Calculating the Real Cost of False Positive Findings in Cancer Screening

The emotional, clinical, and financial consequences of false positive screening results highlight the need for more precise diagnostics that detect clinically meaningful cancers while minimizing unnecessary interventions, according to Jason Hafron, MD.

“False positives may be the price we pay for finding cancer early, but we should always be working to lower that cost,” Hafron said in an interview with OncLive®.

In the interview, Hafron discussed the frequently overlooked burden of false positive cancer screening results, including their lasting toll on patients, their downstream clinical consequences, and the importance of clear patient communication and improved risk stratification.

He also highlighted examples of tests that are designed to stratify patient risk with more specificity, including the IsoPSA test, which helps categorize prostate cancer risk by analyzing the structure of prostate-specific antigen (PSA) proteins to determine whether elevated levels in a patient may be due to cancer or other factors.¹ A single-center retrospective study showed that among 1578 patients with elevated PSA levels who underwent IsoPSA testing, the risk of developing clinically significant prostate cancer was lower in patients with initial low IsoPSA indices vs those with initial high IsoPSA indices.² These findings support the use of the IsoPSA test to determine whether patients can safely avoid follow-up prostate cancer screening.

Hafron is the chief medical officer and medical director of Clinical Research at the Michigan Institute of Urology, as well as a professor of urology at the William Beaumont School of Medicine at Oakland University in Royal Oak.

OncLive: Discussions about the benefits of cancer screening and surveillance often focus on early detection. How are the consequences of false positive findings overlooked in these discussions?

Hafron: Early detection remains one of the greatest tools we have in the fight against cancer. However, when we talk about the benefits of screening, false positive [results] can often get overlooked. Every screening test involves a tradeoff between sensitivity and specificity. The more aggressively we look for cancer, the more benign findings we find. We understand that at the population level, but patients don’t experience it that way. For them, a positive result is a cancer scare.

The goal of screening isn’t to find more abnormalities. It’s to find the right abnormalities. We need to keep pushing toward diagnostics that don’t force us to choose between sensitivity and specificity. The good news is, the field is moving in that direction. A real-world example I use in my own practice is the IsoPSA Test. It analyzes the same protein measured in standard PSA screening but in a fundamentally different way, giving us a more accurate picture of whether an elevated PSA level is caused by cancer or something benign. Tests like these signal a meaningful shift in what’s possible [in cancer screening], and I’m excited about where we’re headed.

What are the real-world effects of false positive results on patients’ emotional well-being, anxiety levels, and quality of life?

The emotional effect can be immediate and significant. Most patients, when they hear the word “positive,” assume they have cancer until proven otherwise, which often leads to anxiety, sleep disruption, difficulty concentrating, and strain on family relationships. These patients are thinking about mortality, finances, their jobs, and what comes next. The period of uncertainty alone carries weight, and even [if additional test results] ultimately come back benign, that emotional burden doesn’t always disappear.

For us, this is a test result that’s part of a larger diagnostic workup. For patients, it can be [part of] the worst week of their lives. A false positive may not be cancer, but the fear it creates is very real.

In your experience, how long can the psychological effects of a false positive finding persist, even after malignancy has been ruled out?

This varies considerably. Some patients feel immediate relief once cancer is excluded, whereas others carry that anxiety for months or even years. A false positive result can permanently change how a patient relates to their own health, making them hypervigilant about every new symptom or follow-up test. Some patients have told me that they continue to worry that something was missed, even after they’ve been fully cleared.

In my experience, waiting is often harder than undergoing the testing itself. This is especially common for patients who are living with an elevated risk of developing prostate cancer, whether due to family history or genetic predisposition. Even when these patients are screened annually, the 12 months between tests can be filled with anxiety. I’ve seen newer tests, like the IsoPSA Test for prostate cancer risk assessment, where the results hold up meaningfully over time. That diagnostic stability is valuable for these patients because it gives them something concrete to hold onto between visits rather than leaving them in a state of worry.

How do false positive results affect patient trust in the health care system and their willingness to undergo future screening or follow-up testing?

It depends on the patient. Some come out of the experience more engaged with their health care and more diligent about follow-up, whereas others walk away frustrated by the emotional toll, additional testing, and out-of-pocket costs. When communication around a false positive result is poor, trust in the screening program itself can deteriorate. Add up a few false positives over time, and we see patients become reluctant to participate in future screening, which carries its own risks.

Setting expectations up front is critical. Patients need to understand before they start [testing] that false positive results are an unavoidable part of effective screening and that the system is designed to catch and correct them. I tell my team that patients will tolerate uncertainty better than poor communication. How we explain a false positive often matters as much as the false positive itself. The reality is that trust isn’t built when everything goes right; it’s built when we guide patients through uncertainty with honesty and clarity.

What types of cancers or screening modalities tend to be associated with the greatest burden of false positive findings?

Several come to mind, including lung cancer screening with low-dose CT, breast cancer screening with mammography, prostate cancer screening with PSA testing, and incidental thyroid nodule detection. Any highly sensitive screening modality can generate false positive results; that’s almost inherent to how these tests work. However, I’d push back on framing this as a problem with specific tests or cancer types. The issue is less about the modality and more about how we apply it and what we do next. The real question is: How do we improve risk stratification, so we’re not reflexively escalating every abnormal finding? The issue is not the test itself, but the balance between finding cancer early vs over-evaluation.

Beyond patient anxiety, what are the downstream clinical consequences of false positive results?

Every false positive creates a ripple effect, such as additional scans, repeat labs, specialist referrals, consultations, biopsies, and invasive procedures that carry their own risks and adverse effects. There’s also the time away from work and the financial burden on patients, not to mention the use of critical health care resources that could be directed somewhere else. Not every abnormal finding is harmful, but every abnormal finding has consequences. A benign biopsy is good news, but it is still a procedure the patient had to undergo. The goal has to be improving risk stratification and diagnostic accuracy, so we maximize the benefits of screening and minimize the unnecessary interventions.

Cancer screening saves lives. That’s not up for debate. But false positives are an inevitable consequence of effective screening, and we cannot afford to underestimate their emotional, physical, and financial effect on patients.

The future of cancer screening isn’t simply earlier detection; it’s smarter detection, so we can reduce unnecessary worry for the patients who don’t have cancer. The IsoPSA Test and Cx Bladder Triage are strong examples of what that looks like in practice. They are a reminder that we must keep pushing to refine testing in ways that benefit both patients and clinicians. I’m hopeful that similar technology can be applied to other widespread cancers, to find every cancer that matters and disturb as few healthy people as possible. That’s the standard we should hold ourselves to.

References

1. For clinicians. IsoPSA. Accessed September 28, 2026. https://www.isopsa.com/for-clinicians/?utm_term=&utm_campaign=IsoPSA+Awareness&utm_source=adwords&utm_medium=ppc&hsa_acc=9924027646&hsa_cam=23003000114&hsa_grp=&hsa_ad=&hsa_src=x&hsa_tgt=&hsa_kw=&hsa_mt=&hsa_net=adwords&hsa_ver=3&gad_source=1&gad_campaignid=23003010881&gbraid=0AAAABBGNgCO3mV7u7t2f99nS_YoNQPL3F&gclid=EAIaIQobChMI_qrriKeSlwMVsUP_AR3BLi7bEAAYASAAEgI8jvD_BwE
2. Abdallah N, Campbell RA, Benidir T, et al. Low baseline IsoPSA index is associated with a prolonged low risk of clinically significant prostate cancer diagnosis in men with an elevated PSA. Urology. 2025;201:69-75. doi:10.1016/j.urology.2025.01.019