Prostate-specific Antigen Velocity Research Articles

Abstract LB-178: Oxidation markers in relation to prostate cancer and BPH and progression of prostate cancer

Abstract Prostate cancer (PCa) is the leading cancer affecting men of all races in the U.S. Benign prostatic hyperplasia (BPH) is prostate enlargement and is not malignant. BPH and PCa have similar symptoms and both have elevated PSA levels. A biomarker which can distinguish PCa from BPH will help the diagnosis of PCa and avoid unnecessary biopsies. Further, many PCa patients after prostatectomy can have recurrence. Currently, PSA is the only monitoring marker for recurrence; however, the underlying mechanism for recurrence is unknown. A mechanistic marker that can predict the progression and recurrence this will allow us to design prevention strategies. Many animal studies have linked oxidative stress with PCa progression and recurrence. The aim of this study is to compare the levels of several oxidation markers between PCa and BPH, and compare the levels of oxidation marker in different stages of PCa and determine their associations with PSA velocities after prostatectomy. We have measured multiple oxidation markers including lipid, protein, DNA, carbohydrate and global oxidation markers. We have collected blood samples among 15 BPH and 22 prostate cancer patients who have prostatectomy. We have found that levels of advanced glycation end products (AGEs), a marker of glucose oxidation, formed under nonenzymatic glycation of lipids and proteins, are higher in PCa patients than BPH. However, among PCa patients, AGEs levels are lower among those with Gleason score higher than 7 than those with Gleason score less than 7. Finally, we have found F2-isoprostanes, a well-established lipid oxidation marker, are associated with PSA velocities among PCa patients who had prostatectomy. Our results suggest that AGEs can help distinguish BPH and PCa but are associated with lower grade PCa. Measurement of F2-isoprostanes, a marker of lipid oxidation can predict PCa progression among men with prostatectomy. Citation Format: Tianying Wu, Bruce Bracken, Susan Kasper. Oxidation markers in relation to prostate cancer and BPH and progression of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-178.

The Change in Neutrophil Lymphocyte Ratio from the First to the Last Repeat Prostate Biopsy Proposed as a Marker of Carcinogenesis

Introduction: We investigated whether the change in the neutrophil lymphocyte ratio (NLR) from the first to the last repeat prostate biopsy (ΔNLR) could be the diagnostic tool or not for prostate cancer (PCa) detection. Materials and Methods: We retrospectively evaluated medical records of men who had undergone repeat prostate biopsy. The investigated parameters were white blood cell, neutrophil, lymphocyte counts, NLR at the last prostate biopsy, ΔNLR, prostate-specific antigen (PSA), PSA density (PSAD), and PSA velocity. Exclusion criteria were the presence of cancers other than prostate origin, medication, and diseases which induce the change of NLR. Results: A total of 301 men who had undergone repeat prostate biopsy were selected for this study. After applying exclusion criteria, 223 patients were included. Of these patients, 94 were diagnosed with PCa (Group I) and 129 with no malignancy (Group II). Only a single patient had metastasis. On evaluating the area under the receiver operating characteristic curve of all study parameters, ΔNLR was the most accurate marker, followed by PSAD and then NLR measured at the last biopsy. Conclusions: ΔNLR was the most accurate marker to improve the total predictive value in repeat prostate biopsy for diagnosing PCa.

(P20) Decreased PSA Nadir as a Result of Dose-Escalated Stereotactic Body Radiation for Patients With Low- and Intermediate-Risk Prostate Cancer

