Antigen Velocity Research Articles

The application of the template positioning transperineal prostate biopsy in the first prostate biopsy negative patients

Objective To assess the safety and efficiency of systematic transperineal ultrasound guided template positioning biopsy for the high-risk population of prostate cancer.Methods From January 2010 to January 2012 a total of 42 high-risk men of prostate cancer underwent systematic ultrasound guided biopsy using the transperineal template positioning technique.All patients got at least one previous biopsy,and all the patients showed negative results,including prostatic intraepithelial neoplasia,and/or atypical small cell acinar proliferation.During the follow-up,all the patients still had high prostate specific antigen (PSA) velocity (＞ 0.75 μg/L) or high PSA level (＞ 10 μg/L).Results A mean of 18.7 biopsy cores had been obtained.Cancer was identified in 19 of the 42 men (44％).The mean Gleason score was 6 (from 4 to 9).Mean prostate volume in the positive and negative biopsy groups was 44 and 71 ml.The only significant independent influence factor for positive biopsy was prostate volume (P ＜ 0.05).The positive rate showed no statistic difference in term of presence of PIN,AHH,the number of biopsy sites,or PSA value (P ＞0.05).Adenocarcinoma was found in transition zone in 14 of 19 cases (74％),and 5 (36％) was positive only in the transition zone.Complications were rare and self-limiting,including hematuria (29％)and urinary retention (0.9％).Conclusions Systematic transperineal template positioning biopsy of the prostate is a safe and precise biopsy technique in patients who remain at high-risk for prostate adenocarcinoma. Key words: Prostate cancer; High-risk; Biopsy

Differences in characteristics of men with localised prostate cancer who demonstrate low, intermediate or high prostate‐specific antigen velocity

Current diagnostic tools are inadequate for reliable prediction of prostate cancer (PCa) aggressiveness in patients with localised disease. This results in many patients being exposed to potentially unnecessary invasive treatment and its associated morbidities. In order to develop appropriate treatment strategies, it is essential to understand the differences between patients who will develop aggressive disease and those who will not. A longitudinal study was conducted in men with localised PCa on active surveillance for their disease in which 140 subjects were followed every 3 months for up to 5 years. Change in prostate-specific antigen (PSA) over time (PSA velocity) was used as a marker for PCa progression. Subjects were categorised as slow, intermediate and fast progressors based on tertiles of PSA velocity. Differences in baseline markers were investigated using logistic regressions. Two approaches were used, slow progressors were compared with fast progressors (model 1) and slow progressors were compared with combination of intermediate and fast progressors (model 2). Aspirin was negatively associated with high PSA velocity in model 1 (odds ratio (95% confidence interval): 0.24 (0.06, 0.94), P-value = 0.04) and model 2 (odds ratio = 0.22 (0.08, 0.59), P-value = 0.003), whereas smoking was positively associated with high PSA velocity in model 1 (1.03 (0.92, 1.13), P-value = 0.01). These findings highlight the role of aspirin and smoking in PCa progression. They have potential towards risk stratification as well as PCa prevention and hence need to be investigated further.

A comparative performance analysis of total prostate‐specific antigen, percentage free prostate‐specific antigen, prostate‐specific antigen velocity and urinary prostate cancer gene 3 in the first, second and third repeat prostate biopsy

