Prostate Cancer Articles

Articles

  • CARG tool’s ability to predict older prostate cancer patients’ risk of toxicity: Beyond the Abstract

    Prostate cancer is one of the leading causes of cancer death in American men and mostly affects men above age 65. [1]  The American Cancer Society predicts 161,360 new cases of prostate cancer and 26,730 deaths from prostate cancer in the United States in the year 2017. [1]  Although fewer than 10% of people are diagnosed with de novo metastatic disease, many men with early stage prostate cancer will eventually develop metastatic disease. The initial treatment of metastatic disease is androgen deprivation therapy, but this is only effective for a few years, after which the disease continues to progress.  At this point it is referred to as metastatic castrate resistant prostate cancer (mCRPC).  About 10-20% of people are diagnosed with mCRPC within 5 years of a diagnosis of prostate cancer, but more than 50% of patients with mCRPC die within 3 years. [2]  mCRPC is currently defined as the progression of the prostate cancer despite castrate levels of testosterone (usually defined as <1.7nmol/L). [2]  Progression to mCRPC is typically associated with worsening symptoms, declining quality of life and worsening pain.  However, mCRPC may be helped by other forms of hormone therapy such as the androgen receptor axis-targeted (ARAT) agents Abiraterone and Enzalutamide because it is not completely hormone-refractory. [3]  Patients who become resistant to ARAT therapy usually are considered for chemotherapy. [4]  In 2004, docetaxel became the standard of care for mCRPC. Later, cabazitaxel was also found to be beneficial in patients with mCRPC that progressed after receiving docetaxel therapy. [2]

    Chemotherapy

    Chemotherapy remains the treatment of choice in symptomatic mCRPC, but survival benefits after undergoing chemotherapy are modest (on the order of a few months).  In comparison to mitoxantrone (the prior standard chemotherapy agent), docetaxel was associated with better pain control, quality of life and more frequent PSA responses. [5]  However, chemotherapy can also be associated with significant toxicity, with 18-44% rates of grade 3 or higher toxicity.  National Cancer Institute Common Terminology Criteria for Adverse Events defines grade 3 as severe, grade 4 as life-threatening or disability and grade 5 as death. [6]  Common toxicities from chemotherapy include neutropenia, generalized weakness, bone pain, fatigue, peripheral edema and mucositis.  The most common grade 3 to 5 toxicities with docetaxel are: neutropenia, leucopenia, anemia, fatigue, infection and dehydration. [5]

    Currently, there is a need to find tools that can help identify men who may be more or less likely to experience serious toxicity from chemotherapy because it could help during treatment decision-making. Predicting toxicities would help doctors determine the side effects and toxicities that specific patients might develop before prescribing the treatment.  This way, it would make it easier for them to determine which treatment method would work, at which dose and method of delivery.  Making a more informed decision can be important in this setting because of the increased risk of death or functional decline.  It is especially helpful to be able to predict these toxicities in older adults because the risk of toxicity increases with age.  In practice, chemotherapy is less likely to be given to older adults due to the concerns about their ability to tolerate it. [6]  Many older adults tend to place an increasing value on avoiding treatments that adversely affect their quality of life or functional independence. [7]  Since older adults have a higher risk of toxicity and place an increasing importance on quality of life, oncologists may find it harder to suggest the best treatment option.  Hence, it would be useful to be able to predict toxicities from chemotherapy.  This advancement in toxicity prediction would also help select up-front treatment modifications such as dose reduction or the addition of colony-stimulating factors to reduce toxicity.

    Tools such as the Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 5-point scale are currently used to determine risk by assessing a patient’s level of function and capability to perform self-care.  Although this tool is a prognostic factor for survival and may help select which patients should not get chemotherapy, it is a poor predictor of toxicity risk because it is subjective, being subject to bias and high interobserver variability. [8]  Oncologist judgement in stratifying patients into those at lower or higher risk of toxicity may be better, but it has rarely been formally compared against measures such as the ECOG PS.  Finally, the agreement between currently used tools such as PS and clinical judgement by oncologists is still quite low. [9]

    Our study sought to identify tools that could help inform treatment decision-making by improving the ability to predict a patient’s risk of chemotherapy toxicity.  Distinguishing men at lower and higher risk of severe toxicity in men with mCRPC would help make better treatment decisions and allow a more informed decision about the risks and benefits of chemotherapy.  In patients with very high risks of toxicity that may counterbalance any perceived benefits, there are four main options besides conventional dose chemotherapy: (a) reduced-dose chemotherapy; (b) use of colony-stimulating factors to reduce neutropenia and related complications; (c) alternative, gentler agents or clinical trials of novel therapies; (d) best supportive care.  While our study did not focus on which treatment might be best, we sought to validate the Vulnerable Elders Survey-13 (VES-13) and Cancer and Aging Research Group (CARG) tool in mCRPC with the goal of helping a clinician’s judgment. 

