bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.