bluuebunny/crossref_metadata_2025 huggingface dataset:
Frequency, predictors, and outcomes of urine drug test among patients with advanced cancer on chronic opioid therapy at an outpatient supportive care clinic.
Authors: Arthur Joseph Anthony , Edwards Tonya , Hui David , Waletich-Flemming Jessica Marie , Reddy Suresh K. , Liu Diane D , Wu Jimin , Bruera Eduardo
Published: February 2017

94

Background: Data on the utilization and outcomes of urine drug tests (UDT) among advanced cancer patients is limited. The main objective of this study was to determine the factors associated with UDT ordering and results in advanced cancer outpatients. Methods: A retrospective chart review of 1058 patients seen from March 2014 to November 2015 at an outpatient supportive care clinic was conducted. Sixty-one patients on chronic opioid therapy who underwent UDT were identified. A control group of 120 patients who did not undergo UDT was selected for comparison of information on demographic and clinical characteristics. Results: 61/1058 patients (6%) underwent UDT. 33/61 patients (54%) had abnormal results. Multivariate analysis found that the odds ratio for UDT ordering was 3.9 in CAGE positive patients (p = 0.002), 4.41 in patients less than 45years (p < 0.001), 5.58 in patients with moderate to severe pain (ESAS pain score ≥ 4) (p < 0.001), 0.27 in patients with advanced cancer stage, (p = 0.008), and 0.25 in patients with moderate to severe fatigue (p = 0.001). Among 52 abnormal UDT results in 33 patients, the most common opioid findings were: prescribed opioids absent in urine (14/52, 27%) and un-prescribed opioids in urine (13/52, 25%). Conclusions: UDT was used infrequently among advanced cancer patients receiving outpatient chronic opioid therapy. Younger age, CAGE positivity, early cancer stage or NED status, higher pain intensity, and lower fatigue were significant predictors of UDT ordering. More than 50% of UDTs were abnormal. More research is necessary to better characterize aberrant opioid use in advanced cancer patients.
A 17-gene genomic prostate score (GPS) as a predictor of biochemical (BCR) and clinical recurrence (CR) in men with surgically treated intermediate- and high-risk prostate cancer (PCa).
Authors: Klein Eric A. , Zhang Nan , Crager Michael , Maddala Tara , Febbo Phillip G. , Thomas Shibu , Gormley Michael , Ricci Deborah Sokol , Falzarano Sara Moscovita , Magi-Galluzzi Cristina , Lawrence H. Jeffrey
Published: February 2017

104

Background: The biopsy-based GPS (scale 0-100) is validated as an independent predictor of adverse pathology in men with low- and intermediate-risk PCa. We wished to examine the association of GPS with BCR and CR in higher-risk disease. Methods: We performed exploratory analyses of data from a prior development study of radical prostatectomies from 441 men with AUA low-, intermediate- and high-risk disease, using a cohort sampling design (Klein et al. Eur Urol 2015). Multivariable Cox proportional hazards models were employed with the cohort sampling weights. Since these data were used in the selection of genes and coefficients for GPS, hazard ratios (HR) and other estimates based on GPS were corrected for regression to the mean (RM), and Storey’s method was applied to hypothesis tests for GPS to control the false discovery rate (FDR). Results: All estimates are RM-corrected. Broad, overlapping ranges of GPS values were observed across all AUA risk groups. GPS was strongly associated with BCR (HR 1.64 for 20 GPS units, p<0.001, FDR q-value < 0.1%) and CR (HR 2.79 for 20 GPS units, p < 0.001; FDR q-value < 0.1%), after adjusting for AUA risk group. Intermediate-risk patients with GPS > 40, who represented 41% of all intermediate-risk patients, had estimated 3-year BCR risk and 10-year CR risk similar to high-risk patients (Table). Conversely, high-risk patients with GPS≤ 40, who represented 63% of all high-risk patients, had a 3-year BCR risk and a 10-year CR risk similar to men with intermediate-risk disease. High-risk patients with GPS > 40 had 3-year BCR risk of almost 50% and 10-year CR risk of 35%. Conclusions: GPS appears to provide improved risk stratification for BCR and CR in AUA intermediate- and high-risk PCa. These findings require confirmation in an independent cohort of patients. [Table: see text]
Toxicity in a multimodality approach of radical prostatectomy with radiation and hormonal therapy.
Authors: Loeb Stacy , Adam Meike , Tennstedt Pierre , Huber Wolfgang , Bernard Juergen , Tilki Derya , Graefen Markus , Huland Hartwig , Schlomm Thorsten
Published: February 2017

