Month: April 2022

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

The current shortage of semaglutide (Ozempic), an important diabetes drug, has an unusual origin: too many people without diabetes are taking it. Here’s how that happened, and how we might course-correct to help ensure that those with the greatest need for this medicine can get it.

A diabetes drug with an important side effect: Weight loss

Semaglutide (Ozempic) was first approved by the FDA in 2017 to help people with type 2 diabetes keep blood sugar under control. But during pre-approval studies, researchers noticed a remarkable side effect: people lost weight. For example, in one pivotal study, average losses for those receiving one milligram a week of semaglutide were:

• nearly 10 pounds lost over 30 weeks
• nearly 5% overall body weight lost
• waist size shrank 1.6 inches.

This side effect helped people with type 2 diabetes because excess weight is a major risk factor for the condition. Among other health benefits, weight loss can lower blood sugar and blood pressure, and reduce the need for other diabetes medications.

Turning a side effect into a selling point

Unintended weight loss would usually be listed as a side effect for a study medication. But ads for Ozempic didn’t list it with the other possible side effects; instead, it was featured as a benefit. The Ozempic “Tri-Zone” (a phrase concocted by marketers, not medical experts) promised improved blood sugar control, lower cardiovascular risk, and weight loss.

At the bottom of the ad, fine print that’s easy to miss states: “Ozempic is not a weight loss drug.” Talk about mixed messages!

The makers of Ozempic saw the potential of semaglutide as a weight loss drug for people without diabetes. Sure enough, clinical trials confirmed that overweight and obese people taking semaglutide also lost substantial weight. Semaglutide received FDA approval in 2021 for people with obesity (BMI of 30 or greater), or who were overweight (with a BMI of 27 to 29.9) and had a medical problem related to excess weight, such as high blood pressure or high cholesterol. As a weight loss drug, it was rebranded as Wegovy.

The only difference between the two drugs? The maximum approved dose of semaglutide is a bit higher with Wegovy than Ozempic.

How social media fueled the Ozempic shortage

Soon after the approval of Wegovy, celebrities and social media influencers began taking it and sharing glowing weight loss experiences. What’s more, medicines approved for specific uses in the US can be prescribed off-label for any use: up to 38% of all prescriptions written in the US are off-label (note: automatic PDF download). So, it’s likely some of the viral run on Wegovy was fueled by people who wanted to lose weight but had no medical reason to take it.

After high demand put Wegovy in short supply, many turned to Ozempic to lose weight. And that contributed to a shortage of Ozempic, threatening the health of people with type 2 diabetes who rely on the drug.

Readjust priorities and limit irresponsible prescribing

This situation couldn’t have happened without physicians or other health care professionals willing to write Ozempic prescriptions for people who did not have diabetes or another medical reason to use semaglutide. And that suggests an obvious solution: limit prescriptions for Ozempic to people with diabetes. For many drugs, a prior authorization process requires certain conditions be met before a prescription can be filled. This could be done for Ozempic.

And of course, we should encourage people who don’t have diabetes not to request a prescription for Ozempic. While that message is unlikely to show up in a drug ad, public service announcements could do the trick.

The bottom line

Drug ads often urge you to ask your doctor if a treatment is right for you. But we already know a key piece of the answer for Ozempic: if you don’t have diabetes, don’t ask for a diabetes medicine to help with weight loss. There are better ways to get the help you need to reach a healthy weight if you are overweight or obese. Talk to your doctor about a full range of treatment options. And if your weight is already in a healthy range, it’s not a good idea to take a medication to become thinner.

Finally, to keep vitally important medicines available for those who need them most, health care professionals must prescribe them responsibly. Responsible requests by their patients could help.

About the Author

Robert H. Shmerling, MD,

Senior Faculty Editor, Harvard Health Publishing; Editorial Advisory Board Member, Harvard Health Publishing

Dr. Robert H. Shmerling is the former clinical chief of the division of rheumatology at Beth Israel Deaconess Medical Center (BIDMC), and is a current member of the corresponding faculty in medicine at Harvard Medical School. … See Full Bio View all posts by Robert H. Shmerling, MD

Imagine this as a morning routine that replaces your first cup of coffee:

You wake up feeling a bit foggy, so you slip on a wearable device that looks like an extra-thick headband. You turn on the power source and settle in while electrical current flows into your brain. Twenty minutes later, feeling more focused and energized, you start your busy day feeling grateful for this new technology.

If this scenario sounds strange to you, I’m with you. And yet, hype around transcranial direct current stimulation (tDCS) is growing for an expanding list of conditions such as depression, ADHD, and even Alzheimer’s disease. A recent ad for one tDCS device urges you to “elevate your performance.” But before you give this a try, read on.

