Predictive value of isoform -2 proprostate-specific antigen and its derived indexes for prostate cancer patients with PSA 4-20 ng/mL / 现代泌尿外科杂志

【Objective】 To evaluate the predictive value of isoform [-2] proprostate-specific antigen, p2 PSA (p2PSA) and its derived indexes for prostate cancer in a Chinese cohort with PSA 4-20 ng/mL. 【Methods】 A total of 139 males scheduled for biopsy were enrolled in the prospective study from Nov.2021 to Jun.2022. The total PSA (tPSA), free PSA (fPSA), fPSA/tPSA (f/t) and p2PSA were collected, and the percentage of p2PSA(%p2PSA) and prostate health index(PHI) were calculated. The predictive value of p2PSA and its derived indexes were compared with traditional indexes with receiver operating characteristic (ROC) curve and Logistic analysis. 【Results】 Prostate cancer was found in 54 cases (38.8%). There were significant statistical differences in tPSA(10.68 vs.8.14, P=0.021), f/t(0.13 vs.0.16, P=0.006), p2PSA(30.25 vs.19.81, P<0.001), %p2PSA(21.52 vs.13.15, P<0.001) and PHI(64.3vs.38.2, P<0.001) between prostate cancer patients and non-prostate cancer patients. The area under the ROC curve (AUC) of tPSA, fPSA, %fPSA, p2PSA, %p2PSA and PHI were 0.63, 0.51, 0.63, 0.71, 0.73, and 0.80, respectively. The inclusion of %p2PSA and PHI significantly increased the prediction efficiency of the basic prediction model (AUCbase+PHI=0.81, AUCbase+%p2PSA=0.78, AUCbase=0.67). With 35 as the recommended cut-off value of PHI, the incidence of meaningless puncture was reduced by 25.8%(36/139). 【Conclusion】 The application of p2PSA and its derived indexes have good predictive value for patients with PSA 4-20 ng/mL. The combined detection of %p2PSA and PHI can significantly increase the detection efficiency of prostate cancer and reduce the incidence of meaningless prostate puncture by 25.8%.

Can we omit systematic biopsies in patients undergoing MRI fusion-targeted prostate biopsies? / 亚洲男科学杂志(英文版)

Magnetic resonance imaging (MRI)-targeted prostate biopsy is the recommended investigation in men with suspicious lesion(s) on MRI. The role of concurrent systematic in addition to targeted biopsies is currently unclear. Using our prospectively maintained database, we identified men with at least one Prostate Imaging-Reporting and Data System (PI-RADS) ≥3 lesion who underwent targeted and/or systematic biopsies from May 2016 to May 2020. Clinically significant prostate cancer (csPCa) was defined as any Gleason grade group ≥2 cancer. Of 545 patients who underwent MRI fusion-targeted biopsy, 222 (40.7%) were biopsy naïve, 247 (45.3%) had previous prostate biopsy(s), and 76 (13.9%) had known prostate cancer undergoing active surveillance. Prostate cancer was more commonly found in biopsy-naïve men (63.5%) and those on active surveillance (68.4%) compared to those who had previous biopsies (35.2%; both P < 0.001). Systematic biopsies provided an incremental 10.4% detection of csPCa among biopsy-naïve patients, versus an incremental 2.4% among those who had prior negative biopsies. Multivariable regression found age (odds ratio [OR] = 1.03, P = 0.03), prostate-specific antigen (PSA) density ≥0.15 ng ml-2 (OR = 3.24, P < 0.001), prostate health index (PHI) ≥35 (OR = 2.43, P = 0.006), higher PI-RADS score (vs PI-RADS 3; OR = 4.59 for PI-RADS 4, and OR = 9.91 for PI-RADS 5; both P < 0.001) and target lesion volume-to-prostate volume ratio ≥0.10 (OR = 5.26, P = 0.013) were significantly associated with csPCa detection on targeted biopsy. In conclusion, for men undergoing MRI fusion-targeted prostate biopsies, systematic biopsies should not be omitted given its incremental value to targeted biopsies alone. The factors such as PSA density ≥0.15 ng ml-2, PHI ≥35, higher PI-RADS score, and target lesion volume-to-prostate volume ratio ≥0.10 can help identify men at higher risk of csPCa.

