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Prognostic Effect of Performance Status on Outcomes of Patients with Colorectal Cancer Receiving First-Line Chemotherapy: A Meta-analysis

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Abstract

Background

Performance status (PS) is a variable derived from the assessment of a patient’s functional status, originally proposed to predict drug toxicity. However, despite its characteristic of being subjective and unidimensional, it has become one of the most important prognostic variables for patients with metastatic colorectal cancer (mCRC). In light of the considerable progressive prolongation of median overall survival (OS) of patients with mCRC, it is unclear whether PS continues to be a valid prognostic factor. This article aims to perform a meta-analysis to verify the current prognostic role of PS.

Methods

A search on two databases of prospective trials of first-line chemotherapy in mCRC patients, published in English from 1991 to 2020, was done by predefined criteria. After the selection of phase III trials evaluating the prognostic role of PS, a meta-analysis has been performed.

Results

Thirteen trials were included in the meta-analysis. They reported a reduction in the risk of death with a PS 0 compared to a PS 1 or more (HR 0.63, CI 0.54–0.72; 13 studies), which was confirmed for the comparison between PS 0 and PS 1. However, the study found significant heterogeneity (Q = 68.10; p-value < 0.001) and high-grade inconsistency (I2 = 82.38%). Therefore, to explore the reasons for the heterogeneity, a univariate meta-regression was performed, which suggested a possible moderating activity for liver metastases and timing of metastasis.

Conclusions

PS is a reliable prognostic factor for patients with mCRC receiving first-line chemotherapy but is poorly evaluated in phase III trials.

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Data Availability

The data presented in this study are available on request from the corresponding author.

References

  1. Ferlay J, Colombet M, Soerjomataram I, Dyba T, Randi G, Bettio M, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer. 2018;103:356–87.

    Article  CAS  PubMed  Google Scholar 

  2. Karnofsky DA, Abelmann WH, Craver LF, Burchenal JH. The use of nitrogen mustards in the palliative treatment of carcinoma. With particular reference to bronchogenic carcinoma. Cancer. 1948;1:634–56.

  3. West HJ, Jin JO. Performance status in patients with cancer. JAMA Oncol. 2015;1:998.

    Article  PubMed  Google Scholar 

  4. Cheng S, Qureshi M, Pullenayegum E, Haynes A, Chan KK. Do patients with reduced or excellent performance status derive the same clinical benefit from novel systemic cancer therapies? A systematic review and meta-analysis. ESMO Open. 2017;2:e000225.

  5. Renfro LA, Goldberg RM, Grothey A, Sobrero A, Adams R, Seymour MT, 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 Cancérologie Digestive Database. J Clin Oncol. 2017;35:1929–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Zelen M. Keynote address on biostatistics and data retrieval. Cancer Chemother Rep. 1973;3–4:31–42.

    Google Scholar 

  7. Prasad KT, Kaur H, Muthu V, Aggarwal AN, Behera D, Singh N. Interconversion of two commonly used performance tools: an analysis of 5844 paired assessments in 1501 lung cancer patients. World J Clin Oncol. 2018;9(7):140–7.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Blijham G, Wagener T, Wils J, de Greve J, Buset M, Bleiberg H, et al. Modulation of high-dose infusional fluorouracil by low-dose methothrexate in patients with advanced or metastatic colorectal cancer: final results of a randomized European Organization for Research and Treatment of Cancer study. J Clin Oncol. 1996;14:2266–73.

    Article  CAS  PubMed  Google Scholar 

  9. Saltz LB, Cox JV, Blanke C, Rosen LS, Fehrenbacher L, Moore MJ, et al. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. N Engl J Med. 2000;343:905–14.

    Article  CAS  PubMed  Google Scholar 

  10. Schilsky RL, Levin J, West WH, Wong A, Colwell B, Thirlwell MP, et al. Randomized, open-label, phase III study of a 28-day oral regimen of eniluracil plus fluorouracil versus intravenous fluorouracil plus leucovorin as first-line therapy in patients with metastatic/advanced colorectal cancer. J Clin Oncol. 2002;20:1519–26.

    Article  CAS  PubMed  Google Scholar 

  11. Chibaudel B, Bonnetain F, Tournigand C, Bengrine-Lefevre L, Teixeira L, Artru P, et al. Simplified prognostic model in patients with oxaliplatin-based or irinotecan-based first-line chemotherapy for metastatic colorectal cancer: a GERCOR study. Oncologist. 2011;16:1228–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Sanoff HK, Sargent DJ, Campbell ME, Morton RF, Fuchs CF, Ramanathan RK, et al. Five-year data and prognostic factor analysis of oxaliplatin and irinotecan combinations for advanced colorectal cancer: N9741. J Clin Oncol. 2008;26:5721–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Colucci V, Gebbia V, Paoletti G, Giuliani F, Caruso M, Gebbia N, et al. Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico dell’Italia Meridionale. J Clin Oncol. 2005;23:4866–75.

