Martin G Sanda

Emory University, Atlanta, Georgia, United States

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Publications (191)943.47 Total impact

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    ABSTRACT: Given the limited sensitivity and specificity of prostate-specific antigen (PSA), its widespread use as a screening tool has raised concerns for the overdiagnosis of low-risk and the underdiagnosis of high-grade prostate cancer. To improve early-detection biopsy decisions, the National Cancer Institute conducted a prospective validation trial to assess the diagnostic performance of the prostate cancer antigen 3 (PCA3) urinary assay for the detection of prostate cancer among men screened with PSA.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 11/2014;
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    ABSTRACT: Cure rates for localized high-risk prostate cancers (PCa) and some intermediate-risk PCa are frequently suboptimal with local therapy. Outcomes are improved by concomitant androgen-deprivation therapy (ADT) with radiation therapy, but not by concomitant ADT with surgery. Luteinizing hormone-releasing hormone agonist (LHRHa; leuprolide acetate) does not reduce serum androgens as effectively as abiraterone acetate (AA), a prodrug of abiraterone, a CYP17 inhibitor that lowers serum testosterone (< 1 ng/dL) and improves survival in metastatic PCa. The possibility that greater androgen suppression in patients with localized high-risk PCa will result in improved clinical outcomes makes paramount the reassessment of neoadjuvant ADT with more robust androgen suppression.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 10/2014;
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    ABSTRACT: The National Cancer Institute (NCI) Symptom Management and Health-Related Quality of Life Steering Committee convened four working groups to recommend core sets of patient-reported outcomes to be routinely incorporated in clinical trials. The Prostate Cancer Working Group included physicians, researchers, and a patient advocate. The group's process included 1) a systematic literature review to determine the prevalence and severity of symptoms, 2) a multistakeholder meeting sponsored by the NCI to review the evidence and build consensus, and 3) a postmeeting expert panel synthesis of findings to finalize recommendations. Five domains were recommended for localized prostate cancer: urinary incontinence, urinary obstruction and irritation, bowel-related symptoms, sexual dysfunction, and hormonal symptoms. Four domains were recommended for advanced prostate cancer: pain, fatigue, mental well-being, and physical well-being. Additional domains for consideration include decisional regret, satisfaction with care, and anxiety related to prostate cancer. These recommendations have been endorsed by the NCI for implementation.
    Journal of the National Cancer Institute. 07/2014; 106(7).
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    ABSTRACT: Aurora kinase A (AURKA) gene amplification has been documented in 67% of hormone-naive prostate cancer cases that progress to a highly aggressive variant of castrate-resistant disease, clinically referred to as "neuroendocrine" prostate cancer, "small cell" prostate carcinoma, or "anaplastic" prostate cancer. Therefore, AURKA amplification is a potential prognostic biomarker that may help to identify patients with prostate cancer who are at high risk for developing castrate-resistant disease with clinical features of small cell carcinoma. Furthermore, AURKA inhibitors are currently being tested in clinical trials. In a previous study, we found AURKA amplification in 6 cases of prostate cancer with Paneth cell-like cells. This morphologic pattern has been suggested to represent low-grade neuroendocrine differentiation (NED) with generally favorable prognosis. We sought to investigate the frequency of AURKA amplification and the histologic characteristics of prostate cancer with Paneth cell-like NED. Twenty-five cases from 172 prostatectomies were evaluated for the presence of 18 morphologic features and AURKA amplification. Most prostate cancers with Paneth cell-like NED had macronucleoli (92%), basophilic appearance (88%), perineural invasion (72%), and nuclear stratification (76%). The frequency of AURKA amplification was 45%, present throughout the examined tumor nodule including areas without Paneth cell-like cells. When histologically similar cases with and without AURKA amplification were compared, this gene alteration was associated with larger extent of Paneth cell-like NED identified at magnification ×20 (P = .015), higher percentage of Paneth cell-like NED throughout the tumor nodule (P = .033), ductal features (P = .02), and higher overall Gleason grade (P = .039). AURKA amplification was not associated with age, serum prostate specific antigen, or tumor stage. The high frequency of AURKA amplification (45%) in localized prostate cancer with Paneth cell-like NED and its potential prognostic significance warrant further investigation.
