Predictive Value Of Prostate-specific Antigen Research Articles

The Predictive Value of Prostate-Specific Antigen Density: A Retrospective Analysis of Likert 3 Multiparametric MRI of the Prostate.

Background Many international studies have covered the predictors of prostate cancer, but there is limited information pertaining to Likert 3 MRI scores and the diagnosis of clinically significant prostate cancer (cs-PCa). Therefore, this study aimed to assess the detection rate of significant prostate cancer in men with a Likert 3 score multiparametric MRI (mp-MRI) and the predictive value of prostate-specific antigen (PSA) density in detecting significant prostate cancer. Methods This is a retrospective analysis of patients referred for suspected confined prostate cancer. Inclusion criteria were patients with prostate mp-MRIscore of Likert 3 and a prostate biopsy performed. Exclusion criteria included grossly abnormal feeling prostate, no biopsy performed, and an mp-MRI score (Prostate Imaging-Reporting and Data System/Likert) of 1, 2, 4, and 5. cs-PCawas defined as ≥ Gleason 3+4 prostate cancer. PSA density (PSAD) was calculated from MRI estimation of prostate volume. PSAD and histology results were subjected to receiver operating characteristic (ROC) curve analysis with the intention to assess the detection rate of significant prostate cancer in men with Likert 3 mp-MRI and the predictive value of PSAD in detecting significant prostate cancer. Results A total of 819 eligible men had a pre-biopsy mp-MRI scan taken between October 2019 and March 2022. A total of 177 men (21.6%, n = 819) were Likert 3 positive, and 31 did not proceed to take prostate biopsies. A total of 146 patients were included in the study. The median PSAD was 0.19 in men with cs-PCa. Prostate cancer was detected in 42 men (28.8% of the total included set), of which 27 (18.5%) had a Gleason 3+3 prostate cancer and 15 (10.3%) had Gleason ≥ 3+4 prostate cancer. Therefore, 35.7% (n = 42) of biopsy-positive men with Likert 3 mp-MRI had cs-PCa. The ROC curve analysis confirms that PSAD is a predictor of cs-PCa. The optimal PSAD threshold was 0.16 (95% CI: 0.14-0.19), which gives an accuracy of 0.7371, a sensitivity of 0.7333, and a specificity of 0.7375. Conclusion The specificity of PSAD is arguably insufficient for it to stand alone as a decision-making tool when counseling men with equivocal mp-MRI on whether or not to undergo prostate biopsy. A predictive model will need to incorporate other independent risk factors.These may include lesion size, multiplicity, location of lesion(s), and age.

Long-term survival after low-dose-rate brachytherapy for prostate cancer: the Royal Surrey experience.

To assess the long-term treatment efficacy of low-dose-rate (LDR) brachytherapy for the treatment of localized prostate cancer. Cause-of-death annotation in our prospective database was supplemented with death certificate information obtained via an internal audit of patients treated from 1999 to 2017 with LDR prostate brachytherapy as monotherapy or as combination with androgen deprivation therapy and/or external beam radiotherapy. Overall and disease-specific survival were the primary outcomes, estimated with Kaplan-Meier and competing risks multi-state models. Clinical variables influencing mortality were assessed with Cox proportional hazards regression in a sub-analysis of men to assess the predictive value of prostate-specific antigen (PSA) level at 48 months post implant. The audit process began in October 2017 and culminated in June 2020 with a curated series of 2936 patients. All-cause and prostate cancer-specific death prevalence were 11% and 2.9%, respectively. The median (range) follow-up time was 10 (3-21) years and the median (range) time to death from any cause was 9 (3-21) years. At 15 years post implant the overall and prostate cancer-specific survival probability were 81% and 95%, respectively. The 15-year cumulative incidence rates of death not due and due to prostate cancer were 14% and 5%, respectively. A greater risk of death due to prostate cancer was conferred by increasing age at therapy (hazard ratio [HR] 1.1, P < 0.001), advanced clinical stages relative to T1a-T2a (HR 1.9, P = 0.048 for T2b; HR 2.7, P = 0.023 for T2c-T3b) and a 48-month PSA level >1.0 ng/mL (HR 6.8, P < 0.001). This study constitutes the largest retrospective analyses of long-term mortality outcomes from prospectively collected prostate brachytherapy data and confirms the excellent treatment efficacy of LDR prostate brachytherapy for localized prostate cancer. T2 clinical stage subdivisions and 48-month PSA level >1.0 ng/mL appear to be strong indicators of prostate cancer-related survival.

