Padraig Warde

Publications of Padraig Warde

• Utility of serum tumor markers during surveillance for stage I seminoma.

  Authors: Danny Vesprini, Peter Chung, Shaun Tolan, Mary Gospodarowicz, Michael Jewett, Martin O'Malley, Joan Sweet, Malcolm Moore, Tony Panzarella, Jeremy Sturgeon, Linda Sugar, Lynn Anson-Cartwright, Padraig Warde

  Cancer. 04/2012;

  BACKGROUND: The serum tumor markers α-fetoprotein (AFP), β-human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH) are often measured as part of surveillance protocols in patients withBACKGROUND: The serum tumor markers α-fetoprotein (AFP), β-human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH) are often measured as part of surveillance protocols in patients with stage I seminoma. In this study, the authors evaluated the utility of routine measurement of these markers in the detection of disease relapse. METHODS: Data were gathered from a prospectively maintained database of patients who underwent surveillance for stage I testicular seminoma diagnosed between 1982 and 2005 at Princess Margaret Hospital. Patients were followed on a predefined schedule with physical examination (PE), serum tumor markers, abdominopelvic computed tomography, and chest x-rays. The records of patients who relapsed were examined for details of imaging and serum tumor markers throughout the period of follow-up until the time of relapse. RESULTS: Of the 527 patients who were managed by surveillance, 75 patients (14%) relapsed at a median follow-up of 72 months. Of these, 65 patients relapsed within the first 3 years and had routine serum tumor markers measured. In total, 11 patients had abnormal tumor markers at the time of relapse (AFP, 0 patients; HCG, 6 patients; LDH, 4 patients; and HCG and LDH, 1 patient). Only 1 patient had an elevated tumor marker (LDH) before relapse, as defined by an abnormal imaging study (n = 64) or physical examination (n = 1), for which the treatment and outcome were not affected. CONCLUSIONS: Serum tumor marker levels did not aid in the early diagnosis of disease relapse in patients with stage I seminoma who were managed with surveillance. The current results indicated that routine measurement of serum tumor markers can be discontinued safely in seminoma surveillance schedules. Cancer 2012. © 2012 American Cancer Society.

• Pre-treatment risk stratification of prostate cancer patients: A critical review.

  Authors: George Rodrigues, Padraig Warde, Tom Pickles, Juanita Crook, Michael Brundage, Luis Souhami, Himu Lukka

  Canadian Urological Association journal = Journal de l'Association des urologues du Canada. 04/2012; 6(2):121-7.

  The use of accepted prostate cancer risk stratification groups based on prostate-specific antigen, T stage and Gleason score assists in therapeutic treatment decision-making, clinical trial designThe use of accepted prostate cancer risk stratification groups based on prostate-specific antigen, T stage and Gleason score assists in therapeutic treatment decision-making, clinical trial design and outcome reporting. The utility of integrating novel prognostic factors into an updated risk stratification schema is an area of current debate. The purpose of this work is to critically review the available literature on novel pre-treatment prognostic factors and alternative prostate cancer risk stratification schema to assess the feasibility and need for changes to existing risk stratification systems. A systematic literature search was conducted to identify original research publications and review articles on prognostic factors and risk stratification in prostate cancer. Search terms included risk stratification, risk assessment, prostate cancer or neoplasms, and prognostic factors. Abstracted information was assessed to draw conclusions regarding the potential utility of changes to existing risk stratification schema. The critical review identified three specific clinically relevant potential changes to the most commonly used three-group risk stratification system: (1) the creation of a very-low risk category; (2) the splitting of intermediate-risk into a low- and high-intermediate risk groups; and (3) the clarification of the interface between intermediate- and high-risk disease. Novel pathological factors regarding high-grade cancer, subtypes of Gleason score 7 and percentage biopsy cores positive were also identified as potentially important risk-stratification factors. Multiple studies of prognostic factors have been performed to create currently utilized prostate cancer risk stratification systems. We propose potential changes to existing systems.

• Tumor Hypoxia Predicts Biochemical Failure following Radiotherapy for Clinically Localized Prostate Cancer.

  Authors: Michael Milosevic, Padraig Warde, Cynthia Ménard, Peter Chung, Ants Toi, Adrian Ishkanian, Michael McLean, Melania Pintilie, Jenna Sykes, Mary Gospodarowicz, Charles Catton, Richard P Hill, Robert Bristow

  Clinical cancer research : an official journal of the American Association for Cancer Research. 04/2012; 18(7):2108-14.

