Trecerea de la tratamentul curativ la îngrijiri paliative la pacienții cu cancer avansat

Background

Why stop the treatment?

“In situations in which the disease can no longer be controlled, quality of life becomes even more critical.” (ESMO Guideline)

Why it is so difficult to stop the treatment?

It is normal to associate new treatments with hope. Unfortunately, there are situations in which hope can be misleading, and you are more likely to be harmed by new treatments than helped by them.

Just as it takes courage to try a new treatment, it also takes courage to say: “No more, it’s time to stop”⁽¹⁾.

Things to consider when it is difficult to stop the treatments

If the patient is in this situation, his remaining life is precious, and he/she is likely to be better off using time and energies doing important things with family and friends than spending time in hospitals or clinics receiving treatments that are unlikely to be beneficial which may instead be harmful.

If the patient is not sure that what oncologist is saying is correct, he/she should ask for a second opinion.

The ESMO guideline recommend: “although it is your life, you cannot insist that an oncologist gives you a treatment if he/she feels it will harm you without benefit. If you are having difficulties in coping, either physically or emotionally, ask your oncologist if he/she can arrange for a palliative care consultation or for help from a psychologist, chaplain or social worker”⁽¹⁾.

Clinical tools that can help the decision
to discontinue treatment

To convince the patient that antitumor treatment should be interrupted, there are several tools that demonstrate the patient’s condition and life expectancy, knowing that chemotherapy is actually contraindicated in the last month of life.

1. Palliative Performance Scale (PPS)⁽²⁾

Population: patients who have received a palliative care consultation at an academic medical center. If your patient is in hospice, use the hospice version of the PPS.

Outcome: one-month mortality, six-month mortality, median survival in months.

Palliative Performance Scale Score

1. Is your patient in the inpatient (hospital) or outpatient (home or clinic) setting?

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2. Does your patient have cancer or a non-cancer serious illness, primarily?

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3. If you know your patient’s PPS score, input it here and you will then skip ahead to the next page.

Unknown

If you don’t know your patient’s PPS score, complete the following five questions to determine their score:

4. How ambulatory is this patient?

Select

5. What is the patient’s daily level of activity? Is there any evidence of disease?

Select above first

6. How much self-care assistance does this patient require?

Select above first

7. How much oral intake does this patient have?

Select above first

8. What is this patient’s level of consciousness?

2. Palliative Prognostic Index (PPI)⁽³⁾

It predicts survival in terminally ill patients based on five criteria.

a) Palliative Performance Scale

• 10-20 (+4)
• 30-50 (+2.5)
• >60 (0).

b) Oral intake

• Severely reduced (< mouthfuls) (+2.5)
• Moderately reduced (> mouthfuls) (+1)
• Normal (0).

c) Edema

• Present (+1)
• Absent (0).

d) Dyspnea at rest

• Present (+3.5)
• Absent (0).

e) Delirium

• Present (+4)
• Absent (0).

Palliative Prognostic Index Score (PPI) = 11 points.

Note: If the PPI is greater than 6, survival is less than three weeks (sensitivity – 80%; specificity – 85%)⁽³⁾.

3. Blood hematological and biochemical predictors of survival

A) Serum albumin

• Low serum albumin is a strong independent predictor of poor survival in advanced cancer.
• It reflects both nutritional status and systemic inflammation.
• Hypoalbuminemia (

B) C-Reactive Protein (CRP)

• Elevated CRP indicates systemic inflammation and is associated with reduced survival.
• Often used in combination with albumin in prognostic scores (e.g., Glasgow Prognostic Score).

C) Lactate dehydrogenase (LDH)

• High LDH is a marker of tumor burden, tissue breakdown and aggressive disease.

Elevated LDH is independently associated with worse prognosis in many advanced cancers.

D) Total bilirubin

• High bilirubin is associated with poor survival, especially in cancers with liver involvement.

E) Neutrophil-to-lymphocyte ratio (NLR)

• High NLR (>3-5) is a marker of systemic inflammation and immunosuppression.
• Consistently associated with worse survival in various advanced malignancies.

F) Hemoglobin

• Low hemoglobin (anemia) is associated with poor prognosis, reflecting chronic disease, nutritional status, or marrow involvement.

G) Other markers

• D-dimer: elevated levels are associated with hypercoagulability and poor prognosis.
• Creatinine and urea: renal dysfunction is a negative prognostic factor.
• Alkaline phosphatase: elevated in bone and liver metastases, associated with worse outcomes.

Composite prognostic scores

Several validated prognostic models incorporate these biochemical markers.

• Glasgow Prognostic Score (GPS/mGPS): combines CRP and albumin.
• Palliative Prognostic Score (PaP): includes clinical and laboratory parameters.
• Prognosis in Palliative Care Study (PiPS-B): incorporates blood results for more accurate survival prediction.

Six Adaptable Prognostic (SAP) models: use albumin, neutrophil count and LDH.

What is the Modified Glasgow Prognostic Score (mGPS)?

The mGPS is calculated using:

• C-Reactive Protein (CRP) level
• Serum albumin level.
• The score ranges from 0 to 2, with higher scores indicating poorer prognosis.
• Score 0: CRP ≤ 10 mg/L.
• Score 1: CRP > 10 mg/L.
• Score 2: CRP > 10 mg/L and albumin < 35 g/L.

Score interpretation

Score 0: best prognosis

Normal inflammatory status.

Significantly better survival rates.

Score 1: Intermediate prognosis

Elevated systemic inflammation.

Approximately 70-80% reduction in survival compared to score 0.

Score 2: Poor prognosis

Significant inflammation and poor nutritional status.