Research progress of prostate health index in the diagnosis and treatment of prostate cancer / 中华泌尿外科杂志

Despite the increasing number of patients was diagnosed with prostate cancer due to widespread cancer screening, PSA testing does not differentiate between lethal and slow-growing inert prostate cancers. This leads to a proportion of patients being over-diagnosed and consequently over-treated.The current study has found that PSA exists as a precursor to post-translational modification, and that [-2]proPSA originates only from the peripheral zone of the prostate. Furthermore, the study has shown that prostate health index (PHI) calculated from [-2]proPSA, fPSA, and PSA has a higher positive predictive value for prostate cancer, making it useful in the diagnosis of clinically significant prostate cancer. This article reviews the progress of research related to PHI in prostate cancer diagnosis and treatment.

Application of free/total prostate-specific antigen ratio, peripheral blood neutrophil-to-lymphocyte ratio, interleukin-6 and prostate health index density detection in early diagnosis of prostate cancer / 肿瘤研究与临床

Objective:To investigate the clinical application of free/total prostate-specific antigen (f/tPSA), peripheral blood neutrophil-to-lymphocyte ratio (NLR), interleukin-6 (IL-6) and prostate health index density (PHID) detection in the early diagnosis of prostate cancer.Methods:The clinical data of 160 patients with abnormal prostate specific antigen (PSA) who were admitted to the Second Affiliated Hospital of Xuzhou Medical University from January 2020 to January 2022 were retrospectively analyzed. According to the pathological results of prostate biopsy or electrical resection, the patients were divided into prostate cancer group (68 cases) and benign prostatic hyperplasia group (92 cases), and 50 male healthy physical examiners in the Second Affiliated Hospital of Xuzhou Medical University during the same period were selected as healthy control group. All enrolled members were tested for total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA), and prostate specific antigen isoform 2 (p2PSA), IL-6 and other indicators, and the f/tPSA, prostate health index (PHI), PHID and NLR were calculated. Receiver operating characteristic (ROC) curve was plotted to compare the efficacy of each index in diagnosing and differentially diagnosing prostate cancer and benign prostatic hyperplasia.Results:The serum levels of tPSA, fPSA, p2PSA, PHI and PHID in the prostate cancer group were higher than those in the benign prostatic hyperplasia group and the healthy control group (all P < 0.05), and the serum f/tPSA was lower than that in the benign prostatic hyperplasia group and the healthy control group ( P < 0.05). The area under the curve (AUC) of PHID for the diagnosis of early stage prostate cancer was the largest [0.915 (95% CI 0.864-0.966)], followed by PHI [0.884 (95% CI 0.823-0.944)]. The sensitivity of both f/tPSA and PHI in diagnosing early stage prostate cancer was 86.80%, which was higher than other indicators; the specificity of PHID in diagnosing early stage prostate cancer was 94.00%, which was higher than other indicators. The AUC of f/tPSA for the diagnosis of benign prostatic hyperplasia was the largest [0.828 (95% CI 0.739-0.917)], followed by PHID [0.826 (95% CI 0.760-0.892)]. The sensitivity of f/tPSA in diagnosing benign prostatic hyperplasia (85.90%) was higher than other indicators, and the specificity of PHI in diagnosing benign prostatic hyperplasia (94.00%) was higher than other indicators. The AUC of fPSA, PHID, f/tPSA and p2PSA in differentiating early stage prostate cancer and benign prostatic hyperplasia were 0.752 (95% CI 0.663-0.841), 0.730 (95% CI 0.647-0.812), 0.713 (95% CI 0.623-0.803), 0.710 (95% CI 0.629-0.791), respectively, and there was no significant difference in each pairwise comparison (all P > 0.05). The sensitivity of NLR in differentiating early stage prostate cancer and benign prostatic hyperplasia was 91.20%, which was higher than other indicators, and the specificity of fPSA in differentiating early stage prostate cancer and benign prostatic hyperplasia was 94.00%, which was higher than other indicators. Conclusions:The f/tPSA, PHI and PHID detection have certain clinical values in the early diagnosis of prostate cancer, and can provide references for early diagnosis, early treatment and prognosis evaluation of high-risk population of prostate cancer.