Prostate cancer (CaP) is characterized by a low a/b ratio relative to surrounding normal tissue, and consequently a therapeutic gain could be achieved with dose escalation. While potentially ablative PSA nadirs have been demonstrated following LDR brachytherapy, the ability to achieve ablation following stereotactic body radiation therapy (SBRT) remains unclear. The purpose of this study was to report the clinical outcomes, PSA kinetics, and toxicities in patients with low and intermediate-risk CaP treated on a prospective, Phase I/II, IRB approved dose-escalated SBRT trial. From 2011 to 2016, 26 patients with low and intermediate-risk CaP received 40, 45, and 50 Gy in five fractions to the prostate and seminal vesicles in cohorts of 9, 10, and 7 patients (pts). Self-reported QOL was prospectively measured from the Expanded Prostate Cancer Index Composite (EPIC) and International Prostate Symptom Score (IPSS) at baseline and intervals of every 3 months for the first two years followed by every 6 months thereafter. Common Toxicity Criteria for Adverse Events v. 4.03, data was collected to observe acute and late toxicities. No pts received androgen deprivation therapy. Median follow-up was 4.8 years. A PSA nadir <0.5 ng/ml was seen in 22%, 80%, and 71% of patients receiving 40, 45, and 50 Gy, and <0.2 ng/ml in 11%, 50%, and 71% of patients after 3 years. After 5 years, a PSA nadir <0.5 ng/ml was achieved in 100% of patients receiving 45 Gy compared to 33% receiving 40 Gy. PSA nadir was significantly reduced when comparing cohorts receiving 45 or 50 Gy to 40 Gy one to five years following treatment (p<0.02). PSA velocity was not significantly different among treatment groups, demonstrating a sharp initial decline followed by gradual reduction at -1.394, -0.706, -0.330, -0.160, -0.104, -0.070, and -0.050 ng/mL/month, after 3 months, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years. A benign PSA bounce was observed in 8 patients (32%) at a median bounce height of 0.72 ng/ml after 18 months, demonstrating a trend towards an increased bounce height with increasing fractional dose. There was an acute increase in EPIC and IPSS scores followed by a return to baseline over two years. Acute Grade 2 urinary toxicity occurred in 10 pts with no significant difference among treatment arms. The three patients experiencing late Grade 2 toxicity were in the 45 or 50 Gy cohort. There were no Grade 3 or higher toxicities. Univariate analysis revealed that Grade 2 toxicity was associated with prostate size >60 cc (p<.01). One biochemical failure was observed in the 40 Gy arm after 3.6 years resulting in a freedom from biochemical failure rate of 96% at 5 years. Prostate cancer specific survival was 100% and actuarial overall survival was 96%. This small prospective dose-escalation study identified that higher doses of 45 and 50 Gy, respectively are associated with improved PSA nadir without increased risk of GU or GI toxicity. Further follow-up is needed to assess PSA freedom from recurrence and late toxicity.

PET/CT With 68Ga-PSMA in Prostate Cancer: Radiopharmaceutical Background and Clinical Implications

In the last twenty years, positron emission tomography / computed tomography (PET/CT) with radiolabeled choline, represented the most powerful imaging modality for prostate cancer (PCa). However, the low positive detection rate of the technique for PSA < 1 ng/ml prompted the development of other tracers for imaging PCa. We performed a critical review of 68Ga-PSMA, a receptor ligand tracer, which has been identified as the most promising radiopharmaceutical for imaging PCa. The most promising feature of this radiopharmaceutical is the high positive detection rate for prostate specific antigen (PSA) levels < 1 ng/ml or less (i.e., PSA < 0.5 ng/ml). 68Ga-PSMA detection rate is also sensitive to PSA kinetics, expressed either as PSA doubling time or PSA velocity. There are initial results indicating that 68Ga-PSMA may significantly affect the clinical management of PCa patients, even though the additional advantages in comparison to radiolabeled choline need to be further supported in future perspective studies. Other clinical implications, such as whether 68Ga-PSMA PET/CT predicts PCa-specific survival, have not yet been investigated. Numerous clinical studies have been published, some of them with histopathological verification so that despite the recent introduction in the clinical field reliable estimation of sensitivity and specificity of 68Ga-PSMA PET/CT have been obtained through meta-analyses. Most clinical studies with PET/CT with 68Ga-PSMA are retrospective, single-institutional studies and in many cases include heterogeneous patient cohorts. Thus, multidisciplinary, well-throughout prospective trials are needed to better define the clinical implications of 68Ga- PSMA PET/CT in PCa patients. The increasing availability of positron emission tomography / magnetic resonance (PET/MR) hybrid devices promotes the use of this radiopharmaceutical especially at initial staging when identification of tumor localization and of extra-prostatic disease represent clinically relevant questions. PSMA cold ligands can also be labeled with beta emitters with good chemical stability so that 68Ga-PSMA PET/CT can be used to guide radiometabolic therapy of advanced metastatic PCa patients through 177Lu-labeled PSMA ligands. PSMA labeled ligands appear very promising for diagnosis and treatment of PCa.

Is Serum Prostate-Specific Antigen a Reliable Prostate Cancer Marker in Liver Transplant Candidates.