107

Background: While the optimal use and timing of secondary therapy after radical prostatectomy remain controversial, there are limited data on the patient-reported outcomes following multimodality therapy. Our objective was to assess the impact of additional radiation and/or hormonal therapy on long-term urinary continence, quality of life and potency after radical prostatectomy. Methods: Among 13150 men treated by radical prostatectomy (RP) from 1992-2013, 905 underwent secondary radiation therapy (RP+RT), 407 received androgen deprivation therapy (RP+ADT) and 688 a combination of RT and ADT (RP+RT+ADT). Urinary function, sexual function and quality of life were evaluated annually using self-administrated validated questionnaires. Urinary function was assessed by the use of the number of pads in 24h (analyzed as 0 pads, safety only, 1-2, or ≥ 3 pads). Potency was defined as ≥ 3 points out of 5 on the question whether erections were hard enough for penetration. Quality of life was assessed using a score from 0-100%.The distribution of urinary function, sexual function and quality of life were plotted as a function of time after bootstrap analysis (n = 1000) of a propensity score matched cohort. Results: Urinary function. The distribution of 0 pads and 1 safety pad between patients with a) RP and RP+RT was 72.3% vs. 67.9% and 16.7% vs. 18.6%; b) between RP and RP+HT was 64.5% vs. 55.5% and 16.1% vs. 21.9%; c) between RP and RP+RT+ADT was 67.4% vs. 54.8% and 17.7% vs. 21.8% and d) between RP+RT and RP+RT+ADT was 64.5% vs. 55.5% and 16.1% vs. 21.9%. Potency. The distribution of potency between patients with a) RP and RP+RT was 62.9% vs. 40.0%; b) between RP and RP+HT was 59.1% vs. 29.3%; c) between RP and RP+RT+ADT was 57.4% vs. 24.0% and d) between RP+RT and RP+RT+ADT was 44.2% vs. 32.1%. Quality of life. The distribution of a score of 83.3%-100% between patients with a) RP and RP+RT was 67.9% vs. 57.4%; b) between RP and RP+HT was 57.8% vs. 41.7%; c) between RP and RP+RT+ADT was 59.3% vs. 48.2% and d) between RP+RT and RP+RT+ADT was 60.0% vs. 41.2%. Conclusions: Secondary therapy after radical prostatectomy has a negative influence on urinary function, potency and quality of life.
Long-term comparative toxicity of LDR versus HDR prostate brachytherapy ± EBRT and evaluation of risk hazard over time: A SEER-Medicare analysis.
Authors: Tward Jonathan D. , Jarosek Stephanie , Chu Haitao , Shrieve Dennis C. , Elliott Sean
Published: February 2017

108

Background: Severe urinary adverse events (UAEs) include surgical treatment of urethral stricture, urinary incontinence and radiation cystitis. Our objective is to compare the incidence of late UAEs after low dose rate BT (LDR) and high dose rate BT (HDR) as well as LDR+EBRT and HDR+EBRT. Methods: We identified men treated with LDR (n=12,801), HDR (n=685), LDR+EBRT (8,518) and HDR+EBRT (n=2,392) from the SEER-Medicare Database. The populations were balanced by propensity weighting and the Kaplan-Meier incidence of severe UAEs was compared. Propensity-weighted Cox proportional hazards models were used to compare the adjusted hazard of UAEs. These UAEs were compared to a cohort of men not treated for prostate cancer. Results: Median follow-up was 4.3 years. At 8 years, the propensity weighted cumulative UAE incidence was highest after HDR+EBRT (28%) and lowest after LDR (17%; see Figure). The absolute excess risk over non-treated controls of a UAE at 8 years was 1.9%, 3.8%, 8.4% and 12.9% for the LDR, HDR, LDR + EBRT, and HDR + EBRT respectively. This translates into a number needed to harm of 53, 26, 12, and 8 persons. There is no statistical difference in severe UAE risk between HDR vs. LDR or between HDR+EBRT vs. LDR+EBRT. The additional risk for developing a UAE related to treatment for LDR, LDR+EBRT, and HDR+EBRT, was greatest within the 2 years following treatment, and continued to decline over time. For HDR monotherapy, the risk was greatest within the first 4 years, and then declined. The risk of developing a severe UAE matched the baseline risk of the control population for all treatments at 4 years following therapy. Conclusions: LDR and HDR brachytherapy are statistically indistinguishable for late severe urinary adverse events. However, combination radiotherapy (either HDR+EBRT or LDR+EBRT) increases the risk of severe UAEs compared to HDR alone or LDR alone. In the 8 years following brachytherapy treatment, the increased risk of urinary toxicity occurs almost exclusively within the 2 years following therapy, and then declines to a baseline hazard. The hypothesis that late urinary radiation toxicity accelerates over time is not supported by this study.
Postoperative radiotherapy treatment evolution in prostate cancer patients: A trend moving away from guidelines?
Authors: Arrojo Elisabeth E. , Martinez Alvaro , Ghilezan Michael , Forman Jeffrey D. , Fernandez Eduardo
Published: February 2017

111

Background: Randomized prospective clinical trials have demonstrated the benefit of adding postoperative radiotherapy (P-RT) for patients with prostate cancer with adverse pathological factors who underwent radical prostatectomy. Based on scientific evidence, the American Urological Association and American Society of Therapeutic Radiologists and Oncology, recommend offering P-RT to this type of patients. Methods: Retrospective analysis of 156,795 patients with prostate cancer diagnosed between 2004 and 2012, who underwent radical prostatectomy. The clinic-pathological information has been extracted from the database "Surveillance Epidemiology and End Results Program". Stage IV patients, and those with "Unknown" information on the type of surgery, radiotherapy, stage or grade, were excluded. Results: Stage II was the most common (81.9%), followed by stage III (18% of the patients). A 60% of the patients had Gleason > / = 8. Only 11.7% of the patients were > / = 70 years old. Treatment with P-RT decreased significantly between 2004 and 2012 (-0.44%; p = 0.0003). Analyzed by subgroups, P-RT decreased significantly in stage II (-0.72%; p < 0.0001) and III (-2.69%; p = 0.005), in patients with Gleason 6-7 (-1.05%; p = 0.0002) and > / = 8 (-1.79%; p = 0.0001) and < 70 years (-0.37%; p = 0.0001), whereas in > / = 70 years decreased but not significantly (-0.53%; p = 0.13). Conclusions: The use of P-RT in patients with prostate cancer who underwent radical prostatectomy is declining. What is most striking, is that the magnitude of this decline, is greatest in patients with higher risk factors, as the percentage of patients with Gleason score > / = 8 and/or Stage III (extracapsular invasion and/or involvement of seminal vesicles) receiving P-RT, declined more than the decline in the percentage of patients with Gleason 6-7 and/or stage II receiving P-RT, which clearly departs from the recommendations contained in the main treatment guidelines.
Expanded criteria in men on active surveillance monitored by MRI-TRUS fusion biopsy.
Authors: Frye Thomas P , Abboud Steven F. , Ho Richard , Fascelli Michele , Chelluri Raju , George Arvin Koruthu , Choyke Peter L. , Turkbey Baris , Wood Bradford J. , Pinto Peter A.
Published: February 2017