    Article  CAS  PubMed  Google Scholar 

  14. Giachetti S, Bjarnason G, Garufi C, Genet D, Iacobelli S, Tampellini M, et al. Phase III trial comparing 4-day chronomodulated therapy versus 2-day conventional delivery of fluorouracil, leucovorin, and oxaliplatin as first-line chemotherapy of metastatic colorectal cancer: the European Organisation for Research and Treatment of Cancer chronotherapy group. J Clin Oncol. 2006;24:3562–9.

    Article  Google Scholar 

  15. De Gramont A, Buyse M, Cortinas Abrahantes J, et al. Reintroduction of oxaliplatin is associated with improved survival in advanced colorectal cancer. J Clin Oncol. 2007;25:3224–9.

    Article  PubMed  Google Scholar 

  16. Tebbutt NC, Wilson K, Gebski VJ, Burzykowski T, Quinaux E, Cervantes A, et al. Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: results of the Australasian Gastrointestinal Trials Group randomized phase III MAX study. J Clin Oncol. 2010;28:3191–8.

    Article  CAS  PubMed  Google Scholar 

  17. Pectasides D, Papaxoinis G, Kalogeras KT, Eleftheraki AG, Xanthakis I, Makatsoris T, et al. XELIRI-bevacizumab versus FOLFIRI-bevacizumab as first-line treatment in patients with metastatic colorectal cancer: a Hellenic Cooperative Oncology Group phase III trial with collateral biomarker analysis. BMC Cancer. 2012;12:271.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Guren TK, Thomsen M, Kure EH, Sorbye H, Blimelius B, Pfeiffer P, et al. Cetuximab in treatment of metastatic colorectal cancer: final survival analyses and extended RAS data from the NORDIC-VII study. Brit J Cancer. 2017;116:1271–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Aparicio T, Lavau-Denes S, Phelip JM, Maillard E, Jouve JL, Gargot D, et al. Randomized phase III trial in elderly patients comparing LV5FU2 with or without irinotecan for first-line treatment of metastatic colorectal cancer (FFCD 2001-02). Ann Oncol. 2016;27(1):121–6.

  20. Cremolini C, Loupakis F, Antoniotti C, Lonardi S, Masi G, Salvatore L, et al. Early tumor shrinkage and depth of response predict long-term outcome in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab: results from phase III TRIBE trial by the Gruppo Oncologico del Nord Ovest. Ann Oncol. 2015;26:1188–94.

    Article  CAS  PubMed  Google Scholar 

  21. Sargent DJ, Kohne CH, Sanoff HK, Bot BM, Seymour MT, de Gramont A, 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;27:1948–55.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;381:752–62.

    Article  PubMed  Google Scholar 

  23. Takahashi M, Takahashi M, Komine K, Yamada H, Kasahara Y, Chikamatdu S, et al. The G8 screening tool enhances prognostic value to ECOG performance status in elderly cancer patients: a retrospective, single institutional study. PLoS ONE. 2017;12:e0179694.

  24. Boakye D, Rillmann B, Walter V, Jansen L, Hoffmeister M, Brenner H. Impact of comorbidity and frailty on prognosis in colorectal cancer patients: a systematic review and meta-analysis. Cancer Treat Rev. 2018;64:30–9.

    Article  PubMed  Google Scholar 

  25. Li D, Soto Perez de Celis E, Hurria A. Geriatric assessment and tools for predicting treatment toxicity in older adults with cancer. Cancer J. 2017;23(4):206–10.

  26. van der Vlies E, Kurk SA, Roodhart JML, Gerritse FL, Pelgrim TC, Vos JM, et al. The relevance of geriatric assessment for older patients receiving palliative chemotherapy. J Geriatr Oncol. 2020;11:482–7.

    Article  PubMed  Google Scholar 

  27. Decoster L, Vanacker L, Kenis C, Prenen H, van Cutsem E, van der Auwera J, et al. Relevance of geriatric assessment in older patients with colorectal cancer. Clin Colorectal Cancer. 2017;16(2):e221–9.

    Article  PubMed  Google Scholar 

  28. Aparicio T, Jouve JL, Teillet L, Gargot D, Subtil F, Le Brun-Ly V, et al. Geriatric factors predict chemotherapy feasibility: ancillary results of FFCD 2001-02 phase III study in first-line chemotherapy for metastatic colorectal cancer in elderly patients. J Clin Oncol. 2013;31:1464–70.