    Human pathology 06/2014; · 3.03 Impact Factor
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    ABSTRACT: The hormonal milieu influences immune tolerance and the immune response against viruses and cancer, but the direct effect of androgens on cellular immunity remains largely uncharacterized. We therefore sought to evaluate the effect of androgens on murine and human T cells in vivo and in vitro. We found that murine androgen deprivation in vivo elicited RNA expression patterns conducive to IFN signaling and T-cell differentiation. Interrogation of mechanism showed that testosterone regulates T-helper 1 (Th1) differentiation by inhibiting IL-12-induced Stat4 phosphorylation: in murine models, we determined that androgen receptor binds a conserved region within the phosphatase, Ptpn1, and consequent up-regulation of Ptpn1 then inhibits IL-12 signaling in CD4 T cells. The clinical relevance of this mechanism, whereby the androgen milieu modulates CD4 T-cell differentiation, was ascertained as we found that androgen deprivation reduced expression of Ptpn1 in CD4 cells from patients undergoing androgen deprivation therapy for prostate cancer. Our findings, which demonstrate a clinically relevant mechanism by which androgens inhibit Th1 differentiation of CD4 T cells, provide rationale for targeting androgens to enhance CD4-mediated immune responses in cancer or, conversely, for modulating androgens to mitigate CD4 responses in disorders of autoimmunity.
    Proceedings of the National Academy of Sciences of the United States of America. 06/2014;
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    ABSTRACT: To modify the Prostate Cancer Prevention Trial risk calculator (PCPTRC) to predict low- vs high-grade (Gleason grade ≥7) prostate cancer and incorporate percent free-prostate-specific antigen (PSA).
    Urology 06/2014; 83(6):1362-8. · 2.42 Impact Factor
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    ABSTRACT: In men with PCa, large variations of PROs after RP or high-dose RAD might be related to between-country differences of medical and sociodemographic variables, and differences in PROs before treatment in the sexual and urinary domains. In 1908 patients with localized PCa from Norway, the United States, or Spain, the relation between medical (prostate-specific antigen, Gleason score, cT-category) and sociodemographic variables (age, education, marital status) before treatment was investigated. Using the Expanded Prostate Cancer Index Composite questionnaire, PROs before treatment within the sexual and urinary domains were also considered. Compared with the European patients, American patients were younger, fewer had comorbid conditions, and more had a high education level. Fifty-three percent of the US men eligible for RP had low-risk tumors compared with 42% and 31% among the Norwegian and the Spanish patients, respectively. Among the Spanish RAD patients, 54% had had low-risk tumors compared with 34% of the American and 21% of the Norwegian men planned for RAD, respectively. Compared with the European patients, significantly fewer US patients reported moderate or severe sexual dysfunction and related problems. In most subgroups, the number of patients with sexual or urinary dysfunction exceeded that of patients with bother related to the reported dysfunction. Statistically significant between-country differences were observed in medical and sociodemographic variables, and in PROs before treatment within the sexual and urinary domains. Large differences between reported dysfunction and related problems within the sexual and urinary domains indicate that dysfunction and bother should be reported separately in addition to calculation of summary scores. The documented differences, not at least regarding PROs, might in part explain the large variation of side effects after treatment evident in the medical literature.
    Clinical Genitourinary Cancer 01/2014; · 1.43 Impact Factor
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    ABSTRACT: Purpose We expanded the clinical usefulness of EPIC-CP (Expanded Prostate Cancer Index Composite for Clinical Practice) by evaluating its responsiveness to health related quality of life changes, defining the minimally important differences for an individual patient change in each domain and applying it to a sexual outcome prediction model. Materials and Methods In 1,201 subjects from a previously described multicenter longitudinal cohort we modeled the EPIC-CP domain scores of each treatment group before treatment, and at short-term and long-term followup. We considered a posttreatment domain score change from pretreatment of 0.5 SD or greater clinically significant and p ≤0.01 statistically significant. We determined the domain minimally important differences using the pooled 0.5 SD of the 2, 6, 12 and 24-month posttreatment changes from pretreatment values. We then recalibrated an EPIC-CP based nomogram model predicting 2-year post-prostatectomy functional erection from that developed using EPIC-26. Results For each health related quality of life domain EPIC-CP was sensitive to similar posttreatment health related quality of life changes with time, as was observed using EPIC-26. The EPIC-CP minimally important differences in changes in the urinary incontinence, urinary irritation/obstruction, bowel, sexual and vitality/hormonal domains were 1.0, 1.3, 1.2, 1.6 and 1.0, respectively. The EPIC-CP based sexual prediction model performed well (AUC 0.76). It showed robust agreement with its EPIC-26 based counterpart with 10% or less predicted probability differences between models in 95% of individuals and a mean ± SD difference of 0.0 ± 0.05 across all individuals. Conclusions EPIC-CP is responsive to health related quality of life changes during convalescence and it can be used to predict 2-year post-prostatectomy sexual outcomes. It can facilitate shared medical decision making and patient centered care.
