bluuebunny/crossref_metadata_2025_split huggingface dataset:
PSA doubling time (PSADT) and serum testosterone (T) during intermittent androgen deprivation (IAD) in patients with biochemically relapsed prostate cancer (BRCP; M0): Potential predictive implications.
Authors: Keizman D. , Huang P. , Antonarakis E. S. , Sinibaldi V. J. , Carducci M. A. , Denmeade S. R. , Eisenberger M. A. 
Published: February 2017

150 Background: The systemic management of patients with BRPC remains controversial. IAD is commonly employed. Aims: To evaluate the PSA dynamics and serum T in pts with BRPC treated with IAD until the development of PSA refractoriness or clinical evidence of metastatic disease. Methods: Data were retrospectively analyzed in all pts with BRCP treated with GnRH at PSA thresholds according to pre-treatment PSADT (10-15ng/mL, 15-20, and 20-30 for PSADT ≤3 mos, 3-9 mos, and ≥ 9 ms, respectively) and continued until PSA nadir. Antiandrogen (AA) was added for PSA > 1.0 ng/mL after 3 mos). Follow-up (FU) consisted of PSA and T q3 mos. Cycles were repeated at the above preselected PSA thresholds and continued until lack of PSA response. Scans were obtained prior to cycles and at the time of CRPC state. Mixed effects model was used to study PSADT change over cycles. Multivariate cox regression model was used to identify prognostic variables. Results: From 1995-2010, with a mean FU of 71 mos (range 22-183 months), 96 pts received a mean of 2.8 cycles (range 1-9) of IAD; 58 (60%) remain on treatment and 38 (40%) were switched to continuous ADT due to PSA refractoriness (n=11) or positive scans (n=27). PSADT at the first off treatment (tx) interval (mean 3.1, 0.59-30.5 range, median 2.3) was significantly shorter than the baseline (p<0.0001; mean 9.7, range 0.27-53.9, median 7.34) but remained relatively stable (p=0.29) in subsequent cycles. PSADT adjusted for T recovery (≥3 ms after T recovery to ≥ 150 ng/dL) was significantly longer (p=0.006) than that based only on all PSA determinations (mean 5.4, range 1.31-30.5, median 3.7 versus mean 3.1, range 0.59-30.5, median 2.3). Significant factors associated with probability of PSA refractoriness were pre-IAD PSADT (≥ 6 vs <6 ms), first off tx interval PSADT (≥3 ms vs <3m), the use of AA during first tx cycle, and PSA nadir during the first tx interval (<0.1 vs ≥0.1 ng/mL). Conclusions: Our data suggest that PSADT becomes shorter after the initial cycle of IAD and correlate with T recovery. PSA dynamics and need for AA to enhance PSA nadir are associated with PSA refractoriness in pts BRPC treated with IAD. No significant financial relationships to disclose.
On-target activity of neoadjuvant cixutumumab and combined androgen deprivation therapy for high-risk prostate cancer: A phase II trial.
Authors: Dean J. P. , Montgomery R. B. , Wan J. , Cohen P. , Haugk K. , Corman J. M. , Ellis W. J. , Dalkin B. L. , Ludwig D. L. , Plymate S. R. 
Published: February 2017

