Higher Prostate-specific Antigen Research Articles

Real-world PROCEED registry data: Sipuleucel-T in elderly men with metastatic castration-resistant prostate cancer (mCRPC).

177 Background: Managing patients ≥ 80 years old (yo) with mCRPC is challenging, given the high prevalence of comorbidities, polypharmacy, organ dysfunction, and reduced performance status (PS). Balancing treatment benefit with safety and quality of life is particularly germane for this group. Sipuleucel-T, an autologous cellular immunotherapy for mCRPC, is generally well-tolerated. Prior analyses from PROCEED, a large registry for sipuleucel-T in men with mCRPC, demonstrated that upregulation of immune cells in these elderly patients is similar to that of younger men. Here, we report on this clinical experience. Methods: PROCEED enrolled men with mCRPC treated with sipuleucel-T given every 2 weeks x 3, with no dose adjustment for organ dysfunction or drug interactions. The elderly cohort included those ≥ 80 yo. Men were followed until death, study withdrawal, or a minimum of 3 years. Results: Of 1902 patients who received ≥1 sipuleucel-T infusion, 374 (19.7%) were ≥ 80 yo. Compared to men < 80 yo (Table), this cohort was 14 years older, had worse Eastern Cooperative Oncology Group (ECOG) PS and higher prostate-specific antigen (PSA) at baseline. All grade (16.3% elderly v. 13.7% younger) and grade 3-5 (10.7% elderly v. 9.9% younger) serious adverse events were comparable between groups. However, the median overall survival (OS) of elderly men was 10.7 mo shorter than that of younger men (< 80 yo). Conclusions: Sipuleucel-T was generally well-tolerated in those ≥ 80 yo in a real-world setting and may be considered a first-line option for the elderly with asymptomatic or minimally symptomatic mCRPC. As expected, OS was shorter than in younger patients. Clinical trial information: NCT01306890. [Table: see text]

Sensitivity of fluorine-18-fluoromethylcholine PET/CT to prostate-specific antigen over different plasma levels: a retrospective study in a cohort of 192 patients with prostate cancer.

Several factors have been identified that predict positive fluorine-18-fluoromethylcholine (F-FCH) PET/CT result in patients with prostate cancer undergoing PET/CT for biochemical failure. Among these factors, prostate-specific antigen (PSA) is the single factor most consistently associated with the prediction of positive F-FCH PET/CT. In this study, we wished to confirm this finding and expand it in a large series of patients. We retrospectively analyzed 192 patients with prostate cancer who were recruited from the Nuclear Medicine Department of the Sant'Andrea Hospital of La Spezia, Italy, from March 2013 to March 2018 and who underwent F-FCH PET/CT owing to biochemical failure after radical prostatectomy. Median trigger PSA was 2.57 ng/ml. The overall positive detection rate of F-FCH PET/CT was 60.9%. The percent of positive scans was 30.5% for PSA less than 1 ng/ml, 59.4% (38/64) for PSA between 1 and 5 ng/ml, and 88.4% for PSA greater than 5 ng/ml (P<0.001). On univariate regression analysis, high PSA levels, biochemical failure during antiandrogenic therapy at the time of PET/CT, and older age significantly (P<0.05) predicted positive F-FCH PET/CT result. On multivariate regression analysis, only high PSA levels and biochemical failure during antiandrogenic therapy maintained the statistical significance (P<0.05). However, when the analysis was restricted to patients with PSA less than 1 ng/ml, PSA lost the statistical significance. Receiver operating characteristic analysis revealed an area under the curve of 0.795. The PSA cutoff value that best distinguished PET/CT-positive from PET/CT-negative patients was 2.57 ng/ml. Sensitivity and specificity at this PSA value were 66.7 and 76.0%, respectively. This study confirms that PSA robustly predicts positive PET/CT result with radiolabeled choline. Unfortunately, this study also confirms the limited sensitivity of F-FCH PET/CT for PSA less than 1 ng/ml, which currently represents the weakest point of the technique.