115

Background: Active surveillance (AS) is an established option for men with prostate cancer. Studies have shown that multiparametric-MRI along with MRI-TRUS fusion-guided biopsy (FB) may better assess risk in patients eligible for AS, compared to 12-core biopsy, due to improved detection of clinically significant cancers. The objective is to evaluate the performance of expanded criteria eligibility in men on AS being monitored with MRI-TRUS guided biopsy. Methods: Men on AS were included if they had mp-MRI and pathology data for 2 or more FB sessions. FB procedures consisted of targeted biopsies and random 12 core biopsies. Men participated in AS with low and intermediate risk prostate cancer, Gleason score ≤ 3+4=7 with no restriction on percent core involvement or number of cores positive. Progression was defined by patients with initial Gleason 3+3=6 to any Gleason 4, and Gleason 3+4=7 disease progressing to a primary Gleason 4 or higher. Results: 124 men on AS met study criteria. Low risk men had a mean age of 61.3 years versus intermediate risk men with a mean age of 65.5 years (p=0.0062). Mean PSA levels of the low and intermediate risk groups were 5.8 and 5.76 ng/ml (p=0.95), respectively. The mean length of follow-up was 22.56 months (range: 3.6 – 74.4 mo). Rates of pathologic progression in the intermediate and low risk patients were, 38.5% vs. 28.5% (p=0.33). Intermediate risk men had a mean progression-free survival (PFS) of 2.8 years compared to low risk men of 3.9 years (p=0.27). Patients were stratified according to established AS criteria (Epstein, Toronto, PRIAS) and rates of progression are summarized in the Table. 69% of patients met Epstein criteria for AS of which 29.4% (20/68) progressed compared to 28.5% for the low risk cohort overall. Conclusions: Men in our cohort who met strict criteria for AS had the same rate of progression as the entire expaned criteria low risk cohort, 29.4% vs 28.5%, respectively. Our data suggests that with accurate initial Gleason classification other AS criteria such as percent core or number of cores positive have no added benefit in predicting which men may have reclassification or progression of disease. [Table: see text]
Copy number alterations of P53, RB1, and MDM2 as prognostic markers in intermediate-risk prostate cancer.
Authors: Mahamud Osman , Chua Melvin , Lalonde Emilie , So Jonathan , Dal Pra Alan , Berlin Alejandro , Orain Michèle , Picard Valerie , Hovington Helene , Bergeron Alain , Fradet Yves , Têtu Bernard , Zafarana Gaetano , Meng Alice , Livingstone Julie , Pintilie Melania , Fraser Michael , van der Kwast Theodorus , Boutros Paul , Bristow Robert G.
Published: February 2017

117

Background: We interrogated copy number alternations (CNA) of p53, Rb1 and MDM2 as prognostic determinants of biochemical failure in localized intermediate-risk prostate cancer. Methods: Using Affymetrix Oncoscan array technology, we characterized copy number alterations (CNA) for 284 D’Amico-classified intermediate-risk prostate cancers. Of the 284 patients, 143 underwent image-guided radiotherapy (IGRT), while 141 underwent radical prostatectomy (RadP). Biochemical-relapse free survival (bRFS) was assessed as a clinical end-point, with biochemical failure defined using the Phoenix and AUA criteria for IGRT and RadP patients, respectively. Results: We observed allelic losses ofp53 and Rb1 in 23.9% (n = 68) and 31.0% (n = 88) and allelic gains of MDM2 in 3.17% (n = 9) in our cohort, respectively. 7.7% (n = 22), 1.1% (n = 3) and 0.4% (n = 1) of all cases exhibited concurrent losses of p53 and Rb1, p53 loss and MDM2 gain, and concurrent p53/Rb1 loss and MDM2 gain, respectively. Patients with allelic losses of p53, Rb1 and allelic gain of MDM2 loci exhibited increased percent genome aberration (PGA) (Mean 9.2 vs. 6.1 p < 0.001; 10.1 vs. 5.4 p < 0.001; 18.1 vs. 6.5 p < 0.001 respectively). Rb1 loss and MDM2 gain were not significant predictors of bRFS, independent of treatment modality. Allelic loss of p53 was predictive of poor bRFS in the RadP cohort (HR = 1.86, 95% CI 1.10-3.16, p = 0.022), but not for IGRT patients (HR = 1.16, 95% CI 0.63-2.12, p = 0.629). Additionally, patients in the RadP cohort with concurrent losses of p53 and Rb1 also had a higher likelihood of poorer bRFS (HR = 2.32, 95% CI 1.1-4.93, p = 0.029). On multivariate analysis, incorporating PGA and pre-treatment PSA, concurrent p53/Rb1 losses, but not single p53 loss, was prognostic for bRFS in patients who underwent RadP (p53/Rb1 losses, HR = 2.16, 95% CI 1.0-4.65, Wald's p = 0.05; p53loss, HR = 1.62, 95% CI 0.94-2.79, Wald's p = 0.08). Conclusions: In a cohort of men with intermediate-risk prostate cancers, we identified an unfavourable subgroup of patients harbouring concurrent copy number losses of p53 and Rb1 that was associated with an adverse prognosis of biochemical failure following radical prostatectomy.
Salvage brachytherapy for locally recurrent prostate cancer following definitive radiation therapy.
Authors: Kollmeier Marisa , Harneja Niyati , Lin Mary , McBride Sean Matthew , Zelefsky Michael J.
Published: February 2017