    The Journal of Urology. 01/2014; 191(3):638–645.
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    ABSTRACT: Here, we sought to determine whether peptide vaccines designed harbor both class I as well as class II restricted antigenic motifs could concurrently induce CD4 and CD8 T cell activation against autologous tumor antigens. Based on our prior genome-wide interrogation of human prostate cancer tissues to identify genes over-expressed in cancer and absent in the periphery, we targeted SIM2 as a prototype autologous tumor antigen for these studies. Using humanized transgenic mice we found that the 9aa HLA-A*0201 epitope, SIM2237-245, was effective at inducing an antigen specific response against SIM2-expressing prostate cancer cell line, PC3. Immunization with a multi-epitope peptide harboring both MHC-I and MHC-II restricted epitopes induced an IFN-γ response in CD8 T cells to the HLA-A*0201-restricted SIM2237-245 epitope, and an IL-2 response by CD4 T cells to the SIM2240-254 epitope. This peptide was also effective at inducing CD8+ T-cells that responded specifically to SIM2-expressing tumor cells. Collectively, the data presented in this study suggest that a single peptide containing multiple SIM2 epitopes can be used to induce both a CD4 and CD8 T cell response, providing a peptide-based vaccine formulation for potential use in immunotherapy of various cancers.
    PLoS ONE 01/2014; 9(4):e93231. · 3.53 Impact Factor
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    ABSTRACT: Background In men with prostate cancer ( PCa) large variations of patient-reported outcomes ( PROs) after radical prostatectomy (RP) or high-dose radiotherapy (RAD) may be related to between-country differences of pre-treatment medical and socio-demographic variables , as well as to differences in pre-treatment PROs in the sexual and urinary domain. Methods In 1908 patients with localized PCa from Norway, USA or Spain the relation was investigated between pre-treatment data on medical (PSA, Gleason score , cT-category ) and socio-demographic variables (age, education ,marital status). Using the EPIC questionnaire pre-treatment PROs within the sexual and urinary domain were also considered . Results Compared to the European patients American patients were younger, fewer had co-morbid conditions and more had a high education level. Fifty-three % of the US-men eligible for RP had low-risk tumors compared to 42% and 31% among respectively the Norwegian and the Spanish patients. Among the Spanish RAD patients 54% had had low- risk tumors compared to respectively 34% of the American and 21% of the Norwegian men planned for RAD. Compared to the European patients significantly fewer US patients reported moderate or severe sexual dysfunction and related problems. In most subgroups the number of patients with sexual or urinary dysfunctions exceeded that of patients with bother related to the reported dysfunction. Conclusions Statistically significant between-country differences were observed in pre-treatment medical and socio-demographic variables, as well as in pre-treatment PROs within the sexual and urinary domain. Large differences between reported dysfunction and related problems within the sexual and urinary domain indicate that dysfunction and bother should be reported separately in addition to calculation of summary scores. The documented differences, not at least regarding PROs, may in part explain the large variation of post-treatment side effects evident in the medical literature.
    Clinical Genitourinary Cancer 01/2014; · 1.43 Impact Factor
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    ABSTRACT: Purpose To evaluate rectal dose and post-treatment patient-reported bowel quality of life (QOL) following radiation therapy for prostate cancer. Methods Patient-reported QOL was measured at baseline and 2-years via the expanded prostate cancer index composite (EPIC) for 90 patients. Linear regression modeling was performed using the baseline score for the QUANTEC normal tissue complication probability model and dose volume histogram (DVH) parameters for the whole and segmented rectum (superior, middle, and inferior). Results At 2-years the mean summary score declined from a baseline of 96.0–91.8. The median volume of rectum treated to ⩾70 Gy (V70) was 11.7% for the whole rectum and 7.0%, 24.4%, and 1.3% for the inferior, middle, and superior rectum, respectively. Mean dose to the whole and inferior rectum correlated with declines in bowel QOL while dose to the mid and superior rectum did not. Low (V25–V40), intermediate (V50–V60) and high (V70–V80) doses to the inferior rectum influenced bleeding, incontinence, urgency, and overall bowel problems. Only the highest dose (V80) to the mid-rectum correlated with rectal bleeding and overall bowel problems. Conclusions Segmental DVH analysis of the rectum reveals associations between bowel QOL and inferior rectal dose that could significantly influence radiation planning and prognostic models.