  Tumor hypoxia is an important determinant of outcome in many human malignancies and is associated with treatment resistance and metastases. The aim of this study was to determine the effect ofTumor hypoxia is an important determinant of outcome in many human malignancies and is associated with treatment resistance and metastases. The aim of this study was to determine the effect of hypoxia in patients with prostate cancer treated with radiotherapy. Tumor hypoxia was measured in 247 patients with clinically localized prostate cancer before radiotherapy, with or without hormonal therapy. The median pO(2) was 6.8 mm Hg and the median hypoxic percentage less than 10 mm Hg (HP(10)) was 63%. The median follow-up was 6.6 years. The 5-year biochemical relapse-free rate (bRFR) was 78%. Prostrate-specific antigen and Gleason score were both associated with biochemical relapse and formed a baseline clinical model. The effect of hypoxia was found to vary with the duration of patient follow-up. HP(10), when added to the clinical model, was an independent predictor of early bRFR (P = 0.019). The relationship between hypoxia and early bRFR was more pronounced when the analysis was restricted to 142 patients with bulk tumor at the site of the oxygen measurements (P = 0.004). Hypoxia was the only factor predictive of local recurrence in 70 patients who had biopsies conducted during follow-up (P = 0.043), again with the effect being greatest early after completing treatment. This is the largest clinical study of prostate cancer hypoxia with direct measurement of tumor oxygen levels. It shows that hypoxia is associated with early biochemical relapse after radiotherapy and also with local recurrence in the prostate gland. Clin Cancer Res; 18(7); 2108-14. ©2012 AACR.

• Hypoxia, Androgen Deprivation and Systemic Metastases in Prostate Cancer (In Response to "Antivascular Effects of Neoadjuvant Androgen Deprivation for Prostate Cancer: An In Vivo Human Study Using Susceptibility and Relaxitivity Dynamic MRI": In Regard to Alonzi R et al. (Int J Radiat Oncol Biol Phys 2011;80(3):721-727).

  Authors: Alan Dal Pra, Michael Milosevic, Richard Hill, Bradley Wouters, Padraig Warde, Robert G Bristow

  International journal of radiation oncology, biology, physics. 03/2012; 82(4):1319.

• Testicular cancer survivors' supportive care needs and use of online support: a cross-sectional survey.

  Authors: Jacqueline L Bender, David Wiljer, Matthew J To, Philippe L Bedard, Peter Chung, Michael A S Jewett, Andrew Matthew, Malcolm Moore, Padraig Warde, Mary Gospodarowicz

  Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 03/2012;

  INTRODUCTION: The supportive care needs of testicular cancer survivors have not been comprehensively studied. Likewise, there is limited research on their use of the Internet or social mediaINTRODUCTION: The supportive care needs of testicular cancer survivors have not been comprehensively studied. Likewise, there is limited research on their use of the Internet or social media applications-tools that are popular among young adults and which could be used to address their needs. METHODS: Two hundred and four testicular cancer patients receiving care at an urban cancer center completed a questionnaire assessing supportive care needs and the use and preferences for online support. We examined the associations between patient characteristics and met or unmet supportive care needs and the use of testicular cancer online communities. RESULTS: Respondents had more met (median 8.0, interquartile range (IQR) 10.0) than unmet (median 2.0, IQR 7.0) needs. The majority (62.5%) reported at least one unmet need, most commonly (25%) concerning financial support, body image, stress, being a cancer survivor, and fear of recurrence. Patients who were younger, had nonseminoma testicular cancer, or received treatment beyond surgery had more needs, and those who were unemployed had more unmet needs. The majority of respondents (71.5%) were social media users (e.g., Facebook), and 26% had used a testicular cancer online support community. Reasons for nonuse were lack of awareness (34.3%), interest (30.9%), trust (4.9%), and comfort using computers (2.5%). Users were more likely to speak English as a first language and have more needs. CONCLUSIONS: At least one in four testicular cancer survivors has unmet needs related to financial support, body image, stress, being a cancer survivor, and fear of recurrence. A web-based resource may be a useful strategy to consider given the high prevalence of social media use in this sample and their desire for online support. Efforts are needed to raise awareness about online peer support resources and to overcome barriers to their use.

• Pathological predictors for site of local recurrence after radiotherapy for prostate cancer.

  Authors: Supriya Chopra, Ants Toi, Nathan Taback, Andrew Evans, Masoom A Haider, Michael Milosevic, Robert G Bristow, Peter Chung, Andrew Bayley, Gerard Morton, Danny Vesprini, Padraig Warde, Charles Catton, Cynthia Ménard

  International journal of radiation oncology, biology, physics. 03/2012; 82(3):e441-8.