    VES-13

    The VES-13 is a brief (3-4 minutes), self-report tool that measures vulnerability.  The initial purpose of developing this tool was to better screen older persons at risk of health deterioration. [10]  In the original study, vulnerable older people were defined as persons age 65 and older who were at increased risk of functional decline or death over 2 years. [10]  The instrumental activities of daily living (IADLs) and activities of daily living (ADLs) that the VES-13 focuses on include shopping, performing light housework, managing finances, preparing meals, using the telephone, bathing, dressing, transferring, toileting, walking across the room, and eating. [10]   However, its ability to predict grade 3-5 chemotherapy toxicity has yet to be studied. 

    CARG 

    The CARG tool uses a combination of 11 parameters, including age, tumor and treatment characteristics, laboratory data, and specific geriatric assessment parameters to help predict grade 3-5 chemotherapy toxicity in older patients with cancer.  It categorizes people into low, intermediate and high risk of severe chemotherapy toxicity, in our case grade 3+ chemotherapy toxicity.  It does include a geriatric assessment questionnaire with 6 domains: functional status, co-morbidity, psychological state, social activity, social support, and nutrition.  The purpose of developing the CARG tool was to identify risk factors for chemotherapy toxicity in older adults undergoing various chemotherapy regimens and create a user-friendly risk stratification schema for chemotherapy toxicity. [6]  The CARG tool was derived from a study of 500 patients undergoing a variety of chemotherapy regimens for various solid tumors. The CARG tool was recently validated externally [11] and helps to identify patients at greatest risk of chemotherapy toxicity.  Although the CARG tool has been proven in a mixed cohort of patients with various cancers, there are no validation data for patients with mCRPC, and only 10% of the patients in the original study had genitourinary cancers. [6]  Since different chemotherapy regimens have different toxicity risks, it is important to validate such tools in a more homogeneous cohort to ensure findings are similar to mixed cohorts. 

    Oncologist Judgment

    For our study, we had each patient’s medical oncologist rate the patient’s risk of chemotherapy toxicity on a 10-point scale.  “Oncologists are left with little guidance when it comes to identifying risk factors other than chronologic age or performance status, neither of which has been shown to predict well in heterogeneous older adult populations.” [6] 

    Methods

    We recruited men aged 65 or older with mCRPC who were starting either first-line chemotherapy (receiving chemotherapy for the first time) or second-line chemotherapy (stopped first-line chemotherapy because of disease progression, toxicity, or other reasons).  All but two (4%) participants received docetaxel-based chemotherapy, and the majority (n=29, 63%) received the standard dose of 75 mg/m2 every 3 weeks.  Ten (22%) received a dose of 60 mg/m2, whereas 5 (11%) received a lower dose than this.  Subjects were recruited either prior to starting chemotherapy or within the first two cycles as long as there was no dose reduction.  Men unable to come for study visits or with a life expectancy of less than 3 months, a major neuropsychiatric abnormality, or limited English were excluded from the study.

    We collected socio-demographic and medical information on all subjects at baseline, as well as physical performance measures (grip strength, timed up and go, and timed chair stands).  The CARG and VES-13 tools were administered as well.  The CARG toxicity prediction model was used to stratify patients into three groups (low, intermediate, and high risk) based on risk for grade 3+ chemotherapy toxicity.  The VES-13 was used to measure vulnerability, which was defined by a score of 3 or greater.  This cut-off point follows the conventional scoring system, but we also examined cut-offs of 2 or greater and 4 or greater.  We also asked each subject’s treating physician to provide an estimate of the risk of chemotherapy toxicity on a scale from 1 (lowest risk) to 10 (highest risk).  Oncologists were not told the results of the other assessment tools used in the study. 

    Following the baseline visit, follow-up assessments were performed after each cycle of chemotherapy (every 3 weeks) and after the final cycle.  At each visit, a trained research coordinator recorded chemotherapy-related toxicities using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4).  Laboratory-based toxicities such as neutropenia were based on blood tests performed every three weeks.  These same procedures were followed to record toxicity for men who were recruited after already having started chemotherapy, including for cycles administered before being enrolled on the study.

