What is the significance of the Karnofsky Performance Status (KPS) in determining treatment eligibility?

Karnofsky Performance Status in Treatment Eligibility

The Karnofsky Performance Status (KPS) is a validated 11-level scale (0-100) that assesses functional capacity and serves as both a prognostic indicator and treatment eligibility criterion, with KPS ≥60 generally supporting active treatment consideration and KPS <60 indicating best supportive care only. 1

Understanding the KPS Scale

• KPS is an ordered scale ranging from 0 to 100 in 10-point increments that evaluates patient health status across three domains: activity level, work capacity, and self-care ability 1, 2
• Lower KPS scores are directly associated with poorer survival outcomes and more serious illness 1, 2
• The scale demonstrates moderately high interrater reliability (correlation coefficient 0.97) when used by trained observers 3
• KPS shows strong construct validity with correlation to physical function measures and predictive validity for survival (r = 0.30 in terminal cancer patients) 4, 3

Clinical Thresholds for Treatment Decisions

For patients with advanced or metastatic cancer, KPS ≥60 (equivalent to ECOG PS ≤2) supports consideration of systemic therapy, while KPS <60 (equivalent to ECOG PS ≥3) indicates best supportive care alone. 1

• Patients with KPS ≥60 should be offered best supportive care with or without systemic therapy, or enrollment in clinical trials 1
• Patients with KPS <60 should receive best supportive care only, as they are unlikely to tolerate or benefit from active treatment 1
• The threshold of KPS ≤70 (equivalent to ECOG PS 2-4) correlates with significantly lower overall survival and progression-free survival compared to KPS 80-100 1

Prognostic Significance

• KPS accurately predicts early death when scores are low at initial assessment 4
• High initial KPS scores do not necessarily predict long survival, as rapid deterioration can occur 4
• Rapidly dropping KPS scores can predict patient deterioration and death within a few months, though with limited precision 4
• KPS is incorporated into composite prognostic tools like the Palliative Prognostic Score (PaP) to predict 30-day survival probability 2

Important Limitations and Caveats

• KPS is inherently subjective and susceptible to investigator bias, particularly at borderline values between categories 1
• Clinicians tend to assign higher KPS scores to patients aged >65 compared to younger patients, despite no objective difference in physical activity 1
• KPS is less predictive of cancer-related outcomes in older adults (age ≥65), who represent the majority of cancer patients 1
• Current performance status scales cannot differentiate whether poor functional status is due to disease burden (potentially reversible with effective treatment) or comorbid conditions 1
• When comparing KPS to ECOG PS, ECOG demonstrates superior ability to discriminate patients with different prognoses 5

Evolving Perspective on Eligibility Criteria

• The American Society of Clinical Oncology (ASCO) and Friends of Cancer Research recommend expanding performance status eligibility criteria to be more inclusive, particularly for patients with ECOG PS 2 (KPS 60-70) 1
• Simulation studies demonstrate that including modest numbers of lower-functioning patients has minimal impact on trial outcomes, with only modest effects on hazard ratios and statistical power 1
• Broadening eligibility criteria increases trial enrollment speed, improves participant diversity, reduces disparities, and enhances generalizability of results to real-world populations 1
• For patients whose poor performance status stems from high disease burden, effective treatment may improve functional status through tumor control and symptom relief 1

Practical Application Algorithm

When assessing treatment eligibility using KPS:

1. KPS 80-100: Candidate for standard multi-drug regimens including clinical trials 1
2. KPS 60-70: Candidate for two-drug chemotherapy regimens or clinical trials; reserve three-drug regimens only for medically fit patients with frequent toxicity monitoring access 1
3. KPS <60: Best supportive care only; systemic therapy not recommended 1
4. Consider the etiology: If poor KPS is primarily disease-related rather than comorbidity-related, treatment may improve functional status 1
5. Reassess frequently: Rapidly declining KPS warrants transition to supportive care 4