What is transcranial direct current stimulation?

Brain stimulation therapies aim to activate or inhibit parts of the brain. tDCS has been around for years, but its popularity has spiked over the last decade.

tDCS devices use headgear that may look like a swim cap or headband to position electrodes against the scalp. When a power source is switched on, the electrodes deliver low levels of electrical current to the brain. A typical session lasts 20 to 30 minutes and may be repeated over days or weeks.

Three better-known brain stimulation therapies are:

• Transcranial magnetic stimulation (TMS): A device worn over the forehead stimulates specific areas of the brain by changing nearby magnetic fields. TMS is cleared by the FDA to treat depression that hasn’t responded to standard medicines, and for obsessive-compulsive disorder.
• Electroconvulsive therapy (ECT): An electric current flowing through electrodes placed at specific locations on the scalp causes a brief seizure while a patient is under anesthesia. In use since the late 1930s, ECT can be highly effective for severe depression that hasn’t responded to standard therapies. It uses higher levels of electrical current than tDCS. That’s why it requires close medical supervision and is generally administered in a hospital or specialized clinic.
• Deep brain stimulation (DBS): Electrodes surgically implanted in specific areas of the brain generate electrical pulses. DBS is used to treat conditions such as Parkinson’s disease, epilepsy, or tremors that don’t improve with medicines.

What claims are made for tDCS?

The brain normally functions by sending and receiving tiny electrical signals between nerve cells. Stimulating specific regions of the brain with low levels of electricity might improve focus or memory, mood, or even dementia, according to tDCS advocates.

Some claims say tDCS can

• improve mental clarity, focus, and memory
• increase energy and motivation
• relieve so-called brain fog following COVID-19, Lyme disease, or other conditions
• reduce depression or anxiety
• reduce cravings among smokers or people with drug addiction
• improve symptoms of ADHD or Alzheimer’s disease.

Does tDCS work?

The jury is still out. Research suggests that tDCS holds promise for certain conditions, but techniques tested through research may differ from devices sold commercially for at-home use. For example, electrodes may be positioned more precisely over an area of the brain, and how current is delivered, session length, or number of sessions may differ.

Currently, small, short-term studies show that tDCS may benefit people with:

• Depression: An analysis of 10 randomized trials found some participants were more likely to report fewer symptoms of depression, or remission of depression, after a course of tDCS treatment compared with sham treatment.
• Alzheimer’s disease: A review of seven studies found that tDCS lasting 20 to 40 minutes improved memory and other cognitive measures in people with mild to moderate Alzheimer’s disease.
• ADHD: One randomized trial of 64 adults with ADHD found improved attention after 30 minutes of tDCS daily for a month.

The FDA has not cleared tDCS for any health condition, and it is considered investigational. More research with positive results and reassuring safety data are needed before tDCS gets a thumbs-up from regulators.

That’s probably why some ads for tDCS note in fine print that it is not a medical device and is only for recreational use.

Does tDCS have downsides?

While the FDA assesses tDCS as safe for adults, there are downsides to consider. For example, treatment may cause itching, irritation, or small burns at the sites of the electrodes. Some users complain of fatigue or headache.

There are no large, long-term studies of tDCS, so overall safety is uncertain. Some experts believe at-home use raises many questions, such as how much of the brain beyond targeted areas is affected, what inconsistent approaches to tDCS use might do, and how long changes in the brain — intended or not — could last.

Very limited research has been done in children. So, the consequences for a child’s developing brain aren’t clear.

Finally, tDCS devices can be expensive (several hundred dollars or more), and generally are not covered by health insurance.

The bottom line

It’s not yet clear how tDCS should be used, or who is most likely to benefit from it. If you’re interested in pursuing tDCS, understand that there’s still a lot we don’t know.

If you’re more skeptical and risk-averse (like me), you may want to wait for more definitive research regarding its benefits and risks — and for now, stick with your morning coffee to clear your mind.

Follow me on Twitter @RobShmerling

About the Author

Robert H. Shmerling, MD,

Senior Faculty Editor, Harvard Health Publishing; Editorial Advisory Board Member, Harvard Health Publishing

Dr. Robert H. Shmerling is the former clinical chief of the division of rheumatology at Beth Israel Deaconess Medical Center (BIDMC), and is a current member of the corresponding faculty in medicine at Harvard Medical School. … See Full Bio View all posts by Robert H. Shmerling, MD

When caught early through routine screening, cervical cancer is curable. In the US, roughly 92% of women with early-stage cervical cancer survive five years or longer, compared with only 17% of women with late-stage cervical cancer. So recent research that shows a steep rise in new cases of advanced cervical cancer among white Southern women, and underscores the disproportionate burden of advanced cases among Black Southern women, is worrisome.

