Publications by authors named "Narhari Timilshina"

50 Publications

Association of Chemotherapy, Enzalutamide, Abiraterone, and Radium 223 With Cognitive Function in Older Men With Metastatic Castration-Resistant Prostate Cancer.

JAMA Netw Open 2021 Jul 1;4(7):e2114694. Epub 2021 Jul 1.

Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Importance: Older adults are at greater risk of cognitive decline with various oncologic therapies. Some commonly used therapies for advanced prostate cancer, such as enzalutamide, have been linked to cognitive impairment, but published data are scarce, come from single-group studies, or focus on self-reported cognition.

Objective: To longitudinally examine the association between cognitive function and docetaxel (chemotherapy), abiraterone, enzalutamide, and radium Ra 223 dichloride (radium 223) in older men with metastatic castration-resistant prostate cancer.

Design, Setting, And Participants: A multicenter, prospective, observational cohort study was conducted across 4 academic cancer centers in Ontario, Canada. A consecutive sample of 155 men age 65 years or older with metastatic castration-resistant prostate cancer starting any treatment with docetaxel, abiraterone acetate, enzalutamide, or radium Ra 223 dichloride (radium 223) were enrolled between July 1, 2015, and December 31, 2019.

Exposures: First-line chemotherapy (docetaxel), abiraterone, enzalutamide, or radium 223.

Main Outcomes And Measures: Cognitive function was measured at baseline and end of treatment using the Montreal Cognitive Assessment, the Trail Making Test part A, and the Trail Making Test part B to assess global cognition, attention, and executive function, respectively. Absolute changes in scores over time were analyzed using univariate and multivariable linear regression, and the percentages of individuals with a decline of 1.5 SDs in each domain were calculated.

Results: A total of 155 men starting treatment with docetaxel (n = 51) (mean [SD] age, 73.5 [6.2] years; 34 [66.7%] with some postsecondary education), abiraterone (n = 29) (mean [SD] age, 76.2 [7.2] years; 18 [62.1%] with some postsecondary education), enzalutamide (n = 54) (mean [SD] age, 75.7 [7.4] years; 33 [61.1%] with some postsecondary education), and radium 223 (n = 21) (mean [SD] age, 76.4 [7.2] years; 17 [81.0%] with some postsecondary education) were included. Most patients had stable cognition or slight improvements during treatment. A cognitive decline of 1.5 SDs or more was observed in 0% to 6.5% of patients on each measure of cognitive function (eg, 3 of 46 patients [6.5%; 95% CI, 2.2%-17.5%] in the group receiving chemotherapy [docetaxel] had a decline of 1.5 SDs for Trails A and Trails B). Although patients taking enzalutamide had numerically larger declines than those taking abiraterone, differences were small and clinically unimportant.

Conclusions And Relevance: These findings suggest that most older men do not experience significant cognitive decline in attention, executive function, and global cognition while undergoing treatment for advanced prostate cancer regardless of the treatment used.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.14694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254132PMC
July 2021

Examining the ability of the Cancer and Aging Research Group tool to predict toxicity in older men receiving chemotherapy or androgen-receptor-targeted therapy for metastatic castration-resistant prostate cancer.

Cancer 2021 Jul 2;127(14):2587-2594. Epub 2021 Apr 2.

Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Background: Because multiple treatments are available for metastatic castrate-resistant prostate cancer (mCRPC) and most patients are elderly, the prediction of toxicity risk is important. The Cancer and Aging Research Group (CARG) tool predicts chemotherapy toxicity in older adults with mixed solid tumors, but has not been validated in mCRPC. In this study, its ability to predict toxicity risk with docetaxel chemotherapy (CHEMO) was validated, and its utility was examined in predicting toxicity risk with abiraterone or enzalutamide (A/E) among older adults with mCRPC.

Methods: Men aged 65+ years were enrolled in a prospective observational study at 4 Canadian academic cancer centers. All clinically relevant grade 2 to 5 toxicities over the course of treatment were documented via structured interviews and chart review. Logistic regression was used to identify predictors of toxicity.

Results: Seventy-one men starting CHEMO (mean age, 73 years) and 104 men starting A/E (mean age, 76 years) were included. Clinically relevant grade 3+ toxicities occurred in 56% and 37% of CHEMO and A/E patients, respectively. The CARG tool was predictive of grade 3+ toxicities with CHEMO, which occurred in 36%, 67%, and 91% of low, moderate, and high-risk groups (P = .003). Similarly, grade 3+ toxicities occurred among A/E users in 23%, 48%, and 86% with low, moderate, and high CARG risk (P < .001). However, it was not predictive of grade 2 toxicities with either treatment.

Conclusions: There is external validation of the CARG tool in predicting grade 3+ toxicity in older men with mCRPC undergoing CHEMO and demonstrated utility during A/E therapy. This may aid with treatment decision-making.
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http://dx.doi.org/10.1002/cncr.33523DOI Listing
July 2021

Role of the vulnerable elders survey-13 screening tool in predicting treatment plan modification for older adults with cancer.

J Geriatr Oncol 2021 06 17;12(5):786-792. Epub 2020 Dec 17.

Department of Medicine, University Health Network, Canada; Department of Medicine, University of Toronto, Canada. Electronic address:

Background: The Vulnerable Elders Survey (VES-13) is commonly used to identify older patients who may benefit from Comprehensive Geriatric Assessment (CGA) prior to cancer treatment. The optimal cut point of the VES-13 to identify those whose final oncologic treatment plan would change after CGA is unclear. We hypothesized that patients with high positive VES-13 scores (7-10)have a higher likelihood of a change in treatment compared to low positive scores (3-6).