  29. Aleixo GFP, Choi SK, Tan AJ, Nyrop KA, Deal AM, Wood WA, et al. Is “geriatric” assessment just for older patients? Oncologist. 2020;25:355–8.

    Article  PubMed  Google Scholar 

  30. Nishijima TF, Deal AM, Lund JL, Nyrop KA, Muss HB, Sanoff HK. The incremental value of a geriatric assessment-derived three-item scale on estimating overall survival in older adults with cancer. J Geriatr Oncol. 2018;9(4):329–36.

    Article  PubMed  Google Scholar 

  31. Blagden SP, Charman SC, Sharples LD, Magee LR, Gilligan D. Performance status score: do patients and their oncologists agree? Br J Cancer. 2003;89:1022–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Martin L, Watanabe S, Fainsinger R, Lau F, Ghosh S, Quan H, et al. Prognostic factors in patients with advanced cancer: use of the patient-generated subjective global assessment in survival prediction. J Clin Oncol. 2010;28:4376–83.

    Article  PubMed  Google Scholar 

  33. Kim YJ, Hui D, Zhang Y, Park JC, Chisholm G, Williams J, et al. Differences in performance status assessment among palliative care specialists, nurses, and medical oncologists. J Pain Symptom Manage. 2015;49(6):1050–8.

    Article  PubMed  Google Scholar 

  34. Neeman E, Gresham G, Ovasapians N, Hendifar A, Tuli R, Figlin R, et al. Comparing physician and nurse Eastern Cooperative Oncology Group performance status (ECOG-PS) ratings as predictors of clinical outcomes in patients with cancer. Oncologist. 2019;24:e1460–6.

    Article  CAS  PubMed  Google Scholar 

  35. Boakye D, Jansen L, Schneider M, Chang-Claude J, Hoffmeister M, Brenner H. Personalizing the prediction of colorectal cancer prognosis by incorporating comorbidities and functional status into prognostic nomograms. Cancers. 2019;11:1435.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Van Spall HGC, Toren A, Kiss A, Fowler RA. Eligibility criteria of randomized controlled trials published in high-impact general medical journals: a systematic sampling review. J Am Med Assoc. 2007;297(11):1233–40.

    Article  Google Scholar 

  37. Pignon JP, Tribodet H, Scagliotti GV, Douillard JY, Shepherd FA, Stephens RJ, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE collaborative group. J Clin Oncol. 2008;26:3552–9.

  38. Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365(26):2484–96.

    Article  CAS  PubMed  Google Scholar 

  39. Zubrod CG, Schneiderman MA, Frei E III, Brindley C, Lennard Gold G, Shnider B, et al. Appraisal of methods for the study of chemotherapy of cancer in man: comparative therapeutic trial of nitrogen mustard and triethylene thiophosphoramide. J Chronic Dis. 1960;11:7–33.

    Article  Google Scholar 

  40. Marschner N, Zacharias S, Lordick F, Hegewisch-Becker S, Martens U, Welt A, et al. Association of disease progression with health-related quality of life among adults with breast, lung, pancreatic, and colorectal cancer. JAMA Netw Open. 2020;3(3):e200643.

  41. Sastre J, de la Orden V, Martinez A, Bando I, Balbin M, Bellosillo B, et al. Association between baseline circulating tumor cells, molecular tumor profiling, and clinical characteristics in a large cohort of chemo-naive metastatic colorectal cancer patients prospectively collected. Clin Colorectal Cancer. 2020;19(3):e110–6.

    Article  PubMed  Google Scholar 

  42. Travers A, Jalali A, Begbie S, Semira C, Kosmider S, Ananda S, et al. Real-world treatment and outcomes of metastatic colorectal cancer patients with a poor or very poor performance status. Clin Colorectal Cancer. 2021;20(1):e21–34.

    Article  PubMed  Google Scholar 

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  1. Oncologia Medica & Innovation, Via Aicardi n. 37, Imperia, Italy

    Giuseppe A. Colloca & Antonella Venturino

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  1. Giuseppe A. Colloca
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GAC: conceptualization, design, data acquisition, analysis and interpretation of data, statistical analysis, manuscript preparation and editing, and final review; AV: conceptualization, data acquisition, quality control of data and algorithms, analysis and interpretation of data, statistical analysis, manuscript preparation and editing, and final review.

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Correspondence to Giuseppe A. Colloca.

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Colloca, G.A., Venturino, A. Prognostic Effect of Performance Status on Outcomes of Patients with Colorectal Cancer Receiving First-Line Chemotherapy: A Meta-analysis. J Gastrointest Canc (2023). https://doi.org/10.1007/s12029-023-00983-8

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