Predictors Of Prostate-specific Antigen Research Articles

Pretherapeutic PSMA PET-Derived Semiquantitative Parameters as Predictors of PSA Response in Patients with mCRPC Receiving [ 177 Lu]Lu-PSMA-617 Radioligand Therapy.

Objective [ 177 Lu]Lu-prostate-specific membrane antigen (PSMA)-617 radioligand therapy (RLT) shows promise for metastatic castration-resistant prostate cancer (mCRPC) patients with positive PSMA positron emission tomography (PET) imaging. Identifying high-risk patients is crucial. We evaluated pretherapeutic PSMA PET-derived parameters to predict prostate-specific antigen (PSA) response in patients undergoing [ 177 Lu]Lu-PSMA-617 RLT. Materials and Methods We conducted a retrospective analysis among 27 patients (mean age: 71.0 ± 9.5 years; range: 52-85 years) who underwent PSMA PET/computed tomography (CT) and subsequent [ 177 Lu]Lu-PSMA-617 RLT between March 2019 and January 2023. After excluding patients with liver metastases, the number of patients left for analysis was 21 (14 responders and 7 nonresponders). Tumors were semiautomatically delineated with calculation of total tumor volume (PSMA-TV), lesion uptake (PSMA-TLU = PSMA-TV * standardized uptake value [SUV]mean), and lesion quotient (PSMA-TLQ = PSMA-TV/SUVmean) for each patient. Semiquantitative parameters were analyzed only in patients with mCRPC and no liver metastasis. Results In total, 17/27 patients (62.96%) had a decline in PSA levels; 15/27 patients (55.56%) experienced a decline of > 50%. Pretherapeutic PSMA PET/CT results revealed significant differences in PSMA-TV ( p = 0.003), PSMA-TLU ( p = 0.013), and PSMA-TLQ ( p = 0.011) between responders and nonresponders. SUVmax was significantly correlated to the best percentage change in PSA response after 177 Lu-PSMA-617 treatment ( r = -0.79, p = 0.006). No association was observed between PSMA-TV ( p = 0.367), PSMA-TLU ( p = 0.128), and PSMA-TLQ ( p = 0.556), with the best percentage change in PSA response after 177 Lu-PSMA-617 therapy. Conclusion Pretherapeutic PSMA PET-derived PSMA-TV, PSMA-TLU, and PSMA-TLQ were significant negative predictors of PSA response in patients with mCRPC and no liver metastasis receiving [ 177 Lu]Lu-PSMA-617 RLT.

Factors Predicting Prostate Specific Antigen Failure Following Radical Prostatectomy: Experience with 961 Patients.

To determine disease-related predictors for the occurrence of prostate specific antigen (PSA) failure in Iranian prostate cancer patients who underwent radical prostatectomy. In this cohort study, we enrolled eligible patients with prostate cancer who underwent radical prostatectomy at our center between 2001 and 2018. The primary endpoint was the incidence of postoperative biochemical failure, defined as two consecutive PSA levels >= 0.2 ng/dl. Patients with TNM stage >= III, Gleason score >=8, or baseline PSA above our calculated cut-off level were considered as high risk. Kaplan-Meier survival method and Cox proportional hazards regression analysis were used for determining the biochemical relapse-free survival and its predictors. Data of 959 patients (age=61.2 ± 6.4 years) were analyzed with a median follow up of 36 months (range 6 months to 18 years). A total of 97 patients (10.1%) developed biochemical failure at the time of analysis who had a significantly older age and longer follow-up duration (P=0.024 and P<0.001, respectively). Preoperative PSA level of 8.85 mg/dl could predict the occurrence biochemical failure with a sensitivity of 83.2% and specificity of 39.2% (Area under the curve=0.601, 95% CI: 0.541-0.662; P=0.001). In the multivariate analysis, higher preoperative PSA, Gleason score?8, and high-risk TNM stage were independent predictors for biochemical relapse (P=0.029, P=0.001, and P=0.008, respectively). Preoperative PSA, Gleason score, and TNM stage were independent predictors for biochemical failure following radical prostatectomy in prostate cancer patients. We also determined a lower cut-point for PSA that could predict biochemical failure.