Early Prostate-Specific Antigen (PSA) Change at Four Weeks of the First-Line Treatment Using Abiraterone and Enzalutamide Could Predict Early/Primary Resistance in Metastatic Castration-Resistant Prostate Cancer.

Simple SummarySerum prostate-specific antigen (PSA) level is the most valuable biomarker in prostate cancer. This study investigates the predictive value of achieving >30% PSA decline at four weeks of first-line androgen signaling inhibitors (ASIs) using a multi-institutional cohort dataset of 254 mCRPC patients. The achievement of >30% PSA decline at four weeks is an independent predictor for overall survival (OS). Interestingly, in patients who did not achieve >30% PSA decline at four weeks—an achievement of the >30% PSA decline at 12 weeks is eventually observed in 30.9% of those patients. To identify the variables that discriminate the patient survival in 97 patients without achieving >30% PSA decline at four weeks of the first-line treatment, a multivariate analysis is conducted. The duration of androgen deprivation therapy before CRPC < 12 months and Eastern Cooperative Oncology Group Performance Status ≥ 1 are identified as independent predictors for shorter OS for those patients.The identification of early or primary resistance to androgen signaling inhibitors (ASIs) is of great value for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This study evaluates the predictive value of prostate-specific antigen (PSA) response at dour weeks of first-line ASIs treatment for mCRPC patients. A total of 254 patients treated with ASIs (abiraterone acetate: AA and enzalutamide: Enz) at the first-line treatment are retrospectively analyzed. Patients are stratified according to the achievement of >30% PSA decline at 4 and 12 weeks from the treatment initiation. At four weeks of the treatment, 157 patients (61.8%) achieved >30% PSA decline from the baseline. Thereafter, 177 patients (69.7%) achieved >30% PSA decline at 12 weeks of the treatment. A multivariate analysis exhibits >30% PSA decline at four weeks as an independent predictor for overall survival (OS). We note that 30 of 97 (30.9%) patients who did not achieve >30% PSA decline at four weeks consequently achieved >30% PSA decline at 12 weeks, and had a comparable favorable three years OS rate as the 147 patients achieving >30% PSA decline at both 4 and 12 weeks. To identify the variables that discriminate the patient survival in 97 patients without achieving >30% PSA decline at four weeks, a multivariate analysis is performed. The duration of androgen deprivation therapy before CRPC ≤ 12 months and Eastern Cooperative Oncology Group Performance Status ≥ 1 are identified as independent predictors for shorter OS for those patients. These data offer a concept of early treatment switch after four weeks of first-line ASIs when not observing >30% PSA decline at four weeks—particularly in patients with a modest effect of ADT and poor performance status.

Prognostic role of early PSA drop in castration resistant prostate cancer patients treated with abiraterone acetate or enzalutamide.

Previous studies demonstrated a predictive value of prostate-specific antigen (PSA) kinetics for treatment outcome. Our retrospective study evaluates the prognostic role of early PSA drop in metastatic castration resistant prostate cancer (mCRPC) patients receiving abiraterone acetate (AA) or enzalutamide (E). All mCRPC patients treated with AA or E at the San Luigi Hospital in Orbassano between 2010 and 2018 and at the Ordine Mauriziano Hospital in Turin between 2014 and 2018 were included in this retrospective study. Only patients with an early PSA (measured 28-60 days after the beginning of the treatment) were included in the analysis. Patients were divided in early responders and non-early responders according to early PSA response (drop≥50% from baseline). Univariate and multivariate analyses for progression free survival (PFS) and overall survival (OS) were performed. Of 144 patients with early PSA value, 61 (42.4%) patients received E (docetaxel-naïve 42, post-docetaxel 19) and 83 (57.6%) received AA (docetaxel-naïve 44, post-docetaxel 39). Seventy-five (52.1%) patients achieved early PSA drop. In docetaxel-naïve setting (N.=86), median PFS was 14.9 (with early PSA drop) vs. 8.8 months (without early PSA drop, P=0.001). In post-docetaxel setting (N.=58) median PFS was 11.9 vs. 4.5 months (P<0.001). Globally, median PFS was 14.9 vs. 6.3 months in patients with and without early PSA drop, respectively (P<0.001). In docetaxel-naïve setting, patients with early PSA drop had a median OS of 39.5 vs. 18.8 months (P=0.12). In post-docetaxel setting median OS was 29.6 vs. 10.7 months (P=0.01). Comprehensively, median OS was 31.9 vs. 16.3 (P=0.002) in patients with and without early PSA drop, respectively. At multivariate analysis, early PSA drop confirmed an independent association with PFS (HR 0.21; 95% CI: 0.12-0.38, P<0.001) and OS (HR 0.25; 95% CI: 0.12-0.50, P<0.001). mCRPC patients treated with AA or E, in docetaxel-naïve or post-docetaxel setting, with early PSA drop had significantly better OS and PFS.