    Sample sizes were based on the assumption that we would see the same rate of toxicity as in the original CARG study (i.e. 30% risk of grade 3+ toxicity for the low risk group, 52% for intermediate, and 83% for high) [6] and that equal proportions of patients would be enrolled in each risk group (i.e. one-third for each).  Based on these assumptions, we calculated that we would require 45 patients. 

    Results

    46 men were recruited for the study with a mean age of 75.  These participants had a median PSA level at baseline of 243.7 ng/mL and had relatively few other major medical problems (median Charlson Comorbidity Index score of 0).  Although participants had a fairly high performance status (mean Karnofsky score of 77%), 50% were considered vulnerable based on the VES-13.  Based on the CARG tool, only 2 (4%) patients were considered low risk, 29 (63%) were intermediate, and 15 (33%) were high risk of severe chemotherapy toxicity. 

    Grade 3+ and grade 2 chemotherapy toxicity were experienced by 20% and 67% of patients, respectively.  The most common grade 3-5 toxicities were neutropenia (30%), generalized weakness (23%), and bone pain (15%), and the most common grade 2 toxicities were fatigue (35%), peripheral edema (7%), and mucositis (7%).

    Grade 3+ toxicity was observed in 0 (0%), 5 (17%) and 4 (27%) patients in low, intermediate, and high CARG risk groups respectively, suggesting an incremental pattern across risk groups.  However, this pattern was not statistically significant (p = 0.65).  22% of patients considered vulnerable by the VES-13 experienced grade 3+ toxicity, compared to 17% of patients considered non-vulnerable (p = 0.71).  Age, comorbidity, Karnofsky performance score, and baseline physical performance measures did not seem to be predictors of grade 3+ toxicity.  In addition, oncologist judgment of toxicity risk was a relatively poor predictor of actual toxicity.

    The ability of the CARG tool to predict grade 2 toxicity appeared to be higher than the ability of the VES-13 to predict these toxicities, but this was not statistically significant, likely due to our small sample size (p = 0.072 for CARG, 0.75 for VES-13).  Limiting the analyses to only those participants who were recruited prior to starting chemotherapy did not alter the findings.

    The rates of grade 3+ toxicity found in our cohort were relatively low overall: only 20% compared to the 53% observed in the original CARG study.  The same pattern was found in the three individual risk groups, with lower rates of toxicities observed in each compared to the original CARG study.  However, the rate of toxicity in our cohort was similar to rates reported in other studies of older men with mCRPC.  For example, the TAX327 trial by Tannock et al. reported severe adverse events in 26% of subjects, and grade 3+ neutropenia in 32%. [5]

    Although we did not find statistically significant results for either of the tools tested, we did observe three key findings in our study.  First, the risk of grade 3+ toxicity with docetaxel-based chemotherapy in the mCRPC population is lower overall and across CARG risk groups compared to the rates observed in the original study, which used data from patients with a variety of cancers.  However, we still found that there was a gradient of toxicity risk across the different CARG risk groups (i.e. 0% in low, 17% in moderate, and 27% in the high risk group).  Therefore, there is a need for further validation studies conducted with older men with mCRPC.

    Second, our data on the performance of the VES-13 are the first in this population.  Even though our findings were negative, we believe they warrant further investigation because of the ease of use and emerging value of the VES-13 in other geriatric oncology settings (e.g. 12).  Third, we also provided the first data looking at oncologist judgment of toxicity risk, and compared that to the CARG and VES-13 tools.  For tools to be useful in a busy clinical setting, they must provide better predictive ability than the usual clinical care.  Therefore, further investigation in this area is important.

    Some other limitations include the fact that we conducted our study at a single academic cancer center, limiting generalizability, and did not use the CRASH tool, another popular tool for predicting toxicities. [13]  Future studies should directly compare the CRASH and CARG tools in the mCRPC setting.  Lastly, the 10-point rating scale we used for oncologist predictions has not been validated in this context, and we did not provide any numerical anchors.  Therefore, the different ratings may have meant different things to different oncologists.  Further investigation is warranted in these areas.

    Conclusion

    In summary, toxicity with docetaxel in a cohort of older men in usual clinical practice was lower than predicted by the CARG tool.  Although the CARG tool appeared to differentiate those at lower versus higher risk of chemotherapy toxicity and was better than clinician judgement or ECOG PS, a larger validation study is needed.

