Fatigue and Cancer

Fatigue is subjective, which means it’s hard to measure and diagnose. Unlike “tiredness,” fatigue involves feeling constantly drained, lethargic, and sometimes physically unable to move. Generally not relieved by a good night’s sleep, fatigue affects between 10 and 20% of the population, and is more common in women.

For DC area lawyer R.D., her fatigue worsened over the course of 10 years, with a brief improvement when she lost weight. Based on testing, R.D. tried taking iron (via infusions and supplements) for low ferritin and Synthroid for low thyroid. To improve nighttime sleep, she took magnesium supplements, as well as gabapentin for periodic limb movement disorder (legs moving while asleep). She also used a C-Pap (continuous positive airway pressure) machine to counter sleep apnea. But her greatest concern remained: “I fell asleep when I didn’t want to.”

After two years, with R.D.’s persistence, doctors ordered GI testing that showed worrisome cells suggesting early-stage cancer, and scheduled surgery to investigate and remove those cells. In a recent study on fatigue that included over 250,000 patients, the 12-month cancer risk was higher in men 65+ and women 80+ compared with the general population, with nearly half diagnosed within three months of their first fatigue complaints. The risks were higher for leukemia, pancreatic cancer, and brain cancer.

Fatigue linked to cancer has several possible causes. Cancer cells, particularly in the GI system, use calories and nutrients that the body needs for energy, according to cancer.gov. Blood cancers in particular—like leukemia, lymphoma, and multiple myeloma—affect bone marrow, which reduces the production of healthy red blood cells and makes it harder for sufficient oxygen to reach the tissues. Other cancers can affect hormone levels.

A DC-area concierge physician’s office advises patients to get both the Galleri blood test ($750) and a whole-body MRI ($2,000) “every year or two.” Though not recommended by national physician- and disease-related organizations, or covered by insurance, several multi-cancer early detection (MCED) blood tests can help investigate persistent symptoms, notably fatigue, and make possible early, non-invasive responses to indications of cancer.

Diagnostic MCED blood-testing is constantly gaining “real-world experience,” according to U.S. multi-center research published on nature.com. MCED tests look for proteins or genetic factors—for example in “cell-free” or circulating DNA that’s been released from cells—that reveal change patterns indicating the presence of cancer, as well as where the cancer started.

Cancers in the U.S. that lack regular preventive health services screening recommendations—making costs higher and testing unavailable to most people—cause about 70% of cancer deaths among those age 50 to 79. Using MCED tests on more than 50,000 individuals with no family history of cancer, the researchers found early cancers in areas of the body that have no regular screening recommendations, like the head, neck, ovaries, and kidneys.

Recently, though, a clinical trial of the Galleri Multi-Cancer Detection Test was temporarily put on hold, “likely due to poor clinical performance,” according to Toronto researchers. They compare the Galleri test to blood testing from Theranos, which raised millions of dollars for a product that didn’t work. And in just-published results, according to the New York Times, the most recent MCED study looking at 142,000 healthy adults “failed to reduce late-stage cancer diagnoses.”

Timing is an important limitation of MCED tests, because the results provide only a moment-in-time snapshot of cancer health that could change in the months or even weeks following the test. Proliferating in recent years from Silicon Valley start-ups, DIY at-home tests also offer single-moment health snapshots more conveniently and cheaply than cancer testing. These can detect, for example, disturbances in the gut microbiome that can help explain fatigue and health issues throughout the body.

While the risk of false positives has proved low for MCED tests, a different problem is the detection of “incidentalomas”—benign findings that are difficult to characterize and measure, and thus set off a “cascade of care” leading to further tests.

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Before considering MCED testing, genetic analysis can help determine an individual’s risk, as up to 10% of all cancers are caused by inherited genetic changes, according to the National Cancer Institute. Fred Hutch Cancer Center geneticist Heather Cheng explained that identifying patients with inherited cancer risk variants will give them “more treatment options.”

“Only 63% of patients with breast cancer and only 55% of patients diagnosed with ovarian cancer [had] received genetic testing for BRCA1 or BRCA2” reported a Fred Hutch Cancer Care study. According to the report, “though they’re also linked to BRCA1 and BRCA2, only 15% of patients with pancreatic cancer and 6% of eligible patients with prostate cancer received genetic testing.”

For anyone with a family risk of colon cancer, blood tests that detect DNA fragments from early-stage cancer could become part of routine blood work at annual physicals, which would be especially useful for those under the recommended screening age of 45.

On the other hand, the blood tests reveal the presence only of about 13% of large polyps that could be pre-cancerous, while the fecal test Cologuard detects 43% and a colonoscopy finds 94%, UC San Diego gastroenterologist John Carethers told the New York Times. Abnormal results on both the Cologuard and blood test still require a follow-up colonoscopy to look for polyps and remove them.

With my family risk for colon cancer, regular colonoscopies seem to be the most likely way of finding polyps that also allows doctors to immediately excise them. Worries remain, though, during the three to five years between exams when polyps can develop and become cancerous. For my children, as long as they are under the recommended age for screening, blood testing is too expensive. But awareness of how cancer can be linked to subtle symptoms like fatigue could encourage everyone to become persistent squeaky wheels when needed.