Patient management tactics with primary detected prostate-specific antigen increase

The main screening test for prostate cancer is the determination of prostate-specific antigen (PSA) in the blood. Increasing of the PSA level above 4 ng/ml is an indication for a detailed clinical examination of the patient. At the same time only in a quarter of cases with a PSA level of 4 to 10 ng/ml prostate cancer is diagnosed, and in 7080% of cases prostatic hyperplasia and prostatitis are diagnosed.&#x0D; Objective: to determine the need for anti-inflammatory treatment in the initial detection of elevated PSA blood levels within the gray area in men over 50 years of age to minimize the number of puncture biopsies of the prostate.&#x0D; Materials and methods. The study was divided into 2 parts. Part 1 a retrospective study, in which results of the histological examinations of the prostate gland of 297 men after a puncture biopsy about an increase in the PSA level of more than 4 ng/ml were analyzed. Part 2 a prospective study in which 118 men over 50 years of age with a primary increase in the PSA level from 4 to 9 ng/ml received anti-inflammatory treatment to monitor the dynamics of the PSA level.&#x0D; Results: the appointment of anti-inflammatory treatment allows in 69% cases to avoid puncture biopsy of the prostate, increase the predictive value of PSA, reduce the frequency of post-puncture complications of inflammatory genesis.&#x0D; Conclusion: the appointment of anti-inflammatory treatment is advisable when the primary increase in blood PSA levels to 9 ng/ml.

Does obesity modify prostate cancer detection in a European cohort?

IntroductionTo investigate prostate-specific antigen (PSA) accuracy and digital rectal examination (DRE) accuracy in detecting prostate cancer according to body mass index (BMI) in Spanish men with an indication of the first prostate biopsy.Material and methodsWe reviewed the clinical and histopathological data of 1,319 patients who underwent transrectal ultrasound-guided prostate needle biopsy. The patients were categorised according to the BMI as follows: <25 kg/m2 (normal weight); 25–29.9 kg/m2 (overweight); and ≥30 kg/m2 (obese). Receiver operator characteristic curves were used to assess PSA accuracy and DRE accuracy by calculating the area under the curve.ResultsThe obesity rate of the cohort was 14%. PSA accuracy for predicting prostate cancer in each BMI category was 0.52, 0.58 and 0.62, respectively (p = 0.01). After stratification by DRE findings, there was no difference in the performance accuracy of PSA in predicting the presence of cancer across BMI groups in abnormal DRE (p = 0.90). Serum PSA, DRE and BMI were strong predictors of prostate cancer diagnosis (odds ratio 1.07, 2.02 and 1.4, respectively; p <0.001). When the DRE was abnormal, a BMI ≥30 increased the risk of prostate cancer twice. With the addition of BMI to the model, the area under the curve of the combined PSA and DRE for diagnosing prostate cancer improved from 0.60 to 0.63.ConclusionsThe predictive value of PSA in predicting prostate cancer is not poorer in the obese population and the predictive value of an abnormal DRE in cancer detection is significantly modified by the patient’s BMI.

Predictive value of prostate-specific antigen for prostate cancer: a nested case-control study in EuroSIDA.