Study Type - Diagnosis (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Risk factor assessment in the repeat biopsy setting is affected by a decreasing diagnostic accuracy of each single risk factor (e.g. DRE, tPSA, %fPSA, complexed PSA, PSA density or PSAV] with increasing number of prostate biopsy sessions. PCA3 shows impressive diagnostic performance in the initial and early repeat biopsy settings. In a head-to-head comparison we demonstrate the concept that the number of previous repeat biopsy session strongly influences performance characteristics of biopsy risk factors, including PCA3. While the novel diagnostic marker would have avoided a considerable number of unnecessary biopsies in the first repeat biopsy scenario, its effects dissipated at second and ≥ third repeat biopsies. To compare the performance characteristics of prostate cancer risk factors such as total prostate-specific antigen (tPSA), percentage free PSA (%fPSA), PSA velocity (PSAV) and urinary prostate cancer gene 3 (PCA3) at first, second and ≥ third repeat biopsy session. Patients (n= 127) aged ≤70 years, with suspicious digital rectal examination (DRE) and/or persistently elevated age-specific total PSA levels (2.5-6.5 ng/mL) and/or suspicious prior histology (atypical small acinar proliferations [ASAPs]≥ two cores affected by high-grade prostatic intra-epithelial neoplasia [HGPIN]) undergoing either a first, second, or ≥ third repeat biopsy were investigated using a 12- or 24-core biopsy scheme. PSAV (≥ three values collected over ≥12 months) was calculated using the log-slope method. PCA3 scores were assessed using the Progensa assay®. After stratification according to the number of previous biopsies (first, second and ≥ third), calculation of specificity, positive and negative predictive values (PPV, NPV) and the proportion of avoided unnecessary repeat biopsies (PAB) compared with tPSA at fixed sensitivity thresholds (75, 85 and 95%) were performed. Finally, accuracy estimates (area under the curve [AUC]) were quantified for each repeat biopsy scenario. At repeat biopsy, overall prostate cancer (PCa) detection was 34.6%. At first repeat biopsy, PCA3 predicted PCa best (AUC = 0.80) and would have avoided 72.2% of repeat biopsies (75% sensitivity) compared with tPSA. At second repeat biopsy, %fPSA demonstrated the highest accuracy (AUC = 0.82) and would have avoided 66.7% of repeat biopsies (75% sensitivity) compared with tPSA. At ≥ third repeat biopsy, again %fPSA demonstrated the highest accuracy (AUC = 0.70) and would have avoided 45.0% of repeat biopsies (75% sensitivity) compared with tPSA. The main limitation of our study resides in its small sample size. The findings of the present study promote the concept that the number of previous repeat biopsy sessions strongly influences the performance characteristics of biopsy risk factors. Total PSA was no significant risk factor in the entire analysis. By contrast, %fPSA performed best at second and ≥ third repeat biopsy. PSAV's diagnostic potential was reserved to patients at second and ≥ third repeat biopsy. Finally, PCA3 demonstrated the highest diagnostic accuracy and potential to reduce unnecessary biopsies at first repeat biopsy. However, this advantage dissipated at second and ≥ third repeat biopsy.

Pretreatment prostate‐specific antigen velocity is associated with development of distant metastases and prostate cancer mortality in men treated with radiotherapy and androgen‐deprivation therapy

In men with prostate cancer, pretreatment prostate-specific antigen (PSA) velocity (PSAV) has been demonstrated as a predictor of biochemical and survival outcomes in patients undergoing radical prostatectomy (RP). The utility of pretreatment PSAV in predicting outcomes after radiotherapy (RT), with or without androgen-deprivation therapy (ADT), is less certain. This study was undertaken to determine whether pretreatment PSAV is associated with biochemical disease-free survival, patterns of recurrence, and survival outcomes in men treated with radiation therapy and ADT. Two hundred seventy-seven patients with intermediate- and high-risk prostate cancer treated with RT and ADT formed the study cohort. Kaplan-Meier survival estimates and Cox regression analyses were used to evaluate whether PSAV was associated with disease outcomes. The median age of diagnosis was 70 years, and the median follow-up was 6.8 years. Men with a PSAV in the highest quartile tended to have higher risk disease at presentation (P = .028). After adjustment for known prognostic factors and duration of ADT, men who had a PSAV in the highest quartile had an increased risk of distant metastasis (hazard ratio [HR], 4.0; 95% confidence interval [95% CI], 1.61-9.9 [P = .003]) and prostate cancer-specific mortality (HR, 2.75; 95% CI, 1.27-5.95 [P = .01]) compared with men who had a lower PSAV, but had no increase in the risk of local recurrence (P = .76). A high pretreatment PSAV was associated with distant metastasis and prostate cancer-specific mortality but not with local recurrence. A high pretreatment PSAV may signify the presence of occult metastatic disease. Randomized trials are needed to determine whether more aggressive intervention is required in men who present with high pretreatment PSAV.

Prostate-Specific Antigen (PSA) and PSA Velocity: Competitors or Collaborators in the Prediction of Curable and Clinically Significant Prostate Cancer

Prostate-Specific Antigen (PSA) and PSA Velocity: Competitors or Collaborators in the Prediction of Curable and Clinically Significant Prostate Cancer