Methods: Retrospective review of a customized database of all patients seen for pre-treatment assessment in an academic geriatric oncology clinic from June 2015 to June 2019. Various VES-13 cut points were analyzed to identify those individuals whose treatment was modified after CGA. Area under the curve (AUC) was calculated and subgroups of patients treated locally or systemically were also examined to determine if performance varied by treatment modality.

Results: We included 386 patients with mean age 81, 58% males. Gastrointestinal cancer was the most common site (31%) and 60% were planned to receive curative treatment. The final treatment plan was modified in 59% overall, with 52.7% modified with VES-13 scores 7-10, 50.8% with scores 3-6 and 28.1% with scores <3 (P = 0.002). VES-13 performance in predicting treatment modification was similar for cut points 3 (AUC 0.58), 4 (0.59), 5 (0.59), and 6 (0.59) and in those considering local treatment vs. chemotherapy.

Conclusions: A positive VES-13 score was associated with final oncologic treatment plan modification. A high positive score was not superior to the conventional cut point of ≥3.
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http://dx.doi.org/10.1016/j.jgo.2020.12.002DOI Listing
June 2021

Does Time Spent on Active Surveillance Adversely Affect the Pathological and Oncologic Outcomes in Patients Undergoing Delayed Radical Prostatectomy?

J Urol 2020 Sep 7;204(3):476-482. Epub 2020 Apr 7.

Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, Ontario, Canada.

Purpose: Pathological and oncologic outcomes of delayed radical prostatectomy following prostate cancer active surveillance are not well established. We determined the pathological and oncologic outcomes of favorable risk, Grade Group 1, prostate cancer managed with active surveillance and progressing to radical prostatectomy for clinically significant prostate cancer (Grade Group 2 or greater).

Materials And Methods: Between 1992 and 2015, 170 men with favorable risk prostate cancer underwent delayed radical prostatectomy for clinically significant prostate cancer (ASRP) at the Princess Margaret Cancer Centre. Pathological and oncologic outcomes of the ASRP cohort were compared with a matched cohort treated with up-front radical prostatectomy (405) immediately before surgery. Biochemical recurrence-free survival, overall survival and cancer specific survival were compared. We examined the association between delayed radical prostatectomy and adverse pathology at radical prostatectomy and biochemical recurrence using logistic and Cox regression analyses, respectively.

Results: Median time spent on active surveillance before radical prostatectomy was 31.0 months. At radical prostatectomy pT3 (extraprostatic extension, seminal vesicle invasion), positive surgical margin and pN1 rates were comparable between the 2 cohorts. Median followup after radical prostatectomy was 5.6 years. The 5-year biochemical recurrence-free survival rate in the ASRP cohort and up-front radical prostatectomy cohort were 85.8% and 82.4%, respectively (p=0.38). Overall survival and cancer specific survival were comparable between the 2 groups. Delayed radical prostatectomy was not associated with adverse pathological outcomes and biochemical recurrence on regression analyses.

Conclusions: Curative intent radical prostatectomy after a period of active surveillance results in excellent pathological and oncologic outcomes at 5 years. A period of active surveillance does not result in inferior outcomes compared to patients with similar risk characteristics undergoing up-front radical prostatectomy.
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http://dx.doi.org/10.1097/JU.0000000000001070DOI Listing
September 2020

Effects of six months of aerobic and resistance training on metabolic markers and bone mineral density in older men on androgen deprivation therapy for prostate cancer.

J Geriatr Oncol 2020 09 3;11(7):1074-1077. Epub 2020 Mar 3.

Department of Supportive Care, University Health Network, Toronto, ON M5G 2C4, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto ON M5S 1A1, Canada; Faculty of Medicine, University of Toronto, Toronto ON M5S 1A8, Canada.

Background: Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with metabolic perturbations and declines in bone mineral density (BMD). Exercise interventions provide multiple health benefits to older men on ADT; however, their effect on metabolic biomarkers and BMD remains unclear.

Methods: A secondary analysis of a phase II randomized controlled trial was conducted to assess the effect of a six-month moderate-intensity aerobic and resistance exercise program on metabolic biomarkers and BMD in men on ADT. Participants were randomized to three different exercise delivery models: personal training; supervised group exercise; or home-based exercise. Analysis of metabolic biomarkers (lipid profile and glucose) was conducted at baseline, six and twelve months. BMD of the lumbar spine, femoral neck and hip were assessed at baseline and twelve months. Both within- and between-group analyses of change scores adjusted for baseline values were performed.

Results: Forty-eight men (mean age 69.8y) were enrolled. Baseline values of metabolic biomarkers and BMD were comparable between groups and the three groups were combined for the primary analysis. At six months, no changes in metabolic biomarkers were found; however, at twelve months low-density lipoprotein (+0.28 mmol/L; 95%CI, 0.04 to 0.51) and total cholesterol (+0.31 mmol/L; 95%CI, 0.00 to 0.61) were significantly increased from baseline. No changes were found in BMD. In a secondary between-group analysis, no improvements were observed for any metabolic biomarker or BMD measurement.

Conclusions: Different exercise prescription parameters (modality and intensity) or combined diet/exercise interventions may be needed to foster favorable metabolic and skeletal adaptations during ADT.
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http://dx.doi.org/10.1016/j.jgo.2020.02.013DOI Listing
September 2020

The long-term outcomes of Gleason grade groups 2 and 3 prostate cancer managed by active surveillance: Results from a large, population-based cohort.

Can Urol Assoc J 2020 Jun;14(6):174-181

Division of Urology, Departments of Surgery and Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, ON, Canada.

