Clinical utility of multiple secondary combined tests in prostate cancer screening.

INTRODUCTION: The clinical utility of concurrent Prostate Health Index (PHI) and ExosomeDx Prostate Intelliscore (EPI) testing is unclear. We sought to examine the performance of combined PHI and EPI testing on men undergoing elevated PSA work up. MATERIALS AND METHODS: Patients who received both EPI and PHI testing were identified from an institutional database of men referred to urology for an elevated total PSA. Cut points of EPI > 15.6 and PHI ≥ 36 were used to denote a positive test. Patients were placed into one of four groups determined by combination of EPI and PHI results. Demographic variables and biopsy recommendations were compared between groups. The concordance of test positivity between EPI and PHI was compared by Cohen's kappa. Demographic variables and secondary testing results were compared between patients' compliant and non-compliant with prostate biopsy recommendation. Biopsy pathology was compared between groups. RESULTS: A total of 162 patients had both EPI and PHI testing. Median age was 65 years, with a median PSA of 6.64 ng/mL. Age (p = 0.001), PSA (< 0.001) and biopsy recommendation (< 0.001) differed between combined secondary screening test result groups. Seventy-five percent of patients with both a positive EPI and PHI were found to have prostate cancer, with 54.2% being ≥ Gleason 7. Cohen's kappa was 0.19, indicating poor concordance. The AUC of EPI and PHI for clinically significant cancer was 0.563 (95% CI: 0.4331-0.6923) and 0.685 (95% CI: 0.569-0.8) (p = 0.147). CONCLUSIONS: Concurrently positive EPI and PHI indicate increased prostate cancer risk, with combined usage potentially influencing biopsy recommendation and compliance.

Re-thinking How We Use Prostate Health Index for African American Men.

OBJECTIVE: To assess how the validated Prostate Health Index (PHI) risk stratifications perform with African American (AA) men and establish a threshold PHI value to potentially rule out the need for prostate biopsy. MATERIALS AND METHODS: AA men meeting FDA-specified indications for PHI testing (>50 years old, PSA 4-10 and negative DRE) who underwent subsequent biopsy were included. Rates of clinically significant prostate cancer (csPCa, as defined by Gleason score ≥7) across accepted PHI stratifications were recorded. Receiver operator curve (ROC) analysis was undertaken to assess PHI performance to predict csPCa. A phi cutoff providing 90% sensitivity was identified. Among AA men with PSA 4-10 ng/mL, the proportion of men who proceeded to biopsy upon physician recommendation was determined. RESULTS: Two hundred nine patients met primary criteria; 91 (43.5%) of which had csPCA. The area under the curve for PHI predicting csPCa was 0.68 (95% CI: 0.61-0.75). Using a phi threshold of <23.0 to avoid biopsy provided 98.9% sensitivity, 9.3% specificity, and would have avoided 4.7% of biopsies. The proportion of those who proceeded to biopsy upon physician recommendation was 81.8%. CONCLUSIONS: PHI demonstrated limited performance in our cohort, with current stratifications featuring misleadingly low cancer detection rates for these men. Furthermore, PHI had limited use to avoid prostate biopsy, as the proposed threshold of 23.0 only allowed 4.7% of men to avoid biopsy. Further work is needed to assess and optimize PHI usage in AA men; nonetheless, it may still have use in increasing compliance with biopsy recommendation.

Initial Longitudinal Outcomes of Risk-Stratified Men in Their Forties Screened for Prostate Cancer Following Implementation of a Baseline Prostate-Specific Antigen.

PURPOSE: Prostate cancer (PCa) screening can lead to potential over-diagnosis/over-treatment of indolent cancers. There is a need to optimize practices to better risk-stratify patients. We examined initial longitudinal outcomes of mid-life men with an elevated baseline prostate-specific antigen (PSA) following initiation of a novel screening program within a system-wide network. MATERIALS AND METHODS: We assessed our primary care network patients ages 40 to 49 years with a PSA measured following implementation of an electronic health record screening algorithm from 2/2/2017-2/21/2018. The multidisciplinary algorithm was developed taking factors including age, race, family history, and PSA into consideration to provide a personalized approach to urology referral to be used with shared decision-making. Outcomes of men with PSA ≥1.5 ng/mL were evaluated through 7/2021. Statistical analyses identified factors associated with PCa detection. Clinically significant PCa (csPCa) was defined as Gleason Grade Group (GGG) ≥2 or GGG1 with PSA ≥10 ng/mL. RESULTS: The study cohort contained 564 patients, with 330 (58.5%) referred to urology for elevated PSA. Forty-nine (8.7%) underwent biopsy; of these, 20 (40.8%) returned with PCa. Eleven (2.0% of total cohort and 55% of PCa diagnoses) had csPCa. Early referral timing (odds ratio [OR], 4.58) and higher PSA (OR, 1.07) were significantly associated with PCa at biopsy on multivariable analysis (both p<0.05), while other risk factors were not. Referred patients had higher mean PSAs (2.97 vs. 1.98, p=0.001). CONCLUSIONS: Preliminary outcomes following implementation of a multidisciplinary screening algorithm identified PCa in a small, important percentage of men in their forties. These results provide insight into baseline PSA measurement to provide early risk stratification and detection of csPCa in patients with otherwise extended life expectancy. Further follow-up is needed to possibly determine the prognostic significance of such mid-life screening and optimize primary care physician-urologist coordination.

Successful Diagnosis and Treatment of Occult Prostate Cancer Despite Multiple Negative Prostate Biopsies and Negative Prostate MRIs.

Prostate-specific antigen (PSA) values above 100 ng/mL often suggest metastatic prostate cancer. We present the case of a patient with a PSA of 110 ng/mL, 4 negative prostate biopsies, and 4 negative prostate MRIs. After his fifth MRI revealed a PI-RADS 5 lesion, he underwent his fifth transrectal biopsy; this revealed Gleason 3 + 4 = 7. He was found to have organ-confined pT2 disease on subsequent radical prostatectomy pathology. This case highlights that there may be no PSA for which one can assume metastatic disease with certainty. Depending on life expectancy, patients with extremely elevated PSA may still warrant a full staging workup.

Aggressive prostate cancer masquerading as acute prostatitis.

Prostatitis is a common cause of prostate-specific antigen (PSA) elevation but can masquerade underlying prostate cancer. We present a case of a man with undiagnosed prostate cancer whose initial PSA elevation of > 999.0 ng/mL was initially ascribed entirely to prostatitis. In the setting of possible prostatitis clinicians should avoid the knee jerk reaction to blame the totality of PSA elevation on prostatitis. A greatly elevated PSA may be a sign of an underlying prostate cancer and should be explored in the proper clinical setting.