  Rational design of targeted radiotherapy (RT) in prostate cancer (Pca) hinges on a better understanding of spatial patterns of recurrence. We sought to identify pathological factors predictive forRational design of targeted radiotherapy (RT) in prostate cancer (Pca) hinges on a better understanding of spatial patterns of recurrence. We sought to identify pathological factors predictive for site of local recurrence (LR) after external beam RT. Prospective databases were reviewed to identify men with LR after RT from 1997 through 2009. Patients with biochemical failure and biopsy-confirmed Pca more than 2 years after RT were evaluated. Prediction for site of recurrence based on the following pretreatment factors was determined on independent and cluster-sextant basis: presence of malignancy, dominant vs. nondominant percentage core length (PCL) involvement, PCL ≥ or <40%, and Gleason score. Sites of dominant PCL were defined as sextants with peak PCL involvement minus 10%, and >5% for each patient. Forty-one patients with low-intermediate risk Pca constituted the study cohort. Median time to biopsy after RT was 51 months (range, 24-145). Of 246 sextants, 74 were involved with tumor at baseline. When sextants are treated as independent observations the presence of malignancy (77% vs. 22%, p = 0.0001), dominant PCL (90% vs. 46%, p = 0.0001), and PCL ≥40% (89% vs. 68 %, p = 0.04) were found to be significant predictors for LR, although PCL ≥40% did not retain statistical significance if sextants were considered correlated. The vast majority of patients (95%) recurred at the original site of dominant PCL or PCL ≥40%, and 44% also recurred in regions of nondominant PCL <40% (n = 8) and/or benign sampling (n = 14) at baseline. LR after RT predominantly occurs in regions bearing higher histological tumor burden but are not isolated to these sites. Our data highlights the value of spatially resolved baseline pathological sampling and may assist in the design of clinical trials tailoring RT dose prescriptions to subregions of the prostate gland.

• Inverse Relationship Between Biochemical Outcome and Acute Toxicity After Image-guided Radiotherapy for Prostate Cancer.

  Authors: Danny Vesprini, Charles Catton, Lindsay Jacks, Gina Lockwood, Tara Rosewall, Andrew Bayley, Peter Chung, Mary Gospodarowicz, Cynthia Ménard, Michael Milosevic, Alan Nichol, Marketa Skala, Padraig Warde, Robert G Bristow

  International journal of radiation oncology, biology, physics. 11/2011;

  PURPOSE: Prostate cancer patients exhibit variability in normal tissue reactions and biochemical failure. With the use of image-guided radiotherapy (IGRT), there is a greater likelihood that thePURPOSE: Prostate cancer patients exhibit variability in normal tissue reactions and biochemical failure. With the use of image-guided radiotherapy (IGRT), there is a greater likelihood that the differences in normal tissue and tumor response are due to biological rather than physical factors. We tested the hypothesis that prospectively scored acute toxicity is associated with biochemical failure-free rate (BFFR) in prostate cancer patients treated with IGRT. METHODS AND MATERIALS: We retrospectively analyzed BFFR in 362 patients with localized prostate cancer treated with IGRT. We compared BFFR with prospectively collected Radiation Therapy Oncology Group (RTOG) maximum acute gastrointestinal (GI) and genitourinary (GU) toxicity scores. Median follow-up for all patients was 58.3 months after total radiotherapy doses of 75.6-79.8 Gy. RESULTS: Patients reporting RTOG acute GU or GI toxicity scores of ≥2 were considered "sensitive" (n = 141, 39%) and patients reporting scores <2 were considered "nonsensitive" (n = 221, 61%). When calculating biochemical failure (BF) using the American Society for Therapeutic Radiology and Oncology definition at 5 years, 76% (CI 70-82%) of the "nonsensitive" patients were failure free, compared with only 53% (CI 43-62%) of the "sensitive" patients (log-rank test, p < 0.0001). This difference was also observed using the Phoenix definition; "nonsensitive" 5-year BFFR was 81% (CI 74-86%) vs. "sensitive" BFFR was 68% (CI 58-76%; log-rank test p = 0.0012). The difference in BF between cohorts remained significant when controlled for radiation dose (75.6 vs. 79.8 Gy), prognostic stratification (T category, prostate-specific antigen, and Gleason score), and prostate volume. CONCLUSIONS: This study unexpectedly shows that prostate cancer patients who develop ≥Grade 2 RTOG acute toxicity during radiotherapy are less likely to remain BFF at 5 years. These results deserve further study and, if validated in other large IGRT cohorts, additional models would be required to study interaction between normal tissue and tumor biology in prostate cancer patients.

• Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial.

  Authors: Padraig Warde, Malcolm Mason, Keyue Ding, Peter Kirkbride, Michael Brundage, Richard Cowan, Mary Gospodarowicz, Karen Sanders, Edmund Kostashuk, Greg Swanson, Jim Barber, Andrea Hiltz, Mahesh K B Parmar, Jinka Sathya, John Anderson, Charles Hayter, John Hetherington, Matthew R Sydes, Wendy Parulekar

  Lancet. 11/2011; 378(9809):2104-11.

  Whether the addition of radiation therapy (RT) improves overall survival in men with locally advanced prostate cancer managed with androgen deprivation therapy (ADT) is unclear. Our aim was toWhether the addition of radiation therapy (RT) improves overall survival in men with locally advanced prostate cancer managed with androgen deprivation therapy (ADT) is unclear. Our aim was to compare outcomes in such patients with locally advanced prostate cancer. Patients with: locally advanced (T3 or T4) prostate cancer (n=1057); or organ-confined disease (T2) with either a prostate-specific antigen (PSA) concentration more than 40 ng/mL (n=119) or PSA concentration more than 20 ng/mL and a Gleason score of 8 or higher (n=25), were randomly assigned (done centrally with stratification and dynamic minimisation, not masked) to receive lifelong ADT and RT (65-69 Gy to the prostate and seminal vesicles, 45 Gy to the pelvic nodes). The primary endpoint was overall survival. The results presented here are of an interim analysis planned for when two-thirds of the events for the final analysis were recorded. All efficacy analyses were done by intention to treat and were based on data from all patients. This trial is registered at controlledtrials.com as ISRCTN24991896 and Clinicaltrials.gov as NCT00002633. Between 1995 and 2005, 1205 patients were randomly assigned (602 in the ADT only group and 603 in the ADT and RT group); median follow-up was 6·0 years (IQR 4·4-8·0). At the time of analysis, a total of 320 patients had died, 175 in the ADT only group and 145 in the ADT and RT group. The addition of RT to ADT improved overall survival at 7 years (74%, 95% CI 70-78 vs 66%, 60-70; hazard ratio [HR] 0·77, 95% CI 0·61-0·98, p=0·033). Both toxicity and health-related quality-of-life results showed a small effect of RT on late gastrointestinal toxicity (rectal bleeding grade >3, three patients (0·5%) in the ADT only group, two (0·3%) in the ADT and RT group; diarrhoea grade >3, four patients (0·7%) vs eight (1·3%); urinary toxicity grade >3, 14 patients (2·3%) in both groups). The benefits of combined modality treatment--ADT and RT--should be discussed with all patients with locally advanced prostate cancer. Canadian Cancer Society Research Institute, US National Cancer Institute, and UK Medical Research Council.

• Information needs of men on androgen deprivation therapy.

  Authors: Tony Soeyonggo, Padraig Warde, Neil Fleshner, Narhari Timilshina, Shabbir M H Alibhai

  BJU international. 08/2011;

  Study Type - Needs assessment survey Level of Evidence 2b What's known on the subject? and What does the study add? Although androgen deprivation therapy (ADT) is widely used to treat men withStudy Type - Needs assessment survey Level of Evidence 2b What's known on the subject? and What does the study add? Although androgen deprivation therapy (ADT) is widely used to treat men with prostate cancer, little is known about the information needs of patients on ADT. We found that patients are generally very satisfied with using ADT and expressed minimal decisional regret with its use up to four years later. For men receiving ADT in the adjuvant setting, their survival estimates with the addition of ADT were quite reasonable when compared to findings in randomized trails. A key area to enhance patient education appears to be side effects, especially around hot flashes and fatigue, which were also the most bothersome treatment sequelae for patients. OBJECTIVE: •  To evaluate information needs of men receiving androgen deprivation therapy (ADT). PATIENTS AND METHODS: •  A cross-sectional survey was distributed to English-speaking prostate cancer patients receiving ADT adjuvant to radical therapy or for biochemical relapse. •  Three cohorts were recruited based on duration of ADT use: <6 months (cohort 1), 6-18 months (cohort 2) and 18 months to 4 years (cohort 3). •  Several validated questionnaires were used, including the Control Preferences Scale (CPS), Satisfaction with Treatment Decision Scale (SWD) and Decisional Regret Scale (DRS). •  Patients on adjuvant ADT were asked to estimate their overall survival with and without ADT. RESULTS: •  Eighty-five men were recruited, of whom 91.8% were receiving a gonadotrophin-releasing hormone agonist, 4.7% were receiving anti-androgen monotherapy and 3.5% were receiving combined androgen blockade. •  Patients preferred the following decision-making roles: 23.5% active, 50.6% collaborative, 27.0% passive. •  Mean patient satisfaction for ADT use was high at 24.0/30 and decisional regret was low at 7.9/25. •  There was a perceived overall survival benefit of 3.9-6.9% at 5 years, 3.6-17.8% at 10 years and 5.7-18.1% at 15 years with the addition of adjuvant ADT. •  Hot flushes and fatigue were reported as the most common theoretical adverse effects as well as those experienced most commonly by patients. CONCLUSIONS: •  Patients on ADT were generally satisfied with their decisions to start ADT and expressed minimal decisional regret up to 4 years later. •  A key area to enhance patient education appears to be adverse effects, especially around hot flushes and fatigue.