Approximately 140-160% reduction in survival compared to score 0⁽⁵⁾.

When should we stop chemotherapy and other systemic therapy for a cancer patient with poor performance status?

“The decision to cease chemotherapy is one that should be approached with careful consideration and accurate information. Clear communication, compassion and empathy are important components to the therapeutic relationship. Early involvement of palliative care and clear conversations about prognosis and the expected utility of further chemotherapy is essential to conduct the best possible care for cancer patients at the end of life. Currently, there are no clear recommendations for when cessation of chemotherapy should occur. Concise clinical pathways that determine when additional therapy is investigational only and when it is unlikely to offer further improvement either in QoL or disease-free interval should be developed”⁽⁷⁾.

Signs chemotherapy is not working

Signs indicating chemotherapy is not working include that the cancer has not shrunk or has spread to other body parts. If this is the situation, a doctor may diagnose a person with advanced or metastatic cancer.

Some signs and symptoms of advanced cancer can include:

• unintentional weight loss
• feeling weak, tired and lacking in energy
• difficulty breathing or shortness of breath
• unexplainable pain⁽⁹⁾.

Stopping chemotherapy and other systemic anticancer therapy in patients with cancer and poor performance status (typically ECOG 3-4)

International guidelines and best clinical practice

The key considerations are as follows:

General criteria for stopping systemic therapy in poor performance status

1. ECOG Performance Status 3-4

Patients with ECOG 3 (capable of only limited self-care, confined to bed/chair >50% of waking hours) or ECOG 4 (completely disabled, totally confined to bed/chair) generally have a poor prognosis and limited tolerance for systemic therapy.

Guidelines (e.g., ASCO, ESMO, NICE, NHS) recommend stopping systemic anticancer therapy in these patients unless there is a strong, evidence-based recommendation.

2. Lack of clinical benefit

Disease progression on current or multiple prior lines of therapy.

No objective response or symptomatic improvement after a reasonable trial of therapy.

3. Intolerable toxicity

Severe or unmanageable adverse effects, especially if dose reductions or supportive measures have failed.

4. Declining functional status

Worsening performance status despite therapy.

Increasing symptom burden, weight loss, or organ dysfunction.

5. Limited life expectancy

Estimated life expectancy of weeks to a few months, particularly if the patient is not a candidate for further disease-modifying therapy.

6. Patient preference

Patient wishes to discontinue therapy after informed discussion of risks, benefits and likely outcomes.

Specific guidance from major guidelines

• ASCO and ESMO: recommend discontinuing systemic therapy in patients with ECOG 3-4, advanced solid tumors and no further evidence-based treatment options, or when the likelihood of benefit is very low.
• NHS/UK Guidelines: for patients with poor performance status (ECOG 3-4), the rationale for any ongoing treatment must be clearly documented. In most cases, systemic therapy should be stopped unless there is a compelling reason (e.g., highly chemosensitive tumor, reversible cause of poor performance status).
• NICE recommends best supportive care for patients with poor performance status or significant comorbidities.

Investigating the association between chemotherapy use in patients with stage IV and survival

According to a retrospective study that analyzed the use of palliative systemic anti-cancer therapy (SACT) for patients with advanced non-small cell lung cancer, 22% of patients received this therapy within 30 days of death. This was associated with reduced access to palliative care, higher rates of in-hospital death, a decreased use of voluntary assisted dying and palliative sedation, and a shorter median overall survival of four months compared to nine months for patients who did not receive the therapy close to death⁽⁸⁾.

Finally, instead of conclusions, we reproduce the recommendations of ESMO A User’s Manual for Oncology Clinicians:

Stopping treatment does not mean stopping care!

• In situations in which the disease can no longer be controlled, the quality of life becomes even more critical than before.
• Problems relating to physical symptoms, distress and family coping are critically important at this stage.
• Often patients will benefit from the assistance of a palliative care or hospice team to help coordinate the best of care either at home or, if necessary, in a hospital or hospice⁽¹⁾.

Questions to ask your oncologist about your condition

Getting the basic information.

Questions to ask your oncologist when considering your options for anticancer treatments:

• Taking part in a clinical research study. Should I consider an experimental treatment?
• Should I consider complementary medicine and alternative methods?
• Second opinions⁽¹⁾.
   

Palliative care specialists

Palliative care specialists are doctors and nurses with special expertise in managing the physical and psychological consequences of advanced cancer. Working with your oncologist, they can help develop care programs to optimize your comfort, function and support.

Palliative care specialists are not only there to help patients who are dying, and their participation in care has been shown to be of value in helping patients to live better and, sometimes, longer.

Psychologists, psychiatrists or psycho-oncologists: living with advanced cancer can trigger many concerns and negative feelings: anger, fear, sadness, anxiety about what lies ahead and, for some people, even feelings of meaninglessness and hopelessness. The skilled care provided by psychologists, psychiatrists or psycho-oncologists is often extremely helpful in dealing with these sorts of feelings.

Exceptions from stopping chemotherapy and other systemic anticancer therapy in patients with cancer and poor performance status

• Potentially reversible poor performance status: if poor performance status is due to tumor burden and there is a reasonable expectation that therapy could rapidly improve function (e.g., small cell lung cancer, lymphoma), a carefully monitored trial of therapy may be considered.
• Highly chemosensitive malignancies: select hematologic malignancies or germ cell tumors may warrant individualized consideration.   

Corresponding author: Alexandru-Călin Grigorescu E-mail: alexgrigorescu2004@yahoo.com

Conflict of interest: none declared.

Financial support: none declared.

This work is permanently accessible online free of charge and published under the CC-BY licence.