Urine spermine risk score effective for prostate cancer diagnosis

Urine spermine and Spermine Risk Score can be used to support clinical diagnosis of high-grade prostate cancer (HGPCa), results of a recent study by investigators from the Hong Kong Baptist University (HKBU) and the Chinese University of Hong Kong (CUHK) have shown.

Spermine, a type of polyamine, is involved in secretory function of prostate epithelial cells and is concentrated in benign prostate tissue. Reduced spermine level was found in prostate cancer (PCa) with altered cellular architecture and reduced luminal volume. [Prostate Cancer Prostatic Dis 2021, doi: 10.1038/s41391-020-00312-1]

“Our study is the first prospective study investigating the efficacy of urine spermine test in detecting PCa,” said Professor Gary Ka-Leung Wong of the Department of Chemistry, HKBU.

“The test itself is a simple urine test without the need for digital rectal examination [DRE] and prostatic massage, minimizing potential complications [associated with DRE and prostatic massage],” pointed out Professor Chi-Fai Ng of the Department of Surgery, CUHK.

In the study, 600 Hong Kong Chinese men (median age, 66 years) with prostate-specific antigen (PSA) level of 4–20 ng/mL without prior PCa diagnosis were recruited. All men had 30 mL of prebiopsy urine collected for spermine analysis, without prior DRE and prostate message.

At baseline, only 20.8 percent and 13.7 percent of men had MRI scan done prior to prostate biopsy and MRI-guided biopsy, respectively.

“Study results confirmed that urine spermine and Spermine Risk Score are effective at identifying men at high risk of PCa, and can potentially reduce the number of unnecessary prostate biopsies,” said Dr Peter Ka-Fung Chiu of the Department of Surgery, CUHK.

In the study, 30.8 percent and 17.2 percent of men were diagnosed with any-grade PCa and International Society of Urological Pathology Gleason grade (ISUP GG) ≥2 PCa (ie, HGPCa), respectively. Significantly lower spermine levels were detected in men with PCa and HGPCa (both p<0.001).

A 3.0-fold and 3.6-fold increase in risk of PCa and HGPCa were observed in men with spermine level within the lowest vs the highest quartile (any-grade PCa, 49.3 percent vs 16.7 percent; ISUP grade ≥2 PCa, 31.3 percent vs 8.7 percent), respectively.

Multivariate analyses demonstrated that PSA, DRE, prostate volume and spermine were independent predictors for PCa and HGPCa. Spermine Risk Score taking these factors into consideration achieved an area under curve (AUC) of 0.78 for PCa and 0.82 for HGPCa.

At test sensitivity of 90 percent for HGPCa (Spermine Risk Score cut-off, 5.35), 36.7 percent of unnecessary biopsies and 24.4 percent of ISUP GG 1 PCa diagnoses could be avoided, with a negative predictive value (NPV) of 95.4 percent.

With a positive predictive value of 24.5 percent (Spermine Risk Score cut-off, 7), the risk of HGPCa was 24.5 percent and 4.6 percent for Spermine Risk Score of ≥7 and <7, respectively (both p<0.001).

Decision curve analyses showed a net clinical benefit of Spermine Risk Score over spermine, PSA density, or PSA level alone in predicting the risk of PCa and HGPCa, with AUC of 0.81, slope of 0.96 and intercept of -0.05 for HGPCa.

“Thus, the Spermine Risk Score, based on patients’ urine spermine level and other clinical parameters, may serve as a novel and promising approach in HGPCa diagnosis in patients with elevated PSA level,” concluded Wong.