Prevalence and Predictors of Routine Prostate-specific Antigen Screening in Medicare Beneficiaries in the USA: Retrospective Cohort Analysis Using Machine Learning

Objective: To estimate the prevalence and predictors of Prostate-Specific Antigen (PSA) screening among Medicare beneficiary men using machine learning algorithms. Methods: A retrospective cohort analysis used the Medicare Current Beneficiary Survey Public Use File (MCBS PUF) data from 2015 and 2016. Predictors of PSA screening were examined through multivariable logistic regression and machine learning techniques. Results: Over half (56%) of Medicare beneficiary men had PSA screening during 2015-2016. Ages between 65 and 75 years, education above high school, being married, higher annual income (&gt;$25,000), being overweight or obese, and more than 20 outpatient office visits were significant predictors. Conclusion: PSA screening uptake was 56 percent among Medicare beneficiaries and it was driven by beneficiaries’ age, education, marital status, income, body mass index, and number of outpatient visits. Although Medicare provides free annual PSA screening, uptake was higher among high-income beneficiaries. Awareness strategies would help inform privileges for PSA screening under Medicare and the advantages of routine screening for mitigating the health risks.

Factors predicting efficacy and adverse effects of enzalutamide in Japanese patients with castration-resistant prostate cancer: results of retrospective multi-institutional study.

We aimed to evaluate the factors predicting efficacy and adverse effects of enzalutamide in patients with castration-resistant prostate cancer. We retrospectively evaluated data on 345 patients who had received enzalutamide for castration-resistant prostate cancer in 20 hospitals (Kyoto University Hospital and other satellite hospitals). Cox proportional hazards regression analysis was performed to identify factors predicting prostate-specific antigen (PSA) progression after enzalutamide treatment and logistic regression analysis for those associated with development of adverse effects. PSA titers decreased by >50% in 197 patients (57%). The median PSA progression free survival was 163days. Gleason score >8 (HR 2.078, 95% CI 1.37-3.153, P=0.00058), performance status ≥1 (HR 2.292, 95% CI 1.463-3.592, P=0.000296), presence of bone metastasis (HR 1.774, 95% CI 1.019-3.090, P=0.0429), visceral metastasis (HR 2.127, 95% CI 1.215-3.722, P=0.00823), previous steroid treatment (HR 1.780, 95% CI 1.207-2.626, P=0.00361) and docetaxel treatment (HR 1.602, 95% CI 1.051-2.442, P=0.0284) significantly predicted the efficacy of enzalutamide. Adverse effects, including fatigue or appetite loss, occurred in 169 patients (49%), 48 (18%) of whom stopped enzalutamide. Age >75years (HR 1.980, 95% CI 1.270-3.09, P=0.00246) and lower enzalutamide dose (HR 0.437, 95% CI 0.255-1.270, P=0.00249) were significantly associated with development of adverse effects. Enzalutamide treatment is effective in patients with castration-resistant prostate cancer with low Gleason scores, good performance status, without bone or visceral metastasis and no prior steroid or docetaxel treatment. Lower doses of enzalutamide decrease the incidence of adverse effects, especially in older patients.

Circulating Tumor Cells in Biochemical Recurrence of Prostate Cancer

ObjectiveCirculating tumor cells (CTCs) have known prognostic implications in metastatic castration–resistant prostate cancer, but little is known regarding its utility in biochemical recurrence (BR) of prostate cancer. The primary objectives were to determine whether CTCs are measurable in patients with BR and whether it can reliably predict prostate-specific antigen (PSA) increase and PSA doubling times (PSADTs). MethodsBR was identified in patients after prostatectomy or radiation or both, with a PSA increase of ≥ 0.2 for prior prostatectomy or > 2 mg/dL increase for post-nadir in prior radiotherapy. CTCs were enumerated at baseline at the time of study entry using the CellSearch (Janssen Diagnostics, Raritan, NJ) test. ResultsThe median age for all 36 patients accrued was 69.5 years (range, 51-91) with a median PSA of 1.65 ng/mL (range, 0.2-65.8). Gleason scores ranged from 5 to 9 (median, 7). The majority had prostatectomy (n = 25), external beam radiotherapy (n = 9), CyberKnife (Accuray, Sunnyvale, CA) (n = 1), and combined radiohormonal therapy (n = 1). PSADT ranged from 0.35 to 55 months, with a median of 7.43 months. The incidence of positive CTCs was 8.3% (3 patients), of whom 2 had biopsy-proven bony lesions on presenting with equivocal scans and PSADTs of 2.27 and 3.08 months, respectively. The third CTC-positive patient had a PSADT of 4.99 months. ConclusionsObtaining CTCs in unselected patients presenting with BR has a relatively low yield. However, obtaining a positive CTC raises the suspicion of the presence of metastatic disease and may have utility for longitudinal follow-ups of patients with BR.

