Background     The Eastern Cooperative Oncology Group Performance Status scale (“ECOG-PS,” also sometimes referred to as the “Zubrod” score) is one of the most important functional status indices in adult cancer care. Fast Fact #416 discusses functional scales in serious illness in general. This Fast Fact discusses the features and use of the ECOG-PS in more depth. 

History    The use of performance scales in oncology dates to 1948 when Karnofsky explored ways to evaluate the efficacy of the first cytotoxic chemotherapy treatments for lung cancer. The Karnofsky Performance Scale (KPS), which rates an adult’s functional status on 0-100% scale, came out of this work (1). In 1974, the Eastern Cooperative Oncology Group in the US developed the ECOG-PS as a simplified version of the KPS to standardize toxicity and functional assessment for cancer research (2). 

Features of the ECOG-PS    The ECOG-PS is a 6-point (0-5) scale that inversely aligns with the KPS. 

ECOG	Description	KPS (%)
0	Fully active, able to carry on pre-disease performance without restriction.	90-100
1	Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (light housework/office work).	80-90
2	Ambulatory and capable of self-care but unable to carry out work activities. Up and about more than 50% of waking hours.	60-70
3	Capable of limited selfcare, confined to bed/chair more than 50% of waking hours.	40-50
4	Disabled, unable to perform any self-care, and totally confined to bed or chair.	10-30
5	Dead	0

ECOG-PS and prognostication     Multiple studies have shown a strong relationship with solid tumor cancer survival and ECOG-PS, although median survival varies by specific patient population (3-6). 

• In patients with small cell lung cancer, median survival for those with ECOG-PS 3 was 64 days and ECOG-PS 4 was 7 days (7).
• In patients with metastatic colorectal cancer treated with chemotherapy, median survival for those with ECOG-PS 0-1 was 18.4 months, 2 was 10.8 months, and 3-4 was 6.8 months (8).
• In patients receiving chemotherapy for metastatic cancer of unknown primary, those with ECOG-PS 1 had median survival of 25.9 months, 2 was 7.4 months, and 3 was 7 months (9).
• Among terminally ill cancer patients who were receiving supportive only care, an ECOG-PS of 1 had a median survival of 92 days; 2 of 58 days; 3 of 32 days, and 4 of 16 days (10).

Use in chemotherapy research and clinical care     The ECOG-PS is clinically used in making therapeutic decisions such as whether to use cytotoxic chemotherapy, and whether the intensity of such a regimen needs modification. Eligibility for most chemotherapy trials has traditionally required a patient to have an ECOG-PS of 0-1. Clinical trials leading to subsequent FDA drug approval involved less than 5% of patients with an ECOG PS of 2 or greater (11,12), which means that much of our current knowledge of the benefits vs toxicity of chemotherapy is based on patients with ECOG-PS of 0-1. Despite research excluding patients with ECOG-PS of 2, in clinical practice, cytotoxic chemotherapy is commonly recommended for patients with solid tumors and an ECOG-PS of 0-2 (13,14) in most circumstances.

Immunotherapy and ECOG-PS     Immunotherapy treatments have different toxicities than those found with cytotoxic chemotherapy. There are ongoing discussions amongst experts whether a poor ECOG-PS should (or should not) exclude patients from receiving immunotherapy in advanced cancer.

• Overall survival in non-small cell lung cancer has been strongly associated with better ECOG-PS in at least 2 immunotherapy studies (15,16). However, a 2020 meta-analysis of immune checkpoint inhibitor therapy trials did not show any correlation between ECOG-PS and overall survival (17). Importantly, in this meta-analysis, only ECOG-PS of 0 vs 1 or greater were compared, and it is unclear how many patients with ECOG-PS >1 were included in the analysis. 
• In a real-world study of patients with advanced urothelial cancer, similar overall response rates were seen in patients with ECOG-PS of 0-1 and those with ECOG-PS ≥ 2 who received first-line immunotherapy. However, there were significant differences in median overall survival: 15.2 months for those with an ECOG PS 0-1, vs 7.2 months for those with an ECOG PS ≥ 2 (18).
• Overall, it appears immunotherapy is being given to patients with poor ECOG-PS scores who would not be similarly offered cytotoxic chemotherapy. This may be related to hopes for the “Lazarus syndrome,” in which patients with a poor performance status from a high cancer burden (not comorbidities) manifest dramatic responses to immunotherapy over the course of months (19,20). 

Limitations of the ECOG-PS     While meant to be objective, there is significant variability in assessing ECOG-PS. Interestingly, palliative care providers, nurses, and patients themselves assess ECOG-PS as higher (worse) than oncologists for the same patients (21).  The ECOG-PS is meant to capture functional impairments from cancer or cancer treatments. It is difficult to interpret for functional limitations from unrelated processes (e.g., a preexisting spinal cord injury) and it is not validated in children nor for prognostication in people without cancer. 