118

Background: To report the toxicity and outcomes of patients undergoing salvage brachytherapy for locally recurrent prostate cancer. Methods: Between 4/03 and 4/15, 98 patients with biopsy-proven locally recurrent prostate cancer underwent low dose rate (LDR-125Gy) (n=37) or high dose rate (HDR-32Gy in 4 fractions) (n=61) brachytherapy. The median PSA at relapse was 2.57ng/mL (range 0.43-13.5) with median time to relapse was 6 years (range 0.96-14.4y). Gleason score at relapse was upgraded from initial Gleason score in 67 patients (70%) with 38 patients graded ≥8 at relapse. 44 patients also received hormone therapy (median duration of 17.3 months) pre and post-salvage brachytherapy. Patients were followed q3-6months with PSA and symptom assessment. Acute and late (>90days) genitourinary (GU) and gastrointestinal (GI) toxicity was recorded using CTCAE v 4.0 and International Prostate Symptom Score (IPSS). Nadir+ 2 definition was used for PSA failure. Kaplan-Meier method was used for survival analyses. Results: Median followup is 31 months (range 1-101 mos). Median peak IPSS score was 19 with a median time to peak IPSS of 4 mos. Overall, mean change in IPSS from baseline was +2.4. Acute grade ≥3 GU and GI toxicity occurred in 6% and 0%, respectively. Late grade ≥3 GU and GI toxicity occurred in 6% and 4%, respectively. Six patients (6%) developed late urethral strictures requiring intervention, 3 of whom developed subsequent urinary incontinence. Urinary incontinence requiring pads occurred in 16% (16/98). 1 patient developed gross hematuria requiring irrigation. Rectal bleeding was the most common late GI toxicity (14%); however only 2 patients required intervention. PSA relapse occurred in 26/98 (27%) patients and 14/98 (14%) developed distant metastasis during the followup period. The 3 year PSA RFS, DMFS and OS was 70.1%, 92%, and 90.5%, respectively. Conclusions: Salvage brachytherapy is curative for a significant proportion of patients with locally recurrent prostate cancer following radiation therapy. Urinary symptoms peak at 4 months post-brachytherapy. The rate of moderate to severe GU or GI toxicity is 5-15%. Further efforts to reduce toxicity including focal approaches are ongoing.
Efficacy of early and delayed radiation in a prostatectomy cohort adjusted for genomic and clinical risk.
Authors: Den Robert , Yousefi Kasra , Trock Bruce J. , Davicioni Elai , Tosoian Jeffrey J. , Thompson Darby J. S. , Choeurng Voleak , Haddad Zaid , Tran Phuoc T. , Trabulsi Edouard John , Gomella Leonard G. , Lallas Costas D. , Abdollah Firas , Feng Felix Yi-Chung , Dicker Adam , Freedland Stephen J. , Karnes Jeffrey , Schaeffer Edward M. , Ross Ashley
Published: February 2017

12

Background: In 3 published randomized trials, adjuvant radiation therapy (ART) for prostate cancer (PCa) resulted in improved progression free survival. However, the impact on metastases and overall survival is unclear. To date, there have been no published prospective trials examining the impact of salvage radiation therapy (SRT) in this disease state. Hence, we conducted a retrospective, nonrandomized comparative study of ART, SRT, or no radiation following radical prostatectomy (RP) for men with pT3 disease or positive margins (adverse pathologic features, APF). Methods: 422 PCa men treated at 4 institutions with RP and having APF were analyzed with a primary end point of clinical metastasis. ART (n = 111), early SRT (n = 70) and delayed SRT (n = 83) were defined by PSA levels of < 0.2, 0.2 to 0.5, and ≥ 0.5 ng/mL, respectively, prior to RT initiation. Remaining 157 men who did not receive additional therapy prior to metastatic onset formed the no RT arm. Clinical-genomic risk was assessed by CAPRA-S and Decipher. Cox multivariable (MVA) model was used to evaluate the impact of treatment on outcome. Results: During study follow-up, 37 men developed metastasis with a median follow-up of 8 years. Both CAPRA-S and Decipher had independent predictive value on MVA for metastatic outcome (both p < 0.05). On MVA adjusting for clinical-genomic risk, delayed SRT and no RT had an HR of 4.31 (95%CI, 1.20-15.47) and 5.42 (95% CI, 1.59-18.44) for metastasis compared to ART. No significance difference was observed between early SRT and ART (p = 0.28). Men with low to intermediate CAPRA-S and low Decipher have a low rate of metastatic events regardless of treatment selection. In contrast, men with high CAPRA-S and Decipher benefit from ART, however the cumulative incidence of metastasis remains high. Conclusions: The decision as to the timing and need for additional local therapy following RP is nuanced and requires providers and men to balance risks of morbidity with improved oncologic outcomes. This analysis provides the most robust and accurate quantification of risk for these men. Post-RP treatment can be safely avoided for men who are low risk by clinical-genomic risk, whereas those at high risk should favor enrollment in clinical trials.
13-year oncologic and functional outcomes and morbidity in men </= 55 years treated with I-125 brachytherapy +/- external beam radiation and/or androgen deprivation.
Authors: Shasha Daniel , Salant Robert , Sivathayalan Ahalya , Farrell Patrick , Cheetham Philippa , Harrison Louis B
Published: February 2017