153 Background: IMC-A12 (cixutumumab) is a fully human monoclonal antibody which targets the insulin-like growth factor receptor 1. Preclinical data suggests that the combination of androgen deprivation and IMC-A12 is much more effective than either treatment alone. This clinical trial tests the effectiveness of the combined treatment in a neoadjuvant fashion before radical prostatectomy. We have assayed serum samples from the first 18 patients to identify signs of on-target activity in this setting. Methods: Eligible men with high risk localized prostate cancer are defined by one of the following: Gleason score ≥ 8, PSA ≥ 20, Clinical Stage T2c-T3, or a risk for relapse exceeding 50% as defined by the Kattan nomogram. Men are treated for 3 months with goserelin, bicalutamide, and biweekly IMC-A12 infusions (10 mg/kg). The primary objective of the trial is to determine the rate of pathological complete response with an accrual goal of 28 men. Using samples from the first 18 patients on study, serum protein markers were assayed by ELISA and serum PSA and glucose levels were determined by clinical laboratory analysis. Results: Significant increases in c-peptide (1.7-fold, p<0.01), IGF-I (4.1-fold, p<0.01), IGF-II (1.32-fold, p<0.001), IGFBP-3 (1.9-fold, p<0.01), growth hormone (8-fold, p<0.01) were noted after initiation of ADT+IMC-A12, compared to pre-treatment levels. Non-significant increases of insulin (1.9-fold), IGFBP-1 (2-fold), and glucose (1.24-fold) levels were seen. Stratification of patients by nadir PSA levels correlated with residual tumor volume, likelihood of positive surgical margins and likelihood of lymph node metastases. Interestingly, patients with lower nadir PSA levels had smaller increases in c-peptide (50%, p<0.01), insulin (66%, p<0.02) and blood sugar (21%, P<0.01) compared to the patients with higher nadir PSA levels. Conclusions: Combined with ADT in the neoadjuvant setting, IMC-A12 effectively targets the IGF-1R axis in prostate cancer patients. Metabolic differences between patients may alter the efficacy of IMC-A12 in this setting. [Table: see text]
Maintenance of the suppressed level of serum testosterone by administration of three-monthly formulations of luteinizing hormone-releasing hormone agonists at six-month intervals in Japanese patients with prostate cancer: A prospective study.
Authors: Fujii Y. , Yoshida S. , Yokoyama M. , Iimura Y. , Numao N. , Saito K. , Koga F. , Masuda H. , Kawakami S. , Kihara K. 
Published: February 2017

159 Background: Treatment with an LH-RH agonist is a standard alternative to surgical castration for prostate cancer patients. The serum testosterone level is kept at castrate levels continuously during LH-RH agonist therapy in almost all patients (Fujii Y, BJU Int 2008). LH- RH agonists, however, are more expensive than surgical castration, with drugs costing between US $300 and $500 per month in Japan. Recent studies suggest that 3-monthly formulations of LH-RH agonists suppress the serum testosterone levels far longer than the 3-month dosing interval. Methods: A total of 43 Japanese patients with prostate cancer who were treated with 3-monthly LH-RH agonists (23 with 11.25mg leuprolide, and 20 with 10.8 mg goserelin) for one year or longer and whose testosterone levels were kept at castrate level (defined as < 50 ng/dL) were entered into this prospective, longitudinal study. After entry, the 43 men received the same 3-monthly LH-RH agonists at 6-month intervals, and had serum LH and testosterone tests performed at 3-month intervals. Bicalutamide was combined with the LH-RH agonists in 12 of the patients. Results: At entry, median patient age was 74 years (range 59 to 89), median duration of LH-RH agonists treatment was 26 months (12 to 125), and median LH and testosterone levels were <10 ng/dL (<10 to 60) and 5 ng/dL (<5 to 18), respectively. The 43 patients received a total of 162 administrations (median 5, range 1 to 6) of the LH-RH agonists at 6-month intervals, and had a total 335 hormonal tests (median 10, range 2 to12) performed during the median followup period of 30 months. Serum LH and testosterone levels were kept suppressed during the treatment. Of the 43 patients, two had serum testosterone just above the castrate level (54 and 56 ng/dL) once each among their 12 and 8 hormonal assays, respectively. Conclusions: Administration of 3-monthly LH-RH agonists, either leuprolide or goserelin, at 6-month intervals could maintain the castrate level of serum testosterone at least in Japanese prostate cancer patients who have received LH-RH agonists treatment for one year or longer. No significant financial relationships to disclose.
Evaluation of oral cyclophosphamide activity by CTC enumeration in patients with docetaxel-refractory castration-resistant metastatic prostate cancer: Potential utility in primary refractory disease.
Authors: Goodman O. B. , Symanowski J. T. , Fink L. M. , Vogelzang N. J. 
Published: February 2017

