Month: March 2023

It used to be that doctors would automatically recommend treating all men with prostate cancer, even if their initial biopsies suggested the disease would grow slowly (or at all). But during the last several decades, the pendulum on treatment has swung the other way.

Doctors are now likely to advise active surveillance for low- to intermediate-risk cancers that may never turn deadly over the course of a man’s life. Active surveillance involves routine PSA checks, follow-up biopsies, and more recently, magnetic resonance imaging of a patient’s tumor. Treatment is initiated only when — or if — the disease shows signs of progression.

Recent evidence from Johns Hopkins University shows that the long-term risks of metastasis and death from low-grade prostate cancer among men on active surveillance averages just 0.1%. But doctors who care for such men also face a nagging question: which of their patients might have more aggressive cancer that should require closer monitoring? New findings published by the Johns Hopkins team in January provide useful insights.

The researchers’ approach

The researchers in this case zeroed in on the prognostic value of so-called perineural invasion, or PNI, on tumor biopsy samples. PNI simply means that cancer cells are moving into the perineural space between nerves in the prostate and their surrounding tissues. A finding of PNI raises red flags because the perineural space “provides a conduit by which tumor cells can potentially escape the prostate and grow elsewhere in the body,” says Dr. Christian Pavlovich, a urologic oncologist at Johns Hopkins who led the research.

Dr. Pavlovich’s team wanted to know if PNI detected on initial or follow-up biopsies would be associated with higher risks for cancer progression. So they analyzed long-term follow-up data from 1,969 men who had enrolled in an active surveillance research protocol at Johns Hopkins between 1995 and 2021. All the men were diagnosed initially with Grade Group 1 prostate cancer (the least risky form of the disease) and had undergone at least one follow-up biopsy since then.

What did the results show?

Among the 198 men with PNI, 44% of them (87 men in all) eventually progressed to Grade Group 2 prostate cancer, which is a more advanced form of the disease with an intermediate risk of further spread. Conversely, just 26% of the remaining 1,771 men without PNI (461 men) had progressed to Grade Group 2.

Pavlovich emphasizes that despite the new findings, PNI “does not make patients ineligible for active surveillance.” Importantly, the research showed that PNI was not associated with high-risk features, such as cancer in the lymph nodes of patients who wound up having surgery, or post-surgical elevations in PSA that show cancer still lurks in the body.

“What we’ve really shown here is that PNI puts men at a slightly higher risk of extraprostatic extension (cancer cells located just beyond the confines of the prostate),” Pavlovich says. “This is not necessarily a new finding. But PNI only occurs in about 10% of Grade Group 1 patients, and this is the boldest statement yet from the largest study conducted so far.” Pavlovich and his colleagues concluded that PNI provides an inexpensive and readily available indicator for identifying which men on active surveillance will benefit from more intensive monitoring protocols, including MRI and genetic tests.

Dr. Marc B. Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, agrees, while pointing out that PNI evaluations aren’t performed often enough. A PNI analysis of pathology specimens, he says, “along with emerging and sophisticated genetic testing of the tissue samples, may lead to more certainty in our recommendations to patients.”

About the Author

Charlie Schmidt, Editor, Harvard Medical School Annual Report on Prostate Diseases

Charlie Schmidt is an award-winning freelance science writer based in Portland, Maine. In addition to writing for Harvard Health Publishing, Charlie has written for Science magazine, the Journal of the National Cancer Institute, Environmental Health Perspectives, … See Full Bio View all posts by Charlie Schmidt

About the Reviewer

Marc B. Garnick, MD, Editor in Chief, Harvard Medical School Annual Report on Prostate Diseases; Editorial Advisory Board Member, Harvard Health Publishing

Dr. Marc B. Garnick is an internationally renowned expert in medical oncology and urologic cancer. A clinical professor of medicine at Harvard Medical School, he also maintains an active clinical practice at Beth Israel Deaconess Medical … See Full Bio View all posts by Marc B. Garnick, MD

We can feel groggy when our sleep schedule is thrown off even just a little. So what happens when shift work requires people to regularly stay awake through the night and sleep during the day — and how can they protect their health and well-being?

