Cancer Diagnosis Delays During Screening Study; Benefits of Resistance Training

TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, and Rick Lange, MD, president of Texas Tech Health El Paso, look at the top medical stories of the week.

This week’s topics include the benefits of resistance training, staving off chronic low back pain, delays in cancer diagnosis with cell-free DNA screening, and GLP-1 receptor agonists and knee replacement.

Program notes:

0:35 Cell-free DNA screening for cancer and diagnosis delays

1:35 Population-based screening

2:35 24 different companies offer liquid biopsy

3:01 Can we prevent chronic back pain after acute back pain?

4:01 Impact score on chronic back pain

5:01 Real-world setting lacks impact

6:01 Primary care role

7:01 Individual should assess their own back pain

7:25 Resistance training and mortality

8:25 Most benefit with aerobic and resistance training

9:20 GLP-1 agonists and knee arthroplasty

10:20 Using a GLP-1 drug reduced risk of knee arthroplasty

11:23 Can’t imagine using them solely for this purpose

12:25 End

Transcript:

Elizabeth: Is there another benefit to the GLP-1 agonists?

Rick: Does resistance exercise training reduce mortality?

Elizabeth: Can we prevent acute back pain from becoming chronic back pain?

Rick: And cancer diagnosis delay due to liquid biopsies?

Elizabeth: That’s what we’re talking about this week on TTHealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore-based medical journalist.

Rick: And I’m Rick Lange, president of Texas Tech Health El Paso.

Elizabeth: Rick, since we’ve all been talking so much about AI [artificial intelligence], why don’t we turn first to that one that you served up as, hmm, is there a delay when liquid biopsies are used in the diagnosis of cancer? That’s in JAMA.

Rick: Over the many years we’ve been podcasting, we’ve followed the use of liquid biopsies to diagnose cancer in its early stages. We’re talking about taking blood tests that look at cell-free DNA and artificial intelligence that’s used to screen for 50 different types of cancer, with the thought being is that these cancer cells shed DNA into the bloodstream. And by looking for this, can we make a diagnosis of cancer in the early stages when it’s more treatable?

Well, one of the things that people have to consider is not only are there false-negative and false-positive rates, but also how does that affect cancer screening in general? And what this study did was it looked at cancer diagnosis-delay rates associated with a population-based screening using cell-free DNA. So there were 21 different cancer alliance regions in England, eight of which participated in the population-based screening and 13 didn’t. They looked at the diagnostic delay associated with this before the screening and after the screening.

And what they determined was when they compared the regions that did and did not use it, there was about a 5% difference-in-differences estimate between those that had it and those that didn’t have it in terms of the diagnostic delay.

Why is that? In resource-limited areas, if you have a bunch of people that have a positive test in which there may not be cancer, they’ll actually use the resources, so they’re not available for individuals that otherwise need screening. And there’s a false-positive rate associated with this. Either the cancer is so early you can’t find it, or it’s a false positive — there’s no cancer at all.

Elizabeth: Almost everyone I talk to about these tests right now says they are not ready for prime time. They are not ready to be rolled out on a widespread basis and discourages people from having them in spite of all their ads on Sunday television.

Rick: Yeah Elizabeth, there are now 24 different companies that have liquid biopsies. This particular one, by the way, did a very good study that hasn’t yet been published, but the results were released in February of this year. And it showed that the use of it did not increase early detection or reduce detection of advanced cancers, that is stage III or IV. So, you’re right. It’s not ready for prime time.

Elizabeth: Let’s turn to JAMA Internal Medicine, and speaking of also not ready for prime time, this is a look at whether spinal manipulation and clinician-supported self-management can prevent folks who have acute back pain from developing chronic back pain. That’s a real risk. It looks like acute and subacute low back pain often will progress to a chronic condition, and then have people missing work and having to truncate their activities of daily living. If we attempt some interventions in those people we determine to be at risk to transition from acute to chronic states, can we prevent it?

They had a 2 × 2 factorial randomized clinical trial where four interventions were applied for 8 weeks, and those were spinal manipulation therapy — so let’s call that chiropractic-supported self-management — the combination of spinal manipulation or chiropractic and supported self-management, and then guideline-based medical care. And then they used an impact score per the U.S. National Institutes of Health Task Force on chronic low back pain scale to see whether or not any of these things had any impact. They had 928 participants who completed this trial.

They found small differences in this low back pain impact score. The supported self-management medical care had a small impact. The combined self-management and spinal manipulation had a small impact. The medical care and the spinal manipulation therapy alone did not differ. And then adding spinal manipulation to supported self-management did not provide additional benefit. It looks like clinician-supported biopsychosocial self-management was really the best strategy to employ. Still, it had a very small impact and the resources that are necessary to implement it are really pretty onerous. So the editorialist opines that, gosh, in a real-world setting, not in a clinical-trial setting where conditions are optimized, this probably wouldn’t have any impact at all.

Rick: Yeah. And also spinal manipulation therapy didn’t help. And the self-management was a little bit better than the medical management. But as you said, the self-management, which involved education, exercise, cognitive, behavioral, and social strategies to manage the pain, involved using study-trained physical therapists or chiropractors during 60-minute one-on-one sessions. And, unfortunately, that’s not very practical. The routine medical care was provided by physicians or advanced practice practitioners during 15- to 30-minute visits and that’s usually what happens in the real world. If there was a huge benefit, we could say we can justify the cost, but the benefit is minimal compared to usual medical care.