In this study, we aimed to determine whether the prostate-specific antigen level is a reliable marker of prostate cancer in patients with hepatic insufficiency, based on evaluation of alterations in serum prostate-specific antigen levels after liver transplant in patients with hepatic insufficiency. Medical records of all patients who underwent liver transplant at our hospital between January 2003 and June 2017 were retrospectively reviewed. Male patients who were > 40 years old with available pre- and posttransplant serum total prostate-specific antigen levels were included in the study. Our study included 36 male patients with a mean age of 54.6 ± 5.3 years (range, 45-73 y) at the time of liver transplant. The mean pretransplant serum total prostate-specific antigen level was 0.75 ± 0.77 ng/mL, which was significantly lower than the mean posttransplant level of 1.29 ± 1.57 ng/mL (P < .05). The pretransplant serum total prostate-specific antigen level was measured a mean of 4.9 ± 5.4 months before liver transplant versus a mean 27.6 ± 16.3 months after transplant. Prostate-specific antigen velocity was 0.2 ng/mL/year. Biochemical tests of liver function, including the mean serum levels of bilirubin, international normalized ratio, and albumin, were normal after liver transplant at 1.37 ± 2.33 mg/dL, 1.22 ± 0.36, and 4.16 ± 0.69 g/dL, respectively. Serum prostate-specific antigen levels may decrease in patients with hepatic insufficiency/cirrhosis; therefore, a low serum prostate-specific antigen level may not be a reliable marker for excluding prostate cancer in such patients. Transplant surgeons and clinicians must be aware of this so that all male transplant candidates > 40 years old are evaluated via digital rectal examination, regardless of the serum prostate-specific antigen level.

Oligometastatic recurrent prostate cancer detects by fluorine-18-choline positron emission tomography/computed tomography in patients with prostate-specific antigen levels of up to 5 ng/ml.

The aim of this study was to assess the ability of fluorine-18-fluorocholine (F-FCH) PET/computed tomography (CT) to detect oligometastatic disease (OMD) in patients with early recurrence of prostate cancer (PC) [prostate-specific antigen (PSA)≤5 ng/ml]. Between 2010 and 2016, 324 patients with PC and PSA levels of less than or equal to 5 ng/ml were recruited. The mean (SD) age of the patients was 71 (10) years. All patients were treated with a radical prostatectomy±lymphadenectomy. One-hundred and twenty-one patients were under hormonal therapy at the time of PET/CT, whereas 203 were not. The mean (SD) PSA at the time of PET/CT was 1.33 (1.19) ng/ml, the mean (SD) PSA doubling time (PSAdt) was 10 (12) months, and the mean (SD) PSA velocity (PSAvel) was 1.94 (3.31) ng/ml/year. The correlation between continuous and categorical data was assessed using Student's t-test or by analysis of variance and by the χ-test, respectively. Univariate and multivariate analysis was carried out for the identification of clinical variables able to predict the presence of OMD. One-hundred and ninety-three patients had a negative F-FCH PET/CT, whereas 131 (40.4%) had a positive scan. Of these latter patients, 35 had a significant F-FCH uptake in the prostatic fossae, 59 in the lymph nodes, and 37 in bone. PSA levels were significantly different between patients with a positive than those with a negative scan (P<0.001). F-FCH PET/CT was negative in the majority of patients with a PSA of less than or equal to 1 (63.2%) ng/ml. More than 60% of patients with a PSAdt of less than or equal to 6 months had a positive F-FCH PET/CT scan for OMD. PSAvel was higher in patients with a positive scan than those with a negative finding. At univariate analysis, PSA level, PSAdt, and PSAvel were predictors of a positive F-FCH PET/CT for OMD, whereas on multivariate analysis, only PSA level and PSAdt were independent predictors (both P<0.01). Furthermore, PSAdt was the only independent predictor of OMD at the lymph node level. In patients with early recurrence of PC, F-FCH PET/CT is able to detect OMD in 40% of cases. This finding has an important impact on the detection of PC recurrent lesions that could be treated by local therapy to achieve long-term survival or cure.

Predictors for the detection of prostate cancer and clinically significant prostate cancer using TRUS-guided biopsy in patients with negative initial biopsy results.

We aimed to determine the predictors for the detection of prostate cancer and clinically significant prostate cancer in the setting of repeat prostate biopsy using trans-rectal ultrasonography-guided biopsy. A total of 636 patients who underwent repeat prostate biopsy were included. The patients were divided into two groups according to the repeat biopsy results (with vs. without prostate cancer). A multivariable analysis was performed to assess the predictors for the detection of prostate cancer and clinically significant prostate cancer. Prostate cancer was detected in 98 patients (15.4%). Although there was no difference in the prostate-specific antigen velocity, the prostate-specific antigen density was higher in the patients with prostate cancer at the initial (0.14 vs. 0.17ng/mL/cc, p=0.049) and repeat biopsies (0.17 vs. 0.26ng/mL/cc, p<0.001). The proportions of the patients who met the active surveillance criteria were as follows: 22.4% (Johns Hopkins), 30.6% (University of Toronto), 32.7% (University of California at San Francisco), 30.6% (Prostate Cancer Research International Active Surveillance), 27.6% (Memorial Sloan Kettering Cancer Center), and 13.3% (University of Miami). In the multivariable analysis, age, hypoechoic lesion on trans-rectal ultrasonography, and prostate-specific antigen density at the repeat biopsy were the significant predictors for prostate cancer and clinically significant prostate cancer. Trans-rectal ultrasonography before repeat prostate biopsy and the prostate-specific antigen density are useful for selecting patients with a high probability for prostate cancer if repeat trans-rectal ultrasonography-guided biopsy is considered. In addition, these are also helpful for detecting clinically significant prostate cancer.