A retrospective analysis of clinical factors influencing response to treatment with cabazitaxel in patients with metastatic castration resistant prostate cancer.

281 Background: The TROPIC trial demonstrated that cabazitaxel improves overall survival (OS) in mCRPC patients progressing on or after docetaxel; a setting where both abiraterone and enzalutamide are also approved. We evaluated baseline factors that may help predict prostate specific antigen (PSA) response or PSA progression defined as per the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria and OS in mCRPC patients treated with cabazitaxel. Methods: Forty patients from five centres participated in an early access program and were retrospectively reviewed to capture baseline characteristics, disease history, prior and subsequent treatments, PSA response, and OS. The influence of selected variables on PSA response and OS were evaluated by univariate and multivariate stepwise regression analysis. Results: At cabazitaxel initiation, median age was 65, ECOG 0-1 (90%), median PSA was 216 ng/mL, 25% had visceral disease and 70% had pain. Median number of prior docetaxel cycles was 9 and median time from treatment was 9.6 months (5-14.2). Median number of cabazitaxel cycles was 7 (1-27). Fourteen patients received abiraterone before cabazitaxel. In patients with prior abiraterone treatment there was no impact on PSA response compared to patients with no prior abiraterone. In the multivariate regression analysis, presence of visceral disease, low albumin (≤40g/L), low hemoglobin (&lt;100 g/L) and longer time between last docetaxel dose and start of cabazitaxel were correlated with PSA response to cabazitaxel (p&lt;0.10). Age &lt; 65, BMI ≥ 30kg/m2 and presence of pain were linked to an increased likelihood of PSA progression. None of the factors selected were significantly associated with OS. Conclusions: In routine clinical practice, this study suggests that mCRPC patients with visceral disease and a longer time elapsed between last docetaxel dose and start of cabazitaxel may experience a greater PSA response with cabazitaxel.

Expression of androgen and estrogen signaling components and stem cell markers to predict cancer progression and cancer-specific survival in patients with metastatic prostate cancer.

Genes of androgen and estrogen signaling cells and stem cell-like cells play crucial roles in prostate cancer. This study aimed to predict clinical failure by identifying these prostate cancer-related genes. We developed models to predict clinical failure using biopsy samples from a training set of 46 and an independent validation set of 30 patients with treatment-naïve prostate cancer with bone metastasis. Cancerous and stromal tissues were separately collected by laser-captured microdissection. We analyzed the association between clinical failure and mRNA expression of the following genes androgen receptor (AR) and its related genes (APP, FOX family, TRIM 36, Oct1, and ACSL 3), stem cell-like molecules (Klf4, c-Myc, Oct 3/4, and Sox2), estrogen receptor (ER), Her2, PSA, and CRP. Logistic analyses to predict prostate-specific antigen (PSA) recurrence showed an area under the curve (AUC) of 1.0 in both sets for Sox2, Her2, and CRP expression in cancer cells, AR and ERα expression in stromal cells, and clinical parameters. We identified 10 prognostic factors for cancer-specific survival (CSS): Oct1, TRIM36, Sox2, and c-Myc expression in cancer cells; AR, Klf4, and ERα expression in stromal cells; and PSA, Gleason score, and extent of disease. On the basis of these factors, patients were divided into favorable-, intermediate-, and poor-risk groups according to the number of factors present. Five-year CSS rates for the 3 groups were 90%, 32%, and 12% in the training set and 75%, 48%, and 0% in the validation set, respectively. Expression levels of androgen- and estrogen signaling components and stem cell markers are powerful prognostic tools.