Elizabeth: The editorialist says if you don’t have these psychosocial-trained clinicians to deliver this care, they suggest that maybe primary care clinicians can provide it with first-line medications, which I think is even more comical. The notion that somehow a primary care physician is going to be able to have the time to deliver this kind of care is not my experience at all.

Rick: No. They gave it in 5- to 30-minute time periods, and you can use a nurse practitioner to do that. The self-management was an hour spent with trained physical therapists and chiropractors. First of all, there aren’t enough available. Secondly is there’s no reimbursement for that either. And so it’s really not feasible.

Elizabeth: I think the other thing that I was a little confused about, and I didn’t really get definition, was how they determine who is at risk for going from an acute to a chronic state. And there’s apparently a tool to assess that that’s called the STarT Back tool, and I wish I knew a little more about that.

Rick: It’s a nine-item questionnaire that asks about their clinical symptoms, how long they’ve been there, how much does it impact their lifestyle. That questionnaire alone predicts who is more likely to advance to a chronic, low back pain versus those that are more likely to respond acutely.

Elizabeth: Is that something you would suggest to someone who’s suffering from low back pain, they ought to ask themselves?

Rick: I think so because in that circumstance we’re talking about using pharmacologic versus nonpharmacologic methods. And the nonpharmacologic methods you want to particularly address to those individuals that are going to be at high risk because you don’t want to put them on long-term nonsteroidals or steroid therapy, certainly not opiate therapy if you don’t need to.

Elizabeth: Let’s go on to your next one.

Rick: Does resistance training, specifically long-term resistance training, affect mortality? We know for certain that aerobic exercise can reduce mortality — overall mortality, cardiovascular mortality, even cancer mortality — and the question is, what about long-term resistance training?

These investigators address that by looking at three large prospective cohorts: Health Professionals Follow-up Study — it involved primarily physicians — and then two nurse health studies that involved primarily women. Altogether, there were 147,000 participants that were followed up to 30 years.

Compared with no resistance training, individuals that did between an hour and a half to 2 hours per week of resistance training had a 13% lower risk of all-cause mortality, a 19% lower risk of cardiovascular mortality, and a 27% lower risk of neurologic disease mortality. That was regardless of whether individuals were doing aerobic exercise or not.

What about joint analysis, looking at people that participated in both? Well, the individuals that received the most benefit were those that were involved in resistance training and aerobic exercise. It could lower mortality by as much as 45%. Oh, by the way, doing more than 2 hours of resistance training did not result in any additional benefit than the 1.5 to 2 hours per week.

Elizabeth: And let’s just mention this is in The BMJ. I think it’s really interesting that doing more didn’t result in a bigger benefit.

Rick: And there’s some truth to that with aerobic exercise as well. There’s a clear increase to a certain point, and then more vigorous, extremely strenuous exercise doesn’t seem to result in additional benefit.

Elizabeth: Well, it’s also good news because it suggests that one’s commitment to this can be relatively modest.

Rick: And the nice thing is this is true for both men and women.

Elizabeth: Let’s remain in The BMJ then. Is there another benefit to the GLP-1 receptor agonists? In this case, they’re looking at the use of that class of medications and the risk of arthroplasty for knee osteoarthritis. And this is a retrospective database analysis.

We know that, of course, knee osteoarthritis is a leading cause of chronic pain and disability, and many people end up with total knee arthroplasty at some point. They looked at this retrospective cohort study identifying adults who were diagnosed with knee osteoarthritis between Jan. 1, 2010 and Dec. 31, 2024. And then these patients were stratified by their GLP-1 exposure class — the new or any generation of these agents — and their treatment duration. They matched them for all kinds of factors, age, sex, race, musculoskeletal diagnoses, obesity-related conditions, and so on. And they looked at their primary outcome as the cumulative incidence of total knee arthroplasty at years 1, 3, 5, and 8.

Basically, what they found was that, sure enough, if you use a GLP-1 agonist, you had a significantly lower cumulative total knee arthroplasty incidence across all exposure classes, durations, and follow-up intervals. They weren’t huge, but they definitely were present, and they were independent of the weight loss aspect.

This is pretty tantalizing and seems to support evidence from other studies suggesting that these GLP-1 receptor agonists may also have some chondroprotective and anti-inflammatory effects that are independent of the fact that they’re able to produce this weight loss. So they might have some direct disease-modifying activity, and clearly, what needs to happen are prospective randomized trials to see whether this is true.

Rick: Good news, another benefit of taking a GLP-1 receptor agonist. I can’t imagine, though, we would be giving these to people with osteoarthritis in the absence of either obesity or diabetes.

It is somewhat intriguing, though, that regardless of the amount of weight loss and the duration of the effect of reducing total knee arthroplasties was long after the weight loss had occurred suggests that they’re either anti-inflammatory or in some way it protects the cartilage in the knee.

Elizabeth: And suggests maybe that even for people who don’t have obesity, maybe just local injection of these things might be helpful if that really is the mechanism.

Rick: That’s intriguing. I hadn’t thought about that. It does suggest that in addition to just the mechanical effects of obesity or weight on the knee, metabolic health is also associated.

Elizabeth: On that note then, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.

Rick: And I’m Rick Lange. Y’all listen up and make healthy choices