Introduction: Active surveillance (AS) is an accepted management strategy for low-risk prostate cancer (PCa), but its role in the management of favorable intermediate-risk PCa remains controversial. Most reports studying the role of AS for these men generally lack long-term followup and include small numbers of patients. Our objective was to report the outcomes of men diagnosed with Gleason grade groups (GGG) 2 and 3 PCa who were managed expectantly.

Methods: Using administrative datasets and pathology reports, we identified all men who were diagnosed with GGG 2 and 3 PCa and managed expectantly between 2002 and 2011 in Ontario, Canada. Outcomes and associated factors were estimated using cumulative incidence function methods and multivariable Cox regression models, respectively.

Results: We identified 926 men who were managed expectantly (AS [n=374] or watchful waiting [n=552]). The eight-year cancer-specific survival was 94% and 89% for the AS and watchful waiting cohorts, respectively. Among AS men, 266 (71%) received treatment after a followup of approximately eight years. Cumulative AS discontinuation rates at one and five years were 30.5% and 65.1%, respectively.

Conclusions: Expectant management of GGG 2 and 3 PCa may be an option for certain men. Notably for AS patients, the cancer-specific mortality at eight years was 6%, and over 65% of men underwent treatment within five years. Further studies are required to evaluate which patients, based on disease-specific features and competing health risks, would benefit most from a conservative strategy.
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http://dx.doi.org/10.5489/cuaj.6328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654679PMC
June 2020

Age-related cytokine effects on cancer-related fatigue and quality of life in acute myeloid leukemia.

J Geriatr Oncol 2020 04 10;11(3):402-409. Epub 2019 May 10.

Department of Psychiatry, University Health Network, Toronto, Canada.

Objectives: We determined whether cytokines are a potential target to improve cancer-related fatigue (CRF) and quality of life (QOL) in acute myeloid leukemia (AML).

Methods: 219 patients age 18+ undergoing intensive chemotherapy for AML were assessed at up to 4 time points (pre-treatment, 1 month, 6 months, 12 months). CRF and QOL were assessed with validated patient-reported outcome measures with minimum clinically important differences (MCID) of 4 and 10 points, respectively. A panel of 31 plasma cytokines was measured. CRF and QOL were regressed against scaled cytokine values, adjusting for age, gender, time, remission status, and hemoglobin in linear models.

Results: 498 cytokine samples were available. For CRF, the model R was 25.3%, with cytokines explaining 6.9% of the variance. For QOL, corresponding values were 27.9% and 7.4%, respectively. A shift from the 30th to 70th centile distribution of all cytokines was associated with an improvement in CRF by 5.2 points and a 10.2-point improvement in QOL. A shift from 5th to 95th centile in TNF-α but no other single cytokine was associated with a change of >MCID in CRF, but there was no similar association with QOL. Cytokines had greater explanatory power for CRF in older versus younger adults and the most influential cytokines differed by age, particularly TNF-α.

Conclusion: Cytokines explain a relatively small amount of CRF and QOL scores in patients with AML and effects differ by age group. For cytokine-targeted therapies to improve either outcome, multiple cytokines may need to be substantially altered and therapeutic targets may vary with age.
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http://dx.doi.org/10.1016/j.jgo.2019.04.009DOI Listing
April 2020

Editorial Comment.

J Urol 2019 04;201(4):758

University Health Network and University of Toronto , Toronto , Ontario , Canada.

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http://dx.doi.org/10.1097/01.JU.0000554772.48377.2cDOI Listing
April 2019

A phase II randomized controlled trial of three exercise delivery methods in men with prostate cancer on androgen deprivation therapy.

BMC Cancer 2019 Jan 3;19(1). Epub 2019 Jan 3.

University of Calgary, Calgary, AB, T2N 1N4, Canada.

Background: Existing evidence demonstrates that 1:1 personal training (PT) improves many adverse effects of androgen deprivation therapy (ADT). Whether less resource-intensive exercise delivery models are as effective remains to be established. We determined the feasibility of conducting a multi-center non-inferiority randomized controlled trial comparing PT with supervised group (GROUP) and home-based (HOME) exercise programs, and obtained preliminary efficacy estimates for GROUP and HOME compared to PT on quality of life (QOL) and physical fitness.

Methods: Men with prostate cancer on ADT were recruited from one of two experienced Canadian centres and randomized 1:1:1 to PT, GROUP, or HOME. Randomization was stratified by length of ADT use and site. Participants completed moderate intensity aerobic and resistance exercises 4-5 days per week for 6 months with a target 150 min per week of exercise. Exercise prescriptions were individualized and progressed throughout the trial. Feasibility endpoints included recruitment, retention, adherence, and participant satisfaction. The efficacy endpoints QOL, fatigue, and fitness (VO2 peak, grip strength, and timed chair stands) in GROUP and HOME were compared for non-inferiority to PT. Descriptive analyses were used for feasibility endpoints. Between-group differences for efficacy endpoints were examined using Bayesian linear mixed effects models.

Results: Fifty-nine participants (mean age 69.9 years) were enrolled. The recruitment rate was 25.4% and recruitment was slower than projected. Retention was 71.2%. Exercise adherence as measured through attendance was high for supervised sessions but under 50% by self-report and accelerometry. Satisfaction was high and there was no difference in this measure between all three groups. Between-group differences (comparing both GROUP and HOME to PT) were smaller than the minimum clinically important difference on most measures of QOL, fatigue, and fitness. However, two of six outcomes for GROUP and four of six outcomes for HOME had a > 20% probability of being inferior for GROUP.

Conclusions: Feasibility endpoints were generally met. Both GROUP and HOME interventions in men with PC on ADT appeared to be similar to PT for multiple efficacy outcomes, although conclusions are limited by a small sample size and cost considerations have not been incorporated. Efforts need to be targeted to improving recruitment and adherence. A larger trial is warranted.

