When we think about radiation therapy, we typically picture treatments directed at tumors by a machine located outside the body. Now imagine a different scenario — one in which radioactive particles injected into the bloodstream find and destroy individual cancer cells, while leaving healthy cells unscathed.

The drug

One such “radioligand” is already available for certain patients with prostate cancer. Called Lu-PSMA-617 (trade name Pluvicto), it carries a lethal payload of radioactive atoms. The drug binds with a cell protein known as prostate-specific membrane antigen (PSMA), which is abundant on most prostate cancer cells but absent on most normal cells. After sticking to that protein, Lu-PSMA-617 delivers its radioactive cargo, and then the targeted cell dies.

As it currently stands, Lu-PSMA-617 is approved only for very a specific circumstance: eligible patients must have been treated already with chemotherapy for metastatic castration-resistant prostate cancer (mCRPC). During this advanced stage of the disease, prostate-specific antigen (PSA) levels rise despite treatments that block testosterone, a hormone that fuels prostate cancer growth (rising PSA indicates the cancer is progressing).

Doctors will often respond by switching to second-line hormonal treatments that block testosterone in other ways. If those drugs don’t work or become ineffective, then chemotherapy is typically the next option.

But could men with mCRPC bypass chemotherapy — along with its challenging side effects — and start on Lu-PSMA-617 right away? Investigators evaluated that potential strategy during a newly-completed clinical trial.

The study

The PSMAfore phase 3 trial enrolled 468 men with mCRPC. All the men had PSMA-positive tumors, and each of them had been treated already with a second-line testosterone blocker. For most men, that drug was abiraterone; the rest had been treated with a drug called enzalutamide. None of the men had yet been given chemotherapy.

The investigators randomized all the enrolled men into two groups. Men in the treatment group were given infusions of Lu-PSMA-617, while men in the control group were switched to a second testosterone-blocker that they hadn’t yet received.

The findings

After nearly a year and a half of follow-up, Lu-PSMA-617 treatment generated promising results. Crucially, the treated men avoided further cancer progression for a year on average, which was six months longer than progression was avoided in the control group.

Lu-PSMA-617 also produced significant drops in PSA: in 58% of the Lu-PSMA-617-treated men, PSA levels declined by half or more. Just 20% of men in the control group experienced comparable PSA declines. Lu-PSMA-617 was also well tolerated. The most common side effects were dry mouth and minor gastrointestinal symptoms, and treated men also reported less pain and better quality of life.

Commentary

Researchers still need to show that using Lu-PSMA-617 before chemotherapy actually lengthens survival before the FDA will approve this new indication. The enrolled subjects are still being followed, and “hopefully with further follow up, this sequence of treatments may become more widely available,” says Dr. Marc B. Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center.

Added Dr. Garnick, “This study marks another advance in our emerging treatment options for men with advanced prostate cancer, and underscores the methodical progression of pharmaceutical development. When new therapies are introduced, they are studied in patients in whom the treatment options are limited. Fortunately, Lu-PSMA-617 showed excellent results in this population, and the study outlined here suggests that it may be able to move this therapy to even earlier forms of advanced prostate cancer. We anxiously await longer-term follow-up of this important research.”

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

As a kid, I spent many Saturdays romping around my Florida neighborhood imitating Colonel Steve Austin, better known as The Six Million Dollar Man to avid TV watchers in the 1970s.

The popular show featured a bionic man — half human and half machine — who could jump from three-story buildings, leap over six-foot-high walls, and bolt into a full 60-mile-per-hour sprint. Naturally, these actions occurred in slow motion with an iconic vibrating electronic sound effect.

My own bionic moves involved jumping to pluck oranges from tree branches, hopping over anthills, and leaping across narrow ditches while humming that distinctive sound. I didn’t realize it, but this imitation game taught me the foundations of plyometrics — the popular training routine now used by top athletes to boost strength, power, and agility.

What are plyometrics?

Plyometric training involves short, intense bursts of activity that target fast-twitch muscle fibers in the lower body. These fibers help generate explosive power that increases speed and jumping height.

“Plyometrics are used by competitive athletes who rely on quick, powerful movements, like those in basketball, volleyball, baseball, tennis, and track and field,” says Thomas Newman, lead performance specialist with Harvard-affiliated Mass General Brigham Center for Sports Performance and Research. Plyometrics also can help improve coordination, agility, and flexibility, and offer an excellent heart-pumping workout.

