Cognitive Health Gains Focus in Kidney Cancer Survivorship

As survival rates improve, more people are living longer with kidney cancer. Along with longer survival, however, comes a growing awareness of cognitive changes that can affect memory, attention, processing speed, and overall mental clarity.

During a recent presentation at the 2025 International Kidney Cancer Symposium, Dr. David Sheppard, assistant professor at the University of Washington and Fred Hutchinson Cancer Center, discussed why cancer-related cognitive dysfunction is increasingly recognized among survivors and how targeted interventions may help.

“I hope to address the fallout of treatment burden on patients, particularly stress and fatigue. Oftentimes, patients describe fatigue as both physical and mental fatigue, almost as if they are two separate entities. It is [important to understand] this overlap,” Sheppard emphasized in the presentation. “Yes, there is the physical fatigue many patients experience, but there is also emotional and cognitive fatigue. At the center of this is the brain. Although it may sound obvious, the brain is a physical entity and the seat of cognition and emotion. If there is fatigue in the body, it will also affect cognitive and emotional processing.”

Sheppard emphasized that cognitive symptoms are not rare. For many patients, changes in thinking, concentration, and mental stamina can affect daily functioning, work, relationships, and quality of life long after treatment begins or ends.

Cancer Care Can Affect the Brain: Understanding Treatment Burden

Research shows that cancer itself is a risk factor for cognitive dysfunction, even before treatment begins. In kidney cancer, therapies such as antiangiogenic treatments used in first- or second-line settings have been linked to measurable cognitive declines within three to six months of treatment initiation.

Across studies, fatigue consistently increased in all patients receiving these therapies and was strongly associated with worsening cognitive symptoms. Patients who reported more fatigue also reported more problems with quality of life, fatigue, and mood.

Another major contributor to cognitive and emotional strain is treatment burden, defined as the workload of managing cancer care and its impact on daily life. For patients with renal cell carcinoma, this burden can include financial toxicity, time and travel to appointments, medication schedules, and navigating complex healthcare systems.

Although treatment burden has been associated with distress and reduced quality of life in other cancers, it is rarely measured in clinical trials for patients with genitourinary malignancies.

Fatigue, Stress and Fear of Recurrence

Fatigue plays a central role in cancer-related cognitive dysfunction. Although the brain accounts for only approximately 2% of body weight, it consumes roughly 20% of the body’s resting energy. Even though cognitive tasks result in relatively small increases in brain activity, neuropsychological testing and sustained mental effort can significantly increase fatigue.

Research suggests that stress responses, particularly activation of the hypothalamic-pituitary-adrenal axis, may contribute to this fatigue. Chronic psychosocial stress alters activity in brain regions involved in cognitive and emotional processing. Managing stress, therefore, may help reduce abnormal brain activation and support everyday cognitive functioning.

Moreover, fear of recurrence are common among people living with kidney cancer and are closely linked to cognitive and emotional symptoms. In kidney cancer, higher distress levels are often associated with a more recent diagnosis and a lack of understanding about the disease. In other cancers, physical symptom burden and treatment-related costs also contribute significantly.

Addressing fear of recurrence is not only important for emotional health but may also improve cognitive symptoms by reducing chronic stress.

Evidence-Based Interventions Can Help

Sheppard highlighted several interventions with evidence for improving cognitive symptoms and quality of life in cancer survivors. Cognitive rehabilitation programs, such as Memory and Attention Adaptation Training, have shown benefits in randomized trials.

Psychotherapy interventions have also demonstrated effectiveness in managing fear of recurrence and existential distress. Programs such as Fear of Recurrence Therapy, ConquerFear, and InFOCUS share common elements, including mindfulness, relaxation techniques, reframing fear narratives, and strengthening social support systems.

Something patients can do to begin managing their fatigue from home is to consider behavioral strategies. For example, physical activity has the strongest evidence for improving both physical and cognitive fatigue in cancer survivors

What This Means for Patients and Providers

Sheppard emphasized that cognitive changes in kidney cancer are multifactorial and often driven by fatigue, stress, mood, and treatment burden. Addressing these factors can meaningfully improve quality of life.

“Clinically, the key issue is that if we are considering treatment burden and cognition, we need to ask patients about their stress and fatigue. That is the starting point: being open to these conversations. This may include implementing some recommendations directly or referring patients to specialists with expertise in these areas,” Sheppard concluded.

Reference

1. “Overcoming Cognitive Effects of Treatment Burden,” by Dr. David Sheppard. Presented at: 2025 International Kidney Cancer Symposium ; Nov. 13-15, 2025; Denver, Colorado.

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