Study shows IsoPSA’s predictive ability for clinically significant prostate cancer

Patients with a low baseline IsoPSA index had a reduced risk of developing clinically significant prostate cancer compared with those who had a high baseline index, according to data published in Urology.¹

According to the authors, these findings support the use of IsoPSA to determine which patients with a high prostate-specific antigen (PSA) level may safely avoid follow-up testing.

Christopher J. Weight, MD

"In this large study of over 1500 men with an elevated PSA, we found that a low IsoPSA is incredibly reassuring,” said senior author Christopher J. Weight, MD, center director for urologic oncology at Cleveland Clinic, in a news release on the findings.² “We found that not only was there a very low risk for prostate cancer at the time of the low IsoPSA, but very few men (~4%) went on to develop prostate cancer in the following 2.5 years. This means that most men with an elevated PSA can feel comfortable forgoing further invasive testing if they also have a low IsoPSA."

In total, the study included 1578 patients, of whom 541 patients had a low IsoPSA index (median 4.4; IQR, 3.6 to 5.2) and 1037 had a high IsoPSA index (median, 8.9; IQR 7.3 to 11.6). A low IsoPSA index was defined as 6 or lower, and a high IsoPSA index was defined as greater than 6.

The median PSA at the time of IsoPSA testing was 6.3 ng/mL (IQR, 5.1 to 8.3) in the low IsoPSA cohort vs 6.8 ng/mL (IQR, 5.3 to 9.7) in the high IsoPSA cohort (P < .001).

Among those with a low baseline IsoPSA (n = 541), 4.3% (23) were found to have clinically significant prostate cancer on subsequent biopsy. Of those who underwent MRI (n = 204), 23.5% (48 of 204) were found to have suspicious lesions (PIRADS 4 or higher).

Among patients who had a high baseline IsoPSA (n = 1037), 35.3% were found to have clinically significant prostate cancer on subsequent biopsy. Of those who underwent MRI (n = 712), 48% (342 of 712) were found to have suspicious lesions.

A grade group 3 or higher lesion was found on biopsy in 2.3% of patients in the low IsoPSA cohort vs 12.1% of patients in the high IsoPSA cohort (P < .001). Additionally, 2.2% of patients in the low IsoPSA cohort underwent radical prostatectomy compared with 15.4% of patients in the high IsoPSA cohort (P < .001).

Patients in the low IsoPSA cohort also demonstrated a lower rate of clinically significant prostate cancer compared with those in the high IsoPSA cohort at all time points assessed.

Specifically, in the low IsoPSA cohort, the risk of developing clinically significant prostate cancer was 0.4% (95% CI, 0.1% to 1.6%) at 12 months, 2.5% (95% CI, 1.4% to 4.4%) at 24 months, and 6.3% (95% CI, 4% to 9.6%) at 30 months. In the high IsoPSA cohort, the risk of clinically significant prostate cancer was 5.9% (95% CI, 4.6% to 7.6%) at 12 months, 31.7% (95% CI, 28.3% to 35.4%) at 24 months, and 49.5% (95% CI, 45.3% to 53.9%) at 30 months.

According to the authors, these findings endorse the use of IsoPSA to aid in biopsy decisions. However, they also note that further longer-term studies are warranted.

“Our results suggest that most men with IsoPSA Index [of 6 or lower] can avoid prostate biopsy, especially if they have a recent negative biopsy,” the authors wrote. “While our study is the first to report the results of a median follow-up time of 24 months, we acknowledge that this time frame is relatively short in the context of the natural history of [prostate cancer], thus the need for future studies with longer follow-up times.”

REFERENCES

1. 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:S0090-4295(25)00031-7. doi:10.1016/j.urology.2025.01.019

2. Cleveland Diagnostics announces landmark longitudinal study published in Urology. News release. Cleveland Diagnostics. Published online and accessed April 23, 2025. https://www.businesswire.com/news/home/20250423808261/en/Cleveland-Diagnostics-Announces-Landmark-Longitudinal-Study-Published-in-Urology