IntroductionAlthough prostate cancer (PCa) incidence is lower in HIV+ men than in HIV− men, the usefulness of prostate-specific antigen (PSA) screening in this population is not well defined and may have higher false negative rates than in HIV− men. We aimed to describe the kinetics and predictive value of PSA in HIV+ men.MethodsMen with PCa (n=21) and up to two matched controls (n=40) with prospectively stored plasma samples before PCa (or matched date in controls) were selected. Cases and controls were matched on date of first and last sample, age, region of residence and CD4 count at first sample date. Total PSA (tPSA), free PSA (fPSA), testosterone and sex hormone binding globulin (SHBG) were measured. Conditional logistic regression models investigated associations between markers and PCa. Sensitivity and specificity of using tPSA >4 µg/L to predict PCa was calculated. Mixed models were used to describe kinetics.ResultsSixty-one men were included with a median six (IQR 2–9) years follow-up. Time between last sample and PCa was seven (4–11) months. Cases and controls were well matched at first sample, with a median age of 51 (IQR 48–57) and CD4 of 437 (243–610) cells/mm3. Median tPSA [2.8 (IQR: 1.6–4.6) and 0.8 (0.5–1.2) µg/L] and fPSA [0.4 (0.2–0.8) and 0.3 (0.2–0.4) µg/L] levels were higher in cases than controls at first sample. Both tPSA and fPSA increased significantly over time in cases (Figure 1), to a median at last sample of 6.1 (4.7–9.5) and 0.9 (0.6–1.3) µg/L, respectively, but were stable in controls, with a median at last sample of 0.8 (0.5–1.4) and 0.2 (0.2–0.4) µg/L (Figure). Higher levels of tPSA and fPSA were associated with higher odds of PCa at first sample [OR for 2-fold higher 4.7 (CI: 1.7–12.9) and 5.4 (1.7–17.4)]. Elevated tPSA values in cases were detectable ≥5 years before PCa (p<0.01). Testosterone [overall median 19.4 (IQR 15.3–23.9) nmol/L at first sample) and SHBG [50.0 (34.0–66.0) nmol/L] levels were similar in cases and controls at first and last sample (all p>0.7). The most informative predictor of PCa was tPSA (AUC=0.9), followed by fPSA (0.8). Testosterone (AUC = 0.5) and SHBG (0.5) were poor predictors of PCa. Overall, tPSA level >4 µg/L had 99% specificity and 37% sensitivity. Performance was best in the year prior to PCa (specificity: 99%, sensitivity: 88%).ConclusionsPSA was highly predictive of PCa in HIV+ men. Our results indicate that PSA screening in HIV+ men may be useful, and further work is needed to identify potentially age-related cut-offs to maximize sensitivity and specificity to identify those for further evaluation at early stages of PCa.

Commentary on “Asymptomatic prostatic inflammation in men with clinical BPH and erectile dysfunction affects the positive predictive value of prostate-specific antigen.” Agnihotri S, Mittal RD, Kapoor R, Mandhani A, Department of Urology & Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.: Urol Oncol 2014; [Epub ahead of print]. doi: 10.1016/j.urolonc.2014.03.004.

ObjectiveTo test the hypothesis that sexual dysfunction in elderly men with benign prostatic hyperplasia leads to prostatic inflammation, diagnosed by prostatic fluid interleukin-8 (IL-8), which lowers the positive predictive value of prostate-specific antigen (PSA). MethodsOverall, 160 men with lower urinary tract symptoms between 50 and 75 years of age with an elevated PSA level of more than 4ng/ml with normal digital rectal examination and 50 age-matched controls with normal PSA level were prospectively evaluated for prostatic fluid IL-8 levels. Erectile dysfunction was measured by self-administered questionnaire of the Sexual Health Inventory for Men. Total and free serum PSA levels and IL-8 in prostatic fluid were measured 6 to 8 weeks after a course of 400mg of ofloxacin and 20mg of piroxicam given daily for 2 weeks. Transrectal ultrasonography-guided biopsy was done only when PSA level did not decrease less than 4ng/ml. ResultsMean ages of patients and controls were 63.18 (standard deviation [SD]±7.10) and 60.18 (SD+6.02) years, respectively. Mean concentration of IL-8 in prostatic fluid of the patients was significantly higher, i.e., 6,678pg/ml (SD±1,985.7) than in control, i.e., 1,543pg/ml (SD±375.7) (P<0.001). Following anti-inflammatory treatment, there was a significant decrease in the mean level of IL-8 from baseline to 5,622pg/ml (SD±1,870.66) (P<0.001). Corresponding to this, a significant decrease was noted in total PSA levels to less than 4ng/ml in 105 (65.62%) patients. Men with the highest levels of IL-8 had a greater degree of erectile dysfunction. ConclusionMen with symptomatic benign prostatic hyperplasia and erectile dysfunction had significant inflammation of the prostate to cause spurious rise in PSA level resulting in an unnecessary biopsy.

