Trajectories of body weight change and survival among patients with mCRC treated with systemic therapy: Pooled analysis from the ARCAD database

Published:August 20, 2022DOI:


      • Weight loss is proportional to the risk of death among mCRC patients.
      • Weight loss ≥5% is associated with significantly shorter survival.
      • Median overall survival was 20.5 months if there was no weight loss.
      • Median overall survival was 11.9 months if ≥ 5% weight loss at 3 months.



      Higher body mass index is associated with a higher incidence of colorectal cancer (CRC) but also with improved survival in metastatic CRC (mCRC). Whether weight change after mCRC diagnosis is associated with survival remains largely unknown.


      We analysed individual patient data for previously untreated patients enrolled in five phase 3 randomised trials conducted between 1998 and 2006. Weight measurements were prospectively collected at baseline and up to 59.4 months after diagnosis. We used stratified multivariable Cox models to assess the prognostic associations of weight loss with overall and progression-free survival, adjusting for other factors. The primary end-point was a difference in overall survival (OS) between populations with weight loss and stable or increasing weight.


      Data were available for 3504 patients. The median weight change at 3 months was −0.54% (IQR −3.9 … +1.5%). We identified a linear trend of increasing risk of death associated with progressive weight loss. Unstratified median OS was 20.5, 18.0, and 11.9 months (p < 0.001) for stable weight or gain, <5% weight loss, and ≥5% weight loss at 3 months, respectively. Weight loss was associated with a higher risk of death (<5% loss: aHR 1.18 [1.06–1.30], p < 0.002; ≥5% loss: aHR 1.87 [1.67–2.1], p < 0.001) as compared to stable or increasing weight at 3 months post-baseline (reference), while adjusting for age, sex, performance, and a number of metastatic sites.


      Patients losing weight during systemic therapy for metastatic colorectal cancer have significantly shorter OS. The degree of weight loss is proportional to the observed increased risk of death and remains evident among underweight, normal weight, and obese individuals. On-treatment weight change could be used as an intermediate end-point.


      The creation and management of the database containing the individual patient data from the original randomised trials is supported by the Aide et Recherche en Cancérologie Digestive Foundation.