121

Background: Young patients are most often recommended prostatectomy because few radiation series have reported long-term outcomes specifically for this age group. We now address that deficit by presenting single-institution 13-year oncologic outcomes and morbidity after I-125 prostate brachytherapy (BRT). Methods: Between 1998-2014, 227 patients < 55 years were prospectively followed after PCa treatment with BRT +/- external-beam irradiation +/- androgen deprivation. NCCN risk stratification identified 99 low-, 51 intermediate-, 77 high- + very-high-risk patients treated. Endpoints include Phoenix biochemical control (BC), prostate-cancer-specific survival (PCSS), overall survival (OS), and urinary, bowel, and sexual complications. Results: With a minimum and median follow-up of 26 and 72.3 months, respectively the 13-year actuarial rate of BC, PCSS, and OS for low-risk disease: 97.8%, 100%, 100%, respectively; for intermediate-risk disease: 94.0%, 100%, 88.1%, respectively and for high + very-high-risk disease 83.6%, 89.9%, 77.6%, respectively. Only 3 patients died of prostate cancer. Multivariate analysis demonstrated race, EBRT use, ADT use, PSA > 10, PSA > 20, GS > 7, T3a, T3b, smoking, diabetes as significant for BC and PCSS (p < 0.05). Permanent incontinence occurred only in the one patient who underwent TURP, 4 transient urethral strictures were all successfully dilated, and no other grade 3 intestinal or urinary complications were reported. In the 77.5 % potent at baseline, preservation was reported at 5 and 10-years overall in 75.8 % and 54.6 %, and with PDE5-I, 83.3% preserved potency at 10-years. Conclusions: Patients < 55 years achieve excellent and durable prostate cancer control at 13 years after I125 BRT, most notably in high-risk, with prostate cancer specific mortality uncommon in all but very-high-risk group. Significant urinary or bowel morbidity is uncommon, and potency preservation is expected with PDE5-I. We conclude age < 55 years should not be used to discriminate against LDRBT.
Association of baseline prostate atrophy with lower tumor volume in men with prostate cancer on repeat biopsy.
Authors: Moreira Daniel M. , Andriole Gerald L. , Castro Ramiro , Freedland Stephen J.
Published: February 2017

122

Background: We have previously shown baseline prostate atrophy (PA) was independently associated with lower prostate cancer (PC) risk. Beyond PC risk, for those who develop PC it is unclear whether PA is associated with smaller, less aggressive and/or less advanced tumors. Thus, we evaluated whether baseline PA and PA severity in men with initial negative biopsy for PC was associated with PC volume at the 2-year repeat prostate biopsy. Methods: Retrospective analysis of 763 men 50-75 years-old with negative baseline prostate biopsy and positive 2-year repeat biopsy for PC with complete data in the REDUCE study. Presence and severity of PA, and tumor volume were determined by central pathology. The association of PA at baseline biopsies with 2-year repeat biopsy cancer volume variables was evaluated with linear and Poisson regressions and controlling for age, race, body-mass index (BMI), digital rectal exam (DRE), prostate volume, baseline and pre-repeat biopsy prostate-specific antigen (PSA) and treatment arm. Results: PA was detected in 458 (60%) baseline biopsies and was considered mild in 398 (87%) and moderate in 60 (13%) cases. Patients with PA had significantly larger prostates and lower baseline and pre-repeat biopsy PSA (P < 0.01). PA was unrelated to race, BMI, DRE or treatment arm. At 2-year biopsy, men with baseline PA had significantly lower overall mean total tumor volume (2.04µL vs 3.02µL; P = 0.006), mean number of biopsy cores involved (1.79 vs 2.11; P = 0.001), mean percent of cores involved (17.9% vs 21.2%; P = 0.001), average core involvement (0.20µL vs 0.30µL; P = 0.001) and overall mean percent tumor involvement (1.64% vs 2.35%; P = 0.006) than those without PA. The results were virtually unchanged in multivariable analysis (all P < 0.05 except for overall percent tumor involvement where P = 0.061). In the analysis of PA severity, a biological gradient was observed where moderate PA was associated with greater reduction in tumor volume compared to mild PA (data not shown). Conclusions: In a cohort of men with 2-year repeat prostate biopsy positive for PC after a negative baseline biopsy, baseline PA was associated with lower PC volume. These results suggest PA may be associated with less aggressive PC.
External validation of a prognostic Gleason grade classification system.
Authors: Leapman Michael S. , Cowan Janet E. , Roberge Gray , Eltemamy Mohamed M , Simko Jeff , Carroll Peter , Cooperberg Matthew R.
Published: February 2017

123

Background: We aimed to evaluate a recently proposed prognostic Gleason grading system among two distinct cohorts of men receiving treatment for localized PCa with extended clinical follow. Methods: We identified patients receiving treatment with radical prostatectomy (RP) in two settings: an academic referral center and the multi-center Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) registry. We examined the independent prognostic ability of the proposed grade groups (3+3; 3+4; 4+3; 4+4; 9-10), adjusted for significant clinical and pathological characteristics, on disease recurrence, defined as two consecutive PSA values ≥ 0.2 ng/mL or receipt of salvage treatment, using Cox proportional hazards models. Adjusted pairwise comparisons were made between grade groups. Distant disease endpoints including metastatic progression and prostate cancer specific mortality (PCSM) were similarly evaluated within the CaPSURE cohort. Results: We identified 1,734 men receiving treatment at UCSF with immediate RP with pathologic assessment consistent with the 2005 ISUP modification, and 4,564 men within the CaPSURE database. Median follow up within the UCSF cohort was 33 months (interquartile range, IQR 16-58) and 91 months (IQR 50-135) within CaPSURE. Relative to Gleason grade 3+3, all prognostic Gleason grade groups were independently associated with risk of recurrence among the UCSF cohort (all p < 0.01). Adjusted pairwise comparisons of biopsy and pathologic Gleason groups, except 4+3 versus 4+4, also were statistically significant. Among the CaPSURE cohort, biopsy and pathologic prognostic Gleason grade groups were independently associated with risk of recurrence, metastatic progression and PCSM, though pairwise distinctions between Gleason 4+3 and 4+4 and Gleason 4+4 versus 9-10 were not significant. This study was limited by the comparatively smaller proportion of men receiving radical prostatectomy for higher Gleason grade ( > 4+4) disease. Conclusions: A proposed prognostic Gleason classification system stratifies men according to the risk of recurrence and downstream endpoints. However, the discrimination of outcomes among higher grade disease appeared less robust.
Change in a 17-gene genomic prostate score over time in men with low- and intermediate-risk prostate cancer managed with active surveillance.
Authors: Leapman Michael S. , Cowan Janet E. , Nguyen Hao Gia , Cooperberg Matthew R. , Carroll Peter
Published: February 2017

