenter randomized trial, its clinical advantages translated into more QALYs gained over the first postoperative year and high probability of cost-effectiveness. These findings suggest that, where resources allow, LH may be preferred over OH for selected patients, offering both clinical benefits and acceptable economic value.",

author = "Bram Olij and \{Pilz da Cunha\}, Gabriela and \{ORANGE II PLUS Collaborative\} and Merel Kimman and Francesca Ratti and \{Abu Hilal\}, Mohammad and Troisi, \{Roberto I\} and Sutcliffe, \{Robert P\} and Besselink, \{Marc G\} and Somaiah Aroori and Menon, \{Krishna V\} and Bj{\o}rn Edwin and Mathieu D'Hondt and Valerio Lucidi and Ulmer, \{Tom F\} and Rafael D{\'i}az-Nieto and Zahir Soonawalla and Steve White and Gregory Sergeant and Coolsen, \{Mari{\"e}lle M E\} and Christoph Kuemmerli and Vincenzo Scuderi and Frederik Berrevoet and Aude Vanlander and Ravi Marudanayagam and Tanis, \{Pieter J\} and Dewulf, \{Maxime J L\} and Fichtinger, \{Robert S\} and Eminton, \{Zina B\} and Neumann, \{Ulf P\} and Lloyd Brandts and Pugh, \{Si{\^a}n A\} and Fretland, \{{\AA}smund A\} and Primrose, \{John N\} and \{van Dam\}, \{Ronald M\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2026",

month = apr,

doi = "10.1245/s10434-025-18779-4",

language = "English",

journal = "Annals of Surgical Oncology",

issn = "1068-9265",

publisher = "Springer Science+Business Media",

}

Olij, B, Pilz da Cunha, G, ORANGE II PLUS Collaborative, Kimman, M, Ratti, F, Abu Hilal, M, Troisi, RI, Sutcliffe, RP, Besselink, MG, Aroori, S, Menon, KV, Edwin, B, D'Hondt, M, Lucidi, V, Ulmer, TF, Díaz-Nieto, R, Soonawalla, Z, White, S, Sergeant, G, Coolsen, MME, Kuemmerli, C, Scuderi, V, Berrevoet, F & Vanlander, A 2026, 'Healthcare Utilization, Costs, and Cost-Effectiveness of Patients Undergoing Laparoscopic and Open Hemihepatectomy: A Secondary Analysis of the ORANGE II PLUS Randomized Controlled, Phase 3, Superiority Trial', Annals of Surgical Oncology. https://doi.org/10.1245/s10434-025-18779-4

Healthcare Utilization, Costs, and Cost-Effectiveness of Patients Undergoing Laparoscopic and Open Hemihepatectomy: A Secondary Analysis of the ORANGE II PLUS Randomized Controlled, Phase 3, Superiority Trial. / Olij, Bram; Pilz da Cunha, Gabriela; ORANGE II PLUS Collaborative et al.
In: Annals of Surgical Oncology, 04.2026.

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

TY - JOUR

T1 - Healthcare Utilization, Costs, and Cost-Effectiveness of Patients Undergoing Laparoscopic and Open Hemihepatectomy

T2 - A Secondary Analysis of the ORANGE II PLUS Randomized Controlled, Phase 3, Superiority Trial