Trial Registration: ClinicalTrials.gov: NCT02046837 . Date of registration: January 20, 2014.
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http://dx.doi.org/10.1186/s12885-018-5189-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318980PMC
January 2019

Performance of the Vulnerable Elders Survey 13 screening tool in identifying cancer treatment modification after geriatric assessment in pre-treatment patients: A retrospective analysis.

J Geriatr Oncol 2019 03 9;10(2):229-234. Epub 2018 Nov 9.

Toronto General Hospital, 200 Elizabeth St Room EN14-214, Toronto, Ontario M5G 2C4, Canada. Electronic address:

Purpose: Geriatric assessment (GA) is recommended for older adults ≥ 70 years with cancer to guide treatment selection. Screening tools such as the Vulnerable Elders Survey (VES-13) and G6 have been used to identify patients at highest need of GA. Whether either tool predicts a change in oncologic treatment following GA is unclear.

Methods: Patients attending a geriatric oncology clinic between July 2015 and June 2017 who completed a VES-13 and underwent subsequent GA were included. Clinical information was extracted from a prospectively maintained database. G6 scores were assigned retrospectively. Patients were stratified into those who were "VES-13 positive" (score ≥ 3) and "VES-13 negative" (score < 3). Logistic regression was used to explore the relationship between VES-13 score, G6 score, and treatment modification.

Results: Ninety-nine patients were seen prior to initiating cancer treatment. The median VES-13 score was 7; with 81.8% of patients scoring ≥3. The treatment plan was modified in 47.5% of patients after GA. VES-13 score was predictive of treatment plan modification (63.0% among VES-13 positive versus 16.7% among VES-13 negative patients; p = 0.001). G6 performed similarly to the VES-13. The only statistically significant predictor of treatment change in multivariable analysis was performance status.

Conclusion: VES-13 positive patients are more likely to undergo treatment modification to reduce treatment intensity or supportive care only. The VES-13 may provide oncologists with a rapid, reliable way of identifying vulnerability in older adults with cancer who may need further GA prior to commencing cancer treatment.
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http://dx.doi.org/10.1016/j.jgo.2018.10.018DOI Listing
March 2019

Identification of subgroups of metastatic castrate-resistant prostate cancer (mCRPC) patients treated with abiraterone plus prednisone at low- vs. high-risk of radiographic progression: An analysis of COU-AA-302.

Can Urol Assoc J 2019 Jun;13(6):192-200

Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

Introduction: Radiographic imaging is used to monitor disease progression for men with metastatic castrate-resistant prostate cancer (mCRPC). The optimal frequency of imaging, a costly and limited resource, is not known. Our objective was to identify predictors of radiographic progression to inform the frequency of imaging for men with mCRPC.

Methods: We accessed data for men with chemotherapy-naive mCRPC in the abiraterone acetate plus prednisone (AA-P) group of a randomized trial (COU-AA-302) (n=546). We used Cox proportional hazards modelling to identify predictors of time to progression. We divided patients into groups based on the most important predictors and estimated the probability of radiographic progression-free survival (RPFS) at six and 12 months.

Results: Baseline disease and change in prostate-specific antigen (PSA) at eight weeks were the strongest determinants of RPFS. The probability of RPFS for men with bone-only disease and a ≥50% fall in PSA was 93% (95% confidence interval [CI] 87-96) at six months and 80% (95% CI 72-86) at 12 months. In contrast, the probability of RPFS for men with bone and soft tissue metastasis and <50% fall in PSA was 55% (95% CI 41-67) at six months and 34% (95% CI 22-47) at 12 months. These findings should be externally validated.

Conclusions: Patients with chemotherapy-naive mCRPC treated with first-line AA-P can be divided into groups with significantly different risks of radiographic progression based on a few clinically available variables, suggesting that imaging schedules could be individualized.
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http://dx.doi.org/10.5489/cuaj.5586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6570594PMC
June 2019

Statin use and time to progression in men on active surveillance for prostate cancer.

Prostate Cancer Prostatic Dis 2018 11 6;21(4):509-515. Epub 2018 Jun 6.

Division of Urology, Department of Surgery, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.

Purpose: Recent evidence suggests that statins may improve prostate cancer outcomes; however, their role in active surveillance (AS) is poorly characterized. We aimed to evaluate the association between statin use at diagnosis and time to progression on AS.

Materials And Methods: Data were obtained from a prospectively maintained cohort of men undergoing AS between 1995 and 2016 at our institution. All men satisfied the low-risk criteria: Gleason score <7, <4 positive cores, <50% involvement of any core, and prostate-specific antigen level <10.0 ng/dL. Kaplan-Meier curves and multivariable Cox proportional hazards were used to assess statin exposure at diagnosis and at time to pathological progression (failing to meet the low-risk criteria at biopsy) and therapeutic progression (first of pathological progression or initiation of definitive therapy). Reclassification at confirmatory biopsy (first postdiagnostic biopsy) and progression beyond confirmatory biopsy were evaluated independently.

Results: Low-risk criteria were met by 797 men. Reclassification at the confirmatory biopsy occurred in 194 (24%) men, 51 (26%) of whom were statin users. Statin use was not associated with reclassification at confirmatory biopsy (odds ratio (OR): 1.24, 95% confidence interval (CI): 0.77-1.99). Among the remaining 603 men (median age: 63 years; follow-up: 60 months; 23% statin users), 149 (24%) had pathologic progression, while 200 (33%) had therapeutic progression. Statin exposure was not associated with pathological (multivariable hazard ratio (HR) 0.79, 95% CI: 0.51-1.23) or therapeutic (multivariable-HR 0.81, 95% CI: 0.55-1.19) progression beyond the confirmatory biopsy. Sensitivity analyses did not alter conclusions.