124

Background: A biopsy-based RT-PCR assay (Oncotype DX Prostate Assay) providing a Genomic Prostate Score (GPS) as a measure of tumor aggressiveness has been validated as a predictor of adverse pathologic and oncologic outcomes. We sought to evaluate the change in GPS results among men with favorable-risk prostate cancer (PCa) managed with active surveillance (AS). Methods: We identified men with low and intermediate-clinical risk PCa managed with AS at our institution receiving a minimum of two GPS tests on serial prostate biopsy. GPS ranges from 0 (least) to 100 (most aggressive disease). We described the change in assay results and clinical risk designation over time and reported the subsequent clinical outcome (definitive treatment versus continued AS). For men receiving treatment with radical prostatectomy (RP) the occurrence of adverse pathological findings was defined by the presence of high grade (Gleason pattern ≥ 4+3) or non-organ confined disease ( ≥ pT3a). Results: 31 men were identified who underwent serial GPS testing at a median of 12 months. The median change in GPS was an increase of 1 point (IQR -7, 13). Fourteen (45%) patients experienced an increase in NCCN risk classification, including 3 from very-low to intermediate and 11 from low to intermediate risk. Following serial GPS testing 7 patients (23%) underwent radical prostatectomy. Among surgically treated patients, 3 had adverse pathology due to pT3a disease and the mean change in GPS prior to treatment was an increase of 13 points (IQR -7, 18); all of whom were intermediate clinical risk at the time of surgery. This study was limited by the small sample size and the uncontrolled decision to pursue definitive therapy. Conclusions: Serial change in a tissue based gene expression assay on serial biopsy during AS was non-static. Magnitude of GPS change may identify men at risk for adverse pathological findings, although larger series are required to validate such an endpoint during AS.
Psychological state and trait correlates of quality of life prior to radiotherapy for prostate cancer.
Authors: Walker Sara J , Chen Yiyi , Paik Kyungjeen , Mirly Brandy , Fields Alexis K , Thomas Charles R. , Hung Arthur
Published: February 2017

129

Background: Improvement in cancer treatment has increased need to focus on survivors’ quality of life (QOL). Survivors often experience psychological stress, with impact on QOL and disease-related mortality. Better understanding the heterogeneity in individuals’ psychological adjustment to cancer diagnosis and treatment may help identify the most valid screening practices and patients most in need of psychosocial support. The specific aim of the current study investigates correlates of psychological state and trait with QOL prior to radiotherapy for localized non-metastatic prostate cancer. We hypothesized 1) positive correlations with QOL and trait Extraversion, Openness, and Conscientiousness, and 2) negative correlations between QOL and state depression/anxiety and trait Neuroticism. Methods: The PHQ-9, GAD-7, and NEO-FFI-3 assessed depressive state, anxiety state, and personality traits, respectively. The FACT-P assessed physical, social, emotional, and functional well-being. Our sample (n=29) had median age of 68 (range 52-79) and education of 16 years (range 10-20). Race/ethnicity: 89% European-American, 4% African-American, 7% Other. Association between constructs was assessed by Pearson’s correlation coefficient. Results: Higher depression, anxiety, and Neuroticism were negatively associated with physical (p < 0.04), emotional (p < 0.01), and functional (p < 0.02) well-being, and well-being related to prostate cancer-specific concerns (p < 0.01). Trait Agreeableness was associated with emotional (p < 0.01) and functional (p < 0.01) well-being. Extraversion was associated with social (p < 0.05) and functional (p < 0.02) well-being. Openness was associated with functional well-being only (p < 0.03). Contrary to hypothesis, Conscientiousness did not significantly correlate with any measured aspect of QOL. Conclusions: Assessing psychological risk and protective factors prior to radiotherapy may help identify patients in most need of psychosocial supports, informing effective screening protocols and individualized treatment planning. Future directions include prospectively measuring predictive value of baseline risk and protective factors on post-treatment QOL.
Outcomes in patients with high-risk prostate cancer treated with definitive versus adjuvant radiation therapy.
Authors: Tumati Vasu , Jacobs Corbin , Ying James , Roehrborn Claus G , Lotan Yair , Margulis Vitaly , Pistenmaa David A. , Kim Dong W. , Hannan Raquibul
Published: February 2017

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Background: 20% of men with prostate cancer (PCa) are diagnosed with high-risk disease. The optimal therapy for these patients, prostatectomy followed by adjuvant radiation therapy (ART) or definitive radiation with androgen deprivation (DRT), is still unclear. Previous randomized trials failed to accrue; therefore we sought to answer this using an IRB-approved retrospective cohort study. Methods: High-risk PCa was defined using NCCN criteria. Adjuvant radiation was defined as radiotherapy started within 6 months of prostatectomy. Biochemical progression-free survival (BPFS), castrate resistance-free survival (CRFS), distant metastasis-free survival (DMFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were calculated using Kaplan-Meier estimates. Biochemical failure was defined using the AUA definition in the ART group and by the Phoenix definition in the DRT group. Castrate resistance was defined as ≥2 episodes of rising PSA with testosterone <50 ng/ml or rising PSA despite second line anti-androgen. Statistical analysis was performed using log rank and Cox testing. Results: 60 men with high-risk PCa treated between 1992-2011 were included in the ART group and 154 men were included in the DRT group. 58% of men in the ART group received short course of androgen depravation therapy (ADT). Nearly all men received 2 years of ADT in the DRT group. The median follow up for the ART group was 62 months and 55 months for the DRT group. Men in ART group were younger (p<0.0001) and had a lower pre-treatment PSA (p=0.0338). Log rank testing revealed the ART group had worse BPFS (5 year: 57% vs. 71%; p=0.008), but there was no difference in the other endpoints including CRFS (p=0.9693), DMFS (p=0.7345), PCSS (p=0.5481), or OS (p=0.2557). On multivariable analysis ADT use, ADT length, type of treatment, and stage were not predictive of BRFS whereas Gleason score was (p=.0001). Conclusions: This study suggests that for high-risk PCa patients there is no difference between DRT and ART with regards to BPFS, CRFS, DMFS, PCSS, or OS. Therefore, over a short follow-up period, there does not appear to be a difference between these approaches. Prospective trials are required to validate this finding.
Feasibility of robot-assisted radical prostatectomy in elderly patients: Comparative analysis of the peri-surgical/oncological outcomes with younger patients.
Authors: Iwata Takehiro , Saika Takashi , Edamura Kohei
Published: February 2017