AU - Olij, Bram

AU - Pilz da Cunha, Gabriela

AU - ORANGE II PLUS Collaborative

AU - Kimman, Merel

AU - Ratti, Francesca

AU - Abu Hilal, Mohammad

AU - Troisi, Roberto I

AU - Sutcliffe, Robert P

AU - Besselink, Marc G

AU - Aroori, Somaiah

AU - Menon, Krishna V

AU - Edwin, Bjørn

AU - D'Hondt, Mathieu

AU - Lucidi, Valerio

AU - Ulmer, Tom F

AU - Díaz-Nieto, Rafael

AU - Soonawalla, Zahir

AU - White, Steve

AU - Sergeant, Gregory

AU - Coolsen, Mariëlle M E

AU - Kuemmerli, Christoph

AU - Scuderi, Vincenzo

AU - Berrevoet, Frederik

AU - Vanlander, Aude

AU - Marudanayagam, Ravi

AU - Tanis, Pieter J

AU - Dewulf, Maxime J L

AU - Fichtinger, Robert S

AU - Eminton, Zina B

AU - Neumann, Ulf P

AU - Brandts, Lloyd

AU - Pugh, Siân A

AU - Fretland, Åsmund A

AU - Primrose, John N

AU - van Dam, Ronald M

PY - 2026/4

Y1 - 2026/4

N2 - BACKGROUND: Laparoscopic hemihepatectomy (LH) has favorable short-term outcomes compared with open hemihepatectomy (OH), including shorter hospital stay. An in-depth healthcare utilization and cost-effectiveness analysis of the international multicenter ORANGE II PLUS randomized controlled trial comparing LH and OH was performed.PATIENTS AND METHODS: Patients were randomly assigned to LH or OH in 16 European centers from October 2013 to January 2019. Costs were determined as a product of unit costs using patient-level, clinician-reported resource utilization up to 90 days. Item-specific resource use per country was presented. The measure of effect was quality-adjusted life year (QALY). Cost and effect differences were compared between treatment arms using nonparametric bootstrapping, from a Dutch healthcare cost perspective. A cost-effectiveness analysis was performed to establish the incremental cost-effectiveness ratio (ICER), i.e., costs per QALY gained, for LH compared with OH 1 year postoperatively.RESULTS: Among 332 patients randomized to LH (n = 166) and OH (n = 166), intraoperative costs were higher for LH (LH 13,208 € versus OH 9437 €), while postoperative costs were lower for LH (LH 5774 € versus OH 7703 €). Longer operative time and greater instrument use contributed to higher intraoperative costs, while shorter hospital stays contributed to lower postoperative costs. Mean overall costs per patient were higher in LH (LH 18,982 € versus OH 17,141 €). The QALYs gained over 1 year postoperative were mean (standard deviation [SD]) 0.834 (0.218) for LH and mean 0.795 (0.237) for OH. The ICER was 36,677 € per additional QALY gained, and uncertainty analyses showed that LH had a 77% probability of being cost-effective compared with OH at a willingness-to-pay (WTP) threshold of 80,000 €.CONCLUSIONS: Although LH was more costly than OH, in a multicenter randomized trial, its clinical advantages translated into more QALYs gained over the first postoperative year and high probability of cost-effectiveness. These findings suggest that, where resources allow, LH may be preferred over OH for selected patients, offering both clinical benefits and acceptable economic value.

AB - BACKGROUND: Laparoscopic hemihepatectomy (LH) has favorable short-term outcomes compared with open hemihepatectomy (OH), including shorter hospital stay. An in-depth healthcare utilization and cost-effectiveness analysis of the international multicenter ORANGE II PLUS randomized controlled trial comparing LH and OH was performed.PATIENTS AND METHODS: Patients were randomly assigned to LH or OH in 16 European centers from October 2013 to January 2019. Costs were determined as a product of unit costs using patient-level, clinician-reported resource utilization up to 90 days. Item-specific resource use per country was presented. The measure of effect was quality-adjusted life year (QALY). Cost and effect differences were compared between treatment arms using nonparametric bootstrapping, from a Dutch healthcare cost perspective. A cost-effectiveness analysis was performed to establish the incremental cost-effectiveness ratio (ICER), i.e., costs per QALY gained, for LH compared with OH 1 year postoperatively.RESULTS: Among 332 patients randomized to LH (n = 166) and OH (n = 166), intraoperative costs were higher for LH (LH 13,208 € versus OH 9437 €), while postoperative costs were lower for LH (LH 5774 € versus OH 7703 €). Longer operative time and greater instrument use contributed to higher intraoperative costs, while shorter hospital stays contributed to lower postoperative costs. Mean overall costs per patient were higher in LH (LH 18,982 € versus OH 17,141 €). The QALYs gained over 1 year postoperative were mean (standard deviation [SD]) 0.834 (0.218) for LH and mean 0.795 (0.237) for OH. The ICER was 36,677 € per additional QALY gained, and uncertainty analyses showed that LH had a 77% probability of being cost-effective compared with OH at a willingness-to-pay (WTP) threshold of 80,000 €.CONCLUSIONS: Although LH was more costly than OH, in a multicenter randomized trial, its clinical advantages translated into more QALYs gained over the first postoperative year and high probability of cost-effectiveness. These findings suggest that, where resources allow, LH may be preferred over OH for selected patients, offering both clinical benefits and acceptable economic value.

UR - https://www.scopus.com/pages/publications/105025151459

U2 - 10.1245/s10434-025-18779-4

DO - 10.1245/s10434-025-18779-4

M3 - Article

C2 - 41385067

SN - 1068-9265

JO - Annals of Surgical Oncology

JF - Annals of Surgical Oncology

ER -

Olij B, Pilz da Cunha G, ORANGE II PLUS Collaborative, Kimman M, Ratti F, Abu Hilal M et al. Healthcare Utilization, Costs, and Cost-Effectiveness of Patients Undergoing Laparoscopic and Open Hemihepatectomy: A Secondary Analysis of the ORANGE II PLUS Randomized Controlled, Phase 3, Superiority Trial. Annals of Surgical Oncology. 2026 Apr. Epub 2025 Dec 12. doi: 10.1245/s10434-025-18779-4

Healthcare Utilization, Costs, and Cost-Effectiveness of Patients Undergoing Laparoscopic and Open Hemihepatectomy: A Secondary Analysis of the ORANGE II PLUS Randomized Controlled, Phase 3, Superiority Trial

Abstract

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