bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes after post-operative radiation therapy.
Authors: Nguyen Hao , Cary Clint , Appa Ayesha , Cowan Janet E. , Welty Christopher J , Roach Mack , Shinohara Katsuto , Carroll Peter 
Published: February 2017

138 Background: Adjuvant radiotherapy following radical prostatectomy has been shown to improve prostate-specific antigen (PSA) recurrence free survival for patients with high-risk pathologic features. However, an alternative strategy is careful follow-up after surgery and selective salvage radiation therapy. We aim to investigate voiding and sexual function, and oncological outcomes of patients who underwent adjuvant radiotherapy (ARD) or salvage radiotherapy (SRT) after radical prostatectomy (RP). Methods: We conducted a retrospective analysis of patients with localized prostate cancer treated with open or robotic assisted laparoscopic RP at the University of California, San Francisco (UCSF) from 2002 to 2013. Primary outcomes were voiding and sexual function, PSA recurrence-free survival (PRFS), combined bone metastasis free-survival/cancer-specific survival (BMFS/CSS), and overall survival (OS). Survival outcomes were analyzed using the Kaplan-Meier method. Results: Among 2,908 men in the study, mean age was 60, median PSA was 5.9 ng/ml, and median PSA density was 0.19 at diagnosis. Median follow-up was 28 months (IQR 8-61). Of those with high risk pathologic features, 1,086 patients did not undergo post-RP radiation (NRT), 109 had ART, and 156 had SRT. All patients had comparable pre-treatment sexual and voiding function. However, patients treated with ART or SRT had worse sexual function (SHIM scores) at 4 years post-RP compared to patients without radiation (5.2 (ART/SRT) versus 11.1 (NRT), p=0.01). There were no differences in voiding function at 4 years between the three groups. PRFS at 4 years was 92% for NRT, 82% for ART, and 55% for SRT cohort, log-rank p<0.01. Four-year BMFS/CSS and OS both were 98% and were similar for all groups. In a sub-analysis of men with stage pT2/3a, positive margins, and negative lymph nodes, PRFS were 86% (NRT) and 90% (ART). The PRFS following SRT was 63%. Conclusions: This study provides novel information on both oncological and functional outcomes for men managed with surgery and post-operative radiation therapy at UCSF. Such information allows for better pre- and post-operative counseling of men. Further analyses are required to better determine which men benefit from immediate adjuvant radiation as compared to a strategy of surveillance followed by selective salvage radiation.
The effect of pathologic T-stage and Gleason score on cancer-specific survival in patients with positive surgical margins after surgery for high-risk prostate cancer.
Authors: Tosco Lorenzo , Van Poppel Hendrik , Van den Broeck Thomas , Bastian Patrick , Briganti Alberto , Chun Felix K. , Gontero Paolo , Hsu Chien Yeh , Karnes R. Jeffrey , Marchioro Giansilvio , Sanchez-Salas Rafael , Spahn Martin , Tombal Bertrand , Van Der Poel Henk , Joniau Steven 
Published: February 2017

140 Background: High-risk prostate cancer (HRPC) is a challenging disease and the role of surgery is often considered in the context of a multimodal approach but patients with positive section margins (R1) disease have not always the same cancer-specific survival (CSS). The current study aims to analyze current postoperative pathological features in order to predict CSS of HRPC patients with R1, but with negative lymph nodes (pN0), treated with surgery. Methods: From a multi-institutional retrospective cohort of 5,876 HRPC patients treated by radical prostatectomy and pelvic lymph node dissection, 1541 patients with pN0 and R1 were selected. Following surgery, adjuvant EBRT and/or ADT were delivered according to institutional protocols. Patients were subdivided into four groups according to pT stage (pT≥3 and pT<3) and p-Gleason score (pGS≥8 and pGS<8). Kaplan-Meier plots with log-rank tests and a Cox proportional hazards model were applied to study CSS. All significance levels were set at 0.05. MedCalc was used for all statistical analyses. Results: Median age at surgery was 66 years (42-89). Of all patients, 399 (25.9%) had GS≥8 and 999 (64.8%) had pT≥3 at definitive histopathology. Patients were classified as COMBO groups: C1 (423; 27.4%; GS<8,pT<3), C2 (674; 43.7%; GS<8, pT≥3), C3 (83; 5.4%; GS≥8, pT<3), C4 (362; 23.5%; GS≥8, pT≥3). Adjuvant EBRT and ADT, respectively, were delivered in C1 3%/5%, C2 15%/21%, C3 21%/20%, C4 28%/40%. Kaplan-Meier plots demonstrated statistically different 10-yr CSS between groups: C1 97%, C2 93.8%, C3 85.1% and C4 77.3% (p<0.0001). COMBO groups were also compared using a Cox model and results are shown in the Table. Conclusions: COMBO groups demonstrated to be able to subdivide margin-positive, pN0 HRPC into 4 demarcated groups with significantly different CSS. This subdivision could be considered an easy-to-use tool which can help for counseling patients for adjuvant treatment strategies. [Table: see text]
Greatest percent involved core length and the risk of death from prostate cancer in men with highest Gleason score 7 or higher.
Authors: Cheney Matthew David , Chen Ming-Hui , Zhang Danjie , Phillips John Gary , Loffredo Marian J. , D'Amico Anthony Victor 
Published: February 2017