What factors might be at play, and how can people best protect themselves? Two Harvard experts share their insights.

Human papilloma virus and cervical cancer: What to know

Human papilloma virus (HPV) causes nine out of 10 cervical cancers. In 2023, 13,960 women in the US will be diagnosed with cervical cancer and 4,310 will die from it, according to American Cancer Society estimates.

Pap test screening can detect this cancer early, when it’s easiest to treat. And testing for HPV has been approved as an additional screening test for cervical cancer. It can be used alone or with a Pap test.

What did the research focus on and learn?

The study was published online in International Journal of Gynecological Cancer. Researchers combed through cervical cancer data submitted to the United States Cancer Statistics program between 2001 and 2018, and national survey findings on Pap screening and HPV vaccination. During this period, nearly 30,000 women were diagnosed with late-stage cervical cancer, which has spread to other parts of the abdomen and body.

Early-stage cervical cancer cases have been dropping for most groups in the US in recent years. But advanced cervical cancer cases have not declined within any US racial, ethnic, or age group over the last 18 years.

New diagnoses of advanced disease rose 1.3% annually during the study period. Southern white women ages 40 to 44 saw an annual rise of 4.5% in advanced cases. Southern Black women ages 55 to 59 were diagnosed nearly twice as often as white women with early and advanced cases.

What else is important to understand?

The new study showed that women living in the South are less likely to be vaccinated against HPV or screened for cervical cancer. But lower screening rates likely don’t fully explain the rise in late-stage cases in that region, says Dr. Ursula Matulonis, chief of the Division of Gynecologic Oncology at Dana-Farber Cancer Institute.

“Most cervical cancer cases continue to be diagnosed early,” Dr. Matulonis says. “These new findings suggest that cases involving a more aggressive cell type called adenocarcinoma are also increasing. Often found higher up in the cervical canal, this is harder to detect with a Pap smear.”

Older women are especially vulnerable. Rates of late-stage cervical cancer are higher — and survival is worse — among women 65 and older than among younger women, according to a study in California. One possible reason? They may not have received the recommended number of screening tests with normal results before they stopped having Pap smears, says Dr. Sarah Feldman, a gynecologic oncologist at Brigham and Women’s Hospital.

HPV vaccine protects against cervical cancer

The HPV vaccine is FDA-approved for use in females ages 9 through 26. The first group of vaccinated adolescents, now in their 20s, have clearly benefited: invasive cervical cancer rates among women 20 to 24 dropped by 3% each year from 1998 through 2012.

“That’s pretty impressive,” Dr. Matulonis says. “And those decreases span race and ethnicity, which isn’t always the case in women’s cancers.”

What steps can you take to protect against cervical cancer?

Dr. Feldman offers this guidance around cervical cancer prevention and detection.

• HPV vaccination. All children should be vaccinated against HPV between ages 9 and 12, well before sexual activity begins. “The most important thing for future generations in cervical cancer prevention is vaccinating that generation,” Dr. Feldman says.
• Routine screening. Regardless of vaccination status or whether they’re sexually active, women should begin having screening tests for cervical cancer in their 20s and continue through age 65. Discuss the right intervals with your doctor. Current screening guidelines take into account when you start screening and whether results of tests are normal:
  • If you start at 21: Have a Pap test every three years until 30.
  • If you start at 25: Seek an HPV test first.
  • At age 30: If all screening tests so far have been normal, have HPV testing every five years. Continue this screening until age 65.
  • Don’t stop screening at 65 unless all test results are normal, including at least two results in the last 10 years and one in the last five years.
  • If any testing led to abnormal results, you may need to continue screening beyond age 65.

An HPV infection, rather than sexual activity alone, is the factor that places people at risk, Dr. Feldman says.

“A lot of older women may have a new sexual partner in their 50s. A new HPV infection raises risk for cervical cancer roughly 20 years later,” Dr. Feldman says. “If HPV test results are persistently negative through age 65, the risk of developing cervical cancer in your 70s is low.”

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

About the Reviewer

Howard E. LeWine, MD, Chief Medical Editor, Harvard Health Publishing

Howard LeWine, M.D., is a practicing internist at Brigham and Women’s Hospital in Boston, Chief Medical Editor at Harvard Health Publishing, and editor in chief of Harvard Men’s Health Watch. See Full Bio View all posts by Howard E. LeWine, MD