    Radiotherapy and Oncology 01/2014; · 4.52 Impact Factor
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    ABSTRACT: Background Robot-assisted laparoscopic radical prostatectomy (RALP) has become increasingly common; however, there have been no nationwide, population-based, non–claims-based studies to evaluate differences in outcomes between RALP and open radical retropubic prostatectomy (RRP). Objective To determine surgical, oncologic, and health-related quality of life (HRQOL) outcomes following RALP and RRP in a nationwide cohort. Design, setting, and participants We identified 903 men in the Health Professionals Follow-up Study diagnosed with prostate cancer between 2000 and 2010 who underwent radical prostatectomy using RALP (n = 282) or RRP (n = 621) as primary treatment. Intervention Radical prostatectomy. Outcome measurements and statistical analysis We compared patients undergoing RALP or RRP across a range of perioperative, oncologic, and HRQOL outcomes. Results and limitations Use of RALP increased during the study period, constituting 85.2% of study subjects in 2009, up from 4.5% in 2003. Patients undergoing RALP compared to RRP were less likely to have a lymph node dissection (51.5% vs 85.4%; p < 0.0001), had less blood loss (207.4 ml vs 852.3 ml; p < 0.0001), were less likely to receive blood transfusions (4.3% vs 30.3%; p < 0.0001), and had shorter hospital stays (1.8 d vs 2.9 d; p < 0.0001). Surgical, oncologic, and HRQOL outcomes did not differ significantly among the groups. In multivariate logistic regression models, there were no significant differences in 3- or 5-yr recurrence-free survival comparing RALP versus RRP (hazard ratios: 0.98 [95% confidence interval (CI), 0.46–2.08] and 0.75 [95% CI, 0.18–3.11], respectively). Conclusions In a nationwide cohort of patients undergoing surgical treatment for prostate cancer, RALP was associated with shorter hospital stay, and lower blood loss and transfusion rates than RRP. Surgical oncologic and HRQOL outcomes were similar between groups. Patient summary We studied men throughout the United States with prostate cancer who underwent surgical removal of the prostate. We found that robot-assisted laparoscopic radical prostatectomy resulted in shorter hospital stay, less blood loss, and fewer blood transfusions than radical retropubic prostatectomy. There were no differences in cancer control or health-related quality of life.
    European Urology 01/2014; · 10.48 Impact Factor
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    ABSTRACT: After being diagnosed with prostate cancer, men must assimilate information regarding their cancer. Satisfaction with information reflects the evaluation of information sources used prior to treatment to select a therapy. We sought to describe the use and helpfulness of several information sources available to prostate cancer survivors and to identify factors associated with satisfaction with information. A total of 1204 men with newly diagnosed prostate cancer enrolled in the prospective, multi-center Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment (PROST-QA) study. The validated Satisfaction with Information (SWI) domain of the Service Satisfaction Scale-Cancer (SCA) was administered to subjects two months following treatment, and the relationship between several factors, such as demographics, socioeconomic factors, cancer severity and types of information sources used, and satisfaction with information were evaluated using multiple regression. Sources of information endorsed by subjects varied by race, education, and study site. The most helpful sources were treatment description by the treating physician (33.1%), internet sites (18.9%) and books (18.1%). In multiple variable models, patient age (p=0.005) and information provided by the physician regarding their own patients' outcomes (p=0.01) were independently associated with patient satisfaction with information provided. A variety of information sources were used and endorsed as helpful by subjects, although results for a physician's own patients was the only source independently associated with satisfaction with information. Providing patients with information about possible or expected courses of care and outcomes may improve satisfaction.