Consensus Report on Controversial Use of 5-Alpha-Reductase Inhibitor in Patients with Benign Prostatic Hyperplasia under Taiwan National Health Insurance Regulations

Introduction: Although the National Health Insurance regulations for 5-alpha-reductase inhibitor (5ARI) use is well documented, urologists and medical claims review committee members have sometimes felt confused when determining claims for 5ARI use in certain circumstances. Thus, a consensus meeting was held to discuss how to use 5ARI appropriately in such circumstances. Materials and Methods: The expert urologists and medical claim review committee members reviewed seven controversial cases with related clinical evidence and voted for approval of the use of 5ARI after vigorous discussion. Results: Among the seven cases, a consensus was achieved in four. First, transrectal ultrasound of the prostate was not necessary if the patient already had other images. Second, prescribing 5ARI was affirmed in patients who had high prostate-specific antigen but who refused biopsy. Third, the normal prostate-specific antigen range was based on the 2003 version of the consensus of prostatic cancer of the National Health Research Institutes. Four, 5ARI could be prescribed in patients with improved clinical data but who were unable to meet the other regulatory criteria. Finally, of the three remaining cases, one case was denied, and in two cases, half of the members approved, and half rejected the claim for 5ARI use. Conclusion: This consensus report provided clarification for Taiwanese urologists and medical claims review committee members on reimbursable use of 5ARI in controversial cases.

Prognosis of patients with prostate cancer and middle range prostate - specific antigen levels of 20 - 100 ng / mL.

ABSTRACTIntroduction:Prostate - specific antigen (PSA) is a useful biomarker for detection of prostate cancer (PCa) and for risk classification in addition to TNM classification and Gleason score (GS). We reported the role of PSA in patients with low (< 20 ng / mL) and extremely high (≥ 100 ng / mL) PSA levels. However, it is unclear whether a correlation exists between middle range PSA levels (20 – 100 ng / mL) at diagnosis and prognosis.Materials and Methods:Between January 2000 and December 2014, 1873 patients underwent prostate biopsy at Kanazawa University Hospital. Of 802 patients who were diagnosed with PCa, 148 patients with middle range PSA levels (20 – 100 ng / mL) were retrospectively analyzed.Results:The percentage of patients with T3 – 4 consistently increased as PSA levels increased from 20 to 100 ng / mL. Although the percentage of patients with GS ≥ 8 or metastases increased as PSA levels increased up to approximately 70 ng / mL, there was no significant increase between 70 and 100 ng / mL. PCa - specific and castration - resistant PCa - free survivals were adversely associated with PSA levels up to 70 ng / mL, but not between 70 and 100 ng / mL.Conclusion:PSA is a useful biomarker for predicting prognosis at levels between 20 and 70 ng / mL. However, PSA cannot be used as a prognostic factor in patients with PCa and PSA levels ≥ 70 ng / mL. When the PSA level reaches approximately 70 ng / mL, prognosis might bottom and reach a plateau.

Incidence of prostate cancer among patients with prostate-related urinary symptoms: A single institution series in 10 years.

Purpose:The aim of the study is to correlate between the value of digital rectal examination (DRE), serum prostate-specific antigen (PSA), and transrectal ultrasound (TRUS) as predictors for diagnosing prostate cancer in patients with voiding symptoms.Materials and Methods:A total of 1610 male patients seen over a period of 10 years in a single institution had prostate-related voiding problems. Routine studies including DRE and serum PSA were done to all patients. TRUS and TRUS biopsy were performed for patients with suspected prostatic cancer based on abnormal DRE findings and/or serum PSA levels.Results:TRUS biopsy revealed prostate cancer in 206 out of 1610 patients with prostate-related voiding problems (13%), 40% had abnormal PSA and 28% had abnormal DRE. Combined abnormal PSA and DRE revealed cancer in 63% of patients. This percentage increased to 90% when TRUS was also abnormal, but dropped to 54% when TRUS was normal.Conclusions:DRE together with serum PSA and TRUS have the highest predictable values for diagnosis of prostate cancer among patients with voiding symptoms. In the absence of abnormal TRUS, PSA and DRE together are more predictable than either alone. Serum PSA alone is more predictable than DRE. Random prostate biopsies should be performed in the presence of high serum PSA, and/or abnormal findings by DRE in male patients with urinary symptoms suggestive of the prostate disease.

