Original Study| Volume 20, ISSUE 1, e21-e34, March 2021

Download started.


Real-World Treatment and Outcomes of Metastatic Colorectal Cancer Patients With a Poor or Very Poor Performance Status

Published:August 12, 2020DOI:



      The management of metastatic colorectal cancer patients with a poor performance status (PS) continues to be a clinical dilemma, with the potential activity and safety of treating this population remaining poorly understood. Few of these patients are enrolled onto clinical trials, and poor PS is often multifactorial.

      Patients and Methods

      We analyzed the Treatment of Recurrent and Advanced Colorectal Cancer registry to describe treatment practices and outcomes in poor (Eastern Cooperative Oncology Group [ECOG] PS 2) and very poor PS (ECOG PS > 2) patients to explore the relationship between age, tumor burden, comorbidities, and PS, and to evaluate the benefit of systemic therapy. Standard descriptive statistical methods, Kaplan-Meier analysis, and a multivariate Cox regression model were used.


      Of 2769 registry patients (diagnosed January 2009 to June 2018), 329 (12%) and 182 (7%) patients had a poor and very poor PS, respectively. Good PS patients were more likely to receive systemic therapy than poor and very poor PS patients (85%, 55%, and 21.5%, P < .0001), but clinician assessed response was observed in all subsets (53%, 41%, and 29%, P = .0003). Treatment with chemotherapy was associated with longer median overall survival across PS groups. Exploratory analysis based on comorbidity score and tumor burden subgroups demonstrated a consistently positive overall survival association with treatment. Benefit was observed where poor overall survival was attributable to medical comorbidities and to tumor burden.