Long-term impact of positive surgical margins on biochemical recurrence after radical prostatectomy: Ten years of follow-up

Objective. Positive surgical margins (PSMs) in men undergoing radical prostatectomy (RP) for prostate cancer are associated with an increased risk of biochemical recurrence. This study evaluated the long-term (>10 year) impact of PSMs on biochemical recurrence after RP in adjuvant treatment-naïve pT2–pT4 N0 men and determined predictors of prostate-specific antigen (PSA) failure. Material and methods. The institutional registry of 1276 patients who underwent RP at Henri Mondor Hospital from 1988 to 2001 was reviewed, identifying 403 patients with regular follow-up at the time of analysis. The study included 108 patients with PSMs who did not receive neoadjuvant or adjuvant therapy before PSA relapse. Median follow-up was 12.2 years. PSA failure was defined by a PSA rising by more than 0.2 ng/ml and biochemical recurrence-free survival (RFS) was estimated using the Kaplan–Meier method. Cox proportional hazard regression models were used to analyse clinicopathological variables associated with biochemical recurrence. Results. Biochemical recurrence 10 years after RP was 33.5% for patients regardless of the margin status. The 10-year biochemical RFS was 73% in men with negative margins compared to 49% in the case of PSM (p < 0.001). In multivariate analysis, margin status was a significantly predictive for PSA failure (hazard ratio 1.46, p = 0.04). After stratification by pathological stage, margin status was significantly predictive for biochemical RFS in pT2 (p < 0.001) and pT3a (p < 0.001), whereas the impact of PSM did not reach significance in pT3b (p = 0.16). Conclusions. After 10-year follow-up, PSMs remain an independent risk factor of biochemical RFS after RP with less relevant impact in pT3b disease. Randomized prospective trials are needed to determine the place of adjuvant versus delayed radiotherapy.

Expression of Neutral Endopeptidase, Endothelin-1, and Nuclear Factor Kappa B in Prostate Cancer: Interrelations and Associations with Prostate-Specific Antigen Recurrence after Radical Prostatectomy

Objective. To study the impact of the neutral endopeptidase (NEP)/neuropeptides (NPs) axis and nuclear factor kappa B (NFκB) as predictors of prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP). Patients and Methods. 70 patients with early-stage PC were treated with RP and their tumor samples were evaluated for expression of NEP, endothelin-1 (ET-1) and NFκB (p65). Time to PSA recurrence was correlated with the examined parameters and combined with preoperative PSA level, Gleason score, pathological TNM (pT) stage, and surgical margin (SM) assessment. Results and Limitations. Membranous expression of NEP (P < 0.001), cytoplasmic ET-1 (P = 0.002), and cytoplasmic NFκB (P < 0.001) were correlated with time to PSA relapse. NEP was associated with ET-1 (P < 0.001) and NFκB (P < 0.001). ET-1 was also correlated with NFκB (P < 0.001). NEP expression (P = 0.017), pT stage (P = 0.013), and SMs (P = 0.036) were independent predictors of time to PSA recurrence. Conclusions. There seems to be a clinical model of NEP/NPs and NFκB pathways interconnection, with their constituents following inverse patterns of expression in accordance with their biological roles and molecular interrelations.

Clinical efficacy of primary combined androgen blockade for Japanese men with clinically localized prostate cancer unsuitable for local definitive treatment: a single institution experience