164 Background: Men with highest Gleason Score (GS) ≥ 7 and a lower GS (Combo GS) have a decreased risk of prostate cancer (PC) specific mortality (PCSM) following radiation therapy (RT) or RT and androgen deprivation therapy (ADT). Whether this risk is modulated based on the greatest percent involved core length (GPC) is unknown and investigated in the current study. Methods: The study cohort consisted of 333 men with GS ≥ 7 PC consecutively treated between 12/1989 and 7/2000 using RT (n = 268; 80%) or RT and 6 months of ADT (n = 65; 20%). Biopsy core and tumor lengths were used to calculate the GPC. Competing risks regression assessed whether increasing GPC was associated with an increased risk of PCSM in men with or without ComboGS adjusting for prognostic factors, age, and treatment. Results: After a median follow-up of 5.36 years (IQR: 3.22-7.61 years) 92 (28%) men died, 28 (30%) from PC. Increasing GPC was significantly associated with an increased risk of PCSM (AHR: 1.02; 95%CI: 1.00, 1.03; p=0.02) (Table). Men with GPC ≥ 50% vs. < 50% had significantly higher estimates of PCSM when ComboGS was present (p< 0.001) vs. absent (p=0.55). Of the 127 men with ComboGS and GPC < 50%, 83% were treated with RT alone and 2 PC deaths were observed; none in men with GS 7 and favorable intermediate-risk PC. Conclusions: Men treated with RT for ComboGS, GPC < 50%, GS 7 and favorable intermediate-risk PC may not require ADT to reduce the risk of PCSM. [Table: see text]
Pelvic exenteration in patients with nonmetastatic, locally advanced castration-resistant prostate cancer.
Authors: Donahue Timothy F. , Morris Michael J. , Hilton William M. , Scher Howard I. , Bochner Bernard H. 
Published: February 2017

168 Background: A subset of patients who present with localized prostate cancer (PCa) do not develop metastatic disease and recur locally after definitive primary therapy, local salvage therapy, hormones, and systemic intervention. We report our experience in patients with non-metastatic, locally advanced castration resistant prostate cancer (CRPC) treated with radical cystectomy or pelvic exenteration (RC/PEx). Methods: Institutional review board (IRB) approved retrospective review of all patients undergoing RC/PEx for non-metastatic, locally recurrent CRPC after definitive and salvage therapies. Patients were excluded if RC/PEx was for complications of definitive therapy alone. Results: Of 31 patients who had RC/PEx for PCa, 20 met inclusion criteria. Initial therapy was RP (4), XRT (6), brachytherapy (4), brachy/XRT (3), ADT/chemo (2), and ADT alone (1). Five patients had salvage XRT. All received ADT at relapse and 11 had chemotherapy prior to RC/PEx. RC/PEx was performed a median of 8.16 years (0.7 to 24.5) after PCa diagnosis. Patients had pT2b (1), pT3 (5), and pT4 (14) disease at surgery. Lymph nodes were clinically negative in all patients but pathologically positive in six, negative in nine, and not resected in five. Concurrent resections included rectum (12), pelvic wall (6), pubis (1), and iliac vein (1). Eighty five percent of patients had symptoms attributable to locally progressive PCa at RC/PEx including pain, genitourinary or gastrointestinal obstruction and bleeding. All symptomatic patients had relief of disease-related symptoms until recurrence. After a median follow-up of 3.12 years (0.7 to 13.4), nine patients are alive (four have no evidence of disease, five alive with disease), nine dead of disease, and two dead of other causes. Median time to death after RC/PEx was 2.8 years (0.8 to 5.9). For 14 patients who relapsed, metastases developed a median of 398 days (110 to 1,679) after RC/PEx. Ten patients received chemotherapy and 16 had androgen-deprivation therapy after surgery for local recurrence or distant metastases. Median time to chemotherapy after RC/PEx was 346 days (96 to 1,709). Conclusions: For patients with non-metastatic, locally advanced CRPC, RC/PEx to resect symptomatic disease is feasible and appears clinically beneficial. In addition to local control, it may confer significant disease free intervals and relief of symptoms. Even after relapse, performance status was sufficient to undergo systemic therapy.
Biomarker development trial of satraplatin in patients with metastatic castrate-resistant prostate cancer.
Authors: Liaw Bobby Chi-Hung , Seng Sonia Maria , Galsky Matt D. , Tsao Che-Kai , Febbo Phillip G. , Oh William K. 
Published: February 2017