Prostate‐specific antigen velocity and prostate cancer gleason grade and stage

Increased preoperative prostate-specific antigen (PSA) velocity (PSAV) has been associated with increased prostate cancer mortality and higher Gleason scores. The authors evaluated the relation between PSAV, biopsy Gleason score, and pathologic stage in men who were enrolled in a prostate cancer screening trial. Data were analyzed from 1441 men who were enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who received > or =2 PSA screens and were diagnosed with prostate cancer within 1 year of the last screen. PSAV was estimated by using all screening PSA values within 6 years prediagnosis. Both PSA and PSAV were related to biopsy Gleason score. The multivariable odds ratios (OR), controlling for PSA and demographics, for having a Gleason score of 7 to 10 were 1.3 (95% confidence interval [95% CI], 0.9-1.9), 2.2 (95% CI, 1.5-3.3), and 2.3 (95% CI, 1.4-3.9) for men with PSAV values from 0.5 to 1 ng/mL per year, from 1 to 2 ng/mL per year, and >2 ng/mL per year, respectively, compared with men who had PSAV values <0.5 ng/mL per year. The median PSAV was 0.60 ng/mL per year for men with Gleason scores from 2 to 6 versus 0.84 ng/mL per year for men with Gleason scores from 7 to 10 (P < .0001). Among 658 men who underwent prostatectomy, both PSA and PSAV were associated with advanced pathologic stage in univariate analyses; however, when the analysis controlled for clinical stage and biopsy Gleason score, the associations of PSA and PSAV were no longer statistically significant. PSAV and PSA levels were associated independently with biopsy Gleason score. Among men who underwent prostatectomy, PSAV and PSA were not predictive of advanced pathologic stage when the analysis was controlled for biopsy Gleason score and clinical stage. It cannot be determined yet whether PSAV is predictive of long-term prostate cancer outcome in this cohort.

Prostate specific antigen doubling time (PSA-DT) and velocity (PSA-V) provide independent prognostic information in androgen independent prostate cancer (AIPC) patients receiving chemotherapy

4616 Background: PSA-DT and PSA-V at AIPC have each demonstrated prognostic significance in retrospective studies. No study has compared PSA-DT and PSA-V at AIPC to determine if they are independent prognostic factors. Methods: PSA-DT and PSA-V were calculated in 91 AIPC patients treated with taxane chemotherapy. PSA-DT was calculated as log 2 divided by the slope of the linear regression of log PSA versus time, from the first rise above the PSA nadir on androgen deprivation therapy (ADT) until the start of the next treatment. PSA-V was calculated from the slope of the linear regression of the raw PSA values over time. PSA-DT and PSA-V were split into tertiles for analysis. The primary endpoint was overall survival (OS) from the date of AIPC. OS was analyzed using Cox proportional hazards regression. Results: In univariate analysis, shorter PSA-DT and higher PSA-V were associated with decreased OS. Also associated with decreased OS were: higher M stage at dx; PSA nadir on ADT &gt;0.2; &lt;12 wks to failure of ADT; presence of mets, bony mets, low Hb, high AP, and low albumin at AIPC; and type of chemotherapy. In multivariate analysis, PSA-DT ≤12 weeks (HR=3.2), PSA-V &gt;10 ng/ml/yr (HR=2.8), PSA nadir &gt;0.2 on ADT, low Hb, and type of taxane chemotherapy persisted as significant predictors of decreased OS (each p &lt; 0.01). Rapid PSA-DT (≤12 wks) and high PSA-V (&gt;10 ng/ml/yr) predicted the worst prognosis (25 mos median OS, unadjusted); slow PSA-DT (&gt;12 wks) and low PSA-V (≤10 ng/ml/yr) the best prognosis (75 mos); and other combinations had intermediate prognoses (49 and 50 mos). Modifications of PSA-DT calculation such as nadir subtraction did not alter prognostic ability of either component. Conclusions: PSA-V at the start of AIPC contributes prognostic information independent of PSA-DT. Future studies should investigate the relative contribution of each of these factors in predicting survival. No significant financial relationships to disclose.

Preoperative Prostate Specific Antigen Doubling Time and Velocity Are Strong and Independent Predictors of Outcomes Following Radical Prostatectomy

Preoperative Prostate Specific Antigen Doubling Time and Velocity Are Strong and Independent Predictors of Outcomes Following Radical Prostatectomy

Prostate‐specific antigen velocity and survival for patients with hormone‐refractory metastatic prostate carcinoma

The authors investigated whether prostate-specific antigen (PSA) velocity was associated significantly with the time to death after randomization among patients with hormone-refractory metastatic prostate carcinoma (HRMPC) who were treated with cytotoxic, cytotatic, or combination therapy. The study cohort included 213 men with HRMPC who were treated on 3 prospective, randomized Phase II studies between February 1996 and October 2001. Cox regression analysis was used to evaluate whether there was a significant association between PSA velocity and the time to death after randomization, controlling for treatment and known prognostic factors. Increasing PSA velocity was associated significantly with shorter survival after randomization (P = 0.005) controlling for treatment and known prognostic factors. The adjusted hazard ratio for death was 1.8 (95% confidence interval [95% CI], 1.3-2.5; P = 0.0004) for men who had a PSA velocity > 0.0 ng/mL per month compared with men who had a PSA velocity < or = 0.0 ng/mL per month. Estimates of survival 2 years after randomization for these men were 16% (95% CI, 7-25%) and 44% (95% CI, 35-53%), respectively. PSA velocity was associated significantly with the length of survival among men with HRMPC who received cytotoxic, cytostatic, or combination therapy.