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Background: Robot-assisted radical prostatectomy (RARP) has become one of standard treatments for localized prostate cancer. However, a feasibility of RARP in elderly patients has not been clear yet. We performed a comparative analysis of peri-surgical/oncological outcomes for younger and elderly patients underwent RARP. Methods: We reviewed and compared our initial 340 consecutive patients who underwent RARP from 9/2012 to 8/2015 for peri-surgical outcomes, including surgical times, blood loss, complications, pathological findings, continence recovery, and oncological outcomes stratified by age less than 70 and over 70 years. Results: In our cohort, 202 men were age less than 70 and 138 men were ≥70. Preoperative parameters (age, PSA, Gleason score) were similar in both younger and elder groups. Operative time (median: 167 vs. 171 minutes) and estimated blood loss were similar in both groups. One of elder patients (0.7%) needed transfusion. Peri/post-operative complications in both groups appeared to be minimal with no cases of intra-operative open conversion. One of younger patients needed a surgical settlement for port site herniation. Surgical positive margin rates in organ-confined (pT2) disease were also similar (5.6%, younger vs. 9.0%,elder). Continence at 3 months was 82% in elder patients as opposed to 87% in younger patients. Median follow-up period in in elder patients and younger patients were 15.2 and 15.3 months, respectively. Biochemical recurrence free survival rates in elder patients and younger patients were 89.9% and 93.6%, respectively (p=0.1026). Conclusions: In our study, RARP in elderly patients was relatively safe and yielded good oncologic results. RARP is feasible even in elderly patients.
Racial variation in the outcome of subsequent prostate biopsies in men with an initial diagnosis of atypical small acinar proliferation (ASAP).
Authors: Kramer Jordan J. , Libby Robert Scott , Feibus Allison H. , Haney Nora M. , McCaslin Ian R. , Moparty Krishnarao , Thomas Raju , Silberstein Jonathan L. , Sartor A. Oliver
Published: February 2017

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Background: African Americans (AA) are known to have more aggressive prostate cancer (PCa) and a greater probability of death from PCa. We sought to determine predictors of subsequent detection and risk stratification of PCa in a racially diverse group of men who presented with atypical small acinar proliferation (ASAP) on initial prostate biopsy. Methods: Upon receiving IRB approval, a retrospective analysis was performed on men from the Southeast Louisiana Veterans Health Care System and Tulane University Medical Center who presented with ASAP on initial prostate biopsy and subsequently received confirmatory prostate biopsies from September 2000 through July 2015. Confirmatory biopsy with a greater than 3-year interval from the initial were excluded. Self-identified race, age, body mass index (BMI), transrectal ultrasound (TRUS) volume, serum prostate-specific antigen (PSA), PSA velocity (PSAV), PSA density (PSAD), and elapsed time between biopsies were evaluated to determine if they were predictors of subsequent PCa diagnosis in patients with an initial finding of ASAP. Results: Of the 106 men in the analysis cohort, 75 (71%) were AA and 31 (29%) were not African American (non-AA). AA had higher PSA, PSAV, and PSAD (all p < 0.05). Age, BMI and TRUS volume were not statistically different between AA and non-AA. PCa was diagnosed in subsequent biopsy in 42 (40%) patients without significant racial variation; 30 (40%) AA vs 12 (39%) non-AA. Of the 42 men with PCa, 25 (24%) met Epstein pathological criteria for significant disease, although without racial variation; 18 (24%) AA vs 7 (23%) Non-AA. Only 10 (9%) men, again without racial variation, had any component of Gleason 4; 7 (9%) AA vs 3 (10%) non-AA. On multivariate analysis, increasing age, PSA and PSAD were significant predictors of cancer on repeat biopsy while race, BMI, TRUS volume and number of cores with ASAP were not. Conclusions: AA diagnosed with ASAP on initial prostate biopsy do not have increased risk of PCa on confirmatory biopsy compared to non-AA. Regardless of race, most cancers were low grade and lower volume, and AA with ASAP should be managed in a similar manner to non-AA with ASAP.
Pathologic upgrading on confirmatory biopsy in a racially diverse group of men on active surveillance for prostate cancer.
Authors: Feibus Allison H. , Haney Nora M. , Boxberger John , Levy Justin , Libby Robert Scott , Kramer Jordan J. , Ledet Elisa M. , Moparty Krishnarao , Thomas Raju , Lewis Brian E. , Silberstein Jonathan L. , Sartor A. Oliver
Published: February 2017