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        • NCCN
        NCCN Guidelines: Colon cancer. vol. 3. 2021ed2021
        • Loupakis F.
        • Sharma S.
        • Derouazi M.
        • et al.
        Detection of molecular residual disease using personalized circulating tumor DNA assay in patients with colorectal cancer undergoing resection of metastases.
        JCO Precis Oncol. 2021; 5
        • Diehl F.
        • Schmidt K.
        • Choti M.A.
        • et al.
        Circulating mutant DNA to assess tumor dynamics.
        Nat Med. 2008; 14: 985-990
        • Sinicrope F.A.
        • Foster N.R.
        • Yothers G.
        • et al.
        Body mass index at diagnosis and survival among colon cancer patients enrolled in clinical trials of adjuvant chemotherapy.
        Cancer. 2013; 119: 1528-1536
        • Guercio B.J.
        • Zhang S.
        • Venook A.P.
        • et al.
        Body mass index and weight loss in metastatic colorectal cancer in CALGB (alliance)/SWOG 80405.
        JNCI Cancer Spectr. 2020; 4 (pkaa024)
        • Mello M.
        • Moura S.F.
        • Muzi C.D.
        • GuimarAes R.M.
        Clinical evaluation and pattern of symptoms in colorectal cancer patients.
        Arq Gastroenterol. 2020; 57: 131-136
        • Meyerhardt J.A.
        • Kroenke C.H.
        • Prado C.M.
        • et al.
        Association of weight change after colorectal cancer diagnosis and outcomes in the kaiser permanente northern California population.
        Cancer Epidemiol Biomarkers Prev. 2017; 26: 30-37
        • Renfro L.A.
        • Loupakis F.
        • Adams R.A.
        • et al.
        Body mass index is prognostic in metastatic colorectal cancer: pooled analysis of patients from first-line clinical trials in the ARCAD database.
        J Clin Oncol. 2016; 34: 144-150
        • Poterucha T.
        • Burnette B.
        • Jatoi A.
        A decline in weight and attrition of muscle in colorectal cancer patients receiving chemotherapy with bevacizumab.
        Med Oncol. 2012; 29: 1005-1009
        • Shahjehan F.
        • Merchea A.
        • Cochuyt J.J.
        • Li Z.
        • Colibaseanu D.T.
        • Kasi P.M.
        Body mass index and long-term outcomes in patients with colorectal cancer.
        Front Oncol. 2018; 8: 620
        • Vergidis J.
        • Gresham G.
        • Lim H.J.
        • et al.
        Impact of weight changes after the diagnosis of stage III colon cancer on survival outcomes.
        Clin Colorectal Cancer. 2016; 15: 16-23
        • Kocarnik J.M.
        • Hua X.
        • Hardikar S.
        • et al.
        Long-term weight loss after colorectal cancer diagnosis is associated with lower survival: the Colon Cancer Family Registry.
        Cancer. 2017; 123: 4701-4708
        • Kuo Y.H.
        • Shi C.S.
        • Huang C.Y.
        • Huang Y.C.
        • Chin C.C.
        Prognostic significance of unintentional body weight loss in colon cancer patients.
        Mol Clin Oncol. 2018; 8: 533-538
        • Renfro L.A.
        • Goldberg R.M.
        • Grothey A.
        • et al.
        Clinical Calculator for Early Mortality in Metastatic Colorectal Cancer: an Analysis of Patients From 28 Clinical Trials in the Aide et Recherche en Cancerologie Digestive Database.
        J Clin Oncol. 2017; 35: 1929-1937
        • Innominato P.F.
        • Giacchetti S.
        • Moreau T.
        • et al.
        Fatigue and weight loss predict survival on circadian chemotherapy for metastatic colorectal cancer.
        Cancer. 2013; 119: 2564-2573
        • Martin L.
        • Birdsell L.
        • Macdonald N.
        • et al.
        Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index.
        J Clin Oncol. 2013; 31: 1539-1547
        • Kurk S.A.
        • Stellato R.K.
        • Peeters P.H.M.
        • et al.
        Trajectory of body mass and skeletal muscle indices and disease progression in metastatic colorectal cancer patients.
        Am J Clin Nutr. 2019; 110: 1395-1403
        • Hurwitz H.
        • Fehrenbacher L.
        • Novotny W.
        • et al.
        Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer.
        N Engl J Med. 2004; 350: 2335-2342
        • Kabbinavar F.F.
        • Hambleton J.
        • Mass R.D.
        • Hurwitz H.I.
        • Bergsland E.
        • Sarkar S.
        Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer.
        J Clin Oncol. 2005; 23: 3706-3712
        • Van Cutsem E.
        • Kohne C.H.
        • Hitre E.
        • et al.
        Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer.
        N Engl J Med. 2009; 360: 1408-1417
        • Goldberg R.M.
        • Sargent D.J.
        • Morton R.F.
        • et al.
        A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer.
        J Clin Oncol. 2004; 22: 23-30
        • Bokemeyer C.
        • Bondarenko I.
        • Makhson A.
        • et al.
        Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer.
        J Clin Oncol. 2009; 27: 663-671
        • Buyse M.
        • Sargent D.J.
        • Goldberg R.M.
        • de Gramont A.
        • Program A.C.T.
        The ARCAD advanced colorectal cancer database--open for business.
        Ann Oncol. 2012; 23: 281-282
        • Fearon K.
        • Strasser F.
        • Anker S.D.
        • et al.
        Definition and classification of cancer cachexia: an international consensus.
        Lancet Oncol. 2011; 12: 489-495
        • Sanchez-Lara K.
        • Ugalde-Morales E.
        • Motola-Kuba D.
        • Green D.
        Gastrointestinal symptoms and weight loss in cancer patients receiving chemotherapy.
        Br J Nutr. 2013; 109: 894-897
        • Köhne C.H.
        • Cunningham D.
        • Di Costanzo F.
        • et al.
        Clinical determinants of survival in patients with 5-fluorouracil-based treatment for metastatic colorectal cancer: results of a multivariate analysis of 3825 patients.
        Ann Oncol. 2002; 13: 308-317
        • Liu L.
        • Erickson N.T.
        • Ricard I.
        • et al.
        Early weight loss is an independent risk factor for shorter survival and increased side effects in patients with metastatic colorectal cancer undergoing first-line treatment within the randomized Phase III trial FIRE-3 (AIO KRK-0306).
        Int J Cancer. 2022; 150: 112-123
        • Chen R.C.
        • Haynes K.
        • Du S.
        • Barron J.
        • Katz A.J.
        Association of cancer screening deficit in the United States with the COVID-19 pandemic.
        JAMA Oncol. 2021; 7: 878-884
        • Zhang D.
        • Bauer C.
        • Powell-Wiley T.
        • Xiao Q.
        Association of long-term trajectories of neighborhood socioeconomic status with weight change in older adults.
        JAMA Netw Open. 2021; 4e2036809
        • Blauwhoff-Buskermolen S.
        • Versteeg K.S.
        • de van der Schueren M.A.
        • et al.
        Loss of muscle mass during chemotherapy is predictive for poor survival of patients with metastatic colorectal cancer.
        J Clin Oncol. 2016; 34: 1339-1344
        • Prado C.M.
        • Sawyer M.B.
        • Ghosh S.
        • et al.
        Central tenet of cancer cachexia therapy: do patients with advanced cancer have exploitable anabolic potential?.
        Am J Clin Nutr. 2013; 98: 1012-1019
        • Grothey A.
        • Sargent D.
        Overall survival of patients with advanced colorectal cancer correlates with availability of fluorouracil, irinotecan, and oxaliplatin regardless of whether doublet or single-agent therapy is used first line.
        J Clin Oncol. 2005; 23: 9441-9442
        • Antoun S.
        • Bayar M.A.
        • Dyevre V.
        • Lanoy E.
        • Smolenschi C.
        • Ducreux M.
        No evidence for changes in skeletal muscle mass or weight during first-line chemotherapy for metastatic colorectal cancer.
        BMC Cancer. 2019; 19: 847
        • Lieffers J.R.
        • Mourtzakis M.
        • Hall K.D.
        • McCargar L.J.
        • Prado C.M.
        • Baracos V.E.
        A viscerally driven cachexia syndrome in patients with advanced colorectal cancer: contributions of organ and tumor mass to whole-body energy demands.
        Am J Clin Nutr. 2009; 89: 1173-1179
        • Moran B.J.
        • Tzivanakis A.
        The concept of “Obstruction-Free Survival” as an outcome measure in advanced colorectal cancer management.
        Pleura Peritoneum. 2018; 320180101
        • Franko J.
        • Graff T.M.
        • McClairen C.
        Body weight and composition changes, primary tumor side, and resection as survival predictors in metastatic colorectal cancer.
        J Clin Oncol. 2018; 36: 950
        • Blair S.L.
        • Chu D.Z.
        • Schwarz R.E.
        Outcome of palliative operations for malignant bowel obstruction in patients with peritoneal carcinomatosis from nongynecological cancer.
        Ann Surg Oncol. 2001; 8: 632-637
        • Sadeghi B.
        • Arvieux C.
        • Glehen O.
        • et al.
        Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study.
        Cancer. 2000; 88: 358-363
        • Arends J.
        • Baracos V.
        • Bertz H.
        • et al.
        ESPEN expert group recommendations for action against cancer-related malnutrition.
        Clin Nutr. 2017; 36: 1187-1196
        • Muscaritoli M.
        • Arends J.
        • Bachmann P.
        • et al.
        ESPEN practical guideline: clinical Nutrition in cancer.
        Clin Nutr. 2021; 40: 2898-2913
        • van der Werf A.
        • van Bokhorst Q.N.E.
        • de van der Schueren M.A.E.
        • Verheul H.M.W.
        • Langius J.A.E.
        Cancer cachexia: identification by clinical assessment versus international consensus criteria in patients with metastatic colorectal cancer.
        Nutr Cancer. 2018; 70: 1322-1329