      In routine clinical care, a substantial proportion of poor and very poor PS patients receive active treatment, which is often associated with meaningful clinical benefit.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Clinical Colorectal Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • 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
        • Chan M.
        • Hugh-Yeun K.
        • Gresham G.
        • Speers C.H.
        • Kennecke H.F.
        • Cheung W.Y.
        Population-based patterns and factors associated with underuse of palliative systemic therapy in elderly patients with metastatic colon cancer.
        Clin Colorectal Cancer. 2017; 16: 147-153
        • Heedman P.A.
        • Canslätt E.
        • Henriks G.
        • Starkhammar H.
        • Fomichov V.
        • Sjödahl R.
        Variation at presentation among colon cancer patients with metastases: a population-based study.
        Color Dis. 2015; 17: 403-408
        • Sanoff H.K.
        • Sargent D.J.
        • Campbell M.E.
        • et al.
        Five-year data and prognostic factor analysis of oxaliplatin and irinotecan combinations for advanced colorectal cancer: N9741.
        J Clin Oncol. 2008; 26: 5721-5727
        • Simmonds P.C.
        Palliative chemotherapy for advanced colorectal cancer: systematic review and meta-analysis. Colorectal Cancer Collaborative Group.
        BMJ. 2000; 321: 531-535
        • de Gramont A.
        • Figer A.
        • Seymour M.
        • et al.
        Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer.
        J Cinical Oncol. 2000; 18: 2938-2947
        • Saltz L.B.
        Colorectal cancer.
        N Engl J Med. 2000; : 905-914
        • Falcone A.
        • Ricci S.
        • Brunetti I.
        • et al.
        Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nor.
        J Clin Oncol. 2007; 25: 1670-1676
        • Goldberg R.M.
        • Rothenberg M.L.
        • Van Cutsem E.
        • et al.
        The continuum of care: a paradigm for the management of metastatic colorectal cancer.
        Oncologist. 2007; 12: 38-50
        • Miller K.A.
        • Siscovick D.S.
        • Sheppard L.
        • et al.
        Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer.
        N Engl J Med. 2007; 356: 2301-2303
        • Douillard J.Y.
        • Siena S.
        • Cassidy J.
        • et al.
        Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer.
        Ann Oncol. 2014; 25: 1346-1355
        • Van Cutsem E.
        • Köhne C.H.
        • Láng I.
        • et al.
        Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status.
        J Clin Oncol. 2011; 29: 2011-2019
        • Giantonio B.J.
        • Catalano P.J.
        • Meropol N.J.
        • et al.
        Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200.
        J Clin Oncol. 2007; 25: 1539-1544
        • Sargent D.J.
        • Köhne C.H.
        • Sanoff H.K.
        • et al.
        Pooled safety and efficacy analysis examining the effect of performance status on outcomes in nine first-line treatment trials using individual data from patients with metastatic colorectal cancer.
        J Clin Oncol. 2009; 27: 1948-1955
        • Shitara K.
        • Yokota T.
        • Takahari D.
        • et al.
        Cetuximab plus FOLFOX for patients with metastatic colorectal cancer with poor performance status and/or severe tumor-related complications.
        Case Rep Oncol. 2010; 3: 282-286
        • Jehn C.F.
        • Böning L.
        • Kröning H.
        • Pezzutto A.
        • Lüftner D.
        Influence of comorbidity, age and performance status on treatment efficacy and safety of cetuximab plus irinotecan in irinotecan-refractory elderly patients with metastatic colorectal cancer.
        Eur J Cancer. 2014; 50: 1269-1275
        • Carter G.C.
        • Landsman-Blumberg P.B.
        • Johnson B.H.
        • et al.
        KRAS testing of patients with metastatic colorectal cancer in a community-based oncology setting: a retrospective database analysis.
        J Exp Clin Cancer Res. 2015; 34: 1-8
        • Crosara Teixeira M.
        • Marques D.F.
        • Ferrari A.C.
        • et al.
        The effects of palliative chemotherapy in metastatic colorectal cancer patients with an ecog performance status of 3 and 4.
        Clin Colorectal Cancer. 2015; 14: 52-57
        • Dréanic J.
        • Dhooge M.
        • Barret M.
        • et al.
        Anti-epidermal or anti-vascular endothelial growth factor as first-line metastatic colorectal cancer in modified Glasgow prognostic score 2′ patients.
        J Cachexia Sarcopenia Muscle. 2015; 6: 231-236
        • Kennedy A.
        • Cohn M.
        • Coldwell D.M.
        • et al.
        Updated survival outcomes and analysis of long-term survivors from the MORE study on safety and efficacy of radioembolization in patients with unresectable colorectal cancer liver metastases.
        J Gastrointest Oncol. 2017; 8: 614-624
        • Kanemoto Y.
        • Tsurita G.
        • Kurokawa T.
        • Azuma Y.
        • Yazawa K.
        • Murakami Y.
        A case of an elderly patient with high-grade colorectal cancer in poor general condition who showed near complete response to chemotherapy and achieved long-term survival.
        Int J Surg Case Rep. 2019; 58: 186-189
        • Mitani S.
        • Taniguchi H.
        • Sugiyama K.
        • et al.
        The impact of the Glasgow prognostic score on survival in second-line chemotherapy for metastatic colorectal cancer patients with BRAF V600E mutation.
        Ther Adv Med Oncol. 2019; 11: 1-11
        • Soares da Silva Rocha L.
        • Riechelmann R.P.
        Treatment of patients with metastatic colorectal cancer and poor performance status: current evidence and challenges.
        Clinics. 2018; 73: e542s
        • Field K.
        • Wong H.L.
        • Shapiro J.
        • et al.
        Developing a national database for metastatic colorectal cancer management: perspectives and challenges.
        Intern Med J. 2013; 43: 1224-1231
        • Charlson M.
        • Szatrowski T.P.
        • Peterson J.
        • Gold J.
        Validation of a combined comorbidity index.
        J Clin Epidemiol. 1994; 47: 1245-1251
        • Albertsen P.C.
        • Moore D.F.
        • Shih W.
        • Lin Y.
        • Li H.
        • Lu-Yao G.L.
        Impact of comorbidity on survival among men with localized prostate cancer.
        J Clin Oncol. 2011; 29: 1335-1341
        • Elshaikh M.A.
        • Vance S.
        • Kamal M.
        • et al.
        Influence of comorbidity on the risk of death.
        Am J Clin Oncol. 2017; 40: 183-188
        • Yang C.C.
        • Fong Y.
        • Lin L.C.
        • et al.
        The age-adjusted Charlson comorbidity index is a better predictor of survival in operated lung cancer patients than the Charlson and Elixhauser comorbidity indices.
        Eur J Cardiothoracic Surg. 2018; 53: 235-240
        • Wu C.C.
        • Hsu T.W.
        • Chang C.M.
        • Yu C.H.
        • Lee C.C.
        Age-adjusted Charlson comorbidity index scores as predictor of survival in colorectal cancer patients who underwent surgical resection and chemoradiation.
        Medicine (Baltimore). 2015; 94: e431
        • Arkenau H.T.
        • Olmos D.
        • Ang J.E.
        • De Bono J.
        • Judson I.
        • Kaye S.
        Clinical outcome and prognostic factors for patients treated within the context of a phase I study: the Royal Marsden Hospital experience.
        Br J Cancer. 2008; 98: 1029-1033
        • Fong Y.
        • Fortner J.
        • Sun R.L.
        • Brennan M.F.
        • Blumgart L.H.
        Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer.
        Ann Surg. 1999; 230: 309
        • Tran B.
        • Kopetz S.
        • Tie J.
        • et al.
        Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer.
        Cancer. 2011; 117: 4623-4632
        • Schnipper L.E.
        • Smith T.J.
        • Raghavan D.
        • et al.
        American Society of Clinical Oncology identifies five key opportunities to improve care and reduce costs: the top five list for oncology.
        J Clin Oncol. 2012; 30: 1715-1724
        • Field K.M.
        • Kosmider S.
        • Jefford M.
        • et al.
        Chemotherapy dosing strategies in the obese, elderly, and thin patient: results of a nationwide survey.
        J Oncol Pract. 2008; 4: 108-113