• Management of stage I testicular seminoma.

  Authors: Gary Mok, Padraig Warde

  Hematology/oncology clinics of North America. 06/2011; 25(3):503-16, vii-iii.

  Adjuvant treatment options for stage I seminoma include surveillance, radiation, and hemotherapy. Despite excellent results for both adjuvant chemotherapy and radiotherapy, many concerns have beenAdjuvant treatment options for stage I seminoma include surveillance, radiation, and hemotherapy. Despite excellent results for both adjuvant chemotherapy and radiotherapy, many concerns have been raised in regards to the potential long-term toxicities of these treatments. To minimize the burden of treatment, there has been a shift away from adjuvant treatments for stage I testicular seminomas toward surveillance protocols for seminoma survivors. This article reviews the evidence for all adjuvant treatment options for stage I testicular seminomas with a particular focus on surveillance.

• Role of principal component analysis in predicting toxicity in prostate cancer patients treated with hypofractionated intensity-modulated radiation therapy.

  Authors: Danny Vesprini, Michael Sia, Gina Lockwood, Douglas Moseley, Tara Rosewall, Andrew Bayley, Robert Bristow, Peter Chung, Cynthia Ménard, Michael Milosevic, Padraig Warde, Charles Catton

  International journal of radiation oncology, biology, physics. 04/2011; 81(4):e415-21.

  To determine if principal component analysis (PCA) and standard parameters of rectal and bladder wall dose-volume histograms (DVHs) of prostate cancer patients treated with hypofractionatedTo determine if principal component analysis (PCA) and standard parameters of rectal and bladder wall dose-volume histograms (DVHs) of prostate cancer patients treated with hypofractionated image-guided intensity-modulated radiotherapy (hypo-IMRT) can predict acute and late gastrointestinal (GI) toxicity. One hundred twenty-one patients underwent hypo-IMRT at 3 Gy/fraction, 5 days/week to either 60 Gy or 66 Gy, with daily online image guidance. Acute and late GI and genitourinary (GU) toxicity were recorded weekly during treatment and at each follow-up. All Radiation Therapy Oncology Group (RTOG) criteria toxicity scores were dichotomized as <2 and ≥2. Standard dosimetric parameters and the first five to six principal components (PCs) of bladder and rectal wall DVHs were tested for association with the dichotomized toxicity outcomes, using logistic regression. Median follow-up of all patients was 47 months (60 Gy cohort = 52 months; 66 Gy cohort = 31 months). The incidence rates of ≥2 acute GI and GU toxicity were 14% and 29%, respectively, with no Grade ≥3 acute GU toxicity. Late GI and GU toxicity scores ≥2 were 16% and 15%, respectively. There was a significant difference in late GI toxicity ≥2 when comparing the 66 Gy to the 60 Gy cohort (38% vs. 8%, respectively, p = 0.0003). The first PC of the rectal DVH was associated with late GI toxicity (odds ratio [OR], 6.91; p < 0.001), though it was not significantly stronger than standard DVH parameters such as Dmax (OR, 6.9; p < 0.001) or percentage of the organ receiving a 50% dose (V50) (OR, 5.95; p = 0 .001). Hypofractionated treatment with 60 Gy in 3 Gy fractions is well tolerated. There is a steep dose response curve between 60 Gy and 66 Gy for RTOG Grade ≥2 GI effects with the dose constraints employed. Although PCA can predict late GI toxicity for patients treated with hypo-IMRT for prostate cancer, it provides no additional information over using more standard DVH parameters.