    Written By: Thavalis Ja, Rathore Ma, Breunis Ha, Alibhai SMHa,b,c
    a. Department of Medicine, University Health Network 

    b. Department of Medicine, University of Toronto 
    c. Institute of Health Policy, Management and Evaluation, University of Toronto 

    References 

    1. American Cancer Society. Key statistics for prostate cancer [Internet]. American Cancer Society Inc.; 2016 [updated 2017 Jan 5]. Available from https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html 
    2. Nussbaum N, George DJ, Abernethy AP, Dolan CM, Oestreicher N, Flanders S, Dorff TB. Patient experience in the treatment of metastatic castration-resistant prostate cancer: state of the science. Prostate Cancer and Prostatic Diseases. 2016 Jun 1;19(2):111-21. 
    3. American Cancer Society. Prostate cancers [Internet]. American Cancer Society Inc.; 2016 [updated 2016 Mar 11]. Available from https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html 
    4. Chi K, Hotte SJ, Joshua AM, North S, Wyatt AW, Collins LL, Saad F. Treatment of mCRPC in the AR-axis-targeted therapy-resistant state. Annals of Oncology. 2015 Oct 1; 26(10):2044-56.
    5. Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Théodore C, James ND, Turesson I, Rosenthal MA. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. New England Journal of Medicine. 2004 Oct 7; 351(15):1502-12.
    6. Hurria A, Togawa K, Mohile SG, Owusu C, Klepin HD, Gross CP, Lichtman SM, Gajra A, Bhatia S, Katheria V, Klapper S. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. Journal of Clinical Oncology. 2011 Aug 1; 29(25):3457-65.
    7. Rose JH, O'Toole EE, Dawson NV, Lawrence R, Gurley D, Thomas C, Hamel MB, Cohen HJ. Perspectives, preferences, care practices, and outcomes among older and middle-aged patients with late-stage cancer. Journal of Clinical Oncology. 2004 Dec 15; 22(24):4907-17. 
    8. Kelly CM, Shahrokni A. Moving beyond Karnofsky and ECOG performance status assessments with new technologies. Journal of Oncology. 2016 Mar 15; 6186543.
    9. Sørensen JB, Klee M, Palshof T, Hansen HH. Performance status assessment in cancer patients. An inter-observer variability study. British Journal of Cancer. 1993 Apr; 67(4):773-5.
    10. Saliba D, Elliott M, Rubenstein LZ, Solomon DH, Young RT, Kamberg CJ, Roth C, MacLean CH, Shekelle PG, Sloss EM, Wenger NS. The Vulnerable Elders Survey: a tool for identifying vulnerable older people in the community. Journal of the American Geriatrics Society. 2001 Dec 1; 49(12):1691-9.
    11. Hurria A, Mohile S, Gajra A, Klepin H, Muss H, Chapman A, et al.  Validation of a Prediction Tool for Chemotherapy Toxicity in Older Adults With Cancer.  Journal of Clinical Oncology. 2016 Jul 10; 34(20:2366-71.
    12. Luciani A, Ascione G, Bertuzzi C, Marussi D, Codeca C, Di Maria G, et al.  Detecting disabilities in older patients with cancer: comparison between comprehensive geriatric assessment and vulnerable elders survey-13.  Journal of Clinical Oncology. 2010 Apr 20; 28(12):2046-50.
    13. Extermann M, Boler I, Reich RR, Lyman GH, Brown RH, DeFelice J, et al. Predicting the risk of chemotherapy toxicity in older patients: The Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score. Cancer. 2011 Nov 9; 118(13):3377-86.
    Read the Abstract
    Published June 1, 2017
  • Carotenoids, retinol, tocopherols, and prostate cancer risk: pooled analysis of 15 studies.

    Individual studies have suggested that circulating carotenoids, retinol, or tocopherols may be associated with prostate cancer risk, but the studies have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease.

    Published October 15, 2015
  • CART cell therapy for prostate cancer: status and promise.

    In recent years, the, chimeric antigen receptor T (CAR-T) cell therapy as an adoptive immunotherapy has received great attention and made great breakthroughs. CAR-T cells show great specificity, targeting, and less major histocompatibility complex restriction in tumor immunotherapy, significantly different from traditional T cells.

    Published January 24, 2019
  • Castrate-resistant prostate cancer: lessons learnt from a pilot study in the palliative care research population.

    Palliative care patients are inherently difficult to recruit to and retain on studies. Even when patients are recruited, it is hard to complete studies with sufficient data. There is a dearth of literature specific to men with castrate resistant prostate cancer (CRPC) and the clinical trials coordinator/research nurse's perspective in improving trial outcomes in palliative care.