Asymptomatic prostatic inflammation in men with clinical BPH and erectile dysfunction affects the positive predictive value of prostate-specific antigen

ObjectiveTo test the hypothesis that sexual dysfunction in elderly men with benign prostatic hyperplasia leads to prostatic inflammation, diagnosed by prostatic fluid interleukin-8 (IL-8), which lowers the positive predictive value of prostate-specific antigen (PSA). MethodsOverall, 160 men with lower urinary tract symptoms between 50 and 75 years of age with an elevated PSA level of more than 4ng/ml with normal digital rectal examination and 50 age-matched controls with normal PSA level were prospectively evaluated for prostatic fluid IL-8 levels. Erectile dysfunction was measured by self-administered questionnaire of the Sexual Health Inventory for Men. Total and free serum PSA levels and IL-8 in prostatic fluid were measured 6 to 8 weeks after a course of 400mg of ofloxacin and 20mg of piroxicam given daily for 2 weeks. Transrectal ultrasonography–guided biopsy was done only when PSA level did not decrease less than 4ng/ml. ResultsMean ages of patients and controls were 63.18 (standard deviation [SD]±7.10) and 60.18 (SD+6.02) years, respectively. Mean concentration of IL-8 in prostatic fluid of the patients was significantly higher, i.e., 6678pg/ml (SD±1985.7) than in control, i.e., 1543pg/ml (SD±375.7) (P<0.001). Following anti-inflammatory treatment, there was a significant decrease in the mean level of IL-8 from baseline to 5622pg/ml (SD±1870.66) (P<0.001). Corresponding to this, a significant decrease was noted in total PSA levels to less than 4ng/ml in 105 (65.62%) patients. Men with the highest levels of IL-8 had a greater degree of erectile dysfunction. ConclusionMen with symptomatic benign prostatic hyperplasia and erectile dysfunction had significant inflammation of the prostate to cause spurious rise in PSA level resulting in an unnecessary biopsy.

Predictive value of PSA and PSA density in the diagnosis of prostate cancer in patients with acute urinary retention

Objective To analyze the clinicopathological characteristics of patients transurethrally cathetered due to acute urinary retention (AUR) and with high prostate specific antigen (PSA),and to evaluate the value of PSA and prostate specific antigen density (PSAD) in the diagnosis of prostate cancer (PCa) in these patients.Methods Data from 95 patients who had been transurethrally cathetered due to AUR and underwent transrectally ultrasound-guided prostate biopsy were retrospectively analyzed.The indications for biopsy in this study were abnormally elevated serum levels of PSA,positive transrectal prostate ultrasound and/or magnatic resonance imaging findings,and abnormal digital rectal examination.The incidence of PCa was recorded according to total PSA levels,while receiver operating characteristic curve (ROC curve) was plotted for appraisement on the predictive value of PSAD.Results The positive biopsy rate was 17.9％ (17/95).The positive rate was 0 (0/21),6.1％ (2/33),13.0％ (3/23) and 66.7％ (12/18) for patients with PSA 4.1-10.0,10.1-20.0,20.1-50.0 and ≥50.1 μg/L,respectively.In patients with PSA≥ 10.1 μg/L,the area under ROC curve of PSAD was 0.935,and the optimal cutoff was ＞ 0.54 mg/L2,while corresponding sensitivity,specificity,positive predictive value,negative predictive value was 94.1％,84.2％,61.5％ and 97.9％,respectively.Conclusions Prostate biopsy should not be performed on all AUR patients with transurethral catheters and elevated PSA levels.Patients with PSA ≥10.1 μg/L and PSAD ＞ 0.54 mg/L2 are at higher risk of PCa diagnosis. Key words: Prostatic neoplasms ; Urinary retention ; Biopsy ; Urinary catheterization ; Prostate-specific antigen

