The Missed Signal: What President Biden’s Diagnosis Reveals About Flawed Prostate Cancer Guidelines

Why smarter PSA metrics—not age limits—should guide screening decisions for older men

Like many others, I was surprised by the recent news that President Biden has been diagnosed with stage 4 aggressive prostate cancer that has spread to his bones. It was also reported that his last PSA test was in 2014 when he was likely around 72 years old. As I had noted in my previous post on prostate cancer, this disease claims around 35,000 lives annually in the U.S.—yet it remains one of the few cancers where metastasis, and thus most deaths, are almost entirely preventable.

The lack of PSA testing is largely due to the U.S. Preventive Services Task Force (USPSTF) recommendation against screening men over 75, based on the belief that the potential harms outweigh the benefits. Their reasoning is that prostate cancer usually progresses slowly—localized cases have a median time of 17 years from diagnosis to death. Since men over 75 typically have a life expectancy of less than 10 years, early detection is considered unlikely to improve outcomes. Given that PSA levels rise with age due to benign prostatic hyperplasia¹ (BPH) and prostatitis², screening in this group is believed to increase diagnoses of non-lethal cancers, leading to unnecessary biopsies (38% false-positive rate at PSA < 6.5 μg/L). Autopsy studies also show 46% of men > 70 harbor incidental prostate cancer, most of which is indolent. Urinary tract infections and alcohol use further elevate false positives. False positives lead to unnecessary biopsies, with complications (bleeding, infection) in 2–5% of cases. Moreover, for every 1,000 men ≥75 screened, 50–100 receive cancer diagnoses, but only 1–2 avoid prostate cancer death.

However, the biggest flaw in the USPSTF recommendation is that it relies on average life expectancy, which doesn't account for individual variation. Many men live well into their 80s and beyond, so it's misguided to assume that a 70-year-old today is unlikely to live another decade. This limitation is starkly illustrated by the former president himself—now 82—who had his last PSA test in 2014 at age 72 and is now battling an aggressive, metastatic cancer. This is further highlighted by data from 2001 to 2021, which shows that prostate cancer incidence was highest among men aged 70 and older—at 586 cases per 100,000 males.

Importance of PSA Velocity, PSA Density and Percent-free PSA

While PSA levels alone have limited diagnostic value, PSA-derived metrics—such as PSA velocity (PSAv), PSA density (PSAd) and Percent-free PSA (fPSA)—significantly enhance the accuracy of prostate cancer detection. These measures help differentiate clinically significant cancers from benign conditions, reducing the need for unnecessary biopsies in older men.

PSAv is the rate of change in PSA over time, measured as ng/mL/year. For example, a rise from 2.0 to 3.5 ng/mL over 2 years corresponds to a PSAv of 0.75 ng/mL/year. For younger men with PSA levels below 4 ng/mL, a PSAv greater than 0.35 ng/mL per year is considered a significant risk factor for prostate cancer. In older men—whose PSA levels typically fall within the 4 to 10 ng/mL range—the risk threshold is higher, with a PSAv cutoff of 0.76 ng/mL per year. It is useful in identifying rapid PSA increases which is suggestive of aggressive cancer. It is important to note that PSAv provides meaningful predictive value only when calculated using at least three PSA measurements taken over a span of 18 months or more.

PSAd is calculated by dividing the PSA level by the prostate volume³. For instance, a PSA of 4.0 ng/mL in a prostate measuring 40 cm³ results in a PSAd of 0.10 ng/mL/cm³. By factoring in prostate size, PSAd helps reduce false positives caused by benign prostatic hyperplasia. Studies have shown that a PSAd below 0.10 ng/mL/cm³ combined with a negative MRI can rule out clinically significant prostate cancer in 96% of cases. Additionally, in a 2020 prospective study, a PSAd of 0.20 ng/mL/cm³ or higher demonstrated 70% sensitivity and 79% specificity for detecting significant cancer, while a PSAd below 0.09 ng/mL/cm³ was associated with just a 4% risk of clinically significant disease.

Percent-free PSA (fPSA) is the ratio of unbound (free) PSA to total PSA in the blood. Unlike total PSA, which includes both free and protein-bound forms, fPSA helps distinguish prostate cancer from benign conditions like benign BPH. A lower fPSA indicates a higher risk of prostrate cancer, particularly aggressive forms.

As the accompanying chart shows, a fPSA less than 10% indicates a high risk of aggressive cancer while a number greater than 25% is likely benign. A Mayo Clinic study found that men over 70 with a fPSA below 10% had a 65% likelihood of prostate cancer, compared to just 16% for those with a fPSA above 25%. fPSA is also very effective in predicting aggressive disease. For instance, in a study with 272 men with PSA 4-10 ng/mL, fPSA less than 15% correlated with higher Gleason scores⁴ (≥8). In fact, men with aggressive prostrate cancer (Gleason ≥7, metastatic) had fPSA less than 14% up to 10 years pre-diagnosis vs. non-aggressive cases. Given President Biden’s current Gleason score of 9, it is highly likely that his fPSA remained below 15% for several years prior to his diagnosis. In summary, fPSA is a critical tool for diagnosing aggressive prostate cancer, particularly in the PSA "gray zone." Lower fPSA values correlate with higher Gleason scores, metastatic potential, and mortality risk. Clinical trials demonstrate that fPSA improves diagnostic accuracy, reduces unnecessary biopsies, and aids in risk stratification. For men over 75, where overtreatment risks are high, fPSA provides a nuanced approach to balancing early detection and harm minimization.

In conclusion, while total PSA alone has limited diagnostic value, a rapid rise in PSA levels—when combined with a high PSA density and a low percent-free PSA—strongly indicates a higher likelihood of aggressive prostate cancer.

Takeaway: President Biden’s advanced prostate cancer diagnosis underscores the shortcomings of current USPSTF screening guidelines for men over 75, which rely heavily on average life expectancy. This post argues for incorporating PSA-derived metrics—such as PSA velocity, PSA density, and percent-free PSA—to better identify aggressive cancers and reduce unnecessary biopsies in older patients.

1. Benign prostatic hyperplasia (BPH), also known as an enlarged prostate, is a non-cancerous condition where the prostate gland grows larger than normal.

2. Prostatitis is an inflammation of the prostate gland. It can be caused by various factors, including bacterial infections, stress, injuries, or nerve irritation

3. Obtained often from MRI or ultrasound.

4. The Gleason score is a system used to grade prostate cancer based on how the cancerous cells look under a microscope. It's a number, ranging from 6 to 10 that helps determine the aggressiveness of the cancer and guide treatment decisions.