Real-Time Elastography in the Diagnosis of Prostate Cancer: Personal Experience:

Prostate cancer is the most common cancer in men. In the future, a significant further increase in the incidence of prostate cancer is expected. The indication to perform a prostate biopsy is digital rectal examination suspicious for prostate cancer, total prostate specific antigen (PSA) value, free PSA/total PSA ratio, PSA density and PSA velocity, and an evidence of hypoechoic area at transrectal ultrasound scan. Unfortunately the specificity and sensibility are still poor. The aim of this retrospective study is to evaluate the specificity and sensibility of real time elastography versus ultrasound transrectal B-mode scan. We retrospectively evaluated 108 pts. having undergone TRUS-guided transrectal prostate biopsy (10 samples). The indication for biopsy is: digital rectal examination, total prostate specific antigen (PSA) value, PSA ratio, PSA density and PSA velocity suspicious for prostate cancer, and/or an evidence of hypoechoic area at transrectal ultrasound scan, and/or hard area at real-time elastography. The mean age of patients is 66.8 years, mean PSA 6.5 ng/mL, and mean ratio 16.5%. We compared the histopathological findings of needle prostate biopsies with the results of transrectal ultrasound and transrectal real-time elastography. 32/108 (29.6%) pts. were positive for prostate cancer (mean Gleason score 7.08), mean PSA 14 ng/mL and mean ratio 9.5%. Transrectal ultrasound scan shows a sensibility of 69% and specificity of 68%. Transrectal ultrasound scan shows a VPP of 51.4%. Transrectal ultrasound scan shows a VPN of 80.9%. Real-time elastography shows a sensibility of 56% and specificity of 85.7%. Real-time elastography shows a VPP of 60.1%. Real-time elastography shows a VPN of 83%. Elastography has a significantly higher specificity for the detection of prostate cancer than the conventionally used examinations including DRE and TRUS. It is a useful real-time diagnostic method because it is not invasive, and simultaneous evaluation is possible while performing TRUS.

Lung uptake of fluorine-18 fluoroethyl-choline PET-CT in patients with prostate cancer.

Metastatic spreading to the lungs is a negative prognostic factor in patients with prostate cancer (PC). Aim of our study was to assess the prevalence of lung PC metastases in patients with fluorine-18 fluoroethyl-choline (F-18-FECh) PET-CT positive lung lesions and the role of Gleason Score (GS) and common biochemical markers in predicting metastatic spreading to the lungs. We retrospectively evaluated the scans of 1283 patients ongoing (F-18-FECh) PET-CT for PC between May 2010 and July 2014. Patients with lung lesion with F-18-FECh uptake were included. Data concerning GS at diagnosis, "trigger" prostate-specific antigen (PSAtr), PSA doubling time (PSAdt), PSA velocity (PSAvel) and ongoing androgen deprivation therapy were collected. PET-CT findings were confirmed by histology or follow-up (FU) and classified as follows: inflammation, primary lung cancer or metastases from tumor other than PC, and lung metastases from PC. Twenty-two patients with F-18-FECh positive lung lesion and available histology or FU were identified. PSAdt was significantly (P=0.029) shorter in patients with lung metastases from PC (median PSAdt 1.7 months, interquartile range [IQR] 1.5-4.1 months) than in patients without lung PC relapse (median PSAdt 6.7 months, IQR 3.9-7.8); PSAvel was significantly (P=0.019) higher in patients with lung metastases from PC (median PSAvel 3.2 ng/mL/month, IQR 0.65-6.65 ng/mL/month) than in patients without lung PC relapse (median PSAvel 0.3 ng/mL/month, IQR 0.2-0.5 ng/mL/month). Patients with lung metastases from PC had significantly (P=0.006) higher GS at diagnosis (median GS 8) than the other ones (median GS 7). Our analysis shows that the prevalence of F-18-FECh positive lung metastases in patients with PC, especially with higher GS at diagnosis, is higher in presence of a steady increase in PSA values, confirmed by higher PSAvel and shorter PSAdt.