Primary hormonal therapy has been mostly used for patients with advanced prostate cancer, as international guidelines do not recommend its use for patients at earlier disease stages. However, there seems to be a discrepancy between the guideline recommendations and clinical practice on the use of primary androgen deprivation therapy for localized prostate cancer in Japan. Therefore, we retrospectively analyzed a single-institution experience in primary combined androgen blockade (CAB) for localized prostate cancer. The study included 187 patients with T1c-T3a prostate cancer unsuitable for local definitive treatment and treated with primary CAB. Clinical outcomes, predictive factors of PSA relapse and adverse events were investigated. The progression-free, disease-specific, and overall survival rates of all patients at 5 years were 63.0, 99.4 and 95.9%, respectively. Of the several parameters isolated as predictors of prostate-specific antigen (PSA) progression, nadir PSA level and the percentage of positive biopsy cores (%PBC) remained as independent prognostic factors on multivariate analysis. Toxicities were mild to moderate and well tolerated. Primary CAB treatment brought initial disease control without relapse in the majority of our selected cases. The %PBC may help predict time to relapse in the pretreatment setting. The results implicate that CAB can be an option as a primary treatment for clinically localized prostate cancer unsuitable for local definitive treatment. To confirm the exact efficacy of primary CAB, these findings should be reviewed in a large cohort of patients with long-term follow-up from various viewpoints, including disease control, toxicities, quality-of-life and medical cost.

Racial/Ethnic Differences in Predictors of PSA Screening in a Tri-Ethnic Population

This study was carried out to identify racial/ethnic differences in predictors of prostate-specific antigen (PSA) screening in a group of prostate cancer patients. In this cross-sectional study, a total of 935 prostate cancer patients were recruited from the Texas Medical Center, Houston, between 1996 and 2004. It included 372 Caucasians, 346 African Americans and 217 Hispanics. A structured questionnaire was used to collect data on socio-demographic and life-style related variables, and self-reported PSA screening history through personal interview. African American (54.4%) and Hispanic patients (42.3%) were significantly less likely (p = 0.004 and p < 0.001, respectively) to report having had PSA screening than Caucasian patients (63.2%). Only annual check-up was found to be a significant predictor of PSA screening in Hispanics. Among Caucasians, education and annual check-up were significant predictors of PSA screening; whereas in African Americans, education, annual check-up, marital status and BMI were significant predictors of PSA screening. The rates of PSAscreening and its predictors varied by race/ethnicity in this tri-ethnic population. Health-education programs and culturally appropriate educational outreach efforts, especially targeted for high-risk groups, are needed to reduce these disparities.

Disproportionate Presentation of High Risk Prostate Cancer in a Safety Net Health System

Most prostate cancer research is based on relatively homogenous cohorts of men, often with comparatively high socioeconomic status. We describe prostate cancer characteristics in men treated in a public health system and hypothesize a disproportionate burden of high risk disease in this population. We created a clinical registry from a review of the medical records of 377 men diagnosed with prostate cancer in the San Francisco General Hospital system, which provides care to underserved, uninsured populations. We compared sociodemographic data and cancer characteristics with those in 2 large prostate cancer databases from a community (CaPSURE™) and an academic (University of California-San Francisco tumor registry) setting to assess differences in risk distribution using the D'Amico and Cancer of the Prostate Risk Assessment scoring systems. Compared to men in CaPSURE or the University of California-San Francisco tumor registry those in the San Francisco General Hospital cohort were nonwhite (76%), insured under Medicaid (31%) or uninsured (8%) and had adverse clinical characteristics, including median prostate specific antigen greater than 10 ng/ml at diagnosis and higher Gleason grade. In addition, the majority of patients (67%) had intermediate or high risk disease based on the D'Amico classification and a higher mean Cancer of the Prostate Risk Assessment score. Using ANOVA for continuous variables and the chi-square test for categorical variables, all comparisons were statistically significant (p <0.001). Men in the San Francisco General Hospital public health system bear a substantially higher burden of high risk disease that those in an academic or a community setting. Populations such as this would benefit most from targeted efforts for early detection and treatment to decrease prostate cancer morbidity and mortality.