Summary    The ECOG-PS is a nearly 50-year-old tool used in both research and oncologic care. It is strongly associated with survival in advanced cancer. Inclusion of more patients with ECOG-PS of ≥ 2 in both immunotherapy and chemotherapy trials is needed to validate its utility in a wider patient population. 

References:

1. Zubrod C, Schneiderman M, Frei 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.
2. Oken MM, Creech RH, Tormey DC et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55.  
3. 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; Sep 21:2(4) 
4. Kawaguchi T, Takada M, Kubo A et al. Performance status and smoking status are independent favorable prognostic factors for survival in non-small cell lung cancer: a comprehensive analysis of 26,957 patients with NSCLC. J Thorac Oncol. 2010 May;5(5):620-30.  
5. Carey MS, Bacon M, Tu D et al. The prognostic effects of performance status and quality of life scores on progression-free survival and overall survival in advanced ovarian cancer. Gynecol Oncol. 2008 Jan;108(1):100-5.
6. Sleijfer S, Ouali M, van Glabbeke M et al. Prognostic and predictive factors for outcome to first-line ifosfamide-containing chemotherapy for adult patients with advanced soft tissue sarcomas: an exploratory, retrospective analysis on large series from the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG). Eur J Cancer. 2010;46(1):72-83.  
7. Baldotto CS, Cronemberger EH, de Biasi P et al. Palliative care in poor-performance status small cell lung cancer patients: is there a mandatory role for chemotherapy? Support Care Cancer. 2012;20(11):2721-7.   
8. Crosara Teixeira M, Marques DF, Ferrari AC 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(1):52-7.   
9. Grajales-Álvarez R, Martin-Aguilar A, Silva JA et al. ECOG is as independent predictor of the response to chemotherapy, overall survival and progression-free survival in carcinoma of unknown primary site. Mol Clin Oncol. 2017;6(5):643-650.  
10. Peng MT, Liu CT, Hung YS et al. Sequential Assessments of the Eastern Cooperative Oncology Group Performance Scale Enhance Prognostic Value in Patients With Terminally Ill Cancer Receiving Palliative Care. Am J Hosp Palliat Care. 2016;33(5):471-6.  

1. Magnuson A, Bruinooge SS, Singh H et al.  Modernizing Clinical Trial Eligibility Criteria: Recommendations of the ASCO-Friends of Cancer Research Performance Status Work Group.  Clin Cancer Res. 2021;27:2424-9.

1. Abi Jaoude J, Kouzy R, Mainwaring W et al. Performance Status Restriction in Phase III Cancer Clinical Trials. J Natl Compr Canc Netw. 2020;18(10):1322-1326. 
2. Sohal DPS, Kennedy EB, Cinar P et a l. Metastatic Pancreatic Cancer: ASCO Guideline Update. J Clin Oncol. 2020;38(27):3217-3230.  
3. Hanna NH, Schneider BJ, Temin S et al.  Therapy for Stage IV Non–Small-Cell Lung Cancer Without Driver Alterations: ASCO and OH (CCO) Joint Guideline Update. J Clin Oncol. 2020; 38(14)1608-1632.
4. Muchnik E, Loh KP, Strawderman M et al. Immune Checkpoint Inhibitors in Real-World Treatment of Older Adults with Non-Small Cell Lung Cancer. J Am Geriatr Soc. 2019;67(5):905-912. 
5. Sehgal K, Gill RR, Widick P et al. Association of Performance Status With Survival in Patients With Advanced Non-Small Cell Lung Cancer Treated With Pembrolizumab Monotherapy. JAMA Netw Open. 2021; Feb 1;4(2) 
6. Yang F, Markovic SN, Molina JR et al. Association of Sex, Age, and Eastern Cooperative Oncology Group Performance Status With Survival Benefit of Cancer Immunotherapy in Randomized Clinical Trials: A Systematic Review and Meta-analysis. JAMA Netw Open. 2020;3(8)
7. Khaki AR, Li A, Diamantopoulos LN et al. Impact of Performance Status on Treatment Outcomes; A Real-World Study of Advanced Urothelial Cancer Treated With Immune Checkpoint Inhibitors.  Cancer. 2020; 126:1208-1216
8. Pluvy J, Brosseau S, Naltet C et al. Lazarus syndrome in nonsmall cell lung cancer patients with poor performance status and major leukocytosis following nivolumab treatment. Eur Respir J. 2017;50(1):1700310.  
9. Pietrantonio F, Loupakis F, Randon G et al. Efficacy and Safety of Immune Checkpoint Inhibitors in Patients with Microsatellite Instability-High End-Stage Cancers and Poor Performance Status Related to High Disease Burden. Oncologist. 2020;25(9):803-809.  
10. Kim YJ, Hui D, Zhang Y et al. Differences in Performance Status Assessment Among Palliative Care Specialists, Nurses, and Medical Oncologists. J Pain Symptom Manage. 2015 Jun;49(6):1050-1058.   

Conflicts of Interest: The authors have declared no relevant conflicts of interest.

Author Affiliations: University of Minnesota Medical School and M Health Fairview, Minneapolis, MN.