    The Journal of urology 12/2013; · 3.75 Impact Factor
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    ABSTRACT: BACKGROUND Data continue to emerge on the relative merits of different treatment modalities for prostate cancer. The objective of this study was to compare patient-reported quality-of-life (QOL) outcomes after proton therapy (PT) and intensity-modulated radiation therapy (IMRT) for prostate cancer. METHODSA comparison was performed of prospectively collected QOL data using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. QOL data were collected during the first 2 years after treatment for men who received PT and IMRT. PT was delivered to 1243 men at a single center at doses from 76 grays (Gy) to 82 Gy. IMRT was delivered to 204 men who were included in the Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment (PROSTQA) study in doses from 75.6 Gy to 79.4 Gy. The Wilcoxon rank-sum test was used to compare EPIC outcomes by modality using baseline-adjusted scores at different time points. Individual questions were assessed by converting to binary outcomes and testing with generalized estimating equations. RESULTSNo differences were observed in summary score changes for bowel, urinary incontinence, urinary irritative/obstructive, and sexual domains between the 2 cohorts. However, more men who received IMRT reported moderate/big problems with rectal urgency (P = 0.02) and frequent bowel movements (P = 0.05) than men who received PT. CONCLUSIONS There were no differences in QOL summary scores between the IMRT and PT cohorts during early follow-up (up to 2-years). Response to individual questions suggests possible differences in specific bowel symptoms between the 2 cohorts. These outcomes highlight the need for further comparative studies of PT and IMRT. Cancer 2014;. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
    Cancer 12/2013; · 5.20 Impact Factor
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    ABSTRACT: Objectives:Prevalence of urinary problems(UP) after prostate cancer treatment is as high as 40% with significant quality of life impact. We compared direct costs of UP treatment across treatment groups and determined predictors of long-term UP costs. Methods:Longitudinal, observational cohort study analyzed demography, treatment, and quality-of-life data from Cancer of Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. UP medication and surgical treatment costs were compared among treatment groups: radical prostatectomy(RP), electron beam radiation therapy(EBRT), brachytherapy(BT), and watchful waiting(WW), for a maximum 14 years and using 2009 costs. Means and proportions were compared using Chi-square and F-statistics to determine significant differences among treatment groups. Bootstrapped regression models compared the relative effects of primary treatment, D'Amico risk groups, age, change in urinary function (UF) and urinary bother (UB) on 3-monthly UP treatment costs. Results: The 3,276 patients were 64.3 years at diagnosis. Distribution of treatment groups was RP(61.6%), BT(17.34%), EBRT(12.45%), BT+EBRT(5.40%), WW(2.08%), and RP+EBRT(1.13%). Mean UP treatment costs across all patients were $144/year. Those greater than 74 years old had highest UP treatment costs($289/year). Multivariate results showed patients in the RP group incurred significantly(18.1%, p<.0001) lower UP treatment costs post-prostate treatment compared to WW, with other treatments not significant. UF change from baseline was not significant but UB changes were associated with 85.6%(p=0.052) higher UP treatment costs. Conclusions:Cost of UP treatment, along with UB score change from baseline, can be an indicator of both the extent of dysfunction and the desire for success and adherence to UP treatments after prostate cancer treatment.
    141st APHA Annual Meeting and Exposition 2013; 11/2013
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    ABSTRACT: Purpose/Objectives: To determine the long-term effects of prostate cancer treatment on spouse quality of life (QOL) at 36 months following treatment.Design: Descriptive-exploratory; community-based study.Setting: Telephone interviews.Sample: 95 female spouses of men treated for early-stage prostate cancer.Methods: A computer-assisted telephone interview was used to evaluate QOL among spouses of prostate cancer survivors at 36 months after initial prostate cancer treatment.Main Research Variables: Lymphedema, demographic information, self-reported comorbid diseases or medical issues, and medication usage.Findings: Spouses who had more negative appraisal of caregiving had lower sexual satisfaction, poorer cancer-specific QOL, and poorer mental QOL. Spouses who perceived bother related to the patient's sexual or hormone function reported more threatening appraisals of caregiving, less sexual satisfaction, and poorer QOL.Conclusions: Spouses continued to experience negative appraisal of caregiving, which affected QOL 36 months after their husbands' treatment for prostate cancer. Additional studies related to factors that influence spouse QOL during survivorship will help guide clinical practice.Implications for Nursing: Healthcare providers must help spouses find strategies that promote positive coping and lessen negative appraisal. Giving caregivers information early in the treatment process will help them understand what to expect over time. Supporting caregivers and helping them manage stress will enhance QOL during survivorship.Knowledge Translation: Spouses who experienced more bother related to urinary, sexual, and hormonal function experience more stress and worse QOL at 36 months post-treatment. Spouse appraisal can have a significant effect on QOL. Offering counseling to couples following treatment for prostate cancer may improve QOL by helping couples manage relationship intimacy.