    Published March 2, 2018
  • Castration-Resistant Prostate Cancer: Sequencing Oral and Infusion Agents.

    To update treatment options and considerations for castration-resistant prostate cancer with specific attention to sequencing of agents based on available evidence and treatment rationale.

    The newest research developments over the last several years include multicenter studies that address the sequencing of therapies to improve the treatment of metastatic castration-resistant prostate cancer.

    Published July 23, 2018
  • Cathepsin L inactivation leads to multimodal inhibition of prostate cancer cell dissemination in a preclinical bone metastasis model.

    It is estimated that ∼90% of patients with advanced prostate cancer develop bone metastases; an occurrence that results in a substantial reduction in the quality of life and a drastic worsening of prognosis.

    Published January 14, 2016
  • Cause of Death in Korean Men with Prostate Cancer: an Analysis of Time Trends in a Nationwide Cohort.

    Despite rapid increase in incidence of prostate cancer (PC) and PC survivors, there are few studies regarding competing causes of death and time trends in Asian population. We conducted a cohort study of 2% nationwide random sample of Korean National Health Insurance employees.

    Published October 12, 2016
  • Caveolin-1 regulates hormone resistance through lipid synthesis, creating novel therapeutic opportunities for castration-resistant prostate cancer.

    Caveolin-1 (Cav-1) is overexpressed in aggressive and metastatic prostate cancer (PCa) and induces PCa cell proliferation. Androgens mediate lipid synthesis through acetyl-CoA carboxylase-1 (ACC1) and fatty acid synthase (FASN).

    Published June 30, 2016
  • CCL5 promotes migration of prostate cancer cells in the prostate cancer bone metastasis microenvironment.

    Chemokines and their receptors have key roles in cancer progression. This study investigated chemokine activity in the prostate cancer bone metastasis microenvironment. Growth and migration of human prostate cancer cells were assayed in cocultures with bone stromal cells.

    Published January 2, 2018
  • CD169(+) macrophages mediate pathological formation of woven bone in skeletal lesions of prostate cancer.

    Skeletal metastases present a major clinical challenge for prostate cancer patient care, inflicting distinctive mixed osteoblastic and osteolytic lesions that cause morbidity and refractory skeletal complications.

    Published May 17, 2016
  • CD24 is a genetic modifier for risk and progression of prostate cancer.

    CD24 plays an oncogenic role in the onset and progression of various human cancers, including prostate cancer. In the present study, we identified two linkage disequilibrium blocks with four recombination hotspot motifs in human CD24 locus.

    Published July 11, 2016
  • CD8+ T Cells Impact Rising PSA in Biochemically Relapsed Cancer Patients Using Immunotherapy Targeting Tumor-Associated Antigens.

    The management of men with prostate cancer (PCa) with biochemical recurrence following local definitive therapy remains controversial. Early use of androgen deprivation therapy (ADT) leads to significant side effects.

    Published March 30, 2020
  • CDO1 Promoter Methylation Is Associated with Gene Silencing and Is a Prognostic Biomarker for Biochemical Recurrence-free Survival in Prostate Cancer Patients.

    Molecular biomarkers may facilitate the distinction between aggressive and clinically insignificant prostate cancer (PCa), thereby potentially aiding individualized treatment. We analyzed cysteine dioxygenase 1 (CDO1) promoter methylation and mRNA expression in order to evaluate its potential as prognostic biomarker.

    Published October 3, 2016
  • Cell-based Hyper-interleukin 6 or Hyper-interleukin 11 secreting vaccines combined with low dose cyclophosphamide in an orthotopic murine prostate cancer model.

    BACKGROUND - Cell based vaccines encoding Hyper-IL-6 (H6) and Hyper-IL-11 (H11) present high activity in murine melanoma and renal cancer model. We evaluated the efficacy of cellular vaccines modified with H6 or H11 combined with cyclophosphamide in orthotopic murine prostate cancer model.

    Published November 19, 2015
  • Cell-intrinsic abrogation of TGF-β signaling delays but does not prevent dysfunction of self/tumor-specific CD8 T cells in a murine model of autochthonous prostate cancer - Abstract

    Adoptive T cell therapy (ACT) for the treatment of established cancers is actively being pursued in clinical trials.

    Published October 10, 2012
  • Cell-lineage specificity and role of AP-1 in the prostate fibroblast androgen receptor cistrome.

    Androgen receptor (AR) signalling in fibroblasts is important in prostate development and carcinogenesis, and is inversely related to prostate cancer mortality. However, the molecular mechanisms of AR action in fibroblasts and other non-epithelial cell types are largely unknown.