Prostate health index for the diagnosis of prostate cancer in Asians in Macau with a PSA level of 4－10 μg/L / 中华男科学杂志

Objective@#To evaluate the prostate health index (PHI) as a tool for the diagnosis of PCa with a PSA level of 4－10 μg/L and determine the best cut-off value of PHI.@*METHODS@#Fifty-eight patients with a PSA level of 4－10 μg/L underwent transrectal ultrasound-guided prostatic biopsy in our hospital between April 2017 and June 2019. We constructed receiver operating characteristic (ROC) curves for the relationship of the biopsy results with the level of PSA, the ratio of ［－2］ proPSA to fPSA and PHI, and calculated the area under the ROC curves (AUC).@*RESULTS@#Prostatic biopsy revealed 18 cases of PCa in the 58 patients (31.0%). Statistically significant differences were observed between the PCa and non-PCa groups in ［－2］ proPSA, %［－2］ proPSA and PHI, but not in tPSA, % fPSA and PSA-density. The AUCs of PSA, % fPSA, PSA-density, ［－2］ proPSA, %［－2］ proPSA and PHI were 0.556, 0.407, 0.533, 0.746, 0.751 and 0.774, respectively. The specificity of PHI was 27.50% (95% CI: 14.6%－43.9%), the highest among the above predictors at 90% sensitivity. By applying PHI to this cohort, 13 cases (22.4%) of unnecessary biopsy could be avoided.@*CONCLUSIONS@#The application of PHI can increase the accuracy of PCa prediction and reduce unnecessary prostatic biopsy.、.

Diagnostic performance of prostate health index (PHI) in predicting prostate cancer on prostate biopsy

@# Prostate health index (PHI) has been shown to have better diagnostic accuracy in predicting prostate cancer (PCa) in men with total prostate-specific antigen (PSA) levels between 4-10ng/ml. However, little is known of its value in men with elevated PSA beyond this range. This study aimed to evaluate the diagnostic performance of PHI in Malaysian men with elevated PSA values ≤ 20ng/ml. Materials and Methods: From March 2015 to August 2016, all men consecutively undergoing transrectal ultrasound (TRUS)-guided prostate biopsy with total PSA values ≤ 20ng/ ml were recruited. Blood samples were taken immediately before undergoing prostate biopsy. The performance of total PSA, %fPSA, %p2PSA and PHI in determining the presence of PCa on prostate biopsy were compared. Results: PCa was diagnosed in 25 of 84 patients (29.7%). %p2PSA and PHI values were significantly higher (p<0.05) in patients with PCa than those without PCa. The areas under the receiver operating characteristic curves for total PSA, %fPSA, %p2PSA and PHI were 0.558, 0.560, 0.734 and 0.746, respectively. At 90% sensitivity, the specificity of PHI (42.4%) was five times better than total PSA (8.5%) and two times better than %fPSA (20.3%). By utilising PHI cut-off >22.52, 27 of 84 (32.1%) patients could have avoided undergoing biopsy. Conclusion: Findings of our study support the potential clinical effectiveness of PHI in predicting PCa in a wider concentration range of total PSA up to 20ng/ml.

Prostate volume does not provide additional predictive value to prostate health index for prostate cancer or clinically significant prostate cancer: Results from a multicenter study in China / 亚洲男科学杂志(英文版)

To evaluate whether prostate volume (PV) would provide additional predictive utility to the prostate health index (phi) for predicting prostate cancer (PCa) or clinically significant prostate cancer, we designed a prospective, observational multicenter study in two prostate biopsy cohorts. Cohort 1 included 595 patients from three medical centers from 2012 to 2013, and Cohort 2 included 1025 patients from four medical centers from 2013 to 2014. Area under the receiver operating characteristic curves (AUC) and logistic regression models were used to evaluate the predictive performance of PV-based derivatives and models. Linear regression analysis showed that both total prostate-specific antigen (tPSA) and free PSA (fPSA) were significantly correlated with PV (all P 0.05). In conclusion, PV-based derivatives (both PHIV and PHID) and models incorporating PV did not improve the predictive abilities of phi for either PCa or clinically significant PCa.