    Oncology Nursing Forum 11/2013; 40(6):567-73. · 1.91 Impact Factor
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    ABSTRACT: Identification of novel vaccine targets is critical for the design and advancement of prostate cancer (PCa) immunotherapy. Ideal targets are proteins that are abundant in prostate tumors while absent in extra-prostatic tissues. The fusion of the androgen-regulated TMPRSS2 gene with the ETS transcription factor ERG occurs in approximately 50 % of prostate cancer cases and results in aberrant ERG expression. Because expression of ERG is very low in peripheral tissue, we evaluated the suitability of this protein as an antigen target in PCa vaccines. ERG-derived HLA-A*0201-restricted immunogenic epitopes were identified through a 3-step strategy that included in silico, in vitro, and in vivo validation. Algorithms were used to predict potential HLA-A*0201-binding epitopes. High-scoring epitopes were tested for binding to HLA-A*0201 using the T2-based stabilization assay in vitro. Five peptides were found to bind HLA-A*0201 and were subsequently tested for immunogenicity in humanized, HLA-A*0201 transgenic mice. The in vivo screening identified three immunogenic peptides. One of these peptides, ERG295, overcame peripheral tolerance in HLA-A*0201 mice that expressed prostate-restricted ERG. Also, this peptide induced an antigen-specific response against ERG-expressing human prostate tumor cells. Finally, tetramer assay showed detectable and responsive ERG295-specific cytotoxic lymphocytes in peripheral blood of HLA-A*0201(+) prostate cancer patients. Detection of ERG-specific CTLs in both mice and the blood of prostate cancer patients indicates that ERG-specific tolerance can be overcome. Additionally, these data suggest that ERG is a suitable target antigen for PCa immunotherapy.
    Cancer Immunology and Immunotherapy 10/2013; · 3.64 Impact Factor
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    ABSTRACT: To expand the clinical usefulness of the Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) by evaluating its responsiveness to health related quality of life (HRQOL) changes, defining the minimally important differences (MID) for an individual patient's change in each domain, and applying it to a sexual outcome prediction model. In 1,201 subjects from a previously described multi-center, longitudinal cohort, we modeled each treatment group's EPIC-CP domain scores at pre-treatment, short-term, and long-term follow-up. We considered post-treatment domain score changes from pre-treatment ≥ 0.5 standard deviations (SD) clinically significant and with a p-value ≤ 0.01 as statistically significant. We determined domain MIDs using the 0.5 pooled SD of the 2, 6, 12, and 24 month post-treatment changes from pre-treatment. We recalibrated an EPIC-CP-based nomogram model predicting 2-year post-prostatectomy functional erections from that developed using EPIC-26. For every HRQOL domain, EPIC-CP was sensitive to similar post-treatment HRQOL changes over time as had been observed using EPIC-26. The EPIC-CP MIDs for changes in the urinary incontinence, urinary irritation/obstruction, bowel, sexual, and vitality/hormonal domains are 1.0, 1.3, 1.2, 1.6, and 1.0, respectively. The EPIC-CP-based sexual prediction model performs well (AUC=0.76) and shows robust agreement with its EPIC-26-based counterpart, with predicted probability differences between models of ≤10% for 95% of individuals and a mean difference of 0.0 (SD=0.05) across all individuals. EPIC-CP is responsive to HRQOL changes during convalescence, and can be used to predict 2-year post-prostatectomy sexual outcomes. Its use can facilitate shared medical decision-making and patient-centered care.
    The Journal of urology 09/2013; · 3.75 Impact Factor
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    ABSTRACT: OBJECTIVES: To establish the value of MRI in targeting re-biopsy for undiagnosed prostate cancer despite multiple negative biopsies and determine clinical relevance of detected tumors. MATERIALS AND METHODS: Thirty-eight patients who underwent MRI after 2 or more negative biopsies due to continued clinical suspicion and later underwent TRUS-guided biopsy supplemented by biopsy of suspicious areas depicted by MRI were identified. Diagnostic performance of endorectal 3T MRI in diagnosing missed cancer foci was assessed using biopsy results as the standard of reference. Ratio of positive biopsies using systematic versus MRI-prompted approaches was compared. Gleason scores of detected cancers were used as surrogate for clinical relevance. RESULTS: Thirty-four percent of patients who underwent MRI before re-biopsy had prostate cancer on subsequent biopsy. The positive biopsy yield with systematic sampling was 23% versus 92% with MRI-prompted biopsies(p<0.0001). Seventy-seven percent of tumors were detected exclusively in the MRI-prompted zones. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of MRI to provide a positive biopsy were 92%, 60%, 55%, 94% and 71%, respectively. The anterior gland and apical regions contained most tumors; 75% of cancers detected by MRI-prompted biopsy had Gleason score≥7. CONCLUSIONS: Clinically relevant tumors missed by multiple TRUS-guided biopsies can be detected by a MRI-prompted approach.
