Cancer-Related Fatigue: An Overlooked Symptom Deserving Center Stage

Fatigue is one of the most common and debilitating symptoms experienced by people with cancer—yet it remains one of the most under-recognized and undertreated. Known clinically as cancer-related fatigue (CRF), this condition is defined by the American Society of Clinical Oncology (ASCO) and the Society for Integrative Oncology (SIO) as:

“A common and distressing side effect of cancer and its treatment, characterized by persistent physical, mental, and emotional exhaustion that is not relieved by rest.”

Unlike normal tiredness, CRF is multifactorial, persistent, and often significantly interferes with daily activities and quality of life. It can begin at any stage—diagnosis, during treatment, or long into survivorship. Studies show that 30–60% of patients experience moderate-to-severe fatigue during therapy, and 20–30% continue to experience fatigue long after treatment ends.

Why Is Cancer-Related Fatigue Often Overlooked?

Despite its prevalence, CRF is frequently under-reported by patients and under-addressed by clinicians. Why? Several reasons:

• Patients may assume fatigue is “normal” and untreatable.

• Oncologists, overwhelmed by complex treatment decisions, may unintentionally de-prioritize symptom management.

• Patients may hesitate to share their fatigue out of fear that treatment will be reduced or stopped.

Fatigue is not an inevitable consequence of cancer, but as a treatable symptom—one that deserves proactive screening and interdisciplinary care.

A Multidisciplinary Challenge Needs a Multidisciplinary Solution

Fatigue can be caused by:

• The cancer itself

• Cancer therapies (chemotherapy, immunotherapy, radiation, hormone therapy)

• Endocrine dysfunction (e.g., checkpoint inhibitor-induced hypothyroidism or adrenal insufficiency)

• Anemia, pain, poor sleep, nutritional deficiencies, mood disorders

• Medication side effects

• Deconditioning and inactivity

• Cognitive and emotional responses to the cancer diagnosis

Because the causes are so varied, no single specialist can manage CRF alone. A team-based approach is essential—one that includes:

• Oncologists

• Endocrinologists

• Primary care providers

• Nurses and pharmacists

• Dietitians and rehab professionals

• Palliative care specialists

• Psychologists and integrative medicine clinicians

Evidence-Based Management: What Works?

In 2023, ASCO and SIO updated their clinical practice guidelines based on a review of 113 randomized controlled trials. Their key findings:

✅ Non-Pharmacologic Interventions (First-Line):

• Exercise: The strongest evidence. Moderate-intensity aerobic activity 3x/week improves fatigue, mood, and function. Both home-based and supervised programs are beneficial.

• Cognitive Behavioral Therapy (CBT): Especially CBT for Insomnia (CBT-I), shown to improve sleep quality and reduce fatigue.

• Mindfulness-based practices: Meditation, yoga, and relaxation training.

• Tai Chi and Qigong: Especially helpful during treatment.

• Acupressure and yoga: Particularly helpful in the post-treatment phase.

❌ Pharmacologic Interventions (Limited Use):

• Psychostimulants (e.g., methylphenidate, modafinil): Inconsistent benefit with significant side effects (anxiety, insomnia, appetite loss, tachycardia).

• Antidepressants: May worsen fatigue due to sedating properties (especially TCAs and paroxetine).

• Supplements (e.g., L-Carnitine): Not recommended due to poor efficacy and potential harm.

• Ginseng: Conditionally recommended, with mixed evidence.

Sleep, Medications, and Lifestyle: The Hidden Drivers of Fatigue

Poor sleep is a major contributor to CRF. Yet many common “solutions”—antihistamines, alcohol, cannabis—may actually disrupt healthy sleep architecture.

• Diphenhydramine may only add 17 minutes of sleep while increasing next-day sedation.

• Alcohol and cannabis can worsen REM sleep over time, leading to dependence and withdrawal insomnia.

• CBT-I is the gold standard, with over 50% of patients achieving remission from insomnia in 6–8 weeks.

Medication side effects must be reviewed carefully—some antidepressants and pain medications can cause or worsen fatigue.

When Exercise Isn’t Possible: The “Energy Bucket” Analogy

For patients unable to exercise due to advanced disease or severe symptoms, energy conservation becomes key. Visualizing energy as a “bucket” that drains with activity and fills with rest helps patients pace their day, prioritize essential tasks, and avoid burnout.

Clinical Pearls for Oncologists

1. Fatigue should be screened routinely. Validated tools include the Brief Fatigue Inventory and PROMIS Fatigue Short Form.

2. Always evaluate for reversible causes—especially endocrine issues, sleep disorders, and medication side effects.

3. Don’t go it alone. Early referral to supportive care, endocrinology, palliative medicine, and behavioral health improves outcomes.

4. Normalize symptom reporting. Patients often hide symptoms from oncologists to avoid treatment interruption.

5. Empower patients with tools like CBT-I, structured exercise, and energy pacing strategies.

Final Thoughts

At Citrus Oncology, we are rethinking how cancer care is delivered—focusing not just on treatment, but on the experience and wellbeing of the patient. Fatigue is real, impactful, and treatable. With collaboration and evidence-based tools, we can help patients regain energy, hope, and control over their lives.

Eric Roeland, MD is an Associate Professor at the Oregon Health and Science University and the Director of the Knight Cancer Institute Symptom Science Research Program. He is a medical oncologist and palliative care specialist whose clinical practice focuses on caring for people living with cancer and poorly controlled symptoms. His research focuses on symptom science, which focuses on minimizing treatment toxicity and optimizing quality of life for people with cancer by identifying, validating, and expanding supportive care drug interventions.