Mean Platelet Volume as an Inflammation Marker, Possible Biomarker of Tumor Detection in Prostate Biopsy

Background: In the diagnosis of prostatic diseases, the need for markers other than prostate specific antigen (PSA) has been increasing in recent years. So, we aimed to determine the predictive value, the neutrophil lymphocyte ratio, platelet-to-lymphocyte ratio and mean platelet volume before prostate biopsy in predicting the results of pathology. Transrectal ultrasound-guided biopsy of the prostate was performed because of high PSA values and compared values of these parameters to predict of pathology results. Methods: 2715 patients who underwent 10 - 12 quadrant transrectal ultrasound-guided prostate biopsies between January 2008 and January 2018 have been evaluated retrospectively. Patients were divided into groups according to the biopsy pathology results by benign (group 1), atypical small acinar proliferation (ASAP) (group 2) and prostate cancer (group 3). A total of 204 patients who were benign prostate hyperplasia in 71 patients (34.8%), atypical small acinar proliferation in 80 (39.21%) and prostate adenocarcinoma (PCa) in 53 patients (25.98%) were included in the study by systematic sampling. Before the biopsy total PSA (tPSA), free PSA (fPSA), rate of percentage of free to total prostate specific antigen (f/tPSA) rate, PSA density (PSA-D), white blood cell (WBC) count, blood neutrophil count (NC), blood lymphocyte count (LC), neutrophil lymphocyte ratio (NLR), mean platelet volume (MPV), platelet count (PLT) and platelet-to-lymphocyte ratio (PLR) were measured and compared in all groups. Differences in continuous variables were assessed using the ANOVA. Logistic regression was used to analyze the linear relationship between predictive variables and pathology results. P Results: NLR and PLR values were lower in group 1 than group 2 and were found statistically significant between in group 1 and group 2 (p: 0.03 and p: 0.02, respectively). MPV value was found 1.7 times higher in patients who were diagnosed with ASAP pathology than those with benign pathologies. Although there was statistically significant increase in MPV values in logistic regression results, no statistically significant diagnostic value was found. In addition MPV value was found 0.5 times higher in patients who were diagnosed patients with ASAP than prostate cancer group. ROC analysis showed that the optimal threshold was 7.65 femtoliter (sensitivity: 51%; specificity: 30%) and was found to be a statistically significant diagnostic value to distinguish groups 2 and 3. The lowest value of MPV was found in group 3. Conclusions: In cases where the PSA value is insufficient in predicting the pathology result, the effect of NLR, PLR and MPV on differential diagnosis can be kept in mind. While NLR and PLR are more useful in the diagnosis of ASAP, MPV is more effective in the diagnosis of malignancy.

Trigeminal Cave Brain Metastasis from Prostate Adenocarcinoma: Case Report and Review of the Literature

The present study presents the case of a 66-year-old patient diagnosed with prostate adenocarcinoma 4 years earlier and treated with prostatectomy, radiotherapy, chemotherapy and hormone therapy but still displaying high prostate-specific antigen (PSA) levels. The patient complaints were double vision and headaches. Upon physical examination, he displayed 6th cranial nerve paresis and 5th cranial nerve paresthesia. A magnetic resonance imaging (MRI) exam was performed, which revealed a mass on the right trigeminal cave. The patient underwent surgical removal of the tumor, and the pathological analysis of the specimen established metastatic prostate cancer as the diagnosis.Brain metastases from prostate cancer are extremely rare and mark advanced disease, with immune system failure and blood-brain barrier breach. Prostate-specific antigen levels do not correlate with the possibility of metastatic disease. Prostate adenocarcinoma is the histologic type most commonly associated with brain metastases, with the meninges being more frequently affected, followed by the brain parenchyma. The neurological symptoms more often displayed are non-focal, such as headaches and mental confusion. Surgery associated with radiotherapy is the most validated treatment.

Retrospective Study of the Significant Predictive Role of Inflammatory Degree in Initial and Repeat Prostate Biopsy Specimens for Detecting Prostate Cancer.

PurposeThe purpose of this study was to determine whether histologic inflammation (HI) in initial and repeat prostate biopsy specimens was significantly associated with the detection of prostate cancer.Materials and MethodsBetween 2005 and 2017, the clinicopathological records of patients with high prostatespecific antigen (PSA) levels who underwent initial and repeat prostate biopsies were retrospectively reviewed. The presence of HI and its degree in each biopsied specimen were interpreted by one uropathologist with 20 years of experience. The association between HI and cancer diagnosis was statistically assessed, with p < 0.05 considered significant, and the cancer and non-cancer groups were compared.ResultsAmong the 522 patients with a median PSA levels of 6.5 ng/dL, including 258 (49.4%) whose cancer was diagnosed following repeat biopsy, the median degrees of HI in the initial and repeat biopsies were 25.0% and 41.7%, respectively. Furthermore, 211 (40.4%) and 247 (47.3%) patients had HI (> 0%) on biopsied specimens, respectively. Comparison of the cancer and noncancer groups revealed that a greater rate of HI specimens in the initial biopsy was associated with fewer prostate cancer diagnoses following repeat biopsy (p < 0.001). Other comparisons between the cancer and non-cancer groups showed that the cancer group had a significantly higher rate of hypertension, whereas those non-cancer group had a significantly higher rate of benign prostatic hyperplasia and prostatitis (p < 0.05).ConclusionA finding of a lesser degree of HI in the initial and a greater degree of HI in the repeat biopsied specimens was associated with the higher probability of cancer diagnosis in patients with high PSA levels.