Conclusions: In our study, statin use at diagnosis was not significantly protective against pathological or therapeutic progression in men undergoing AS for localized, low-risk prostate cancer.
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http://dx.doi.org/10.1038/s41391-018-0053-xDOI Listing
November 2018

Beyond the black box of geriatric assessment: Understanding enhancements to care by the geriatric oncology clinic.

J Geriatr Oncol 2018 11 6;9(6):679-682. Epub 2018 Apr 6.

Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.

Objective: Comprehensive geriatric assessment (CGA) of older adults with cancer aids treatment decision-making and prognostication. Much less is known about the supportive care elements or enhancements to care afforded by the CGA. We characterized the enhancements to care provided by a geriatric oncology clinic and determined how these vary by indication for referral.

Materials And Methods: All patients age 65 or older referred to a single academic geriatric oncology clinic between July 2015 (clinic opening) and June 2017 were included. Treatment enhancements were prospectively recorded in 5 categories: educational support, comorbidity management, symptom management, oncologic treatment delivery, and peri-operative management recommendations. Indications for referral were categorized into 3 groups: pre-treatment (n = 97, 44%), on active treatment (n = 89, 41%), and survivorship phase (n = 33, 15%). Data were analyzed using descriptive statistics and multivariable logistic regression.

Results: 219 patients were seen during the study period (mean age 79.7 years, 69% male). Overall, educational support (96%) and comorbidity management (95%) were the most common enhancements, whereas peri-operative management (10%) was the least common and provided only to pre-treatment patients. Enhancements to cancer treatment delivery were offered more often to patients pre-treatment than on active treatment (61% versus 41%, p < 0.001). Other enhancements to care did not vary by indication for referral.

Conclusion: Educational support and comorbidity management are nearly universally offered. Most enhancements to care do not vary by indication for referral. Understanding the enhancements to care provided by geriatric oncology clinics can help with resource planning and program design.
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http://dx.doi.org/10.1016/j.jgo.2018.03.012DOI Listing
November 2018

Impact of Androgen Deprivation Therapy on Self-Reported Cognitive Function in Men with Prostate Cancer.

J Urol 2018 08 1;200(2):327-334. Epub 2018 Mar 1.

Department of Medicine, University Health Network, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Purpose: Although androgen deprivation therapy is widely used to treat prostate cancer, its effects on cognitive function are unclear. To our knowledge no prior report has examined the impact of androgen deprivation therapy on self-reported cognitive function.

Materials And Methods: Three groups of men 50 years old or older who were matched on age and education were enrolled in the study, including 81 with prostate cancer starting on continuous androgen deprivation therapy, 84 controls with prostate cancer not receiving androgen deprivation therapy and 85 healthy controls. Two scales from the FACT-Cog (Functional Assessment of Cancer Therapy-Cognitive subscale) version 3 were used to assess self-reported cognitive function. Changes in cognitive scores with time were analyzed by 2 approaches, including 1) multivariable regression and 2) calculation of the proportion of subjects per group with a decrease of 1 SD or more. Multivariable regression was applied to assess predictors of a decline in self-reported cognitive function. We also examined relationships between the FACT-Cog and a neuropsychological battery of 15 tests.

Results: Mean participant age was 69 years (range 50 to 87). The mean educational level was 15 years (range 8 to 24). FACT-Cog scores were similar at baseline across the cohorts. Neither analytical approach revealed that androgen deprivation therapy was associated with changes in self-reported cognitive function on either FACT-Cog scale. Mood and fatigue correlated with changes in self-reported cognitive function. The relationship between self-reported and objective cognitive measures was weak (maximum Spearman correlation coefficient 0.14) and only 2 of 30 correlations were statistically significant.

Conclusions: A total of 12 months of androgen deprivation therapy were not associated with self-reported cognitive function changes in older men with nonmetastatic prostate cancer.
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http://dx.doi.org/10.1016/j.juro.2018.02.073DOI Listing
August 2018

Improving bone health in men with prostate cancer receiving androgen deprivation therapy: Results of a randomized phase 2 trial.

Cancer 2018 03 6;124(6):1132-1140. Epub 2017 Dec 6.

Department of Psychosocial Oncology, University Health Network, Toronto, Ontario, Canada.

Background: Strategies to improve bone health care in men receiving androgen deprivation therapy (ADT) are not consistently implemented. The authors conducted a phase 2 randomized controlled trial of 2 education-based models-of-care interventions to determine their feasibility and ability to improve bone health care.

Methods: A single-center parallel-group randomized controlled trial of men with prostate cancer who were receiving ADT was performed. Participants were randomized 1:1:1 to 1) a patient bone health pamphlet and brief recommendations for their family physician (BHP+FP); 2) a BHP and support from a bone health care coordinator (BHP+BHCC); or 3) usual care. The primary efficacy outcome was receipt of a bone mineral density (BMD) test within 6 months. Secondary efficacy outcomes included guideline-appropriate calcium and vitamin D use and bisphosphonate prescriptions for men at high fracture risk. Feasibility endpoints included recruitment, retention, satisfaction, contamination, and outcome capture. The main analysis used logistic regression with a 1-sided P of .10. The trial is registered at ClinicalTrials.gov (identifier NCT02043236).

Results: A total of 119 men were recruited. The BHP+BHCC strategy was associated with a greater percentage of men undergoing a BMD test compared with the usual-care group (78% vs 36%; P<.001). BMD ordering also was found to be increased with the BHP+FP strategy (58% vs 36%; P = .047). Both strategies were associated with higher percentages of patients using calcium and vitamin D, but only the BHP+FP arm was statistically significant (P = .039). No men were detected to be at high fracture risk. All but one feasibility endpoint was met.