What is shift work disorder?

Mounting evidence, including several new studies, paints a worrisome picture of the potential health fallout of nontraditional shift work schedules that affect 15% to 30% of workers in the US and Europe, including factory and warehouse workers, police officers, nurses, and other first responders.

So-called shift work disorder mainly strikes people who work the overnight or early morning shift, or who rotate their shifts, says Eric Zhou, an assistant professor in the Division of Sleep Medicine at Harvard Medical School. It is characterized by significant problems falling and staying asleep, or sleeping when desired. That’s because shift work disrupts the body’s normal alignment with the 24-hour sleep-wake cycle called the circadian rhythm.

“People who work 9-to-5 shifts are typically awake when the sun is up, which is aligned with their body’s internal circadian clock. But for shift workers, their work hours and sleep hours are misaligned with the natural cues to be awake or asleep,” Zhou says. “They’re working against the universe’s natural inclinations — not just their body’s.”

What’s the connection between shift work and health?

A 2022 research review in the Journal of Clinical Sleep Medicine links shift work to higher risks for serious health problems, such as heart attack and diabetes. This research suggests adverse effects can include metabolic syndrome (a cluster of conditions that raises the risks for heart disease, diabetes, and stroke), accidents, and certain types of cancer.

“The research is consistent and powerful,” Zhou says. “Working and sleeping during hours misaligned with natural light for extended periods of time is not likely to be healthy for you.”

How do new studies on shift work boost our understanding?

New research continues to add to and strengthen earlier findings, teasing out specific health effects that could stem from shift work.

• Shift workers on rotating schedules eat more erratically and frequently than day workers, snack more at night, and consume fewer healthier foods with potentially more calories, a study published online in Advances in Nutrition suggests. This analysis reviewed 31 prior studies involving more than 18,000 participants, comparing workers’ average food intake over 24 hours.
• Disrupting the circadian rhythm through shift work appears to increase the odds of colorectal cancer, a malignancy with strong ties to lifestyle factors, according to a 2023 review of multiple studies published online in the Journal of Investigative Medicine. Contributors to this higher risk may include exposure to artificial light at night, along with complex genetic and hormonal interactions, study authors said.

“Cancer understandably scares people, and the World Health Organization recognizes that shift work is a probable carcinogen,” Zhou says. “The combination of chronically insufficient and poor-quality sleep is likely to get under the skin. That said, we don’t fully understand how this happens.”

How can you protect your sleep — and your health?

If you work overnight or early morning shifts, how can you ensure you sleep more soundly and restfully? Zhou offers these evidence-based tips.

Time your exposure to bright and dim light. Graveyard shift workers whose work schedule runs from midnight through 8 a.m., for example, should reduce their light exposure as much as possible after leaving work if they intend to go right to sleep once they return home. “These measures could take the form of wearing blue light–blocking glasses or using blackout shades in your bedroom,” he says.

Make enough time for sleep on days off. “This is often harder than it sounds, because you’ll want to see your family and friends during nonwork hours,” Zhou says. “You need to truly protect your opportunity for sleep.”

Maintain a consistent shift work schedule. “Also, try to minimize the consecutive number of days you spend working challenging shifts,” he says.

Talk to your employer. Perhaps your boss can schedule you for fewer overnight shifts. “You can also ask your doctor to make a case for you to be moved off these shifts or have more flexibility,” Zhou says.

Look for practical solutions that allow you to get more restful sleep. “People engaged in shift work usually have responsibilities to their job as well as their family members, who often operate under a more typical 9-to-5 schedule,” he notes. “The goal is to preserve as strong a circadian rhythm as possible under the abnormal schedule shift work requires.”

About the Author

Maureen Salamon, Executive Editor, Harvard Women's Health Watch

Maureen Salamon is executive editor of Harvard Women’s Health Watch. She began her career as a newspaper reporter and later covered health and medicine for a wide variety of websites, magazines, and hospitals. Her work has … See Full Bio View all posts by Maureen Salamon