    Published September 21, 2016
  • Cellular determinants and microenvironmental regulation of prostate cancer metastasis.

    Metastasis causes more than 90% of cancer-related deaths and most prostate cancer (PCa) patients also die from metastasis. The 'metastatic cascade' is a complex biological process that encompasses tumor cell dissociation (from the primary tumor), local invasion, intravasation, transport in circulation, extravasation, colonization, and overt growth in end organs.

    Published April 20, 2017
  • Cellular identity crisis: antiandrogen resistance by lineage plasticity.

    A recent publication in Science demonstrates the ability of prostate cancer cells to switch lineages from one that is dependent on androgen signaling to a cell type that is not. Known as lineage plasticity, this phenomenon is driven by the transcription factor SOX2 in RB1 and TP53-deficient prostate cancer.

    Published May 8, 2017
  • CHADS2 scores as a predictor of ischemic stroke after radical prostatectomy.

    Patients with prostate cancer have an increased risk of stroke, but their absolute rate of stroke depends on age and comorbid conditions. The Charlson Comorbidity Index Score (CCIS) is a widely accepted measure for risk adjustment in administrative claims data sets.

    Published November 23, 2015
  • Challenging Case: Robot-Assisted Laparoscopic Prostatectomy After Prior Suprapubic Open Prostatectomy.

    Introduction: Given the ubiquity of robot-assisted laparoscopic prostatectomy (RALP) for treatment of localized prostate cancer, more surgeons are encountering challenging cases, either secondary to difficult anatomy, prior abdominal surgery, or prior radiation therapy.

    Published May 27, 2018
  • Changes in Latitude, Changes in Attitudes…and DABGA

    I write today not from the files of the Jimmy Buffet musical collection, nor from a Caribbean Margaritaville-esque cabana, as the reference might suggest (for the unfamiliar, I have been humming his song “Changes in Latitude, Changes in Attitude…for about 2 weeks now)  but rather as a dispatch on the latest development in clinical trials in prostate cancer.  The topic:  Data from the Latitude study that was presented at ASCO by Karim Fizazi and simultaneously published in the New England Journal of Medicine.
    Published June 21, 2017
  • Changes in periprostatic adipose tissue induced by 5α-reductase inhibitors.

    There is increasing interest in periprostatic fat and its influence on prostate cancer aggressiveness. In vitro data suggest that adipose stromal/stem cells (ASCs) can increase production of cytokines and growth factors resulting in invasive growth and metastasis in prostate cancer.

    Published March 22, 2017
  • Changes in physical functioning and muscle strength in men receiving androgen deprivation therapy for prostate cancer: a controlled comparison.

    The purpose of the study is to examine changes in muscle strength and self-reported physical functioning in men receiving androgen deprivation therapy (ADT) for prostate cancer compared to matched controls.

    Published November 16, 2015
  • Changes in prostate cancer grading: Including a new patient-centric grading system.

    The first structured approach to grade prostate cancer based on the underlying histological architecture was developed by Donald Gleason who in 1966 proposed a morphologic classification of prostate cancer and in 1974 demonstrated its clinical significance based on prostate cancer-specific death.

    Published January 1, 2016
  • Changes in Prostate Cancer Presentation Following the 2012 USPSTF Screening Statement: Observational Study in a Multispecialty Group Practice.

    In 2012, the US Preventive Services Task Force (USPSTF) recommended against PSA-based screening for prostate cancer in men of all ages. Following this change, screening declined yet the complete impact on clinical presentation is not well defined in the screen-eligible population.

    Published December 13, 2019
  • Changes in the levels of testosterone profile over time in relation to clinical parameters in a cohort of patients with prostate cancer managed by active surveillance.

    To characterize testosterone profile changes over time in a cohort of prostate cancer (PCa) patients managed with active surveillance (AS) and to assess its correlation with the initial disease characteristics and further progression.

    Published March 29, 2018
  • Changing attitudes towards management of men with locally advanced prostate cancer following radical prostatectomy: A follow-up survey of Australia-based urologists.

    This study examined whether there has been change among Australia-based urologists' knowledge, attitudes and beliefs relating to guideline-recommended adjuvant radiotherapy for men with adverse pathologic features following radical prostatectomy since a prior survey in 2012 and investigated associations between attitudes and treatment preferences.

    Published July 13, 2016
  • Changing clinical trends in 10,000 robot-assisted laparoscopic prostatectomy patients and impact of the 2012 USPSTF statement against PSA screening.