Prostate cancer disparities in Hispanics by country of origin: a nationwide population-based analysis.

We sought to evaluate prostate cancer (PCa) characteristics and outcomes of Hispanics living in the United States by country of origin in the Surveillance, Epidemiology and End Results (SEER) program. Retrospective analysis of 72,134 adult Hispanics with PCa between 1995 and 2014. Origin was Mexican (N = 16,995; 24%), South/Central American (N = 6949; 10%), Puerto Rican (N = 3582; 5%), Cuban (N = 2587; 4%), Dominican (N = 725; 1%), Hispanic not specified (NOS, N = 41,296; 57%), as coded by SEER. Patient and PCa characteristics were analyzed with chi-square and Kruskal-Wallis tests. Overall and PCa survival were analyzed with Kaplan-Meier and Cox models adjusting for baseline variables. At diagnosis, Mexicans had more advanced stage, higher prostate-specific antigen, and higher Gleason score while Cubans and Dominicans had more favorable PCa at diagnosis (all P < 0.05). After a median follow-up of 69 months, 20,317 men died, including 6223 PCa deaths. Compared to Mexicans, Cubans (HR = 1.22, 95% CI = [1.14-1.30]) and Puerto Ricans (HR = 1.15 [1.08-1.22]) had worse overall survival while Dominicans (HR = 0.76 [0.64-0.91]), South/Central Americans (HR = 0.68 [0.65-0.72]), and NOS (HR = 0.81 [0.78-0.84]) had better overall survival. Compared to Mexicans, Cubans (HR = 1.08 [0.96-1.22]) and Puerto Ricans (HR = 1.03 [0.92-1.15]) had similar PCa survival while Dominicans (HR = 0.72 [0.53-0.98]), South/Central Americans (HR = 0.67 [0.60-0.74]), and NOS (HR = 0.68 [0.64-0.73]) had significantly better PCa survival. Among Hispanics in the United States, disparities in PCa characteristics and survival by country of origin exist, with Dominicans, South/Central Americans, and Hispanic NOS having better PCa survival compared to Mexicans, Cubans, and Puerto Ricans.

Hypoechoic versus hypervascular lesion in the diagnosis of prostatic carcinoma

ObjectiveThe goal of this study was to get a better understanding the role of Power Doppler (PDUS) and conventional Gray Scale transrectal ultrasound (TRUS) in targeting prostatic biopsy in men with high prostate-specific antigen (PSA). Patients and methodsA prospective comparative study of 100 men, categorized according to PSA level into two groups: Group (A) with a PSA level (4.0–10.0) ng/ml (Gray zone) and Group (B) with PSA >10.0 ng/ml, above Gray zone. Gray Scale scanning was done, followed by Color Doppler and Power Doppler to test the blood flow all over the prostate and suspicious foci. Twelve systematic TRUS-guided core needle biopsies were performed, and additional biopsies of abnormal lesions on Gray Scale TRUS and PD-TRUS. The demographic data, clinical data, imaging results, laboratory investigations, histopathological report and its correlation with pathological results and any complications during or post the procedure estimated. ResultsThe age of the Group (A) ranged between 50 and 75 years with a mean ± S.D. of 65.7 ± 6.8 years, while in the Group (B), it ranged between 54 and 84 years with a mean ± S.D. of 69.5 ± 6.3 years. TRUS biopsy revealed prostate cancer in 11 (35.5%) out of 31 cases of the Group (A) and 35 (50.7%) out of 69 cases of the Group (B) (p < 0.003). Thirty out of 39 (76.9%) from Group (B) were hypervascular in PDUS (p < 0.04).PDUS sensitivity, specificity, positive predictive value (PPV) and negative predictive values were 74.5%, 85.7%, 84.4% and 76.4%. ConclusionPower Doppler ultrasonography (PDUS) increase the cancer detection rate diagnosis, PDUS combination with Gray Scale TRUS-guided biopsy increases the reliability of the diagnosis of cancer prostate.