Conclusions: Educational strategies to improve bone health care appear feasible and are associated with improved BMD ordering in men receiving ADT. Cancer 2018;124:1132-40. © 2017 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.31171DOI Listing
March 2018

Return to work and work-related disability among AML survivors.

Ann Hematol 2017 Oct 14;96(10):1625-1633. Epub 2017 Aug 14.

Department of Medicine, University Health Network, Room EN14-214, 200 Elizabeth Street, Toronto, ON, M5G 2C4, Canada.

Acute myeloid leukemia (AML) is an aggressive, acute-onset hematological malignancy. Greater use of intensive chemotherapy (IC), supportive care, and stem cell transplantation have led to an increasing number of long-term survivors. Few studies have examined employment issues among AML survivors and to our knowledge, no study has examined the long-term effects of treatment on return to work. This study is the first to utilize a validated measure of work-related limitation and productivity (WLQ-16) to assess the long-term effects of AML treatment on employment rates, work-related limitations, and overall productivity. We examined RTW issues in 111 adult AML 1-year survivors after conventional IC. We found that, over time, the number of employed survivors increased (to 54% by 36 months) while the number of unemployed, retired, and sick leave patients decreased. Among those employed, the majority were employed full time. Employed individuals reported few work-related limitations and productivity loss scores were low, ranging from 3.47% at 18 months to 2.34% at 36 months. These data suggest that, over time, over half of AML survivors who underwent IC regain social, emotional, cognitive, and physical function sufficient to RTW with few limitations.
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http://dx.doi.org/10.1007/s00277-017-3097-4DOI Listing
October 2017

Perceptions of Study Newsletters for Older Cancer Patients in Longitudinal Studies.

J Cancer Educ 2018 04;33(2):463-469

Department of Medicine, University Health Network, 200 Elizabeth Street Room EN14-214, Toronto, ON, M5G 2C4, Canada.

To date, no study has examined the value of providing study newsletters in educating and motivating participants taking part in longitudinal intervention studies and reducing attrition in studies. The study team examined perceptions and satisfaction towards study newsletters, and their potential benefits, in a population of older men with prostate cancer participating in two ongoing longitudinal trials. Two study newsletters issues were mailed out 4 months apart to prostate cancer patients participating in a bone health and/or exercise intervention trial. Participants (n = 133) were invited to complete an 18-item custom-designed survey examining perceptions towards and satisfaction with the newsletter, and provide feedback about what makes an ideal study newsletter. Analyses were primarily descriptive. Resources required to produce a study newsletter were also calculated. Of 133 participants, 83 usable surveys were returned (response rate 62.4%). The mean satisfaction rating for the newsletter was 8.5/10 (SD 1.9) (10 = highly satisfied). Seventy eight percent said the newsletter encouraged them to continue to participate in the study, and 93% indicated that providing such study newsletters should be optional (64%) or mandatory (29%). Each newsletter required 31 h of study personnel time (mostly research student) to produce. Study participants were very satisfied with the newsletter and the majority indicated that study newsletters should be a regular practice in all long-term studies and may improve participant retention. Producing a newsletter is a low-cost method of educating participants in longitudinal studies. Its impact on recruitment and retention should be examined in clinical trials.
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http://dx.doi.org/10.1007/s13187-016-1143-xDOI Listing
April 2018

Stricter Active Surveillance Criteria for Prostate Cancer do Not Result in Significantly Better Outcomes: A Comparison of Contemporary Protocols.

J Urol 2016 12 24;196(6):1645-1650. Epub 2016 Jun 24.

Division of Urology, Departments of Surgery and Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, Ontario, Canada. Electronic address:

Purpose: We reviewed various existing active surveillance criteria and determined the competing trade-offs of the stricter vs more inclusive active surveillance criteria.

Materials And Methods: Men enrolled in an active surveillance program at Princess Margaret Cancer Centre between 1998 and 2014 were identified through a prospectively maintained database. All patients were assessed for entry eligibility into the Prostate Cancer Research International: Active Surveillance, Johns Hopkins, University of Miami, University of California San Francisco, Memorial Sloan Kettering Cancer Center, University of Toronto-Sunnybrook and Royal Marsden protocols. The 2-sided t-test, ANOVA, Wilcoxon rank sum or chi-square tests were used for comparison as appropriate.

Results: Of the 1,365 men identified 1,085 met the Princess Margaret Cancer Centre inclusion criteria. When the Johns Hopkins, Prostate Cancer Research International: Active Surveillance and University of Miami criteria were applied 15.2%, 11.5% and 11.3% of these patients were excluded from active surveillance, respectively. No significant differences were noted between men who met the Princess Margaret Cancer Centre criteria and those who were excluded based on more stringent criteria when grade or volume reclassification was compared. No significant differences in prostate specific antigen velocity or the number of patients who proceeded to seek treatment were noted (p >0.1). Rates of biochemical recurrence among patients who chose to undergo radical prostatectomy after initial active surveillance were not different between men who met the more inclusive vs more exclusive active surveillance protocols.

Conclusions: More selective criteria do not significantly improve short-term outcomes when considering the relative risk of grade reclassification or biochemical failure after treatment. In an era of increased awareness regarding the over diagnosis and overtreatment of prostate cancer, we believe that stricter entry criteria should be reconsidered.
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http://dx.doi.org/10.1016/j.juro.2016.06.083DOI Listing
December 2016

A comparison of the CARG tool, the VES-13, and oncologist judgment in predicting grade 3+ toxicities in men undergoing chemotherapy for metastatic prostate cancer.