PROSTATE-SPECIFIC ANTIGEN (PSA), A BIOMARKER OF NEOPLASTIC PROSTATIC DISEASE

Prostate- specific antigen ( PSA) is a 33 KDa serine protease produced by both normal and neoplastic prostate epithelial cells. The use of PSA as serum biomarker greatly increased the chance to detect prostate cancer at an early and still curable stage . In our study, we want to show that there is a correlation between: patients’ age ( > 50 years old), PSA levels, and the increased incidence of prostate cancer . For our study, we enrolled 253 patients, age 50 to 80 years old, serum PSA levels > 4ng/ml, and no lower urinary tract symptoms. From the 253 patients, 168 patients were age 60 to 80 years old ( lot A) and 85 patients were age 50 to 60 years old ( lot B). From lot A 24 patients (14,28%) had serum PSA levels > 4ng/ml and 18 of them ( 10,71%) were diagnosed histologically with adenocarcinoma of the prostate . In lot B, 4 patients had serum PSA level> 4ng/ml and only one was diagnosed with adenocarcinoma of the prostate. The incidence of prostate cancer was higher in lot A (10,7%) in comparison with patients 50 to 60 years old ( 1,17%). The predictive value of PSA in the diagnosis of prostate cancer is 25 % for patients age 60 to 80 years old.

The impact of prostate‐specific antigen level at diagnosis on the relative survival of 28,531 men with localized carcinoma of the prostate

To evaluate the predictive value of prostate-specific antigen (PSA) in a population-based cohort, the authors analyzed relative survival in all men with localized prostate cancer who were registered in the Swedish National Prostate Cancer Register (NPCR) from 1996 to 2005. All men aged <75 years with localized tumors were identified in the NPCR. A Poisson regression analysis was performed using observed death as response and the expected death rate as offset. The expected and observed numbers of survivors were calculated with stratification for PSA level and 3 categories of tumor differentiation (Gleason score 2-6, 7, and 8-10). The regression model included PSA as linear splines with a breakpoint at a PSA level of 4 ng/mL and with tumor differentiation as a categoric variable. The Poisson regression analysis indicated a U-shaped curve for all 3 groups, with a negative correlation between PSA and relative survival in men with PSA levels <4 ng/mL and a positive correlation for men with PSA levels >4 ng/mL. The correlation was significant for all 3 groups, but the negative correlation between PSA and relative survival was significantly more pronounced in the group with Gleason scores from 8 to 10 than in the other 2 Gleason score groups. The demonstration of an inverse correlation between PSA level and relative survival in the group of men with PSA levels <4 ng/mL indicated the presence of a small but clinically important subgroup with undifferentiated tumors who have cells that have lost the ability to secrete PSA. This group should be taken into consideration when deciding on treatment and when choosing a cutoff level in PSA screening programs.

Negative influence of changing biopsy practice patterns on the predictive value of prostate-specific antigen for cancer detection on prostate biopsy

A correlation between prostate specific antigen (PSA) level and positive prostate biopsy rate was established in an era when biopsy practice patterns were different from what they are today. We evaluated if changes in biopsy practice patterns have affected the ability of PSA to predict cancer detection on prostate biopsy in the current era. Of 3634 prostate biopsies performed from 1993-2005, 1607 met criteria for analysis. Biopsy data were divided into 3 time-cohorts (1993-1997, 1998-2001, and 2002-2005) to assess for practice patterns shifts and correlation between PSA and biopsy results. Significant changes in biopsy practice patterns included an increase in biopsy cores and more frequent use of PSA 2.5-3.99 ng/mL as a biopsy indication. In men with normal DRE, a moderate correlation between PSA and positive biopsy rate did exist from 1993-1997, but was subsequently lost. On multivariate analysis, PSA was not a significant predictor of biopsy result in men with normal DRE. Early in the PSA era, the predictive power of PSA depended on multiple factors: high prevalence of disease, higher prevalence of high-grade disease, and low likelihood of prostate cancer diagnosis in men with low PSA. Now, beyond the culling effect of increased biopsy incidence and with shifted biopsy practice patterns, the correlation between PSA and biopsy result is lost in men with normal DRE. Diagnosing a higher proportion of tumors in men with a PSA between 2.0-4.0 ng/mL has negatively influenced the predictive value of PSA for cancer detection.