Development of a Chinese nomogram based on muti-parametric magnetic resonance for predicting the probability of prostate cancer in patients after initial negative biopsy

Objective: To develop a predictive nomogram based on multi-parametric magnetic resonance imaging (mpMRI) information to identify men more likely to have a cancer diagnosed on repeat prostate biopsy. Methods: The clinical data of 237 patients who received repeat prostate biopsy after initial negative biopsy from Department of Urology of Peking University First Hospital between January 2001 and August 2016 was reviewed. Patient age, body mass index (BMI), serum total prostate-specific antigen (PSA), percent free PSA (f/t), prostate volume (PV), PSA density (PSAD), PSA velocity (PSAV), digital rectal examination (DRE), transrectal ultrasound (TRUS)and mpMRI results were included in the univariate and multivariate analysis. A nomogram was developed using selected variables and the area under the receiver operating characteristic (ROC) curve was calculated as a measure of discrimination. Results: A total of 76 patients (32.07%) had prostate cancer (PCa) detected on repeat biopsy. Based on univariate and multivariate logistic regression analysis, the patient age, PSA, PV, DRE and mpMRI results were independent predictors for the diagnosis of PCa on repeat biopsy. The current nomogram performed well (AUC=0.910) and showed excellent calibration. Conclusions: Multi-parametric magnetic resonance imaging combined with age, PSA, PV and DRE can predict the probability of PCa in patients with initial negative biopsy. The nomogram might help in decision-making for men with prior benign histology before the performance of repeat biopsy.

Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition

Background:Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort.Methods:PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV.Results:1634 participants had ⩾3 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml−l, PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers.Conclusions:PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone.

PSA kinetics following primary focal cryotherapy (hemiablation) in organ-confined prostate cancer patients.

We aim to evaluate prostate-specific antigen (PSA) trends in post-primary focal cryotherapy (PFC) patients. This was an institutional review board-approved retrospective study of PFC patients from 2010 to 2015. Patients with at least one post-PFC PSA were included in the study. Biochemical recurrence (BCR) was determined using the Phoenix criteria. PSA bounce was also assessed. We analyzed rates of change of PSA over time of post-PFC between BCR and no BCR groups. PSA-derived variables were analyzed as potential predictors of BCR. A total of 104 PFC patients were included in our analysis. Median (range) age and follow-up time were 66 (48-82) years and 19 (6.3-38.6) months, respectively. Four (3.8%) patients experienced PSA bounce. The median percent drop in first post-PFC PSA of 80.0% was not associated with BCR (p=0.256) and may indicate elimination of the index lesion. The rate of increase of PSA in BCR patients was significantly higher compared to patients who did not recur (median PSA velocity (PSAV): 0.15 vs 0.04ng/ml/month, p=0.001). Similar to PSAV (HR 9.570, 95% CI 3.725-24.592, p<0.0001), PSA nadir≥2ng/ml [HR (hazard ratio) 1.251, 95% CI 1.100-1.422, p=0.001] was independently associated with BCR. A significant drop in post-PFC PSA may indicate elimination of the index lesion. Patients who are likely to recur biochemically have a significantly higher PSAV compared to those who do not recur. Nadir PSA of less than 2ng/ml may be considered the new normal PSA in focal cryotherapy (hemiablation) follow-up.

Prospective Evaluation of 68Ga-RM2 PET/MRI in Patients with Biochemical Recurrence of Prostate Cancer and Negative Findings on Conventional Imaging.

68Ga-labeled DOTA-4-amino-1-carboxymethyl-piperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (68Ga-RM2) is a synthetic bombesin receptor antagonist that targets gastrin-releasing peptide receptor (GRPr). GRPr proteins are highly overexpressed in several human tumors, including prostate cancer (PCa). We present data from the use of 68Ga-RM2 in patients with biochemical recurrence (BCR) of PCa and negative findings on conventional imaging. Methods: We enrolled 32 men with BCR of PCa, who were 59-83 y old (mean ± SD, 68.7 ± 6.4 y). Imaging started at 40-69 min (mean, 50.5 ± 6.8 min) after injection of 133.2-151.7 MBq (mean, 140.6 ± 7.4 MBq) of 68Ga-RM2 using a time-of-flight-enabled simultaneous PET/MRI scanner. T1-weighted, T2-weighted, and diffusion-weighted images were acquired. Results: All patients had a rising level of prostate-specific antigen (PSA) (range, 0.3-119.0 ng/mL; mean, 10.1 ± 21.3 ng/mL) and negative findings on conventional imaging (CT or MRI, and a 99mTc-methylene diphosphonate bone scan) before enrollment. The observed 68Ga-RM2 PET detection rate was 71.8%. 68Ga-RM2 PET identified recurrent PCa in 23 of the 32 participants, whereas the simultaneous MRI scan identified findings compatible with recurrent PCa in 11 of the 32 patients. PSA velocity was 0.32 ± 0.59 ng/mL/y (range, 0.04-1.9 ng/mL/y) in patients with negative PET findings and 2.51 ± 2.16 ng/mL/y (range, 0.13-8.68 ng/mL/y) in patients with positive PET findings (P = 0.006). Conclusion:68Ga-RM2 PET can be used for assessment of GRPr expression in patients with BCR of PCa. High uptake in multiple areas compatible with cancer lesions suggests that 68Ga-RM2 is a promising PET radiopharmaceutical for localization of disease in patients with BCR of PCa and negative findings on conventional imaging.