Phi-based risk calculators performed better in the prediction of prostate cancer in the Chinese population / 亚洲男科学杂志(英文版)

Risk prediction models including the Prostate Health Index (phi) for prostate cancer have been well established and evaluated in the Western population. The aim of this study is to build phi-based risk calculators in a prostate biopsy population and evaluate their performance in predicting prostate cancer (PCa) and high-grade PCa (Gleason score ≥7) in the Chinese population. We developed risk calculators based on 635 men who underwent initial prostate biopsy. Then, we validated the performance of prostate-specific antigen (PSA), phi, and the risk calculators in an additional observational cohort of 1045 men. We observed that the phi-based risk calculators (risk calculators 2 and 4) outperformed the PSA-based risk calculator for predicting PCa and high-grade PCa in the training cohort. In the validation study, the area under the receiver operating characteristic curve (AUC) for risk calculators 2 and 4 reached 0.91 and 0.92, respectively, for predicting PCa and high-grade PCa, respectively; the AUC values were better than those for risk calculator 1 (PSA-based model with an AUC of 0.81 and 0.82, respectively) (all P < 0.001). Such superiority was also observed in the stratified population with PSA ranging from 2.0 ng ml-1to 10.0 ng ml-1. Decision curves confirmed that a considerable proportion of unnecessary biopsies could be avoided while applying phi-based risk calculators. In this study, we showed that, compared to risk calculators without phi, phi-based risk calculators exhibited superior discrimination and calibration for PCa in the Chinese biopsy population. Applying these risk calculators also considerably reduced the number of unnecessary biopsies for PCa.

Phi-based risk calculators performed better in the prediction of prostate cancer in the Chinese population / 亚洲男科学杂志(英文版)

Risk prediction models including the Prostate Health Index (phi) for prostate cancer have been well established and evaluated in the Western population. The aim of this study is to build phi-based risk calculators in a prostate biopsy population and evaluate their performance in predicting prostate cancer (PCa) and high-grade PCa (Gleason score ≥7) in the Chinese population. We developed risk calculators based on 635 men who underwent initial prostate biopsy. Then, we validated the performance of prostate-specific antigen (PSA), phi, and the risk calculators in an additional observational cohort of 1045 men. We observed that the phi-based risk calculators (risk calculators 2 and 4) outperformed the PSA-based risk calculator for predicting PCa and high-grade PCa in the training cohort. In the validation study, the area under the receiver operating characteristic curve (AUC) for risk calculators 2 and 4 reached 0.91 and 0.92, respectively, for predicting PCa and high-grade PCa, respectively; the AUC values were better than those for risk calculator 1 (PSA-based model with an AUC of 0.81 and 0.82, respectively) (all P < 0.001). Such superiority was also observed in the stratified population with PSA ranging from 2.0 ng ml-1to 10.0 ng ml-1. Decision curves confirmed that a considerable proportion of unnecessary biopsies could be avoided while applying phi-based risk calculators. In this study, we showed that, compared to risk calculators without phi, phi-based risk calculators exhibited superior discrimination and calibration for PCa in the Chinese biopsy population. Applying these risk calculators also considerably reduced the number of unnecessary biopsies for PCa.

Use of prostate health index in diagnosing prostate cancer in Chinese men / 中华外科杂志

Objective@#To investigate the value of prostate health index (PHI) in the diagnosis of prostate cancer in patients with total prostate specific antigen (tPSA) <20 μg/L.@*Methods@#Totally 1 135 patients with tPSA<20 μg/L and prostate biopsy indications at Department of Urology, Fudan University Shanghai Cancer Center from March 2013 to April 2016 were enrolled in this study. They were tested for serum tPSA, free prostate specific antigen and prostate specific antigen isoform 2, from which PHI was calculated. Diagnostic efficacy of PHI and tPSA were evaluated using receiver operating characteristic (ROC) curve analysis. The detection rates of prostate cancer were calculated in different ranges of PHI. Subgroup analysis of 716 patients, who were aged 50 or above with tPSA in the range of 4 to 10 μg/L and digital rectal examination negative, was performed.@*Results@#In the biopsied objects with tPSA<20 μg/L, PHI was significantly higher in prostate cancer patients than that in non-cancer patients (48.4(37.4) vs. 26.5(16.9), U=52 674.00, P=0.000), PHI was also significantly higher in high-grade prostate cancer patients than that of low-grade prostate cancer patients (44.5(30.8) vs. 56.4(42.5), U=23 314.00, P=0.000). The area under the curve (AUC) of PHI for diagnosing prostate cancer was significantly higher than that of tPSA (0.771 vs. 0.627, P=0.000). When PHI was in the range of <27, 27 to <36, 36 to <55 and ≥55, the probability of prostate cancer was 9.4% (95%CI: 7.0% to 12.2%), 16.3% (95%CI: 12.2% to 20.8%), 31.0% (95%CI: 25.9% to 37.3%) and 66.4% (95%CI: 58.9% to 74.2%), respectively. Subgroup analysis showed that the AUC of PHI in diagnosing prostate cancer was significantly higher than that of tPSA (0.764 vs. 0.569, P=0.000). When PHI was in the range of <27, 27 to <36, 36 to <55 and ≥55, the probability of prostate cancer was 8.1% (95%CI: 5.4% to 11.3%), 14.0% (95%CI: 9.1% to 19.9%), 30.8% (95%CI: 23.6% to 38.7%) and 78.8% (95%CI: 66.7% to 88.9%), respectively.@*Conclusion@#PHI is superior to tPSA in the diagnosis of prostate cancer in Chinese men with tPSA<20 μg/L.