Presalvage prostate-specific antigen (PSA) and PSA doubling time as predictors of biochemical failure of salvage cryotherapy in patients with locally recurrent prostate cancer after radiotherapy.

The value of presalvage cryotherapy serum PSA level in predicting biochemical failure in patients with local recurrence of prostate cancer (PCa) after radiotherapy was documented; however, little is known about the predictive value of prostate-specific antigen (PSA) doubling time (DT) in this patient group. The purpose of the current study was to evaluate serum PSA level and PSA DT as predictors of salvage cryotherapy outcomes in patients being treated for postradiotherapy locally recurrent PCa. The charts of patients treated with salvage cryotherapy were retrospectively reviewed for locally recurrent PCa at the M. D. Anderson Cancer Center from January 1980 to July 2004. Patients who received neoadjuvant or adjuvant hormone therapy were excluded. We assessed pre- and postradiotherapy clinical data, pre- and postsalvage cryotherapy clinical data, and other variables. Kaplan-Meier and log rank tests were performed to assess unadjusted survival probabilities and 2-group survival comparisons, respectively. Cox proportional hazards regression models were used to assess the effect of patient characteristics in predicting overall, disease-specific, and biochemical failure-free survival. Forty-nine patients met the eligibility criteria. The median age of patients at diagnosis was 66 years (58-81 years) with the initial clinical stage before radiotherapy most commonly T2 (n = 25) or T3 (n = 21). The median presalvage cryotherapy serum PSA level was 5.9 ng/mL (0.4-23.1 ng/mL) and the presalvage prostatic biopsies were frequently high grade (Gleason grade > or =8 in 51% of patients). The median postsalvage cryotherapy serum PSA level was 0.1 ng/mL (0.1-9.5 ng/mL), and biochemical failure (defined as a serum PSA level > or =2 ng/mL above the postsalvage cryotherapy PSA nadir) occurred in 26 patients. In these 26 patients, there was a statistically significant difference between pre- and postsalvage cryotherapy PSA DTs (12.3 months to 5.6 months, respectively; P = .02). A presalvage cryotherapy serum PSA level >10 ng/mL (P = .002) and PSA DT < or =16 months (P = .06) were found to predict the subsequent risk of biochemical failure. Presalvage PSA and PSA DT can predict biochemical failure of salvage cryotherapy, although the predictive value of PSA DT only trended toward significance. The statistically significant difference in pre- and postsalvage cryotherapy PSA DTs was reflective of aggressive tumor biology.