Prostate-Specific Antigen Trends Predict the Probability of Prostate Cancer in a Very Large U.S. Veterans Affairs Cohort

If prostate-specific antigen (PSA) trends help identify elevated prostate cancer (PCa) risk, they might provide early warning of progressing cancer for further evaluation and justify annual testing. Our objective was to determine whether PSA trends predict PCa likelihood. A biopsy cohort of 361,657 men was obtained from a Veterans Affairs database (1999–2012). PSA trends were estimated for the 310,458 men with at least 2 PSA tests prior to biopsy. Cancer tumors may grow exponentially with cells doubling periodically. We hypothesized that PSA from prostate cancer grows exponentially above a no cancer baseline. We estimated PSA trends on that basis along with five descriptive variables: last PSA before biopsy, growth rate in PSA from cancer above a baseline, PSA variability around the trend, number of PSA tests, and time span of tests. PSA variability is a new variable that measures percentage deviations of PSA tests from estimated trends with 0% variability for a smoothly increasing trend. Logistic regression models were used to estimate relationships between the probability of PCa at biopsy and the trend variables and age. All five PSA trend variables and age were significant predictors of prostate cancer at biopsy (p < 0.0001). An overall logistic regression model achieved an AUC of 0.67 for men with at least 4 tests over at least 3 years, which was a substantial improvement over a single PSA (AUC 0.58). High probability of PCa was associated with low PSA variability (smooth trends), high PSA, high growth rate, many tests over a long time-span and older age. For example, at 4.0 PSA the probability of cancer is 32% for 1 PSA test and increases to 68% for 8 tests over 7 years with smooth, fast growth (0% variability and 50% exponential growth). Our results show that smooth, fast exponential growth in PSA above a baseline predicts an increased probability of PCa. The probability increases as smooth (low variability) trends are observed for more tests over a longer time span, which makes annual testing worth considering. Worrisome PSA trends might be used to trigger further evaluation and continued monitoring of the trends—even at low PSA levels.

Qué debe saber el médico de primaria sobre los nuevos marcadores en el cáncer de próstata

The use of prostate-specific antigen as a diagnostic tool in the screening of prostate cancer is reflected in an increase in the incidence, an increase in diagnosis at initial stages, and an increase in radical therapies, even at the expense of over-treatment in some cases. It is known from the data collected in the literature that not every patient with high prostate-specific antigen needs a biopsy, and that not every patient diagnosed with prostate cancer needs treatment. With the new emerging prostate markers, we will try to improve the specificity of prostate-specific antigen in the grey area (4-10 ng/ml) should be improved. This should avoid unnecessary biopsies. The sensitivity in the detection of significant prostate cancer with low prostate-specific antigen should also be improved in an attempt to reduce the risk of over-treatment. On the other hand, prognostic biomarkers with genomic tests will help to choose the best therapeutic option for the patient.

Oncologic and functional outcome of partial gland ablation with HIFU for localized prostate cancer

We assessed the outcomes of high intensity focused ultrasound as primary treatment of localized prostate cancer in a retrospective series. This represents one of the largest published series of patients at intermediate and high risk. We performed a retrospective multicenter analysis of patients who underwent partial gland ablation between January 2013 and September 2017. Patients with biopsy proven localized disease and limited multifocality based on magnetic resonance imaging who preferred minimally invasive outpatient therapy were treated with the Sonablate® 500 system. Oncologic and functional outcomes were analyzed as well as risk factors for recurrence. A total of 166 procedures were performed in 150 patients. Grade Group 2 or greater was present in 89% of cases. Mean ± SD followup was 24.3 ± 14.4 months. Mean prostate specific antigen decreased 65% from 7.9 ± 6.8 ng/ml to a nadir of 2.7 ± 3.1 ng/ml. Confirmatory biopsies were performed in 87 patients (52%) at high risk for recurrence. Clinically significant cancer (Grade Group 2 or greater) was detected in 37 cases (42%). Patients with a higher number of positive cores, a medial tumor location or higher prostate specific antigen had a higher probability of recurrence. Salvage treatment was done in 37 patients (24.6%), including 16 repeat partial gland ablation procedures. Partial gland ablation with high intensity focused ultrasound therapy was safe and it had a minimal impact on functional outcomes. Local recurrence and/or failure occurred in 42% of patients at high risk for recurrence. Medially located tumors were associated with a higher failure rate. Serious complications were rare. Whole gland treatment was avoided in 81% of patients.