166 Background: Recent data suggest that circulating tumor cell (CTC) enumeration is a surrogate predictive endpoint for survival in metastatic castration-resistant prostate cancer (mCRPC). Data supporting the notion of changing therapy from docetaxel based on CTC numbers is limited in PC, due to a limited experience with second-line systemic therapies following docetaxel failure. Methods: Peripheral blood from patients receiving cyclophosphamide following progression on docetaxel was analyzed by CellSearch Methodology (Veridex, LLC; Warren NJ) enumerate CTC. Circulating tumor cells were enumerated prior to and at least three weeks following the initiation of cyclophosphamide. Patients were categorized as responsive, defined as a follow up CTC of <5 cells or a greater than a 90% decline in counts between CTC determinations, or refractory (all others). Cyclophosphamide responsiveness was then correlated with docetaxel responsiveness using a Fisher-exact test. Results: Twenty two patients received oral cyclophosphamide therapy (50-150 mg/day). Of these, twelve (55%) were clinically primary docetaxel refractory, assessed by either clinical or PSAWG2 criteria while on docetaxel, and ten (45%) were initially responsive but subsequently progressed on docetaxel. Of the twelve patients who were primarily refractory to docetaxel, seven (58%) exhibited a cyclophosphamide response. In the majority of these cases, this response was durable with a complete disappearance of CTC. Conversely, only one patient (10%) who initially responded to docetaxel was sensitive to cyclophosphamide (P=0.031). Conclusions: Using a CTC endpoint cyclophosphamide appears to be active in patients initially refractory to docetaxel, but not those who initially responded. These data support the further evaluation of the potential for selective clinical utility of cyclophosphamide as second-line chemotherapy. [Table: see text]
A phase I study of TRC105 (anti-CD105 monoclonal antibody) in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Adelberg D. , Apolo A. B. , Madan R. A. , Gulley J. L. , Pierpoint A. , Kohler D. R. , Trepel J. B. , Steinberg S. M. , Figg W. D. , Dahut W. L. 
Published: February 2017

171 Background: TRC105 is a human/murine chimeric IgG1 monoclonal antibody to CD105 (endoglin) that inhibits angiogenesis and tumor growth through inhibition of endothelial cell (EC) proliferation, antibody-dependent cellular cytotoxicity and induction of apoptosis. CD105 is highly expressed on proliferating vascular ECs. Preclinical and clinical evidence demonstrates an important role for angiogenesis in mCRPC biology. Methods: The primary objective is to evaluate safety and identify the maximum tolerable dose of TRC105. Secondary objectives include the assessment of TRC105 pharmacokinetics, PSA response rate and overall response rate (ORR). Eligibility requires ECOG performance status (PS) ≤ 2 and progressive mCRPC. Three cohorts of 3-6 patients receive TRC105 at doses of 1, 3 or 10 mg/kg IV over 1–4 hours every 2 weeks of a 4 week cycle. Premedications are dexamethasone, acetaminophen, famotidine, and diphenhydramine. PSA is evaluated prior to each treatment and response is assessed every 2 cycles with imaging studies. Results: Eight patients are enrolled in cohorts 1–3. Median age is 65 (range 47–84), ECOG PS 1 (1–2), Gleason score 8 (6–10), on–study PSA 201 (0.10 – 3,373), and number of prior therapies after gonadotropin-releasing hormone agonist or anti-androgen therapy 2.5 (0–6). Median time on study is 14 weeks (7–16). Dose-limiting toxicity was not observed. Grade 1 to 2 infusion reactions occurred in 4 patients. PSA declines were seen in both patients in cohort 3 (26% and 51% from baseline); each had progressed on docetaxel and at least one second-line agent. Five of 6 evaluable patients with measurable soft tissue disease achieved stable disease (2 in cohort 1, 2 in cohort 2 and 1 in cohort 3); the latter 3 patients in cohorts 2 and 3 remain on study. Conclusions: TRC105 is tolerated at doses up to 10 mg/kg every 2 weeks with early evidence of clinical activity in patients with mCRPC. Accrual is ongoing to evaluate higher doses and more frequent dosing. No significant financial relationships to disclose.
Obese men, higher PSA nadir values after radical prostatectomy (RP), and higher biochemical recurrence (BCR) rates: Results from the SEARCH database.
Authors: Ho T. S. , Aronson W. J. , Terris M. K. , Presti J. C. , Kane C. J. , Amling C. L. , Freedland S. J. 
Published: February 2017