170 Background: While satraplatin, a fourth generation oral platinum analogue, failed to improve overall survival (OS) in an unselected metastatic castrate-resistant prostate cancer (mCRPC) population (Sternberg, JCO 2009), anti-tumor activity was demonstrated, suggesting a “platinum-sensitive” subset of patients. Predictive biomarkers may not only select patients most likely to benefit from novel “targeted” therapies but also from standard (even discarded) cytotoxic agents. Development of predictive biomarkers in mCRPC is hampered by the fact that PC is associated with a long natural history and evolving genetic changes, highlighting the need for immediate pre-treatment metastatic tissue samples for biomarker development. In this trial, we sought to determine the feasibility of obtaining metastatic biopsies in patients with mCRPC treated with satraplatin. Methods: Docetaxel-refractory mCRPC patients underwent image-guided biopsy of metastatic lesions prior to treatment with satraplatin 80 mg/m2 PO on days 1 to 5 of a 35-day cycle and prednisone 5 mg PO twice daily. Biopsy samples are analyzed by whole exome and RNA sequencing, and peripheral blood samples are undergoing transcriptional profiling, to facilitate biomarker development. Results: Thirteen patients were enrolled with a median age of 71 (range: 55 to 80), prostate-specific antigen (PSA) of 82 ng/ml (0.04-3057), and Gleason score 8 (7 to 9). All patients received prior docetaxel, four (31%) had more than or eqaul to two prior chemotherapies, and two (15%) received abiraterone. Drug-related grade 3/4 toxicities included leukopenia (23%), neutropenia (8%), thrombocytopenia (8%), fatigue (8%), renal failure (8%), dysphagia (17%), and diarrhea (8%). A median of four cycles of satraplatin were completed, with declines of serum PSA of greater than or equal to 30% achieved in 4 of 13 patients (31%; 95% CI, 57.3 to 85.4%). Median time to PSA progression was 12.4 weeks (95% CI, 7.2 to 29.7+ weeks). Metastatic pre-treatment biopsies were collected in all study patients; genomic analysis is ongoing. Conclusions: This study confirms that satraplatin has anti-cancer activity in a subset of patients with mCRPC. Trials that require pre-treatment metastatic tumor biopsies are feasible. Analysis of the correlation between molecular signatures and treatment response will be presented at the meeting. Clinical trial information: NCT01289067.
The effect of [-2]proPSA and prostate health index (phi) on the accuracy of the prediction of initial and repeat prostate biopsies compared to tPSA and percent fPSA in young men (age 65 or younger).
Authors: Boegemann Martin , Vincendeau Sébastien , Stephan Carsten , Houlgatte Alain , Krabbe Laura-Maria , Blanchet Jean-Sebastien , Semjonow Axel 
Published: February 2017