Predicting Post–External Beam Radiation Therapy PSA Relapse of Prostate Cancer Using Pretreatment MRI

To investigate whether pretreatment endorectal magnetic resonance imaging (MRI) findings can predict biochemical relapse in patients with clinically localized prostate cancer treated with external beam radiation therapy (EBRT). Between January 2000 and January 2002, 224 patients (median age, 69 years; age range, 45-82 years) with biopsy-proven prostate cancer underwent endorectal MRI before high-dose (≥81Gy) EBRT. The value of multiple clinical and MRI variables in predicting prostate-specific antigen (PSA) relapse at 5 years was determined by use of univariate and multivariate stepwise Cox regression. Clinical variables included pretreatment PSA, clinical T stage, Gleason score, use of neoadjuvant hormonal therapy, and radiation dose. Magnetic resonance imaging variables, derived from retrospective consensus readings by two radiologists, were used to measure intraprostatic and extraprostatic tumor burden. After a median follow-up of 67 months, PSA relapse developed in 37 patients (16.5%). The significant predictors of PSA relapse on univariate analysis were pretreatment PSA, clinical T stage, and multiple MRI variables, including MRI TN stage score; extracapsular extension (ECE) status; number of sextants involved by ECE, all lesions, or index (dominant) lesion; apical involvement; and diameter and volume of index lesion. Pretreatment PSA and ECE status were the only significant independent predictors on multivariate analysis (p < 0.05 for both). Extracapsular extension status was associated with the highest hazard ratio, 3.04; 5-year PSA relapse rates were 7% for no ECE, 20% for unilateral ECE, and 48% for bilateral ECE. Magnetic resonance imaging findings can be used to predict post-EBRT PSA relapse, with ECE status on MRI and pretreatment PSA being significant independent predictors of this endpoint.

Tumour length of the largest focus predicts prostate‐specific antigen‐based recurrence after radical prostatectomy in clinically localized prostate cancer

To investigate the possible significance of tumour dimensional variables, including maximum tumour diameter (MTD), maximum tumour area (MTA) and total tumour volume (TTV), with standard prognostic factors for predicting prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP). Serial whole sections of the prostate from 164 patients who had RP for localized prostate cancer were investigated. Cox proportional hazards regression models were used for univariate and multivariate analyses to test the relationships between biochemical failure and clinicopathological factors, including tumour dimensional variables. The results were analysed retrospectively to develop a prognostic factor-based model for risk stratification. In the univariate Cox proportional hazard model, pathological T stage, Gleason score, perineural invasion, microvascular invasion, positive surgical margins, MTD, MTA and TTV were significantly associated with biochemical failure. In the multivariate Cox proportional hazard model using a stepwise inclusion of these factors, Gleason score, positive surgical margins and MTD were independent indices in association with biochemical failure. Using the three statistically significant variables, the relative risk of biochemical failure could be calculated. These results imply that MTD is possibly one of the most important prognostic factors for predicting biochemical recurrence after RP. As calculating the MTD on the section a rapid, simple and objective method, it can be used instead of the TTV calculation. The prognostic factor- based risk stratification might help clinicians to predict biochemical failure after RP.

Predicting the long-term risk of prostate cancer-specific mortality after radical prostatectomy

5007 Background: Nomograms that predict prostate-specific antigen (PSA) defined biochemical recurrence (BCR) of prostate cancer after radical prostatectomy are the most widely used prediction tools in oncology for treatment decision making and counseling. While BCR universally antedates prostate cancer-specific mortality (PCSM), it is a limited surrogate endpoint due to its variable natural history. Nomograms that accurately predict the risk of PCSM are needed. Methods: Using Fine and Gray competing risk regression analysis, the clinical data and follow-up information of 11,521 patients treated with radical prostatectomy at four academic centers from 1987 to 2005 were modeled to predict PCSM. The model was externally validated on 12,893 patients treated at a separate institution during the same period. Results: The 15-year PCSM and all-cause mortality was 7% and 33%, respectively. The 15-year PCSM for patients with final pathological Gleason score 2–6, 3+4, 4+3, and 8–10 was 1%, 7%, 8%, and 49%, respectively. By pathologic stage, the risks were 2%, 7%, 29%, and 23% for organ-confined, extraprostatic extension, seminal vesicle invasion, and lymph node-positive prostate cancer. Of 3756 patients with organ-confined and Gleason 2–6 cancer, only 1 (0.03%) died from prostate cancer. Primary and secondary Gleason grade (p &lt; 0.001 for both), seminal vesicle invasion (p &lt; 0.001), and year of surgery (p = 0.002) were significant predictors of PCSM. A nomogram predicting 15-year PCSM based on pathologic parameters was accurate and discriminating with an externally-validated concordance index of 0.92. Conclusions: A nomogram has been constructed that predicts the long-term risk of PCSM after radical prostatectomy based on the pathologic grade and stage of the cancer. The presence of poorly differentiated cancer and seminal vesicle invasion are the prime determinants of PCSM. Our study suggests that biomarkers may have limited empiric prognostic utility as PCSM can be accurately predicted once the pathologic features of prostate cancer are known. No significant financial relationships to disclose.

