Research Article: The effect of 3-month finasteride challenge on biomarkers for predicting cancer outcome on biopsy: Results of a randomized trial

Date Published: October 9, 2018

Publisher: Public Library of Science

Author(s): Javier Hernandez, Jonathan Gelfond, Martin Goros, Michael A. Liss, Yuanyuan Liang, Donna Ankerst, Ian M. Thompson, Robin J. Leach, David J. Handelsman.


Finasteride, a 5-alpha reductase inhibitor may have effects on biomarkers such as prostate-specific antigen (PSA) that could be leveraged to improve screening.

To determine the predictive characteristics of biomarkers for prostate cancer for cancer on biopsy following 3 months of finasteride use compared with placebo.

383 men from multiple clinical sites with intermediate prostate cancer risk, without history of prostate cancer, were randomly allocated in a double-blinded manner, 4:1, to receive either finasteride or placebo for 90 days at which time a prostate biopsy was performed.

The primary outcomes were associations of biomarkers with prostate cancer that were tested using multiple logistic regression and area under the receiver operating curves (AUC). Biomarkers for PCA risk (PCA3, TMPRSS2:ERG (T2:ERG) gene product, and PSA) were measured at baseline and at biopsy in a blinded fashion to assess the predictive performance of baseline levels, 90-day levels, and measures of change relative to standard predictors.

A total of 292 (233 finasteride; 59 placebo) randomized patients underwent biopsy and were analyzed. On finasteride, baseline and 90-day measures of PCA3 and T2:ERG had similar moderate discrimination capacity with AUCs 62 to 65% (p-values < 0.001 and 0.001, respectively), but their rates of change had no discrimination ability (AUC 51%, (95% CI 43 to 60% p = 0.72) and 48% (95% CI 44 to 60%, p = 0.62), respectively).) Relative to baseline, the 90-day PCA3 and PSA decreased in the finasteride group by 25% and 50%, respectively (both p<0.001). T2:ERG had a smaller, non-significant change post finasteride treatment (p = 0.08). Short-term finasteride therapy did not improve performance of the most commonly-employed prostate cancer biomarkers. Threshold values for new biomarkers of prostate cancer should be interpreted with caution in patients receiving finasteride until formal validation of test performance in these patients is conducted. Three months of finasteride treatment did not increase the accuracy for predicting the outcome on prostate biopsy but did have a significant effect on biomarker values. Adjustments to thresholds for biopsy for men on finasteride are proposed., NCT01296672.

Partial Text

Prostate cancer (PCA) is the most common non-cutaneous cancer in men living in the United States. A major focus for disease control has been early diagnosis using the prostate-specific antigen (PSA) blood test. There are many challenges with PSA testing. Many patients with prostate cancer, including aggressive cancers, have normal PSA levels[1]. As a screening biomarker, PSA alone has a high false positive rate [2]. Furthermore, the majority of prostate biopsies prompted by elevated PSA tests find no cancer, and these biopsies incur pain, risks of fever, prostatitis, and urine retention [3, 4] as well as substantial costs to the healthcare system [5]. The limitations of PSA screening led the US Preventative Services Task Force to initially recommend against the use of PSA for screening in 2012 [6], although recent changes recommend offering PSA testing to at-risk men age 55–69. Nonetheless, improvements in diagnosis are necessary, and there are promising biomarkers that have evidence for improving screening accuracy. Included among these are the noncoding RNA known as Prostate cancer antigen 3 (PCA3) [7] and TMPRSS2:ERG (T2:ERG) fusion gene. ERG is a member of the Erythroblast Transformation-Specific (ETS) gene family and is commonly fused in prostate cancer to the TMPRSS2 gene (Transmembrane Protease, Serine 2)[8]. These markers are measured by quantitating the level of their RNA transcripts in post-DRE (digital rectal examine) urine from subjects normalized against PSA transcripts.

The management of an asymptomatic man with an elevated PSA is a clinical challenge. While the PSA test is highly-associated with risk of prostate cancer and the risk of potentially-lethal, high-grade prostate cancer, many men undergoing prostate biopsy will be found to be cancer-free or to harbor low-grade, low-volume disease. Higher PSA levels in these men are often due to larger prostate volumes; as these men often have concomitant urinary symptoms, it has been a common practice to treat them with antibiotics or a 5-alpha reductase inhibitor and monitor the fall in PSA. The use of 5-alpha reductase inhibitors to reduce PSA, a greater fall in PSA is often ascribed to prostatic hyperplasia. Traditionally, the prescriber would expect a 50% reduction in finasteride and if the PSA did not fall to ½ the original PSA then cancer may be cause of persistent PSA elevation. Additionally, men with higher PSA values who have had a prior negative biopsy and who are then treated with finasteride may subsequently undergo testing with secondary screening tests such as PCA3. This study was designed to address both the kinetics of change in biomarkers during a 3-month challenge with finasteride as well as biomarker performance and cut-points before and after finasteride administration.




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