Who can safely try plyometrics?

There are many kinds of plyometric exercises. Most people are familiar with gym plyometrics where people jump onto the top of boxes or over hurdles.

But these are advanced moves and should only be attempted with the assistance of a trainer once you have developed some skills and muscle strength.

Keep in mind that even the beginner plyometrics described in this post can be challenging. If you have had any joint issues, especially in your knees, back, or hips, or any trouble with balance, check with your doctor before doing any plyometric training.

How to maximize effort while minimizing risk of injury

• Choose a surface with some give. A thick, firm mat (not a thin yoga mat); well-padded, carpeted wood floor; or grass or dirt outside are good choices that absorb some of the impact as you land. Do not jump on tile, concrete, or asphalt surfaces.
• Aim for just a few inches off the floor to start. The higher you jump, the greater your impact on landing.
• Bend your legs when you land. Don’t lock your knees.
• Land softly, and avoid landing only on your heels or the balls of your feet.

Three simple plyometric exercises

Here are three beginner-level exercises to jump-start your plyometric training. (Humming the bionic man sound is optional.)

Side jumps

Stand tall with your feet together. Shift your weight onto your right foot and leap as far as possible to your left, landing with your left foot followed by your right one. Repeat, hopping to your right. That’s one rep.

• You can hold your arms in front of you or let them swing naturally.
• Try not to hunch or round your shoulders forward as you jump.
• To make this exercise easier, hop a shorter distance to the side and stay closer to the floor.

Do five to 15 reps to complete one set. Do one to three sets, resting between each set.

Jump rope

Jumping rope is an effective plyometric exercise because it emphasizes short, quick ground contact time. It also measures coordination and repeated jump height as you clear the rope.

• Begin with two minutes of jumping rope, then increase the time or add extra sets.
• Break it up into 10- to 30-second segments if two minutes is too difficult.
• If your feet get tangled, pause until you regain your balance and then continue.

An easier option is to go through the motions of jumping rope but without the rope.

Forward hops

Stand tall with your feet together. Bend your knees and jump forward one to two feet. Turn your body around and jump back to the starting position to complete one rep.

• Let your arms swing naturally during the hop.
• To make this exercise easier, hop a shorter distance and stay closer to the floor.
• If you want more of a challenge, hop farther and higher. As this becomes easier to do, try hopping over small hurdles. Begin with something like a stick and then increase the height, such as with books of various thicknesses.

Do five to 10 hops to complete one set. Do one to three sets, resting between each set.

About the Author

Matthew Solan, Executive Editor, Harvard Men's Health Watch

Matthew Solan is the executive editor of Harvard Men’s Health Watch. He previously served as executive editor for UCLA Health’s Healthy Years and as a contributor to Duke Medicine’s Health News and Weill Cornell Medical College’s … See Full Bio View all posts by Matthew Solan

About the Reviewer

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

Dr. Howard LeWine 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

I was in line at a pharmacy recently as the customer ahead of me was picking up her prescription. The pharmacist matter-of-factly said: “that’ll be $850.” All she could say was “really?” She left without her prescription, telling the pharmacist she’d have to call her doctor about a less costly alternative.

Many of us routinely experience sticker shock over drug costs. And ever more dramatic examples suggest there’s no limit. So, let’s talk about ways to minimize what we spend on prescription drugs; how we got to this juncture where some medicines cost more than a million dollars per dose; and what changes are needed in our pricey medication-industrial-complex.

7 ways to minimize your spending on prescription drugs

Consider these seven strategies to pare drug costs. Savings will vary depending on insurance, donut holes, deductibles, and cost-sharing.

• Ask your healthcare provider three questions: Is every medicine you take truly necessary? Is it safe to reduce the dose of any medicines you take? Could a lower-cost or generic drug be substituted?
• If you have health insurance, check the list of preferred medications (the formulary), which tend to cost less than other similar medicines.
• Split pills: In some cases, a prescription will cost less if each pill contains more than your needed dose and can be divided. For example, if you usually take a 25-mg pill, taking half of a 50-mg pill may help you save on drug costs and copays. Ask your pharmacist if the math works for you.
• Ask if a 90-day supply rather than a 30-day supply would reduce copays.
• Look for prescription drug discount programs that offer savings. Restrictions apply and availability varies by location. Also, paying through a discount program might not count toward your insurance deductible or maximum out-of-pocket costs, so it isn’t always less expensive to use these programs.
• Compare prices at different pharmacies and review your options with a pharmacist. Sometimes the price is lower if you don’t use your insurance.
• Consider using an online mail-order service (such as Blink Health or Cost Plus Drug Company). However, spending through these sites may not count toward your insurance deductible. And the prices are not always lower online.