Prostate specific antigen for early detection of prostate cancer: longitudinal study

Objective To evaluate if prostate specific antigen test attains validity standards required for screening in view of recent prostate cancer screening trial results.Design Case-control study nested in longitudinal cohort.Setting Västerbotten...

Immunomagnetic Quantification of Circulating Tumor Cells as a Prognostic Factor of Androgen Deprivation Responsiveness in Patients With Hormone Naive Metastatic Prostate Cancer

We determined whether circulating tumor cells predict prostate specific antigen failure in patients with metastatic prostate cancer before endocrine therapy and compared their prognostic ability with other clinical factors. Circulating tumor cells were enumerated with the CellSearchtrade mark system in whole blood. This system was developed using epithelial cell adhesion molecule antibody based immunomagnetic capture and automated staining methodology. Prostate cancer cell lines (PC3, LNCaP, DU145) and mixed blood from healthy men were analyzed using this system. Blood samples from 80 patients with metastatic prostate cancer before endocrine therapy were analyzed. Circulating tumor cells were then assessed every 3 months after endocrine therapy in these patients. Circulating tumor cell assay accuracy and reliability were determined using prostate cancer cell line (PC3, LNCaP, DU145) spiking experiments, which demonstrated a strong linear correlation (r = 0.99) and a constant recovery rate of 69% +/- 3%, 95% +/- 3% and 89% +/- 2%, respectively. The number of circulating tumor cells found ranged from 0 to 222 per 7.5 ml blood (mean 17 +/- 31, median 14). A threshold of 5 or more circulating tumor cells per 7.5 ml blood was used to evaluate the ability of circulating tumor cells to predict androgen deprivation responsiveness. Of the 80 patients 44 (55%) had 5 or more circulating tumor cells with a median androgen deprivation responsiveness of 17 months compared to more than 32 months for those with fewer than 5 circulating tumor cells (p = 0.007). The presence of circulating tumor cells, nadir prostate specific antigen values and Gleason score were significant parameters predictive of androgen deprivation responsiveness on univariate and multivariate analyses. In this study the presence of 5 or more circulating tumor cells in 7.5 ml blood was associated with androgen deprivation responsiveness in patients with metastatic prostate cancer before endocrine therapy.

Prostate Biopsy Patterns in the CaPSURE Database: Evolution With Time and Impact on Outcome After Prostatectomy

Significant variability exists in the urological community regarding the number of cores that should be taken during prostate biopsy. Using CaPSURE we determined trends in prostate biopsy patterns during the last decade and assessed whether changes in biopsy number have had an impact on outcomes after radical prostatectomy. In CaPSURE between 1995 and 2004 we identified 6,450 men with newly diagnosed prostate cancer who underwent biopsy with 6 cores or greater. The number of cores removed, number of cores positive for cancer and percent of cores containing cancer were analyzed by year of diagnosis. For 1,757 men who underwent radical prostatectomy these variables were entered into Cox proportional hazards models controlling for preoperative prostate specific antigen, biopsy Gleason sum and clinical stage to predict recurrence-free survival. The mean number of removed cores increased from 6.9 in 1995 to 10.2 in 2004 (p <0.0001). The mean number of positive cores remained unchanged from 2.9 in 1995 to 3.2 in 2004 (p = 0.40). The percent of positive cores decreased from 42.6% in 1995 to 32.1% in 2004 (p <0.0001). The number and percent of positive cores were associated with recurrence-free survival after radical prostatectomy throughout the study period (each p <0.001). The percent of positive cores is an independent predictor of disease recurrence after radical prostatectomy. The total number of tissue cores sampled increased during the last decade, thereby driving down the mean percent of positive cores from 42.6% to 32.1%. The trend toward an increasing number of removed cores may have contributed indirectly to improved outcomes after radical prostatectomy in the last decade.