    Magnetic Resonance Imaging 04/2013; · 2.06 Impact Factor
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    ABSTRACT: PURPOSE: To evaluate patients treated with external beam radiation therapy as part of the multicenter Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment (PROSTQA), to identify factors associated with posttreatment patient-reported bowel health-related quality of life (HRQOL). METHODS AND MATERIALS: Pretreatment characteristics and treatment details among 292 men were evaluated using a general linear mixed model for their association with measured HRQOL by the Expanded Prostate Cancer Index Composite instrument through 2 years after enrollment. RESULTS: Bowel HRQOL had a median score of 100 (interquartile range 91.7-100) pretreatment and 95.8 (interquartile range 83.3-100) at 2 years, representing new moderate/big problems in 11% for urgency, 7% for frequency, 4% for bloody stools, and 8% for an overall bowel problems. Baseline bowel score was the strongest predictor for all 2-year endpoints. In multivariable models, a volume of rectum ≥25% treated to 70 Gy (V70) yielded a clinically significant 9.3-point lower bowel score (95% confidence interval [CI] 16.8-1.7, P=.015) and predicted increased risks for moderate to big fecal incontinence (P=.0008). No other radiation therapy treatment-related variables influenced moderate to big changes in rectal HRQOL. However, on multivariate analyses V70 ≥25% was associated with increases in small, moderate, or big problems with the following: incontinence (3.9-fold; 95% CI 1.1-13.4, P=.03), rectal bleeding (3.6-fold; 95% CI 1.3-10.2, P=.018), and bowel urgency (2.9-fold; 95% CI 1.1-7.6, P=.026). Aspirin use correlated with a clinically significant 4.7-point lower bowel summary score (95% CI 9.0-0.4, P=.03) and an increase in small, moderate, or big problems with bloody stools (2.8-fold; 95% CI 1.2-6.4, P=.018). Intensity modulated radiation therapy was associated with higher radiation therapy doses to the prostate and lower doses to the rectum but did not independently correlate with bowel HRQOL. CONCLUSION: After contemporary dose-escalated external beam radiation therapy up to 11% of patients have newly identified moderate/big problems with bowel HRQOL 2 years after treatment. Bowel HRQOL is related to baseline function, rectal V70, and aspirin use. Finally, our findings validate the commonly utilized cut-point of rectal V70 ≥25% as having significant impact on patient-reported outcomes.
    International journal of radiation oncology, biology, physics 04/2013; · 4.59 Impact Factor

Publication Stats

7k Citations
943.47 Total Impact Points

Institutions

  • 2013–2014
    • Emory University
      • Department of Urology
      Atlanta, Georgia, United States
  • 2004–2014
    • Beth Israel Deaconess Medical Center
      • • Division of Urology
      • • Department of Radiology
      • • Department of Surgery
      Boston, Massachusetts, United States
  • 2008–2012
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2008–2011
    • Harvard University
      • Department of Epidemiology
      Boston, MA, United States
  • 1997–2011
    • University of Michigan
      • • Department of Pathology
      • • Department of Urology
      • • Comprehensive Cancer Center
      Ann Arbor, MI, United States
  • 2010
    • McGill University
      • Division of Urology
      Montréal, Quebec, Canada
  • 1994–2010
    • Johns Hopkins Medicine
      • • Department of Pathology
      • • Department of Urology
      Baltimore, MD, United States
  • 2004–2009
    • Brigham and Women's Hospital
      • • Department of Medicine
      • • Department of Pathology
      Boston, MA, United States
  • 1999–2008
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
  • 2007
    • Sheba Medical Center
      Gan, Tel Aviv, Israel
  • 2005
    • Washington University in St. Louis
      • Department of Radiation Oncology
      San Luis, Missouri, United States
  • 2000
    • Prostate Cancer Research Institute
      Los Angeles, California, United States
  • 1994–1995
    • Johns Hopkins University
      • Department of Pathology
      Baltimore, Maryland, United States