Relationship between the metabolic syndrome and the risk of prostate cancer

Objective To evaluate the relationship between the metabolic syndrome and the risk of prostate cancer. Methods The clinical data of 118 patients with primary prostate cancer who were admitted to the Beijing Friendship Hospital, Capital Medical University from February 2013 to September 2017 were retrospectively analyzed.All the patients were divided into metabolic syndrome group (n=50) and non-metabolic syndrome group (n=68) according to the diagnosed standard of metabolic syndrome. The patients′ clinical data were expressed as percentage(%) and collected including age between the two groups, body mass index, blood pressure, fasting blood glucose, triglyceride, high density lipoprotein, low density lipoprotein, prostate volume, prostate specific antigen (PSA) value, Gleason score and TNM staging. The data were analysed by the statistical analysis method. Chi-square test was used to compare the enumeration data. Measurement data were expressed as (±s), and using t test comparison between groups. The relationship between various variable factors and prostate cancer used multivariate logistic regression analysis. Results There was no significantly difference between the two groups including age, blood pressure, triglyceride, low density lipoprotein and Gleason score (P>0.05). The body mass index, fasting blood glucose and prostate volume in the metabolic syndrome group [(26.62±16.43) kg/m2, (8.1±1.7) mmol/L, (50.1±12.2) ml] are significantly higher than in the non-metabolic syndrome group[(22.16±15.64) kg/m2, (6.3±1.5) mmol/L, (40.3±14.1) ml] (P<0.05). The high density lipoprotein and PSA value in the metabolic syndrome group [(0.9±0.4) mmol/L, (21.4±7.9) ng/dl] were significantly lower than in the non-metabolic syndrome group [(1.40±0.64) mmol/L、(36.2±8.2) ng/dl] (P<0.05). The proportion of high-risk prostate cancer in the metabolic syndrome group(62%, 31/50) was significantly higher than that in the non-metabolic syndrome group(33.8%, 23/68), P<0.05. Logistic regression analysis showed that the body mass index and high density lipoprotein hypertension had a positive correlation with high risk of prostate cancer. Conclusions The metabolic syndrome might increase the incidence risk of high risk of prostate cancer. The two components of metabolic syndrome, body mass index and high density lipoprotein, should be paid attention in clinical practice. Key words: Prostatic neoplasms; Metabolic syndrome; Risk factors

Nationwide treatment patterns and survival of older patients with prostate cancer.

To examine the clinical features, applied treatments, and survival of older patients with prostate cancer compared with younger patients. All patients diagnosed with prostate cancer between 2005 and 2015 in the Netherlands were identified from the nationwide population-based Netherlands Cancer Registry (NCR). Patient and tumour characteristics, as well as applied treatments, were described by age groups and prognostic risk groups. Relative survival rates were determined, including multivariable relative survival regression analyses. Additionally, to assess if age was associated with receiving curative treatment, a multivariable logistic regression analysis was performed. In total, 48% of all patients were 70 years of age or older. Older patients had a higher prostate specific antigen (PSA) level, a higher Gleason score, as well as a higher disease stage at diagnosis. The 10-year relative survival decreased with increasing age, and after adjustment for disease stage, Gleason score, PSA level, and comorbidities, older patients had a worse survival rate. Older patients with intermediate- or high-risk disease appeared to be treated less often with curative intent compared with younger patients after adjustment for tumour stage, Gleason score, PSA level, and comorbidities. Older patients with intermediate/high risk prostate cancer treated with curative intent showed a 10-year relative survival rate similar to younger patients. The survival of older patients was worse than younger patients. This might be due to suboptimal treatment, as older patients were less often treated with curative intent. Although the increased risk of treatment complications should be considered, age alone should not be a decisive factor when offering a treatment.