The maximum tumour length in biopsy cores as a predictor of outcome after radical prostatectomy

To evaluate maximum tumour length (MTL) in biopsy cores as a predictor of prostate-specific antigen (PSA)-failure, systemic failure, and death from prostate cancer after radical prostatectomy (RP). We assessed 209 men with clinically localized prostate cancer treated with RP; preoperative variables were correlated with unfavourable pathological characteristics in the RP specimens and with outcome after surgery, using univariate and multivariate analysis. The median (range) MTL was 4 (0.2-19) mm and correlated with adverse pathological findings, including specimen Gleason score (P = 0.003), pT3 (P < 0.001), seminal vesicle invasion (P < 0.001) and lymph node involvement (P = 0.019) in multivariate analysis. Preoperative PSA (P < 0.001), biopsy Gleason score (P = 0.002), and MTL (P = 0.045) were independent predictors of PSA failure, whereas only MTL remained a predictor of systemic-failure (P < 0.001) and death from prostate cancer (P = 0.004). The median (range) follow-up after surgery was 90 (17-152) months, during which 83 patients had PSA failure, 20 developed systemic failure and 15 died from prostate cancer. The MTL correlates well with adverse pathological findings and appears to be an independent predictor of outcome after RP. Patients with a greater MTL might have cancer with an aggressive phenotype and therefore be candidates for more aggressive therapies.

Prognostic Value of CpG Island Hypermethylation at PTGS2, RAR-beta, EDNRB, and Other Gene Loci in Patients Undergoing Radical Prostatectomy

ObjectivesTo evaluate CpG island hypermethylation in a set of candidate genes in prostate cancer (pCA) and its relationship to clinicopathologic parameters and a nomogram predicting prostate-specific antigen (PSA) recurrence after radical prostatectomy. Materials and methodsTissues of 78 prostate carcinomas, 32 benign prostate hyperplasias (BPHs), and prostate cell lines (LNCaP, DU145, PC3, BPH-1) were examined with MethyLight polymerase chain reaction at 13 gene loci (APC, CDC6, CTNNB1, E-Cadherin, EDNRB, FGFR2, GSTP1, NAB2, PKCmu, PTGS2, RAR-beta, RASL11A, WWOX). ResultsAPC, RAR-beta, PTGS2, GSTP1, EDNRB, and CTNNB1 (83%, 71%, 65%, 33%, 14%, 9%, respectively) were methylated in pCA but rarely or not methylated in BPH. NAB2 and CDC6 were hypermethylated frequently in pCA (92%, 67%, respectively) and in BPH (91%, 59%, respectively). FGFR2, WWOX, E-Cadherin, PKCmu, and RASLL1A did not display noteworthy methylation in pCA (0–1%) or in BPH. CpG island hypermethylation at APC, retinoic acid receptor beta (RAR-beta), and PTGS2 discriminated with a sensitivity of 65–83% and a specificity of 97–100% between BPH and pCA. The combination of various genes increased the diagnostic expressiveness. PTGS2 hypermethylation correlated with seminal vesicle infiltration (p=0.047), capsular penetration (p=0.004), and pT stage (p=0.014). RAR-beta methylation was accompanied by a higher cumulative Gleason score (p=0.042). The probability of PSA-free-survival calculated with a Kattan nomogram correlated inversely with CpG island hypermethylation at EDNRB, RAR-beta, and PTGS2. All prostate cancer cell lines displayed a varying degree of demethylation after 5-aza-2′deoxycytidine treatment. ConclusionsCpG island hypermethylation at various gene loci is frequent in prostate cancer and can distinguish between neoplastic and noncancerous tissue. Furthermore, hypermethylation at PTGS2, RAR-beta, and EDNRB inversely correlated with PSA-free-survival according to a Kattan nomogram and has potential prognostic value.