J Geriatr Oncol 2017 01 15;8(1):31-36. Epub 2016 Oct 15.

Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.

Objective: Since the benefits of chemotherapy in treating older men with metastatic castration-resistant prostate cancer (mCRPC) are modest, validated tools that predict the risk of treatment toxicity may aid clinical decision-making. Whether these tools are better than oncologist judgment remains unclear. We compared the Cancer and Aging Research Group (CARG) tool, the Vulnerable Elders Survey-13 (VES-13), and oncologist judgment in predicting toxicity in men with mCRPC undergoing chemotherapy.

Materials And Methods: Men aged 65+ with mCRPC starting first-line or second-line chemotherapy were enrolled in this prospective observational study. At baseline, VES-13 and CARG risk scores were calculated and treating oncologists were asked to rate toxicity risk on a 10-point scale. Toxicity was captured using the Common Terminology Criteria for Adverse Events version 4. Logistic regression was performed to examine relationships between risk prediction tools and the development of grade 3+ toxicity.

Results: 46 patients (mean age 75) were accrued, with most receiving Docetaxel 75mg/m q3weekly. A total of 9 patients (20%, 95% confidence interval (CI) 9-34%) developed grade 3+ toxicity. Using the CARG tool, 0% (95% CI 0-84%), 17% (95% CI 6-36%), and 27% (95% CI 18-55%) of patients in the low, intermediate, and high risk groups developed grade 3+ toxicity, respectively (p=0.65). Although the CARG tool, the VES-13, and oncologist judgment appeared to perform similarly, comparisons were limited by the small sample size.

Conclusion: Chemotherapy for mCRPC was associated with lower than predicted rates of severe toxicity across all predicted risk groups. Further disease-specific validation studies are warranted.
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http://dx.doi.org/10.1016/j.jgo.2016.09.005DOI Listing
January 2017

Multilocular Cystic Renal Cell Carcinoma: Pathological T Staging Makes No Difference to Favorable Outcomes and Should be Reclassified.

J Urol 2016 11 21;196(5):1350-1355. Epub 2016 Jun 21.

Division of Urology, Departments of Surgery and Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, Ontario, Canada. Electronic address:

Purpose: We evaluated survival outcomes of cystic/multilocular cystic renal cell carcinomas in a long-term population based study based on size and pathological tumor stage.

Materials And Methods: We retrospectively reviewed a provincial cancer registry of all histologically proven cases of multilocular cystic renal cancers treated surgically between 1995 and 2008. All cases of cystic necrosis were excluded from study. Primary end points were overall and cancer specific survival estimated using Kaplan-Meier curves. Cox proportional hazards models of univariable and multivariable analyses were used to assess for factors associated with survival.

Results: Of 172 cases of cystic renal cancers 168 with complete data were analyzed, of which 98% were multilocular cystic. Median patient age at treatment was 55 years and 58% of the patients were male. More than 40% of cases were pT1b or greater, 15% were pT2 or greater and most cases were low Fuhrman grade (1-2). At a median followup of 9.75 years overall and cancer specific survival was 82.1% and 100%, respectively. No difference was noted in higher pathological T stage, size or grade. Limitations inherent in population based studies include under ascertainment of cause of death, lack of data on histologically benign cysts that are treated surgically and a lack of central pathology review.

Conclusions: Multilocular cystic renal cell carcinoma has an excellent prognosis, which remains unchanged regardless of tumor size or pathological T stage. This suggests a strong case for nephron and adrenal sparing surgery when indicated, and nonsurgical management when feasible. Since postoperative followup protocols are dictated by staging, we propose that for this entity pathological T staging should be abandoned or reassigned as pT1c to guide clinicians.
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http://dx.doi.org/10.1016/j.juro.2016.05.118DOI Listing
November 2016

Effects of long-term androgen deprivation therapy on cognitive function over 36 months in men with prostate cancer.

Cancer 2017 01 1;123(2):237-244. Epub 2016 Sep 1.

Department of Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada.

Background: Many men with prostate cancer (PC) require long-term androgen deprivation therapy (ADT), but to the authors' knowledge, its effects on cognitive function beyond 1 year are not described.

Methods: Three groups of men aged ≥50 years who were matched based on age and education were enrolled: 77 patients with nonmetastatic PC who initiated continuous ADT, 82 patients with PC who were not receiving ADT (PC controls), and 82 healthy controls. A battery of 14 neuropsychological tests, examining 8 cognitive domains, was administered on 5 occasions over 36 months. Changes in cognitive scores over time were analyzed using 3 approaches: linear mixed effects regression, the percentage of participants per group with declines in ≥1/2 cognitive tests, and a global summary of cognitive change.

Results: The mean age of the study subjects was 68.9 years, with a median of 16 years of education. In mixed effects models adjusted for age and education, ADT use was not found to be associated with significant changes over time in any cognitive test compared with healthy controls. The percentage of participants declining by ≥1.5 standard deviations in ≥2 tests or ≥2 standard deviations in ≥1 tests was similar across groups. A global summary of cognitive change found no statistically significant worsening of cognitive function among ADT users compared with controls. Sensitivity analyses adjusting for duration of ADT and using multiple imputation for missing data did not materially alter the study findings.

Conclusions: The ongoing use of ADT for up to 36 months does not appear to be associated with cognitive decline. Cancer 2017;123:237-244. © 2016 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.30320DOI Listing
January 2017

Analysis of active surveillance uptake for low-risk localized prostate cancer in Canada: a Canadian multi-institutional study.

World J Urol 2017 Apr 22;35(4):595-603. Epub 2016 Jul 22.

Centre hospitalier de l'Université de Montréal (CHUM), Montreal, QC, Canada.