• Stage I seminoma: adjuvant treatment is effective but is it necessary?

  Authors: Peter Chung, Padraig Warde

  Journal of the National Cancer Institute. 02/2011; 103(3):194-6.

• Neoadjuvant radiotherapy for locally advanced and high-risk prostate cancer.

  Authors: John Thoms, Jayant S Goda, Alexender R Zlotta, Neil E Fleshner, Theodorus H van der Kwast, Stéphane Supiot, Padraig Warde, Robert G Bristow

  Nature reviews. Clinical oncology. 02/2011; 8(2):107-13.

  Men presenting with high-risk or locally advanced prostate cancer may benefit from a combination of radiotherapy and surgery to maximize local control. Adjuvant radiotherapy following surgery hasMen presenting with high-risk or locally advanced prostate cancer may benefit from a combination of radiotherapy and surgery to maximize local control. Adjuvant radiotherapy following surgery has improved biochemical progression-free survival, metastasis-free survival, lengthened the time to hormone therapy use and improved overall survival in three randomized-phase III trials. One surprising result of the Southwest Oncology Group (SWOG) 8794 trial and the European Organisation for Research and Treatment of Cancer (EORTC) 22911 trial is that treatment failure was mainly a result of lack of local control. This finding has led to a new appreciation of local control as a determinant of survival and the role for combined modality approaches within a multidisciplinary team in the treatment of high-risk and locally advanced prostate cancer. One emerging novel approach is the use of preoperative or intraoperative radiotherapy in addition to best surgical and systemic treatments. Preliminary results from clinical trials indicate low rates of intraoperative toxic effects, an advantage of short treatment times and smaller image-guided radiotherapy treatment volumes when compared with postoperative radiotherapy. Potential disadvantages include over-treatment of patients and lack of data on long-term toxic effects. We present the published treatment approaches and rational for preoperative and intraoperative radiotherapy and compare these methods to the utility of postoperative radiotherapy.

• Testicular cancer: seminoma.

  Authors: Peter Chung, Padraig Warde

  Clinical evidence. 01/2011; 2011.

  More than half of painless solid swellings of the body of the testis are malignant, with a peak incidence in men aged 25 to 35 years. Most testicular cancers are germ cell tumours and half of theseMore than half of painless solid swellings of the body of the testis are malignant, with a peak incidence in men aged 25 to 35 years. Most testicular cancers are germ cell tumours and half of these are seminomas, which tend to affect older men and have a good prognosis. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in men with stage 1 seminoma (confined to testis) who have undergone orchidectomy? What are the effects of treatments in men with good-prognosis non-stage 1 seminoma who have undergone orchidectomy? What are the effects of maintenance chemotherapy in men who are in remission after orchidectomy and chemotherapy for good-prognosis non-stage 1 seminoma? What are the effects of treatments in men with intermediate-prognosis seminoma who have undergone orchidectomy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 29 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review, we present information relating to the effectiveness and safety of the following interventions: chemotherapy (maintenance, adjuvant, single-agent carboplatin, 3 or 4 cycles, different number of cycles of adjuvant, using bleomycin added to vinblastine plus cisplatin, using etoposide plus cisplatin with or without bleomycin, adding higher doses to a 2-drug chemotherapy regimen using cisplatin or vinblastine); radiotherapy (different adjuvant regimens [20 Gy in 10 fractions to para-aortic area, 30 Gy in 15 fractions to para-aortic area and iliac nodes], different drug combinations, 30-36 Gy in 15-18 fractions); and surveillance.

• Impact of androgen-deprivation therapy on cognitive function in men with nonmetastatic prostate cancer.

  Authors: Shabbir M H Alibhai, Henriette Breunis, Narhari Timilshina, Shireen Marzouk, Diane Stewart, Ian Tannock, Gary Naglie, George Tomlinson, Neil Fleshner, Murray Krahn, Padraig Warde, Sarah Duff Canning

  Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 11/2010; 28(34):5030-7.