Performance of the Prostate Health Index in predicting prostate biopsy outcomes among men with a negative digital rectal examination and transrectal ultrasonography / 亚洲男科学杂志(英文版)

The [-2]proPSA (p2PSA) and its derivatives, the p2PSA-to-free PSA ratio (%p2PSA), and the Prostate Health Index (PHI) have greatly improved discrimination between men with and without prostate cancer (PCa) in prostate biopsies. However, little is known about their performance in cases where a digital rectal examination (DRE) and transrectal ultrasonography (TRUS) are negative. A prospective cohort of 261 consecutive patients in China with negative DRE and TRUS were recruited and underwent prostate biopsies. A serum sample had collected before the biopsy was used to measure various PSA derivatives, including total prostate-specific antigen (tPSA), free PSA, and p2PSA. For each patient, the free-to-total PSA ratio (%fPSA), PSA density (PSAD), p2PSA-to-free PSA ratio (%p2PSA), and PHI were calculated. Discriminative performance was assessed using the area under the receiver operating characteristic curve (AUC) and the biopsy rate at 91% sensitivity. The AUC scores within the entire cohort with respect to age, tPSA, %fPSA, PSAD, p2PSA, %p2PSA, and PHI were 0.598, 0.751, 0.646, 0.789, 0.814, 0.808, and 0.853, respectively. PHI was the best predictor of prostate biopsy results, especially in patients with a tPSA of 10.1-20 ng ml-1. Compared with other markers, at a sensitivity of 91%, PHI was the most useful for determining which men did not need to undergo biopsy, thereby avoiding unnecessary procedures. The use of PHI could improve the accuracy of PCa detection by predicting prostate biopsy outcomes among men with a negative DRE and TRUS in China.

Clinical Use of -2proPSA (p2PSA) and Its Derivatives (%p2PSA and Prostate Health Index) for the Detection of Prostate Cancer: A Review of the Literature

Prostate-specific antigen (PSA) is recognized as an organ-specific marker with low specificity and sensitivity in discriminating prostate cancer (PCa) from other benign conditions, such as prostatic hyperplasia or chronic prostatitis. Thus, in the case of clinical suspicion, a PCa diagnosis cannot be made without a prostate biopsy. [-2]proPSA (p2PSA), a precursor of PSA, has been investigated as a new marker to accurately detect PCa. The aim of this systematic review was to discuss the available literature regarding the clinical validity and utility of p2PSA and its derivatives, p2PSA/fPSA (%p2PSA) and the Prostate Health Index (PHI). A systematic search of the PubMed and Scopus electronic databases was performed in accordance with the PRISMA statement (http://www.prisma-statement.org), considering the time period from January 1990 to January 2014 and using the following search terms: proprostate specific antigen, proenzyme PSA, proPSA, [-2]proPSA, p2PSA, Prostate Health Index, and PHI. To date, 115 studies have been published, but only 35 were considered for the qualitative analysis. These studies suggested that p2PSA is the most cancer-specific form of PSA, being preferentially expressed in PCa tissue and being significantly elevated in the serum of men with PCa. It is now evident that p2PSA, %p2PSA, and PHI measurements improve the specificity of the available tests (PSA and derivatives) in detecting PCa. Moreover, increasing PHI values seem to correlate with more aggressive disease. Some studies have compared p2PSA and its derivatives with other new biomarkers and found p2PSA to be significantly more accurate. Indeed, the implementation of these tests in clinical practice has the potential to significantly increase the physician's ability to detect PCa and avoid unnecessary biopsies, while also having an effective impact on costs. Further studies in large, multicenter, prospective trials are required to confirm these encouraging results on the clinical utility of these new biomarkers.