Spotlight

Steuber et al., pp. 1234–1240 Radical prostatectomy is a very effective treatment for localized prostate cancer. Biochemical recurrence (BCR) of prostate cancer—as indicated by serum prostate-specific antigen (PSA)—is the most likely sign of cancer recurrence after surgical treatment. In about 30% of patients with BCR, the cancer will recur within 10 years of surgery and thus the need to identify this subgroup of patients is crucial. Clinical stage, prostate biopsy histology (the so-called Gleason grade) and pretreatment total serum PSA levels can be used in a model to predict BCR after radical prostatectomy. However, when pretreatment PSA levels are <10 ng/ml, the predictive value of PSA is questionable. This caveat is not trivial as a high proportion of patients present with PSA levels in this range at diagnosis. In an effort to overcome this limitation, the authors investigated whether preoperative levels of human glandular kallikrein (hK2)—a serine protease expressed predominantly in the prostate epithelium—and of free PSA could enhance the prediction model. Increased levels of both proteins have been associated with advanced prostate pathology. By testing serum samples in 461 patients, the authors established a “base” predictive model using the standard factors of total serum PSA, clinical stage and Gleason grade and compared this with a model with hK2 and fPSA as additional predictors. The predictive accuracy of the new model was, in general, not superior. However, it was enhanced significantly (p=0.005) in patients with PSA pretreatment levels <10 ng/ml. Clinically these finding are very relevant as a high proportion of men present with serum PSA <10 ng/ml. Thus, testing hK2 and fPSA levels in preoperative patients to enhance the accuracy of the base predictive model shows promise for this cohort of patients. Porter et al., pp. 1241–1247 ADAMTS is a family of 19 metallopeptidases in which all members are predicted to be catalytically active. Previously, the authors examined ADAMTS gene expression in malignant and normal breast tissue and showed that 11 ADAMTS genes are abnormally expressed. They also demonstrated that one family member—ADAMTS15—is an independent predictor of relapse-free survival in breast cancer patients. In this study, the authors broadened their investigation by determining ADAMTS8 expression, in addition to ADAMTS15, in tumor tissue from 229 breast cancer patients. The median follow-up period for the cohort was 7 years. Using real-time PCR, 23.6% of patients were defined as having high levels of ADAMTS8. This ADAMTS8 high expressing group had a shorter overall survival (OS) time: a 2-fold higher chance of death (hazard ratio (HR) = 2.2, p = 0.004) when compared to the ADAMTS8 low expressing group. On the other hand, ADAMTS15 expression in tumor tissue did not impact OS in patients but, as previously demonstrated, high levels were significantly associated with a prolonged relapse-free survival. Using multivariate Cox analysis regression to estimate the prognostic value of ADAMTS8 and ADAMTS15 expression, the authors demonstrated that the patient subgroup with high ADAMTS8 and low ADAMTS15 had the worst prognosis. This group had a 5-fold higher risk of death (HR=5.4, p < 0.001) when compared to the most favorable group with low ADAMTS8 and high ADAMTS15 levels. These findings strongly suggest that expression levels of ADAMTS8 and ADAMTS15 in breast cancer tissue could be an important prognostic tool. Lee et al., pp. 1285–1291 Previous studies have shown a link between the use of menopausal hormone therapy (HT) and breast cancer risk. This risk is most pronounced with the use of combined estrogen-progestin therapy (EPT) although estrogen therapy (ET) also carries a risk. To date, most data on HT and breast cancer risk have been generated by examining white populations. Using data from an ongoing multi-ethnic cohort -- where the population was enrolled in the USA in California and Hawaii—the authors could address the question of whether breast cancer risk is present in the following ethnic groups: African-American, Native Hawaiian, Japanese-American, Latina, in addition to a White population. Analysis of over 55,000 postmenopausal women showed that current EPT use was associated with an increased risk of breast cancer in all ethnic groups and even for durations of use as short as 0-5 years. The breast cancer risk associated with using EPT was estimated as 29% per 5 years of use (RR5) (RR5=1.29, 95% CI =1.23-1.35). Current ET therapy was associated with a 10% increased risk; past EPT was also associated with an increased risk but this was not statistically significant. Although current use of EPT per 5 years showed an increased risk in all ethnic groups examined, it was most pronounced in Japanese-American (33%) Latina (36%), and White (26%). Current ET use was associated with a risk in all ethnic groups except African-American. This study reaffirms the breast cancer risk associated with HT, in particular with current EPT use, and importantly highlights that this phenomenon occurs across various ethnic groups.

Predictive value of prostate-specific antigen, tumour stage and tumour grade for the outcome of bone scintigraphy in patients with newly diagnosed prostate cancer.

In order to evaluate the negative predictive value of a low prostate-specific antigen (PSA) for a positive bone scan, we performed a retrospective study in a patient material from the Umea region in Northern Sweden. We also evaluated whether different tumour grades could influence this predictive value. Four-hundred-and-forty-six patients of newly diagnosed prostate cancer were reviewed. We analysed different levels of PSA, tumour grade, tumour stage and combinations of these parameters for their use in making a positive bone scintigraphy (BS) prediction. Among 214 patients with PSA <20 ng/ml, 9 showed a positive BS. When tumours of grades 2 and 3 were excluded, the number of positive BS predictions decreased to 6. For 350 of these 446 patients, a classification according to TNM was available; 162 of these 350 had a PSA value <20 ng/ml, and when this group comprised only small and well-differentiated tumours (T1-2, G1), only one of the remaining 81 patients had a positive BS result. We conclude that in most patients with small and well-differentiated tumours (T1-2, G1) and PSA <20, BS staging need not be carried out.