Development and validation of a novel risk score to predict overall survival following surgical clearance of bilobar colorectal liver metastases
Authors: Dasari Bobby V M , Raptis Dimitri , Syn Nicholas , Serrablo Alejandro , Ramia Jose Manuel , Laurenzi Andrea , Sturesson Christian , Pawlik Timothy M , Siriwardena Ajith K , Lesurtel Mickael ,   BiCRLM study collaborators, Novotny Alexander , Kow Alfred , Kourdouli Amar , Belli Andrea , Valdivieso Andres , Hann Angus , de la Hoz Rodríguez Ángela , Oona Anisa Nutu , Pascher Andreas , Frena Antonio , Ivanecz Arpad , Heumann Asmus , Alvarado Ayaya Alonso , Kaldarov Ayrat , Bracke Bart , Hendrikx Bart , Struecker Benjamin , Bjornsson Bergthor , Cutolo Carmen , Frola Carlo , Payá-Llorente Carmen , Pozo Carlos Domingo-del , Teh Catherine , Stöss Christian , Ricci Claudio , Verhoef Cornelis , Dopazo Cristina , Galun Daniel , Hartmann Daniel , Martin David , Vaz da Silva Diego Greatti , Dorcaratto Dimitri , Magouliotis Dimitrios , Moris Dimitrios , Symeonidis Dimitrios , Zacharoulis Dimitrios , Bugra Dursun , Lopez-Garnica Dolores , Jonas Eduard , Muttillo Edoardo Maria , Saladino Edoardo , Francisco Elsa , Hutten Ela , De Raffele Emilio , Felli Emanuele , Balik Emre , Bozkurt Emre , Felekouras Evangelos , Sobutay Erman , Sparrelid Ernesto , Romano Fabrizio , Coimbra Felipe José Fernández , Guido Fiorentini , Primavesi Florian , Izzo Francesco , Berrevoet Frederik , Piccolo Gaetano , Joliat Gaëtan-Romain , Middleton Gary , Makridis Georgios , Sotiropoulos Georgios C , Garcea Giuseppe , Booney Glen , Han Ho-Seong , Ozata Ibrahim Halil , Cho Jai Young , Pudil Jiri , Hammond John , Torres Jorge Brian , Li Jun , Pollok Joerg-Matthias , Ammar Khaled , Kopchak Kostiantun , Taura Kojiro , Serin Kursat , Menon Krishna , Zieniewicz Krzysztof , Perez-Santiago Leticia , Lundgren Linda , Wullaert Lissa , Alderghetti Luca , De Carvalho Luis Abreu , Tschöegl Madita-Magdalena , Marino Marco , Aránzazu María , Ammann Markus , Varona-Bosque Aranzazu , Giuffrida Mario , Garancini Mattia , Scotti Mauro Alessandro , Barabino Matteo , Bernon Marc , Cescon Matteo , Martino Marcello Di , Maestri Marcello , Massani Marco , Sotiropoulou Maria , Forcen Maria Teresa Abadia , Fernandez-Moreno Maria-Carmen , Serradilla-Martín Mario , Zivanovic Marko , Gutiérrez-Díez Marta , Buyuk Melek , Vailas Michail , Sharma Mitesh , D'Silva Mizelle , Protic Mladjan , Fard-Aghaie Mohammad Hossein , Wullaert Lissa , Kumar Nagappan , Marques Narimã , Tomara Nefeli , Mowbray Nicholas G , Demartines Nicolas , Machairas Nikolaos , Ben-Ishay Offir , Kvasivka Oleksandr , Krsmanovic Olivera , Bilge Orhan , Sancho-Pardo Pablo , Line Pal-Dag , Tinguely Pascale , Pessaux Patrick , Sandstrom Per , Lodge Peter , Valle Raffaele Dalla , Homs Roger , Sutcliffe Robert , Lob Sanja , Sánchez-Cabús Santiago , Katou Shadi , Okumura Shinya , Hatano Etsuro , Turk Spela , Farkas Stefan , Patauner Stefan , Stättner Stefan , Löb Stefan , Truant Stephanie , Kapiris Stylianos , Gallagher Tom , Kocisova Tereza , Gruenberger Thomas , Stecca Tommaso , Chapelle Thiery , Abadía-Forcén Teresa , Molina Víctor , Sumarokova Valeriia , Meyer Yannick 
Published: September 2023

Abstract

Background
Bilobar liver metastases from colorectal cancer pose a challenge for obtaining a satisfactory oncological outcome with an adequate future liver remnant. This study aimed to assess the clinical and pathological determinants of overall survival and recurrence-free survival among patients undergoing surgical clearance of bilobar liver metastases from colorectal cancer.

Methods
A retrospective international multicentre study of patients who underwent surgery for bilobar liver metastases from colorectal cancer between January 2012 and December 2018 was conducted. Overall survival and recurrence-free survival at 1, 2, 3 and 5 years after surgery were the primary outcomes evaluated. The secondary outcomes were duration of postoperative hospital stay, and 90-day major morbidity and mortality rates. A prognostic nomogram was developed using covariates selected from a Cox proportional hazards regression model, and internally validated using a 3:1 random partition into derivation and validation cohorts.

Results
A total of 1236 patients were included from 70 centres. The majority (88 per cent) of the patients had synchronous liver metastases. Overall survival at 1, 2, 3 and 5 years was 86.4 per cent, 67.5 per cent, 52.6 per cent and 33.8 per cent, and the recurrence-free survival rates were 48.7 per cent, 26.6 per cent, 19.2 per cent and 10.5 per cent respectively. A total of 25 per cent of patients had recurrent disease within 6 months. Margin positivity and progressive disease at liver resection were poor prognostic factors, while adjuvant chemotherapy in margin-positive resections improved overall survival. The bilobar liver metastases from colorectal cancer-overall survival nomogram was developed from the derivation cohort based on pre- and postoperative factors. The nomogram’s ability to forecast overall survival at 1, 2, 3 and 5 years was subsequently validated on the validation cohort and showed high accuracy (overall C-index = 0.742).

Conclusion
Despite the high recurrence rates, overall survival of patients undergoing surgical resection for bilobar liver metastases from colorectal cancer is encouraging. The novel bilobar liver metastases from colorectal cancer-overall survival nomogram helps in counselling and informed decision-making of patients planned for treatment of bilobar liver metastases from colorectal cancer.