Abstract 2201: Prostate-specific antigen velocity is associated with future prostate cancer mortality among men in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Abstract Higher prostate-specific antigen (PSA) velocity (change in PSA over time) measured after diagnosis or treatment is associated with poorer prognosis for prostate cancer patients. However, less is known about the association between PSA velocity measured prior to a diagnosis of cancer and future prostate cancer mortality. We evaluated whether PSA velocity is associated with the risk of prostate cancer mortality among men without a history of prostate cancer in the screening arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. As part of the PLCO trial, men in the screening arm were offered PSA screening at baseline in the trial and annually thereafter for five years. From the screening arm, we included 33,961 men who had at least two prediagnostic trial PSA measurements (to allow for PSA velocity calculation), among whom 167 later died of prostate cancer. We estimated PSA velocity and initial PSA concentration for each participant from the random slope and random intercept terms in a mixed effects model based on up to the first three trial PSA measures per person since participants varied in the number of available measures. We defined our study baseline for survival analysis as the time of the last PSA measurement used to calculate PSA velocity. Participants were 55 to 79 years of age at our study baseline, and we followed them for up to 18 years (through Dec. 31, 2012) for prostate cancer mortality, with a median follow-up time of 12.7 years (interquartile range: 10.7-14.4 years). We dichotomized PSA velocity as &amp;lt;0.4 vs. ≥0.4 ng/mL/year for comparison with previous studies. We analyzed the association between PSA velocity and prostate cancer mortality using Cox proportional hazards regression, adjusting for initial PSA concentration, age, race, body mass index, our study baseline year, and past finasteride use. Higher PSA velocity was associated with an increased hazard of prostate cancer mortality compared to lower PSA velocity [Hazard Ratio (HR)=2.5, 95% Confidence Interval (CI): 1.7-3.7]. Additional adjustment for family history of prostate cancer or comorbidities did not appreciably alter findings. When we stratified by age at our study baseline, we observed a stronger association among men who were less than 70 years of age (HR=3.1, 95% CI: 1.9-4.9) than among those who were 70 years of age or older (p-interaction=0.04). In conclusion, in this large prospective study, higher prediagnostic PSA velocity was associated with an increased risk of prostate cancer mortality. Our findings suggest a potential benefit of using longitudinal PSA measures in predicting future prostate cancer mortality. Citation Format: Erik Barr, Sonja I. Berndt, John D. Sorkin, Wen-Yi Huang, Kathryn Hughes Barry. Prostate-specific antigen velocity is associated with future prostate cancer mortality among men in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial [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 2201.

External Validation of Models Predicting the Probability of Lymph Node Involvement in Prostate Cancer Patients

BackgroundMultiple statistical models predicting lymph node involvement (LNI) in prostate cancer (PCa) exist to support clinical decision-making regarding extended pelvic lymph node dissection (ePLND). ObjectiveTo validate models predicting LNI in Dutch PCa patients. Design, setting, and participantsSixteen prediction models were validated using a patient cohort of 1001 men who underwent ePLND. Patient characteristics included serum prostate specific antigen (PSA), cT stage, primary and secondary Gleason scores, number of biopsy cores taken, and number of positive biopsy cores. Outcome measurements and statistical analysisModel performance was assessed using the area under the receiver operating characteristic curve (AUC). Calibration plots were used to visualize over- or underestimation by the models. Results and limitationsLNI was identified in 276 patients (28%). Patients with LNI had higher PSA, higher primary Gleason pattern, higher Gleason score, higher number of nodes harvested, higher number of positive biopsy cores, and higher cT stage compared to patients without LNI. Predictions generated by the 2012 Briganti nomogram (AUC 0.76) and the Memorial Sloan Kettering Cancer Center (MSKCC) web calculator (AUC 0.75) were the most accurate. Calibration had a decisive role in selecting the most accurate models because of overlapping confidence intervals for the AUCs. Underestimation of LNI probability in patients had a predicted probability of <20%. The omission of model updating was a limitation of the study. ConclusionsModels predicting LNI in PCa patients were externally validated in a Dutch patient cohort. The 2012 Briganti and MSKCC nomograms were identified as the most accurate prediction models available. Patient summaryIn this report we looked at how well models were able to predict the risk of prostate cancer spreading to the pelvic lymph nodes. We found that two models performed similarly in predicting the most accurate probabilities.