186 Background: Obesity is associated with risk of BCR after RP. It has been suggested this may be due to poor surgical technique and greater risk of positive margins. We examined whether obesity predicted the risk of a detectable PSA nadir after RP (as a measure of residual PSA-producing tissue left behind) and if this accounted for the greater risk of BCR in obese men in the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Methods: We identified 1,011 men treated with RP from 2001 to 2010 in SEARCH who had known data for pre-operative BMI and ultrasensitive PSA nadir within 6 months after RP. The association between BMI (<25, 25-29.9, and >30 kg/m2) and PSA nadir (0, 0.01-0.09, 0.10-0.19, and >0.2) was tested using chi-squared and linear regression adjusting for clinical and pathological characteristics. A proportional hazards model was used to test the association between BMI and BCR adjusted for clinical and pathological characteristics and with and without PSA nadir. Results: Higher BMI was associated with higher PSA nadir (chi-squared, p=0.03). On multivariate analysis, obesity (p<0.001) was associated with higher PSA nadir. Among men with a PSA nadir <0.2 ng/ml (i.e. those who did not recur based upon PSA nadir alone), obesity was associated with BCR when not adjusted for PSA nadir (HR 1.85, 95% CI 1.19-2.89, p=0.007). Adjusting for PSA nadir attenuated, but did not eliminate this association (HR 1.65, 95% CI 1.05-2.59, p=0.03). Even among men with an undetectable PSA nadir, obesity remained significantly associated with BCR (HR 3.45, 95% CI 1.41-8.47, p=0.007). Interestingly, among men with a detectable PSA nadir, but <0.2 ng/ml, obesity did not predict BCR with (HR 1.21, 95% CI 0.71-2.07, p=0.49) or without adjustment for PSA nadir (HR 1.41, 95% CI =0.82-2.41, p=0.22). Conclusions: Obese men are more likely to have a higher PSA nadir suggesting technical issues confound an ideal operation in obese men. However, the increased PSA nadir does not completely explain the higher PSA recurrence rates. These data further support the idea that obesity is biologically associated with prostate cancer progression. No significant financial relationships to disclose.
Biopsy Gleason score and the duration of testosterone suppression among men treated with external beam radiation and six months of combined androgen blockade.
Authors: Martin N. E. , Chen M. , Nguyen P. L. , Beard C. , Kantoff P. W. , D'Amico A. V. 
Published: February 2017

191 Background: An increased duration of testosterone (T) suppression (TS) after 6 months (mo) of combined hormonal blockade (CHB) with an LHRH agonist and an anti-androgen plus external beam radiation therapy (RT) is associated with decreased mortality. We investigated whether the biopsy Gleason score (BGS) was associated with duration of TS. Methods: The study cohort consisted of 120 men with node negative prostate cancer (PCa) treated with RT and 6 mo of CHB between 1996 and 2005 at a single academic and associated suburban center. We defined the duration of TS as the time between the last day of CHB and the date the T returned to ≥252 ng/dL (10% below the lower limit of normal on the assay used). We used Cox regression multivariable analysis to determine whether BGS was significantly associated with the duration of TS following cessation of CHB adjusting for age, PSA, baseline T, clinical tumor category, body mass index and a history of diabetes mellitus. Results: The median age of the cohort was 70.1 years (IQR: 64.7, 73.9). The median time to T rebound (MTR) was 19.5 mo for all men (table). BGS 8-10 had an adjusted hazard ratio (AHR) of 1.85 (95% confidence interval [CI] 1.06-3.22; p=0.03) indicating a faster time to T rebound. Specifically men with BGS 8-10 had a MTR of 14.0 mo compared to 19.5 and 22.4 mo for the Gleason ≤6 and 7 respectively. Increasing age was significantly associated with a longer duration of TS [AHR of 0.95 (95% CI 0.92-0.98; p<0.001)]. Conclusions: A BGS of 8-10 is associated with a shorter period of TS following 6 mo of CHB + RT. These data are consistent with the hypothesis that a factor released from high grade PCa cells may impact T production. [Table: see text] No significant financial relationships to disclose.
Nomograms based on the Tyrol screening data of 2,271 patients to predict prostate cancer biopsy positivity.
Authors: Sooriakumaran P. , John M. , Bektic J. , Bartsch G. , Herman M. , Scherr D. , Tewari A. 
Published: February 2017