Use of Prostate-Specific Antigen Velocity as a Screening Tool for Pre-Biopsy Detection of Prostate Cancer in African-American Men: A Single Institutional Analysis

Use of Prostate-Specific Antigen Velocity as a Screening Tool for Pre-Biopsy Detection of Prostate Cancer in African-American Men: A Single Institutional Analysis

784O - Docetaxel (D) with androgen suppression (AS) for high-risk localized prostate cancer (HrPC) patients (pts) who relapsed PSA after radical prostatectomy (RP) and/or radiotherapy (RT): A randomized phase III trial

Background: HrPC pts with PSA relapse after local therapy may have a poor prognosis and AS may be a therapeutic option. D+AS is standard of care in hormone-naive metastatic PC. We evaluated the benefit of D+AS in HrPC pts with PSA relapse after RP and/or RT. Methods: Multicenter, randomized phase 3 study (NCT00764166) comparing AS (triptorelin, every 3 months for 1 year) versus AS+D (70 mg/m2 Q3W, 6 cycles). To be enrolled, pts needed ≥ 3 rising PSA values >0.2ng/mL (after RP) or > 1ng/mL above nadir (after RT) modified by nadir + 2ng/ml (RTOG-ASTRO Phoenix, 2006) and ≥ 1 of the following criteria: Gleason ≥8, PSA doubling time (PSADT) ≤6 mths, PSA velocity >0.75 ng/mL/year, positive surgical margins (SM), pN1, time from curative therapy to PSA relapse ≤12 months. Pts were stratified on type of local treatment (RP or RT) and PSADT (≤ or > 6 mths). Primary endpoint was PSA-PFS defined by a PSA above 0.2ng/ml and rise ≥ 50% from baseline confirmed by 2 subsequent values. Secondary endpoints were PSA response (decrease ≥50%), radiological progression (rPFS), overall survival (OS) and safety. Results: between 2003-2007, 250 pts (median age 65 years), were randomized to AS+D (arm A, n = 125) or AS (arm B, n = 125). Local treatment: RP (95 pts, 38%), RT (69 pts, 28%) or RP+RT (86 pts, 34%). Risk factors were as follows: Gleason ≥8: 29%, PSADT≤ 6 mths 54%, PSA velocity >0.75 ng/mL/yr 84%, positive SM 37%, pN1 4%, PSA relapse ≤12 mths 45%. 58% of pts had ≥3 risk factors. Six pts had a PSA >20 ng/ml at baseline. There was no significant difference in PSA response (94% vs 98%), PSA-PFS and rPFS between 2 arms (table). Median OS was not mature. Most common grade ≥3 toxicities in arm A were neutropenia (58%), febrile neutropenia (8%) and hair loss (4%). AS toxicities were mainly grade 2 hot flushes (47%) and depression (11%).Table784OAS + D (n = 125)AS alone (n = 125)HR (95%)p-valuePSA-PFS (months)20.7 [19.2-21.5]18.6 [17.6-20.2]0.85 (0.62-1.16)0.31rPFS (years)8.8 [7.7-10.2]9.7 [6.9-10.9]1.01 (0.72-1.40)0.9525eme percentile (OS, years)8.38.11.16 (0.76-1.77)0.49 Open table in a new tab Conclusions: AS+D failed to improve PSA-PFS, rPFS in HrPC pts relapsing PSA after local therapy. Clinical trial identification: NCT00764166 Legal entity responsible for the study: Stéphane OUDARD, MD, PhD Funding: Sanofi Aventis Disclosure: S. Oudard: Honoraria from Sanofi, Novartis, Roche, Ipsen, BMS outside submited work L. Miglianico, E. Sevin, A-C. Hardy Bessard: Fees from Sanofi. C. Chevreau, C. Linassier, S. Culine: Fees from Sanofi, Astellas, Janssen. F. Priou: Fees from Sanofi. P. Beuzeboc: Fees from Sanofis, Astellas, Janssen. G. Gravis: Travel paid by Sanofi, Astellas, Janssen All other authors have declared no conflicts of interest.

Impact of 68Ga-Prostate-Specific Membrane Antigen PET/CT on Prostate Cancer Management.