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Background: To evaluate the clinical variables associated with upgrading at confirmatory biopsy among a racially-diverse group of men with prostate cancer (PCa) who elect Active Surveillance (AS). Methods: Following IRB approval, of the more than 260 men from our multi-institutional prospective AS database we identified 140 that had undergone at least 1 confirmatory biopsy since their initial diagnosis. Patients whose diagnosis was made on TURP, had any Gleason 4 on their initial biopsy or whose initial and confirmatory biopsy were more than 2 years apart were excluded. The analysis cohort included 121 men who had Gleason Score ≤ 6, clinical stage ≤ T2a and PSA ≤ 20 ng/mL. Disease upgrading on confirmatory biopsy was Gleason score ≥ 7. Multiple variables were examined as univariate and MV predictors of upgrading. Results: We identified 121 men who fit inclusion criteria, 55 (45%) African Americans (AA) and 66 non-AA (55%) with a median follow-up of 22 months. The median age was 66, median number of biopsy cores taken at diagnostic biopsy was 12 and median time interval between diagnostic and confirmatory biopsy was 12 months. On confirmatory biopsy, no evidence of disease was noted for 51 (42%) men (26 AA, 25 non-AA), 48 (40%) men (18, AA, 30 non-AA) had findings consistent with their initial biopsy and 22 men (11 AA, 11 non-AA) experienced upgrading at repeat biopsy. Of the 22 (18%) men who were upgraded, 18 (8 AA, 10 non-AA) upgraded to a Gleason score of 7, 3 (2 AA, 1 non-AA) were upgraded to a Gleason score of 8 and 1 (AA) had a Gleason score of 9. In univariate analysis AA race was associated with a greater number of positive cores (p = 0.04) and greater total prostate volume (p = 0.03) at confirmatory biopsy. Multivariate analysis was performed and none of the clinical variables examined (race, age, BMI, PSA, volume, PSAD, number of positive cores, total number of cores, percentage of positive cores, time between biopsies) were associated with upgrading on repeat biopsy. Conclusions: Our findings suggest that race is not associated with an increased risk of upgrading at confirmatory biopsy. AA with low-risk PCa are reasonable candidates for inclusion in most AS protocols and should not be excluded based on race alone.
Effect of androgen deprivation therapy on intraductal carcinoma of the prostate (IDC-P), a prognostic factor for prostate cancer.
Authors: Kato Masashi
Published: February 2017

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Background: The presence of intraductal carcinoma of the prostate (IDC-P) is reported to be an adverse prognostic factor for cancer-specific survival (CSS) in localized and metastatic prostate cancer patients. However, there is no data indicating whether the presence of IDC-P can be affected by ADT (androgen deprivation therapy). Methods: We retrospectively evaluated 152 high risk prostate cancer patients who underwent radical prostatectomy with neoadjuvant ADT. They were diagnosed and treated at author-affiliated hospitals between 1991 and 2005. All patient data was made available from slides prepared from prostate needle biopsy samples and prostatectomy specimens and each patient received ADT before operation. Slides were re-reviewed by a single genitourinary pathologist (T.T.) according to the 2005 International Society of Urological Pathology (ISUP) grading system and presence of IDC-P was defined using previously published diagnostic criteria. Results: Patient median age was 68 years (range 46-80 years). The median iPSA was 32.7 ng/ml (range 2.4-296). The median follow-up period was 109 months (range 11-257). Sixty-one patients (40%) were ≥cT3 and 113 cases (74%) had biopsy Gleason score ≥8. Preoperative median ADT period was 4 months (range 1–20 ). IDC-P component was detected in 54 patients (36%) in needle biopsy and 69 (45%) in prostatectomy. There were 28 patients who died of the disease and 12 patients who died of other causes during follow-up. They were divided in 4 groups according to with or without IDC-P in biopsy/prostatectomy (-/- 68cases ,-/+ 30, +/- 15, +/+ 39). Twenty eight per cent of IDC-P positive cases in biopsy showed disappearance of IDC-P in prostatectomy specimen. Prognosis was the worst in +/+ group and IDC-P disappearance cases (+/-) tended to have better survival than IDC-P existing cases (+/+) in CSS (p = 0.04). Conclusions: In a number of IDC-P-positive cases determined by needle biopsy, the disappearance of IDC-P in prostatectomy specimens after ADT indicates the possibility that part of IDC-P positive patients can occasionally respond to ADT.
First experience of prostate brachytherapy under hypnosedation.
Authors: Chapet Olivier , Rigal Edwige , Udrescu Corina , Hassouni Abdeslam , Ruffion Alain , Piriou Vincent
Published: February 2017

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Background: Hypnosedation is an alternative to general or spinal anesthesia and may reduce bleeding, postoperative recovery time, as well as potential side-effects of anesthesia. In our department, hypnosedation has been used for prostate brachytherapy (PBT). Levels of pain, comfort, anxiety and satisfaction were evaluated prospectively and are reported. Methods: Twenty-seven patients were treated with BT under hypnosedation. Anesthesia was limited to a perineal injection of 30cc of xylocaine. The same radiation-oncologist and the same anesthesiologist performed all the interventions and hypnosedations, respectively. A dose of 145Gy was delivered to the prostate using iodine-125 linked-seeds. In case of pain or discomfort during hypnosedation, the patient could ask to switch from hypnosedation to general anesthesia. Visual Analog Scales (VAS), from 0 to 10 points, were used to evaluated the lowest, mean and highest level of pain, comfort and anxiety. The VAS forms were completed by the patients in the same day (D1), before (anxiety and pain) and after the intervention (pain and comfort), and 8 weeks later (pain and comfort). Results: Only two patients had a general anesthesia, because they didn’t reach the hypnotic level and failed to follow the hypnosedation procedure. In the table below are presented the results (average and range) of the VAS scores for pain and comfort for the remaining 25 patients. Twenty-four (88.9%) patients would choose this approach again and recommend it to other patients. One patient would prefer a general anesthesia due to the discomfort of the position during the procedure (leg cramps). For all the patients, the short post-operative recovery time and their active participation to the treatment were two major advantages of the hypnosedation. Conclusions: To our knowledge, this is the first experience of brachytherapy under hypnosedation. Our first results demonstrate that hypnosedation is a feasible and comfortable alternative method to anesthesia, perfectly suitable for PBT. [Table: see text]