  To evaluate the effects of androgen-deprivation therapy (ADT) on cognitive function in men with nonmetastatic prostate cancer (PC). The following three groups of men age 50 years or older and matchedTo evaluate the effects of androgen-deprivation therapy (ADT) on cognitive function in men with nonmetastatic prostate cancer (PC). The following three groups of men age 50 years or older and matched on age and education were enrolled: patients with PC starting continuous ADT (n = 77), patients with PC not receiving ADT (PC controls, n = 82), and healthy controls (n = 82). A battery of 14 neuropsychological tests, examining eight cognitive domains, was administered at baseline, 6 months, and 12 months. Changes in cognitive scores over time were analyzed using the following three approaches: multivariable linear regression; the proportion of participants per group with 1 standard deviation (SD) or greater declines, and the proportion of participants who declined by at least 1.5 SD on two or more tests. The mean age and education level of participants were 68.9 years (range, 50 to 87 years) and 15.4 years of education (range, 8 to 24 years), respectively. Adjusted for age and education, all three cohorts had similar cognitive scores at baseline other than in one test of working memory. In adjusted regressions, ADT use was not associated with significant changes in the domains of attention/processing speed, verbal fluency, verbal memory, visual memory, or cognitive flexibility at either 6 months (all P > .05) or 12 months (all P > .05). One test each of immediate memory (P = .029), working memory (P = .031), and visuospatial ability (P = .034) were worse among ADT users than controls at 12 months, but these findings were not confirmed using other analytic approaches. There is no consistent evidence that 12 months of ADT use has an adverse effect on cognitive function in elderly men with PC.

• Impact of androgen-deprivation therapy on physical function and quality of life in men with nonmetastatic prostate cancer.

  Authors: Shabbir M H Alibhai, Henriette Breunis, Narhari Timilshina, Calvin Johnston, George Tomlinson, Ian Tannock, Murray Krahn, Neil E Fleshner, Padraig Warde, Sarah Duff Canning, Lawrence Klotz, Gary Naglie

  Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 11/2010; 28(34):5038-45.

  This prospective longitudinal study evaluated the effect of androgen deprivation therapy (ADT) on objective and self-reported physical function. Men with nonmetastatic prostate cancer (PC) startingThis prospective longitudinal study evaluated the effect of androgen deprivation therapy (ADT) on objective and self-reported physical function. Men with nonmetastatic prostate cancer (PC) starting continuous ADT were enrolled in this matched cohort study. Physical function was assessed with the 6-minute walk test (6MWT), grip strength, and the timed-up-and-go (TUG) test, representing endurance and upper and lower extremity strength, respectively. Quality of life (QOL) was measured with the Medical Outcomes Study Short-Form 36 (SF-36) questionnaire. Subjects were assessed at baseline, 3, 6, and 12 months. Two control groups (PC without ADT; no PC), matched on age, education, and baseline function were enrolled. Mixed effects regression models were fitted, adjusting for baseline covariates. We enrolled 87 patients on ADT, 86 PC controls, and 86 healthy controls; groups were similar in age (mean, 69.1 years; range, 50 to 87) and physical function. The 6MWT distance remained stable in the ADT group (P = .96) but improved in both control groups (P < .05). Grip strength declined in the ADT group (P = .04), remained stable in PC controls (P = .31), and improved in healthy controls (P = .008). TUG scores remained stable over time and across groups (P > .10). The SF-36 physical function summary score declined in the ADT group (P < .001), but increased in both control groups (P < .001). Negative effects on outcomes were observed within 3 months of starting ADT and were generally independent of age. Endurance, upper extremity strength, and physical components of QOL are affected within 3 months of starting ADT. Up-front exercise interventions to counteract these losses are warranted.

• Fracture types and risk factors in men with prostate cancer on androgen deprivation therapy: a matched cohort study of 19,079 men.

  Authors: Shabbir M H Alibhai, Minh Duong-Hua, Angela M Cheung, Rinku Sutradhar, Padraig Warde, Neil E Fleshner, Lawrence Paszat

  The Journal of urology. 09/2010; 184(3):918-23.

  Accumulating evidence shows that androgen deprivation therapy is associated with osteoporosis and fragility fractures of the spine, hip and wrist. One study suggested that androgen deprivationAccumulating evidence shows that androgen deprivation therapy is associated with osteoporosis and fragility fractures of the spine, hip and wrist. One study suggested that androgen deprivation therapy may also be associated with nonfragility fractures in older men. Whether other clinical risk factors independently increase the risk of fractures is not certain. Using linked administrative databases in Ontario, Canada, we matched 19,079 men 66 years old or older with prostate cancer with at least 6 months of continuous androgen deprivation therapy or bilateral orchiectomy with men with prostate cancer who had never received androgen deprivation. Matching variables were age, prior cancer treatment, diagnosis year, comorbidity, medication, prior fractures and socioeconomic variables. Primary outcomes were a typical fragility fracture of the spine, hip or wrist and any fracture. Independent predictors of fracture outcomes were assessed with Cox proportional hazards models. At a mean 6.47-year followup androgen deprivation therapy was associated with an increased risk of fragility fracture (HR 1.65, 95% CI 1.53-1.78) and any fracture (HR 1.46, 95% CI 1.39-1.54). Independent predictors of fragility and any fracture were increasing age, prior bone thinning medications, chronic kidney disease, prior dementia, prior fragility fracture and prior osteoporosis diagnosis or treatment (p <0.05). Continuous androgen deprivation therapy for at least 6 months is associated with an increased risk of fracture. Increasing age, prior osteoporotic fracture and dementia are important clinical factors that may warrant greater consideration of anti-osteoporotic therapy in these men.