These measures will help some people more than others and can take up a lot of time. The sad truth is that even if you did everything you could, the impact on your wallet might be small.

Why are medicine costs so high in the US?

My top five contenders are:

Drug makers’ profit motive. Pharmaceutical companies routinely reject this idea. They say it’s expensive to develop new drugs and run the required clinical trials to prove safety and effectiveness. Many promising drugs fail, and the FDA drug approval process is difficult and costly.

Yet one recent study published in JAMA Network Open found no connection between how much a drug company spends on research and development (R&D) for a drug and the drug’s price. Even after accounting for R&D spending, most of the top 30 pharmaceutical companies make billions of dollars in profit. And in Europe, where drug prices are negotiated, the very same drugs made by the same companies for the same health problems typically cost far less than in the US.

Pharmacy benefit managers (PBMs) handle drug benefits for large employers, Medicare, and health insurance companies. PBMs negotiate prices with health insurers and pharmacies. They help decide which drugs to cover and how much patients pay. Their fees and incentives — often a share of total spending on medicines, which might encourage approval of higher-priced drugs — contribute to the costs health consumers wind up paying. A flurry of state and federal legislation is intended to limit what PBMs can do and the transparency of their operations.

Cost-sharing. In recent years, insurers have increasingly shifted costs to patients through higher copays, deductibles, and premiums. Sometimes this is justified by the notion that this incentivizes patients to seek care only when truly necessary; of course, it could also discourage people from seeking care even when warranted.

Legal maneuvers. Many drug makers file numerous patents and sue potential competitors to extend their time holding a monopoly on a particular drug (see example). Or they create “me too” drugs by slightly tweaking an existing drug so they can patent it as a brand-new drug. Some pharmaceutical companies acquire patents for older drugs and then jack up the price. Others have bought or merged with another drugmaker to avoid price competition.

Direct-to-consumer advertising. Drug companies spend billions on ads (nearly $8.1 billion in 2022). Marketing costs raise the price of drugs while boosting demand for newer, heavily promoted drugs. Advertised drugs tend to be far more expensive (and not always better) than older drugs. Perhaps this is why such advertising is banned in most other countries.

What might slow rising drug costs?

Although prescription drug prices are likely to remain high for the foreseeable future, three developments could help slow rising drug prices in the coming years:

• The Inflation Reduction Act of 2022 allows the US government to negotiate drug prices for Medicare, which is expected to lower drug costs. The first 10 price-protected drugs — including the blood thinner apixaban (Eliquis) and the diabetes medicine sitagliptin (Januvia) — take effect in 2026. More drugs will be added to this list each year. If you’re on one of these drugs, the impact could be large. But with more than 20,000 approved drugs on the market, it’s not a solution that will help everyone.
• Recent FDA action allowing Florida to import drugs from Canada, and other proposed federal and state legislation aiming to protect people from high prescription drug prices.
• Organizations advocating for lower prescription drug prices, including AARP, Consumers Union, and Patients for Affordable Drugs, appear to have the attention of lawmakers as never before.

The bottom line

Let’s face it: our complex, broken healthcare system incentivizes those who develop and distribute drugs to set the prices well above what many can afford. And the amount you can chip away on your own is limited. What we really need is an overhaul to remove middlemen who contribute to added cost without always adding value.

Until we get there, do what you can, even if the impact is small. Trying your best to stay healthy could be the most important step you take. After all, the best way to limit how much you spend on prescription drugs is to have no reason to take them.

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

Lung cancer kills more Americans than any other malignancy. The latest American Cancer Society (ACS) updated guidelines aim to reduce deaths by considerably expanding the pool of people who seek annual, low-dose CT lung screening scans.

Advocates hope the new advice will prompt more people at risk for lung cancer to schedule yearly screening, says Dr. Carey Thomson, director of the Multidisciplinary Thoracic Oncology and Lung Cancer Screening Program at Harvard-affiliated Mount Auburn Hospital, and chair of the Early Detection Task Group for the ACS/National Lung Cancer Roundtable. Currently, fewer than one in 10 eligible people in the US follow through on recommended lung screenings.