The Role of YKL-40 in Predicting Resistance to Docetaxel Chemotherapy in Prostate Cancer

Introduction: High baseline YKL-40 serum levels are associated with drug resistance in several solid tumours. However, their role in predicting docetaxel (DOC) resistance in prostate cancer (PCa) is unknown. Methods: Pre-treatment serum levels of YKL-40 and prostate-specific antigen (PSA) were analyzed in 109 castration-resistant prostate cancer patients who underwent DOC-therapy. Responsive patients were retreated by repeated series of DOC. Results were compared with the clinical parameters as well as overall (OS) and disease-specific survival (DSS). Results: YKL-40 but not PSA serum levels were significantly higher in patients with baseline resistance to DOC (p = 0.035). Higher YKL-40 and PSA levels were detected in patients with bone metastasis (p = 0.032; p = 0.010) and in those who were not pre-treated with radical prostatectomy (p = 0.011, p = 0.008). High YKL-40 levels were associated with shorter OS (p = 0.037) and DSS (p = 0.017) in patients who received DOC in the first-line setting. In multivariable analysis, ECOG performance status (p = 0.009), presence of any metastases (p = 0.016) and high PSA levels (p = 0.005) remained independent predictors for DSS. Conclusions: YKL-40 may help to identify patients with baseline resistance to DOC and therefore may help to optimize treatment decisions. In accordance, high pre-treatment YKL-40 serum levels were associated with shorter OS and DSS in patients who received DOC as first-line therapy.

Testosterone treatment and the risk of aggressive prostate cancer in men with low testosterone levels.

PurposeTestosterone treatment of men with low testosterone is common and, although relatively short-term, has raised concern regarding an increased risk of prostate cancer (CaP). We investigated the association between modest-duration testosterone treatment and incident aggressive CaP.Materials and methodsRetrospective inception cohort study of male Veterans aged 40 to 89 years with a laboratory-defined low testosterone measurement from 2002 to 2011 and recent prostate specific antigen (PSA) testing; excluding those with recent testosterone treatment, prostate or breast cancer, high PSA or prior prostate biopsy. Histologically-confirmed incident aggressive prostate cancer or any prostate cancer were the primary and secondary outcomes, respectively.ResultsOf the 147,593 men included, 58,617 were treated with testosterone. 313 aggressive CaPs were diagnosed, 190 among untreated men (incidence rate (IR) 0.57 per 1000 person years, 95% CI 0.49–0.65) and 123 among treated men (IR 0.58 per 1000 person years; 95% CI 0.48–0.69). After adjusting for age, race, hospitalization during year prior to cohort entry, geography, BMI, medical comorbidities, repeated testosterone and PSA testing, testosterone treatment was not associated with incident aggressive CaP (HR 0.89; 95% CI 0.70–1.13) or any CaP (HR 0.90; 95% CI 0.81–1.01). No association between cumulative testosterone dose or formulation and CaP was observed.ConclusionsAmong men with low testosterone levels and normal PSA, testosterone treatment was not associated with an increased risk of aggressive or any CaP. The clinical risks and benefits of testosterone treatment can only be fully addressed by large, longer-term randomized controlled trials.

Prebiopsy biparametric MRI: differences of PI-RADS version 2 in patients with different PSA levels

To validate the diagnostic accuracy of Prostate Imaging-Reporting and Data System (PI-RADS) version 2 in detecting clinically significant prostate cancer (csPCa, Gleason score ≥7) on prebiopsy biparametric MRI (bpMRI) in patients with different prostate-specific antigen (PSA) levels. This retrospective study included 184 patients who underwent prebiopsy bpMRI followed by transrectal ultrasonography-guided biopsy between June 2015 and February 2017. Reader 1 performed a combination of systematic and targeted biopsy with cognitive fusion after reviewing bpMRI and reader 2 reviewed the bpMRIs retrospectively. PI-RADS categories 4 and 5 were considered positive, and the results of the biopsy were considered the reference standard. Diagnostic performance of PI-RADS of bpMRI was evaluated in two PSA groups with a PSA cut-off level of 10ng/ml and compared to PSA and the PSA density using receiver operating characteristics (ROC) curve analysis. csPCa was diagnosed in 24 of 123 patients (19.5%) and 26 of 61 patients (42.6%) in the low and high PSA groups, respectively. A PI-RADS v2 category by either readers 1 or 2 had a significantly better performance to detect csPCa than PSA in both PSA groups. In the high PSA group, only one csPCa was missed by reader 2, but none by reader 1. In the low PSA group, readers 1 and 2 were unable to detect seven and five of the 24 csPCas, respectively. Prebiopsy bpMRI has good performance for detecting csPCa in the high PSA group but may miss small-volume csPCa in the low PSA group.