    To evaluate the clinical trend changes in our robot-assisted laparoscopic prostatectomy (RALP) practice and to investigate the effect of 2012 US Preventive Services Task Force (USPSTF) statement against PSA screening on these trends.

    Published July 26, 2019
  • Changing Incidence of Metastatic Prostate Cancer by Race and Age, 1988-2015.

    Screening for prostate cancer (PCa) has dramatically declined in the United States (US) since the United States Preventive Services Task Force recommended against routine prostate-specific antigen (PSA)-based PCa screening in all men in 2012.

    Published May 22, 2018
  • Characteristics and outcome of Prostate cancer patients with overall biopsy Gleason score 3+4=7 and highest Gleason score 3+4=7 or > 3+4=7.

    Prostate cancer heterogeneity and multifocality might result in different Gleason scores (GS) at individual biopsy cores. According to WHO/ISUP guidelines, the GS in each biopsy core should be recorded with optional reporting of overall GS for the entire case.

    Published November 9, 2017
  • Characteristics of men responding to an invitation to undergo testing for prostate cancer as part of a randomised trial.

    Sociodemographic characteristics are associated with participating in cancer screening and trials. We compared the characteristics of those responding with those not responding to a single invitation for prostate-specific antigen (PSA) testing for prostate cancer as part of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP).

    Published October 19, 2016
  • Characterization and stratification of prostate lesions based on comprehensive multiparametric MRI using detailed whole-mount histopathology as a reference standard.

    The purpose of this study was to characterize prostate cancer (PCa) based on multiparametric MR (mpMR) measures derived from MRI, diffusion, spectroscopy, and dynamic contrast-enhanced (DCE) MRI, and to validate mpMRI in detecting PCa and predicting PCa aggressiveness by correlating mpMRI findings with whole-mount histopathology.

    Published October 3, 2017
  • Characterization of a "low-risk" cohort of grade group 2 prostate cancer patients: Results from the Shared Equal Access Regional Cancer Hospital database.

    To examine if there is a subset of men with grade group 2 prostate cancer who could be potential candidates for active surveillance.

    We used the Shared Equal Access Regional Cancer Hospital database to identify 776 men undergoing radical prostatectomy from 2006 to 2015 with >8 biopsy cores obtained and complete information.

    Published June 10, 2017
  • Characterization of a Prostate- and Prostate Cancer-Specific Circular RNA Encoded by the Androgen Receptor Gene.

    The linear mRNAs transcribed under alternative RNA splicing and overexpression/amplification of the androgen receptor (AR) gene are poor prognostic biomarkers of castrate-resistant prostate cancer (PCa).

    Published December 27, 2019
  • Characterization of adenoviral transduction profile in prostate cancer cells and normal prostate tissue.

    Prostate diseases are common in males worldwide with high morbidity. Gene therapy is an attractive therapeutic strategy for prostate diseases, however, it is currently underdeveloped. As well known, adeno virus (Ad) is the most widely used gene therapy vector.

    Published July 25, 2017
  • Characterization of gradient echo signal decays in healthy and cancerous prostate at 3T improves with a Gaussian augmentation of the mono-exponential (GAME) model.

    A biomarker of cancer aggressiveness, such as hypoxia, could substantially impact treatment decisions in the prostate, especially radiation therapy, by balancing treatment morbidity (urinary incontinence, erectile dysfunction, etc.

    Published June 7, 2016
  • Characterization of infiltrating lymphocytes in human benign and malignant prostate tissue.

    Immune checkpoint blockade has shown promising results in numerous cancer types. However, in prostate cancer (PC), absent or limited responses have been reported. To investigate further, we compared the phenotype of infiltrating T-cells isolated from prostate tissue from patients with PC (n = 5), benign prostatic hyperplasia (BPH) (n = 27), BPH with concurrent PC (n = 4) and controls (n = 7).

    Published August 5, 2017
  • Characterization of site-specifically conjugated monomethyl auristatin E- and duocarmycin-based anti-PSMA antibody-drug conjugates for treatment of PSMA-expressing tumors.

    Rationale: Prostate cancer (PCa) is the most common cancer in men worldwide. In general, PCa responds poorly to chemotherapy. Therefore, antibody-drug conjugates (ADCs) have been developed to specifically deliver highly cytotoxic drugs to the tumor.

    Published November 20, 2017
  • Characterizations of Clinical and Therapeutic Histories for Men With Prostate Cancer-Specific Mortality.