The objective of this study was to assess the impact of 68Ga-prostate-specific membrane antigen (68Ga-PSMA) PET/CT on the management of prostate cancer in patients with biochemical recurrence (BCR). Methods: Documented management plans before and after 68Ga-PSMA PET/CT in 100 patients with BCR were retrospectively reviewed, and changes in plans were recorded. Results: Management changed after 68Ga-PSMA PET/CT in 39 patients (39%). The management changes occurred in 23 (33.8%) of 68 patients with radical prostatectomy and 16 (50%) of 32 patients previously treated with radical radiotherapy. Positive scan results (P < 0.001) and higher prostate-specific antigen (PSA) levels (P = 0.024) were associated with management changes. No significant association with management change was found for Gleason grade, stage, presence of metastatic disease, PSA velocity, or PSA doubling time. Conclusion:68Ga-PSMA PET/CT altered management in 39% of patients with BCR, and changes occurred more often in patients with radical radiotherapy treatment, positive 68Ga-PSMA scan results, and higher PSA levels.

Role of PET-CT with 18F-fluorocholine in biochemical recurrence after treatment of prostate cancer with curative intent

ObjectivesTo analyze the ability of the PET-CT with 18F-fluorocholine (18F-FCH) to detect disease on biochemical recurrence after treatment with curative intent. To determine the clinical variables that would be able to optimize the test's diagnostic yield. Material and methodsA retrospective study of PET-CTs with 18F-fluorocholine performed on 61 patients with prostate cancer who had undergone treatment with curative intent and met the criteria for biochemical recurrence. The results of the PET-CT were categorized into positive or negative and were validated using pre-established criteria. The relationship between the result of the PET-CT and the initial PSA nadir, PSA trigger, rising PSA velocity (PSAva) and PSA doubling time (PSAdt). The relationship between the metastatic sites on the PET-CT and the remaining variables was analyzed. ResultsThere was a 34.4% detection rate of the disease. The initial PSA, PSA nadir, PSA trigger and PSAva showed statistically significant differences according to the result of the PET-CT. The best discriminatory cut-off point between a positive or negative PET-CT for PSA trigger and PSAva was 3.5ng/ml and 0.25ng/ml/month respectively. The PSAdt was significantly lower in patients with remote disease compared to patients with localized disease (5.1 vs 16.8 months, p=0.01). The probability that the PET-CT would detect remote disease vs localized disease was 3.2 times higher if the PSAdt was under 6 months (80% vs 20%, OR: 3.2, p=0.02). In the multivariate analysis, only the initial PSA and not having undergone radical prostatectomy were demonstrated as independent predictive factors of a positive PET-CT result. ConclusionsThe PET-CT with 18F-FCH can detect disease in a high percentage of patients with biochemical recurrence and provides information on its anatomical location. PSA kinetics and the patient's previous treatment are key variables in increasing the test's diagnostic.

Prostate-Specific Antigen and Prostate-Specific Antigen Kinetics in Predicting 18F-Sodium Fluoride Positron Emission Tomography-Computed Tomography Positivity for First Bone Metastases in Patients with Biochemical Recurrence after Radical Prostatectomy.

We evaluated the association between serum prostate specific antigen (PSA) level and kinetics to predict 18F-sodium fluoride positron emission tomography-computed tomography (18F-NaF PET-CT) positivity for first bone metastases in men with biochemical recurrence after radical prostatectomy. All 18F-NaF PET-CT scans that were performed at our institution during 2010–2014 were queried to find patients who demonstrated biochemical recurrence after radical prostatectomy. Records were reviewed to obtain data on PSA levels and kinetics at the time of 18F-NaF PET-CT and pathologic features of the prostatectomy specimen, which were then used for receiver operating characteristic (ROC) analysis to determine predictability for 18F-NaF PET positivity. Thirty-six patients met our inclusion criteria. Of these, 8 (22.2%) had positive 18F-NaF PET-CT scans. Mean values for PSA, PSA doubling time (PSADT), and PSA velocity (PSAV) were 2.02 ng/ml (range: 0.06–11.7 ng/ml), 13.2 months (range: 1.11–60.84), and 1.28 ng/ml/year (range: 0.1–5.28) for 18F-NaF PET-CT negative scans, and 4.11 ng/ml (range: 0.04–14.38 ng/ml), 8.9 months (range; 0.7–27.8), and 9.06 ng/ml/year (range: 0.04–50.2) for 18F-NaF PET-CT positive scans, respectively (P = 0.07, 0.47, and 0.02, respectively, for PSA, PSADT, and PSAV). ROC analysis for 18F-NaF PET-CT positivity resulted in area under the curve (AUC) values of 0.634 for PSA, 0.598 for PSADT, and 0.688 for PSAV. ROC analysis with combined models gave AUC values of 0.723 for a combination of PSA and PSADT, 0.689 for a combination of PSA and PSAV, and 0.718 for grouping of PSA, PSADT, and PSAV. There was no significant association between 18F-NaF PET-CT positivity and primary tumor Gleason score, TN staging, and status of surgical margins. 18F-NaF PET-CT detected first-time osseous metastases in 22.2% of our patients with biochemical recurrence after prostatectomy with the PSA level range ≤11.7 ng/ml. PSAV was statistically significant in predicting 18F-NaF PET-CT positivity. ROC analysis demonstrated higher AUCs when PSA was combined with PSA kinetics parameters.