• High-intensity focused ultrasound for prostate cancer: a practice guideline.

  Authors: Himu Lukka, Tricia Waldron, Joseph Chin, Linda Mayhew, Padraig Warde, Eric Winquist, George Rodrigues, Bobby Shayegan

  Canadian Urological Association journal = Journal de l'Association des urologues du Canada. 08/2010; 4(4):232-6.

  The aim of this practice guideline was to develop evidence-based recommendations for clinicians on the use of high-intensity focused ultrasound (HIFU) in patients with localized prostate cancer. TheThe aim of this practice guideline was to develop evidence-based recommendations for clinicians on the use of high-intensity focused ultrasound (HIFU) in patients with localized prostate cancer. The guideline was developed using the methods of Cancer Care Ontario's Program in Evidence-Based Care (PEBC). The core methodology of the PEBC's guideline development process is systematic review. A comprehensive literature search was undertaken to identify high-quality studies, reviews and other practice guidelines on the use of HIFU in prostate cancer. The evidence formed the basis of the recommendations, which were reviewed and amended where necessary, by clinical experts in medical and radiation oncology and urology. The literature review yielded limited evidence. No randomized controlled trials or meta-analyses comparing HIFU with currently accepted management approaches were identified. The body of evidence is primarily based on data from case series. Internal feedback was provided by the PEBC Genitourinary Disease Site Group membership and the Report Approval Panel. External peer review included targeted review by clinical experts specifically requested to comment on the guideline, and professional consultation through an online survey of health care professionals. HIFU is currently not recommended as an alternative to accepted curative treatment approaches for localized prostate cancer.

• Comparison of low dose with standard dose abdominal/pelvic multidetector CT in patients with stage 1 testicular cancer under surveillance.

  Authors: Martin E O'Malley, Peter Chung, Masoom Haider, Hyun-Jung Jang, Kartik Jhaveri, Korosh Khalili, Tony Panzarella, Padraig Warde

  European radiology. 07/2010; 20(7):1624-30.

  To compare the image quality and acceptability of a low dose with those of standard dose abdominal/pelvic multidetector CT in patients with stage 1 testicular cancer managed by surveillance. OneTo compare the image quality and acceptability of a low dose with those of standard dose abdominal/pelvic multidetector CT in patients with stage 1 testicular cancer managed by surveillance. One hundred patients (median age 31 years; range 19-83 years), 79 with seminoma and 21 with non-seminoma, underwent abdominal/pelvic imaging with low and standard dose protocols on 64-slice multidetector CT. Three reviewers independently evaluated images for noise and diagnostic quality on a 5-point scale and for diagnostic acceptability. On average, each reader scored noise and diagnostic quality of standard dose images significantly better than corresponding low dose images (p < 0.0001). One reader found all CT examinations acceptable; two readers each found 1/100 (1%) low dose examinations unacceptable. Median and mean dose-length product for low and standard dose protocols were 416.0 and 452.2 (range 122.9-913.4) and 931.9 and 999.8 (range 283.8-1,987.7) mGy cm, respectively. The low dose protocol provided diagnostically acceptable images for at least 99% of patients and achieved mean dose reduction of 55% compared with the standard dose protocol.

• Canadian consensus guidelines for the management of testicular germ cell cancer.

  Authors: Lori Wood, Christian Kollmannsberger, Michael Jewett, Peter Chung, Sebastian Hotte, Martin O'Malley, Joan Sweet, Lynn Anson-Cartwright, Eric Winquist, Scott North [......] Jeremy Sturgeon, Mary Gospodarowicz, Roanne Segal, Tina Cheng, Peter Venner, Malcolm Moore, Peter Albers, Robert Huddart, Craig Nichols, Padraig Warde

  Canadian Urological Association journal = Journal de l'Association des urologues du Canada. 04/2010; 4(2):e19-38.