171 Background: Prostate-specific antigen (tPSA) based screening reduces mortality. But recent recommendations do not endorse PSA-screening due to possible over-diagnosis and over-treatment and the resulting harm afflicted to patients. Screening studies showed the maximum benefit in young men age 65 or younger. tPSA and percent free PSA (%fPSA) lack specificity in the diagnosis of PCa. [-2]proPSA and the "prostate health index" (phi) improve this diagnostic specifity in a non-age adjusted population. Markers to diagnose clinicaly relevant cancers in young men are needed. Methods: The clinical performance of [-2]proPSA and phi were evaluated in a multicenter study. A total of 1,362 patients (769 age 65 or younger) scheduled for initial or repeated prostate biopsy (668 with, 694 without PCa, each 10 or more core biopsies) were recruited in four different sites based on PSA level 1.6 to 8.0 ng/mL WHO-calibrated (2-10 ng/mL classically calibrated). Serum samples taken prior to digital rectal examination (DRE) were measured for the concentration of tPSA, fPSA and [-2]proPSA with Beckman Coulter immunoassays on Access 2 or DxI800 instruments. Phi was calculated as: [-2]proPSA/fPSA x √tPSA. Results: In univariate analysis [-2]proPSA/fPSA (%[-2]proPSA) and phi were the best predictors of PCa detection in patients at initial biopsy (AUC: 0,72 and 0,73) and repeated biopsy (AUC: 0,74 and 0,74). Analysis of the data for men age 65 and younger (n=593) showed that %[-2]proPSA and phi significantly improved PCa dectection (AUC: 0,72 and 0,73) as compared with tPSA (AUC: 0,53) or %fPSA (AUC: 0,62). In the detection of significant PCa (based on PRIAS criteria) %[-2]proPSA and phi demonstrated the best performance in the whole cohort and in young men (65 and younger) years as well (AUC 0,68 and 0,73). Conclusions: This multicenter study showed that [-2]proPSA and phi have a superior clinical performance in detecting PCa in the PSA range of 2 to 10 ng/mL compared to tPSA and %fPSA at initial and repeat biopsies. This superiority is maintained for the detection of PCa in young men (age 65 or younger).
Focal nodular prostatic peripheral zone enhancement on CT to predict clinically significant (Gleason 4+3 and higher) prostate cancer.
Authors: Glazer Daniel I. , Davenport Matthew S. , Cohan Richard H. , Ellis James H. , Caoili Elaine M. , Stein Erica B. , Childress John C. , Masch William R. , Brown Jordan M. , Mollard Brett J. , Montgomery Jeffrey S. , Palapattu Ganesh S. , Francis Isaac R. 
Published: February 2017

173 Background: CTs are insensitive for prostate cancer and inaccurate for local prostate cancer staging. However, enhancing peripheral zone nodules can be seen on a CT, and their significance is uncertain. The purpose of this study was to determine whether focal nodular enhancement within the prostatic peripheral zone on a CT is predictive of clinically significant prostate cancer. Methods: Institutional review board approval was obtained and informed consent waived for this Health Insurance Portability and Accountability Act-compliant retrospective study. Forty-three patients with high-grade prostate cancer (Gleason 4+3 [n=14], 3+5 [n=1], 4+4 [n=1], 4+5 [n=19], 5+4 [n=8]) and 96 with cystoprostatectomy-confirmed low-grade (Gleason 3+4 [n=24], 3+3 [n=23]) or absent (n=49) prostate cancer imaged with contrast-enhanced CT within nine months of histology (median: 18 days) comprised the study population. CT images were reviewed by 10 blinded radiologists (five attendings, five residents) who scored peripheral zone enhancement on a scale of 1 (benign) to 5 (malignant). Focal nodular enhancement was considered malignant. Likelihood ratios (LR) and specificities were calculated. Results: Scores of ‘5’ were strongly predictive of clinically significant prostate cancer (pooled LR+: 9.6 [95% CI: 5.8-15.8]) with rare false positives (pooled specificity: 0.98 [942/960, 95% CI: 0.98-0.99]). Attendings outperformed residents (LR+: 14.7 [95% CI: 5.8-37.2] vs. 7.6 [95% CI: 4.2-13.7]) with similar specificity (0.99 [475/480, 95% CI: 0.98-1.00] vs. 0.97 [467/480, 95% CI: 0.96-0.99]). Conclusions: Focal nodular peripheral zone enhancement on a CT is specific and predictive of clinically significant prostate cancer.
Biochemical response to ketoconazole therapy in post-chemotherapy mCRPC patients.
Authors: Roeder M. Andreas , Berg Kasper Drimer , Hunde Daniel , Nerstroem Camilla , Thomsen Frederik Birkebæk , Brasso Klaus , Iversen Peter 
Published: February 2017