What are the major changes in the new ACS lung cancer guidelines?

The updated ACS guidelines are aimed at high-risk individuals, all of whom have a smoking history. And unlike previous ACS recommendations, it doesn’t matter how long ago a person quit smoking. The updated guidelines also lower the bar on amount of smoking and widen the age window to seek screening, which aligns with 2021 recommendations issued by the US Preventive Services Task Force.

These changes combined may mean another six to eight million people will be eligible to have screening.

How many people get lung cancer?

Although lung cancer is the third most common malignancy in the United States, it’s the deadliest, killing more people than colorectal, breast, prostate, and cervical cancers combined. In 2023, about 238,000 Americans will be diagnosed with lung cancer and 127,000 will die of it, according to ACS estimates.

What is the major risk factor for lung cancer?

While people who have never smoked can get lung cancer, smoking and exposure to secondhand smoke is a major risk factor for this illness. Smoking is linked to as many as 80% to 90% of lung cancer deaths, according to the CDC.

Indeed, people who smoke are 15 to 30 times more likely to develop or die from lung cancer than those who don’t. The longer someone smokes and the more cigarettes they smoke each day, the higher their risks.

Is lung cancer easier to treat if found in early stages?

Yes. As with many cancers, detecting lung malignancies in their earliest stages is pivotal to improving survival.

Depending on the type of lung cancer diagnosed, up to 80% to 90% of people with a single, early-stage tumor that can be removed surgically can survive five years or longer, says the American Society of Clinical Oncology. The number of people who survive long-term becomes smaller as tumors grow larger, and if they spread to lymph nodes or other areas of the body.

Should you consider lung CT screening?

The updated ACS guidelines recommend screening if you:

• Are 50 to 80 years old. This age range is expanded from the prior ACS recommended cutoff of 55 to 74.
• Are a current or previous smoker. This includes anyone who smoked, not just smokers who quit within the past 15 years.
• Smoked 20 or more pack-years. This means smoking an average of 20 cigarettes per day for 20 years or 40 cigarettes per day for 10 years. Previously, the eligibility cutoff was 30 or more pack-years.

“While an expansion in the number of people screened for lung cancer will find additional early tumors, it also means more false positives will be detected,” says Howard LeWine, MD, Chief Medical Editor at Harvard Health Publishing. False positives are worrisome spots on a CT scan that are not cancer. But they usually require additional testing, perhaps a biopsy and even surgery for something that was harmless.

Before scheduling a low-dose CT lung screening, you’ll need to talk to a health professional about the screening process, your risks, whether it will be covered by your health insurance. Previously, an in-person medical appointment was required.

Why did the ACS change the years-since-quitting screening requirement?

Much international research suggests that the number of years since someone stopped smoking has little or no bearing on their risk of developing lung cancer, says Dr. Thomson.

“You have an equal likelihood of developing lung cancer whether you quit more than 15 years ago or more recently,” she says. “The recommendations on the national scene say that we need to be screening more people and make it easier to be screened. One of the ways to do that is to drop the quit history requirement.”

If you’re eligible for screening, how often should you have it?

Every year, says the ACS.

But why not screen for lung cancer for several years and then take a break, as is done with a malignancy such as cervical cancer? Research hasn’t been done to demonstrate that this type of approach is safe, Dr. Thomson says.

“We know that a large percentage of lung cancers identified in people through low-dose CT scans are identified after their first year of screening,” she says. “And some forms of lung cancer can move quickly, which is part of the reason it’s as deadly as it is.”

Did all guidelines organizations drop the years-since-quitting requirement?

No. The Centers for Medicare & Medicaid Services (CMS) and the U.S. Preventive Services Task Force — which, along with the ACS and other groups, recommend national standards for screenings — haven’t yet signed on to the ACS approach. These two groups maintain that only smokers who quit 15 or fewer years ago should remain eligible for screening.

However, guidelines issued by the National Comprehensive Cancer Network mesh with the new ACS recommendations by not having a years-since-quitting threshold.

Because Medicare and other health insurers may have slightly different rules to determine payment for lung cancer CT screening, it’s best to confirm this with your health care provider or insurer before getting tested.

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

Dr. Howard LeWine 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