203 Background: There are no published nomograms that predict prostate cancer in a screened population. We describe three nomograms that predict for prostate cancer on biopsy derived from a large screening population. Methods: Patients from the Tyrol screening study of known age, total prostate-specific antigen (tPSA), digital rectal examination (DRE), prostate volume, and percent free PSA (%fPSA), and who underwent an initial prostate biopsy from January 1992 to June 2004, were included (n=2271). Multivariable logistic regression models were used to develop the biopsy positivity predictive nomograms: nomogram 1- age, DRE, tPSA; nomogram 2- age, DRE, tPSA, prostate volume; nomogram 3- age, DRE, tPSA, prostate volume, %fPSA. The predictive accuracy of the models was assessed in terms of discrimination and calibration. External validation of the nomograms was performed by comparison with a urologically referred population of patients who underwent prostate biopsy (n=599). Results: All three nomograms discriminated well between biopsy positive and biopsy negative patients for both the screening and urologically referred cohorts (nomogram 3 better than nomogram 2 better than nomogram 1). All three nomograms were well calibrated internally, but the nomograms under-predicted the probability of a positive biopsy in the urologically referred cohort. Conclusions: Our nomogram based on age, total PSA, and DRE has a good predictive ability to differentiate between screened patients that will show cancer on initial prostate biopsy and those that will not. Adding prostate volume and percent free PSA improves this predictive power further. All three nomograms under-predict prostate cancer in a urologically referred cohort. These simple nomograms may be of value in counseling screened men with raised PSA and/or abnormal DRE regarding the need for biopsy. No significant financial relationships to disclose.
The knowledge and practices of urologists in the United States (US) about standardization of PSA assays.
Authors: Gupta A. , Shariat S. F. , Eastham J. A. , Scardino P. T. , Vickers A. J. , Lilja H. 
Published: February 2017

207 Background: PSA assays can be calibrated to either the WHO or the Hybritech standard. Studies of PSA-based prostate cancer screening have used Hybritech-standardized assays and prostate cancer risk calculators are based on these studies. Testing of patient samples with a WHO calibrated assay gives values that are 22% lower than from those with Hybritech-calibrated assays. Up to 60% of the labs in the US use WHO calibrated assays. We evaluated whether US urologists are aware of the different calibrators and the differences in PSA values. Methods: A random sample of 1,742 US urologists were invited by email to participate in a web-based survey of their knowledge and practices regarding PSA assay standardization. No mention was made of assays or calibration in the invitation. 419 responses were received. Results: Many (56%) US urologists thought that different standards may lead to clinically relevant differences in PSA values. Although 62% reported awareness of the two PSA calibrators, 67% did not know the difference between the two. Only 17% correctly reported the difference between the two standards. Nationally almost 60% of the labs use WHO standardized assays, but in this survey only 5% of the urologists thought that the hospital where they practice used a WHO standardized assay. The rest reported either not knowing the standard (46%) or use of the Hybritech standard (49%). The majority of urologists did not look at the reference range (64%) or for the PSA standard (74%) in the lab reports. Only 25% reported considering the PSA-calibration in their clinical decisions about prostate biopsy, but only a third of them correctly knew the difference between the calibrators. Conclusions: Many US urologists are unaware of the difference caused by WHO versus Hybritech based PSA-assay calibration. Although 60% of clinical laboratories use WHO-calibrated assays, only 5% of urologists are aware of this use in their practice, and a majority of urologists could not correctly explain the difference between the different calibrators. A greater awareness is needed amongst US urologists about the different PSA calibrators, the calibrator in use at their practice, and means to account for different calibrators in clinical decision making. [Table: see text]
The influence of race and treatment choice in 16,508 men treated either conservatively, with radiotherapy, or surgically for clinically localized prostate cancer.
Authors: Sooriakumaran P. , Field T. , John M. , Leung R. , Tewari A. 
Published: February 2017

210 Background: There are known variations in cancer survival based on race and treatment choices. We report the long-term survival probability, based on race, in 16,508 men with localized prostate cancer treated either conservatively or by radiotherapy or radical prostatectomy. Methods: We extracted survival data from tumor registries of six Cancer Research Network sites in the United States. Patients were stratified into four racial groups: Caucasians, African Americans, Hispanics, and Asians. The Cox proportional-hazards regression model was used to compare long-term survival in the three treatment groups. Kaplan-Meier survival curves and competing risk analysis was also performed. Results: Survival was improved for patients who underwent radical prostatectomy compared to radiotherapy or watchful waiting. This was true for all patients combined (Table) as well as for all races individually. Radiotherapy had at least equivalent survival outcomes as watchful waiting in all groups. The differences between treatments were greater for overall survival than for prostate cancer specific survival in all groups, though the extent of the differences varied by race. Conclusions: Radical prostatectomy increases survival in men with localized prostate cancer compared to both radiotherapy and watchful waiting, especially for Caucasian men. Radiotherapy was at least equivalent to watchful waiting for all races. Racial disparities in outcome may influence treatment choices for men with clinically localized prostate cancer. [Table: see text] [Table: see text]