Role of 18F-Choline PET/CT in guiding biopsy in patients with risen PSA levels and previous negative biopsy for prostate cancer

ObjectivesTo study 18F-Choline PET/CT in the diagnosis and biopsy guide of prostate cancer (pCa) in patients with persistently high prostate-specific antigen (PSA) and previous negative prostate biopsy. To compare the clinical risk factors and metabolic variables as predictors of malignancy. MethodsPatients with persistently elevated PSA in serum (total PSA >4ng/mL) and at least a previous negative or inconclusive biopsy were consecutively referred for a whole body 18F-Choline PET/CT.Patient age, PSA level, PSA doubling time (PSAdt) and PSA velocity (PSAvel) were obtained.PET images were visually (positive or negative) and semiquantitatively (SUVmax) reviewed. 18F-Choline uptake prostate patterns were defined as focal, multifocal, homogeneous or heterogeneous. Histology on biopsy using transrectal ultrasound-guided approach was the gold standard.Sensitivity (Se), specificity (Sp) and accuracy (Ac) of PET/CT for diagnosis of pCa were evaluated using per-patient and per-prostate lobe analysis. Receiver-operating-characteristic (ROC) curve analysis was used to assess the value of SUVmax to diagnose pCa.Correlation between PET/CT and biopsy results per-prostate lobe was assessed using the Chi-square test. Univariate and multivariate logistic regression analysis were applied to compare clinical risk factors and metabolic variables as predictors of malignancy. ResultsThirty-six out of 43 patients with histologic confirmation were included. In 11 (30.5%) patients, pCa was diagnosed (Gleason score from 4 to 9). The mean values of patient age, PSA level, PSAdt and PSAvel were: 65.5 years, 15.6ng/ml, 28.1 months and 8.5ng/mL per year, respectively.Thirty-three patients had a positive PET/CT; 18 had a focal pattern, 7 multifocal, 4 homogeneous and 4 heterogeneous. Se, Sp and Ac of PET/CT were of 100%, 12% and 38% in the patient based analysis, and 87%, 29% and 14% in the prostate lobe based analysis, respectively. The ROC curve analysis of SUVmax showed an AUC of 0.568 (p=0.52).On a lobe analysis, poor agreement was observed between PET/CT findings and biopsy results (p=0.097). In the univariate/multivariate analysis, none of clinical and metabolic variables were statistically significant as predictor of pCa. ConclusionCholine PET/CT is a suitable procedure for the detection of pCa in highly selected patients, however, a high rate of false positive should be expected.

Predictive value of different prostate-specific antigen-based markers in men with baseline total prostate-specific antigen

To investigate the predictive value of various molecular forms of prostate-specific antigen in men with baseline prostate-specific antigen <2.0 ng/mL. The case cohort comprised 150 men with a baseline prostate-specific antigen level <2.0 ng/mL, and who developed prostate cancer within 10 years. The control cohort was 300 baseline prostate-specific antigen- and age-adjusted men who did not develop prostate cancer. Serum prostate-specific antigen, free prostate-specific antigen, and [-2] proenzyme prostate-specific antigen were measured at baseline and last screening visit. The predictive impact of baseline prostate-specific antigen- and [-2] proenzyme prostate-specific antigen-related indices on developing prostate cancer was investigated. The predictive impact of those indices at last screening visit and velocities from baseline to final screening on tumor aggressiveness were also investigated. The baseline free to total prostate-specific antigen ratio was a significant predictor of prostate cancer development. The odds ratio was 6.08 in the lowest quintile baseline free to total prostate-specific antigen ratio subgroup. No serum indices at diagnosis were associated with tumor aggressiveness. The Prostate Health Index velocity and [-2] proenzyme prostate-specific antigen/free prostate-specific antigen velocity significantly increased in patients with higher risk D'Amico risk groups and higher Gleason scores. Free to total prostate-specific antigen ratio in men with low baseline prostate-specific antigen levels seems to predict the risk of developing prostate cancer, and it could be useful for a more effective individualized screening system. Longitudinal changes in [-2] proenzyme prostate-specific antigen-related indices seem to correlate with tumor aggressiveness, and they could be used as prognostic tool before treatment and during active surveillance.