174 Background: Ketoconazole for the treatment of metastatic castration resistant prostate cancer (mCRPC) has never been investigated in randomized trials. In fact, although ketoconazole is a less potent inhibitor of the CYP-17 enzyme systems compared to abiraterone, there is no head-to-head evidence demonstrating that this translates into improved survival. We analyzed biochemical response rates in post-chemotherapy mCRPC patients who were treated with ketoconazole 200 mg TID plus prednisone 5 mg BID at a single center in Denmark. Methods: Between 2008 and 2012, where neither abiraterone nor enzalutamide was available in Denmark, a total of 30 post-chemotherapy mCRPC patients were managed with ketoconazole. Percent change in prostate-specific antigen (PSA) and alkaline phosphatase (ALP) from baseline were registered. Overall survival was calculated from the initiation of ketoconazole. Results: At initiation of ketoconazole, median age was 66 (range: 58 to 76). Median PSA was 547 ng/ml (65 to 4,241). Median ALP was 159 U/L (51 to 750). The median number of prior cancer therapies was five (three to nine). The median time on ketoconazole treatment was 150 days (14 to 648). A total of 44% patients had any decline in PSA, whereof 31% experienced a decline of >=50%. At three months, a total of 19 patients still received ketoconazole, whereof 26% sustained a PSA decline of >=50% from baseline. A total of 71% experienced any decline in ALP, whereof 36% experienced a maximum decline of >=50%. At three months, 7 of 19 patients (36%) sustained an ALP decline of >=50% from baseline. At follow-up, 28 of 30 patients had died. The median overall survival was 10.5 months (95%CI: 8.3-12.6). Conclusions: Compared to the post-chemotherapy phase II study of abiraterone (58 patients) our cohort most likely had a larger tumor burden (e.g. higher PSA, more therapies prior to start of ketoconazole). Nonetheless, we demonstrated a reasonably comparable maximum >=50% PSA response-rate (43% in phase II) and three-months response-rate >=50% (36% in phase II). Also a significant decline in ALP was demonstrated here which has not been reported in abiraterone trials. Given the large difference in expenditure, a head-to-head comparison of abiraterone and ketoconazole in mCRPC patients still seem justified.
Leveraging the DNA damage and transcriptional-regulatory roles of PARP-1 as a means to improve prostate cancer therapy.
Authors: Schiewer Matthew Joseph , Steffen Jamin , Tholey Renee , Brody Jonathan Robert , Pascal John , Lin Jianqing , Den Robert , Feng Felix Yi-Chung , Gomella Leonard G. , Dicker Adam , Kelly William Kevin , Knudsen Karen E. 
Published: February 2017

179 Background: The first described roles for PARP-1 were in the repair of DNA damage and genomic maintenance, however, recent studies have identified PARP-1 as harboring critical context-dependent transcriptional regulatory functions. Our group recently discovered that PARP-1 enzymatic activity is a critical effector of androgen receptor (AR) function in models of prostatic adenocarcinoma (PCa), and is recruited to regulatory sites of select AR target genes. Pharmacological inhibition of PARP-1 enzymatic activity results in diminished AR and PARP-1 residency at AR target gene regulatory loci, reduced AR target gene expression (more than 50%), and reduced AR-driven, PCa-associated phenotypes, including castrate-resistant PCa (CRPC) AR function, tumor cell growth, and transition to CRPC. These data, in part, served as critical rationale for current clinical trials combining PARP inhibition and abiraterone for patients with metastatic CRPC NCT01576172 . Given the clinical importance of targeting AR function in PCa, preclinical studies were performed to assess the impact of leveraging the dual roles of PARP-1 as a means to improve therapy for advanced disease. Methods: In vitro and in vivo model systems were utilized to assess impact on AR and tumor growth. Multiple PARP inhibitors were used for additional studies. The impact of PARP-1 on gene expression was also assessed using unbiased analyses. PARP-1 mutants were also utilized to segregate the DNA damage and transcriptional regulatory roles of PARP-1. Results: Critically, PARP-1 inhibitors cooperated with castration to elicit an enhanced therapeutic response, and PARP-1 inhibitors were effective at suppressing CRPC growth in vivo. Multiple PARP inhibitors diminished AR chromatin occupancy, altered AR transcriptional output and reduction in PCa and CRPC cell growth. Conclusions: These data identify PARP-1 as a feasible therapeutic target for advanced prostate cancer. Multiple PARP inhibitors show pre-clinical efficacy in models of PCa and CRPC and merit consideration for clinical trial, and a concept will be presented.