Can advanced disease state, symptoms, and current regimen indicate end of life?

Can Advanced Disease State, Symptoms, and Current Regimen Indicate End of Life?

Yes, specific clinical signs and symptoms in advanced cancer patients reliably indicate approaching end of life, with low performance status, delirium, dyspnea, and cancer anorexia-cachexia syndrome being the most validated prognostic indicators for short-term survival.

Key Prognostic Indicators for End of Life

Most Reliable Clinical Signs (Grade B Evidence)

The following symptoms have proven prognostic significance in advanced cancer patients approaching end of life 1:

• Low performance status is the most reliable prognostic factor to predict short-term survival, particularly when there is deterioration from previously higher scores 1
• Delirium or cognitive failure strongly indicates approaching death 1
• Dyspnea has significant prognostic importance 1
• Cancer anorexia-cachexia syndrome (CACS) including anorexia, weight loss, and dysphagia 1

Laboratory Markers with Prognostic Value

Certain laboratory abnormalities support clinical assessment 1:

• Leukocytosis (Grade B evidence) 1
• Lymphocytopenia (Grade B evidence) 1
• Elevated C-reactive protein (Grade B evidence) 1
• Low pseudocholinesterase, high vitamin B12, and high bilirubin 1

Important caveat: Blood sampling should be weighed against clinical benefit for the individual patient at end of life 1.

Symptom Patterns in the Final Week of Life

Most Prevalent Symptoms (>50% of patients)

In the last week of life, the following symptoms predominate 2:

• Anorexia
• Asthenia (profound weakness)
• Dry mouth
• Confusion
• Constipation

Additional Common End-of-Life Symptoms

Multiple physical and psychological symptoms cluster at end of life 3, 4:

• Pain (present in approximately 196,000 of 1 million hospital deaths) 5
• Breathlessness/dyspnea (244,000 of hospital deaths) 5
• Fatigue (324,000 of hospital deaths) 5
• Nausea and vomiting 3, 5
• Depression 3, 5
• Death rattle, delirium, and terminal agitation specifically in the dying phase 3

Clinical Approach to Prognostication

Algorithmic Assessment Framework

Step 1: Evaluate performance status repeatedly 1

• Deterioration from previously high scores indicates serious worsening of prognosis
• Short-term predictions (days to weeks) are more accurate than long-term predictions due to the "Horizon Effect" 1
• Repeated evaluations at fixed intervals improve accuracy 1

Step 2: Assess for key symptom clusters 1

• Presence of CACS symptoms (anorexia, weight loss, dysphagia)
• Development of dyspnea
• Onset of delirium or cognitive impairment

Step 3: Consider clinical prediction in combination with other factors 1

• Clinical prediction of survival (CPS) should be used with other prognostic factors or scores to improve accuracy (Grade A recommendation) 1
• CPS should be considered as a probability rather than a temporal value 1

Step 4: Obtain second opinion when appropriate 1

• Lack of experience in oncology and palliative care reduces accuracy 1
• A second opinion is valuable if the first physician has a close relationship with the patient 1

Critical Pitfalls to Avoid

Prognostication Errors

Clinicians tend to be overoptimistic: CPS is more than twice as likely to overestimate survival length by a factor of 3 to 5 compared to being overpessimistic 1. This means physicians typically predict patients will live longer than they actually do.

Symptom Management Failures

Undertreatment of dyspnea due to unfounded concerns about respiratory depression from opioids is common, but evidence supports their safety and efficacy when appropriately dosed 6.

At end of life, opioid doses should not be reduced solely for decreased blood pressure, respiration rate, or level of consciousness when necessary for adequate symptom management 6.

When Symptoms Indicate Refractory Suffering

Definition of Refractory Symptoms

Symptoms are considered refractory when they cannot be adequately controlled despite aggressive efforts, and further interventions are 1:

1. Incapable of providing adequate relief
2. Associated with excessive and intolerable morbidity
3. Unlikely to provide relief within a tolerable time frame

Management of Refractory End-of-Life Symptoms

Palliative sedation may be considered as a last resort for refractory terminal restlessness or other intolerable symptoms, with the goal of relieving suffering by inducing decreased awareness 1, 7. The level of sedation should be the minimum necessary to provide adequate relief 7.

Symptom Assessment in Advanced Illness

Validated instruments should be used to assess symptoms in ICU patients with advanced illness to improve symptom detection and treatment, though this represents low-level evidence 1. Key symptoms to evaluate include 1:

• Thirst
• Dyspnea
• Anxiety
• Fatigue
• Delirium
• Sleep disturbance
• Pain

Assessment should be performed routinely at regular intervals and documented, with continuation after interventions 1.

Context for Current Treatment Regimens

In patients with advanced stage cancer who have completed initial or maintenance treatment, symptom monitoring with patient-reported outcome measures is suggested for stage IIIB/IV lung cancer 1. This monitoring can detect symptomatic complications and relapse, potentially allowing for better performance status at relapse and more optimal treatment decisions 1.

However, in end-of-life care defined as the last few weeks or months before inevitable death, the main objective shifts entirely to quality of life, and active cancer treatment should be discontinued 1. Monitoring should focus on symptoms of disease and residual toxicities 1.