    Careful descriptions of men with prostate cancer (PCa)-specific mortality are scant in nontrial settings. The present retrospective review describes the clinical characteristics, timelines, and treatment histories from initial presentation to death in a cohort of men with metastatic, castrate-resistant PCa (mCRPC).

    Published January 4, 2016
  • Characterizing the molecular features of ERG-positive tumors in primary and castration resistant prostate cancer.

    BACKGROUND - The TMPRSS2-ERG gene fusion is detected in approximately half of primary prostate cancers (PCa) yet the prognostic significance remains unclear. We hypothesized that ERG promotes the expression of common genes in primary PCa and metastatic castration-resistant PCa (CRPC), with the objective of identifying ERG-associated pathways, which may promote the transition from primary PCa to CRPC.

    Published March 20, 2016
  • Checkpoint inhibitors in the treatment of urological malignancies.

    Checkpoint inhibitors are monoclonal antibodies attach to several different receptors on T-cells or tumour cells expressing receptors for cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death-1 (PD-1) and their ligand (PD-L1).

    Published August 9, 2017
  • CHEK2 mutation and risk of prostate cancer: a systematic review and meta-analysis.

    CHEK2 encodes for a G2 checkpoint kinase which plays a critical role in DNA repair. Its mutation confers an increased risk of breast cancer. It has also been suggested to increase risks of prostate cancer, but its involvement with this type of cancer has not been confirmed.

    Published December 7, 2015
  • Cheminformatics Driven Development of Novel Therapies for Drug Resistant Prostate Cancer.

    Androgen receptor (AR) is a master regulator of prostate cancer (PCa), and therefore is a pivotal drug target for the treatment of PCa including its castration-resistance form (CRPC). The development of acquired resistance is a major challenge in the use of the current antiandrogens.

    Published May 25, 2018
  • Chemohormonal therapy for metastatic hormone-sensitive prostate cancer: An Asian perspective.

    The treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has been rapidly evolving. In the past, the use of chemotherapy was reserved for metastatic prostate cancer patients who developed castration resistance.

    Published December 4, 2018
  • Chemotherapy at First Diagnosis of Advanced Prostate Cancer - Revolution or Evolution? Findings from a British Uro-oncology Group UK Survey to Evaluate Oncologists' Views on First-line Docetaxel in Combination with Androgen Deprivation Therapy in Castrate

    AIMS - There have been three randomised trials investigating docetaxel in combination with androgen deprivation therapy as first-line therapy for hormone-sensitive metastatic and locally advanced/high-risk prostate cancer.

    Published February 19, 2016
  • Chemotherapy options in castration-resistant prostate cancer.

    The treatment landscape for patients with metastatic castration-resistant prostate cancer (CRPC) is evolving, with recent approvals of immune therapy, novel hormonal therapy, and bone-targeted therapy.

    Published November 24, 2016
  • Chromatin remodeling ATPase BRG1 and PTEN are synthetic lethal in prostate cancer.

    Loss of phosphatase and tensin homolog (PTEN) represents one hallmark of prostate cancer (PCa). However, restoration of PTEN or inhibition of the activated PI3K-AKT pathway has shown limited success, prompting us to identify obligate targets for disease intervention.

    Published December 4, 2018
  • Chronic baseline prostate inflammation is associated with lower tumor volume in men with prostate cancer on repeat biopsy: Results from the REDUCE study.

    Background: To evaluate whether baseline acute and chronic prostate inflammation among men with initial negative biopsy for prostate cancer (PC) is associated with PC volume at the 2-year repeat prostate biopsy in a clinical trial with systematic biopsies.

    Published July 19, 2015
  • Chronic low dose ethanol induces an aggressive metastatic phenotype in TRAMP mice, which is counteracted by parthenolide.

    Despite advances in prostate cancer therapy, dissemination and growth of metastases results in shortened survival. Here we examined the potential anti-cancer effect of the NF-κB inhibitor parthenolide (PTL) and its water soluble analogue dimethylaminoparthenolide (DMAPT) on tumour progression and metastasis in the TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model of prostate cancer.

    Published June 25, 2018
  • Chronic prostatitis/chronic pelvic pain syndrome and prostate cancer: study of immune cells and cytokines.

    Prostate cancer and prostatitis are both significant health concerns. A large number of studies have established that the occurrence of the two is closely related. However, the most common prostatitis, type III chronic prostatitis/chronic pelvic pain syndromes (CP/CPPS), is reported to not correlate with the occurrence of prostate cancer.

    Published November 18, 2019