Purpose: Although the uptake of active surveillance (AS) appears to be increasing in published series, the uptake in most geographic regions remains largely unknown. Our aim was to examine practice patterns around the use of AS in low-risk prostate cancer in Canada. In addition, we examined regional variations in AS uptake, predictors of AS uptake, and persistent use for 12 months.

Methods: This is a retrospective multicentre review of low-risk patients who underwent a prostate biopsy in 2010 in six centres in four provinces (BC, QC, MB and ON). AS was identified based on chart review and required a minimum of 6 months of follow-up after diagnosis without any active treatment.

Results: Of 986 patients, 781 patients (mean age 64 years) were incident cases and over three-quarters (77.3 %) chose AS at diagnosis. There were significant differences in uptake of AS by centre (range 65.0-98.0 %, p ≤ 0.05). Key multivariate predictors of pursuing AS included older age (OR 1.34, p = 0.044), centre (p = 0.021), lower number of cores (OR 1.09, p = 0.025), lower number of positive biopsy cores (OR 0.52, p < 0.001), and lower percent core involvement (OR 0.84, p < 0.001). In total, 516 (85.4 %) men remained on AS over 12 months. Maintenance with AS over 12 months differed by centre, ranging from 64.1 to 93.9 % (p = 0.001). Predictors of maintenance with AS over 12 months included older age, centre, and lower number of positive cores.

Conclusions: Active surveillance is widely practiced across Canada, but important regional differences were observed. Further analyses are required to understand the root causes of differences and to determine whether AS uptake is changing over time.
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http://dx.doi.org/10.1007/s00345-016-1897-0DOI Listing
April 2017

Do quality of life, physical function, or the Wheatley index at diagnosis predict 1-year mortality with intensive chemotherapy in older acute myeloid leukemia patients?

Leuk Res 2016 08 3;47:142-8. Epub 2016 Jun 3.

Department of Medicine, University Health Network, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada. Electronic address:

Treatment decision-making is complicated in older adults with acute myeloid leukemia (AML) because of poor prognosis and significant treatment toxicities. Improved prognostication at the time of diagnosis, such as with the Wheatley Index, may aid clinical decision-making. Pre-treatment quality of life (QOL) or objective physical performance measures (PPMs) may also predict outcomes such as mortality in oncology. We investigated the predictive value of the Wheatley Index, QOL and PPMs at diagnosis on one-year mortality in older (60+ years) AML patients undergoing intensive chemotherapy (IC) in a large AML referral center. AML patients undergoing IC were enrolled in a single-center prospective study. The Wheatley prognostic risk category (good, standard and poor) was determined. Predictors of one-year mortality were assessed with logistic regression. Overall one-year mortality was 37.1%. QOL and PPMs at diagnosis were not good predictors of one-year mortality. Poor Wheatley risk category was the strongest predictor in both univariate and multivariable mortality models (adjusted odds ratio 7.1, 95% confidence interval 1.95-25.5, p<0.001). The Wheatley index may be useful to clinicians and patients by providing an integrated prognostic tool to guide up-front therapy in AML.
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http://dx.doi.org/10.1016/j.leukres.2016.06.001DOI Listing
August 2016

An Increase in Gleason 6 Tumor Volume While on Active Surveillance Portends a Greater Risk of Grade Reclassification with Further Followup.

J Urol 2016 Feb 28;195(2):307-12. Epub 2015 Sep 28.

Department of Uro-oncology, Division of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network; Department of Pathology, Toronto General Hospital, University of Toronto (AE), Toronto, Ontario, Canada; Department of Urology, St. Vincent's Hospital, Melbourne, Australia (L-MW). Electronic address:

Purpose: We evaluated the relative risk of later grade reclassification and outcomes of patients in whom high volume Gleason 6 prostate cancer develops while on active surveillance.

Materials And Methods: A prospectively maintained database was used to identify patients on active surveillance between 1998 and 2013. Tumor volume was assessed based on the number of positive cores and proportion of core involvement. The chi-square and Fisher exact tests were used for analysis as appropriate. The primary end point was the development of grade reclassification, defined as grade only and/or grade and volume at the event biopsy.

Results: A total of 555 men met the study inclusion criteria. Mean followup was 46 months. Overall 70 patients demonstrated an increase in tumor volume at or after biopsy 2. Compared to those men never experiencing volume or grade reclassification, prostate specific antigen at diagnosis was not significantly different (p=0.95), but median prostate volume was smaller in patients who demonstrated volume reclassification (p <0.001). The incidence of pure volume reclassification was 6.8%, 6.1% and 7.8% at biopsy 2, 3 and 4, respectively. Men with volume reclassification were more likely to experience later grade reclassification than those without at 33.3% vs 9.3%, respectively (p <0.0001).

Conclusions: While Gleason 6 prostate cancer has a favorable natural history, it appears that patients on active surveillance who experience volume reclassification are at substantially higher risk for grade reclassification. Thus, urologists should pay close attention to tumor core involvement, and monitoring should be adjusted accordingly for early volume reclassification in younger men and those in good health.
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http://dx.doi.org/10.1016/j.juro.2015.09.081DOI Listing
February 2016

Quality of life and physical function in adults treated with intensive chemotherapy for acute myeloid leukemia improve over time independent of age.

J Geriatr Oncol 2015 Jul 2;6(4):262-71. Epub 2015 May 2.

Department of Medicine, University of Alberta, 11350-83 Avenue, Edmonton, Alberta T6G 2G3, Canada.

Objectives: Intensive chemotherapy (IC) is the primary treatment of acute myeloid leukemia (AML) but is associated with significant toxicity, particularly in older adults. We characterized the impact of AML and its treatment on quality of life (QOL) and physical function in younger (age 18-59) and older (age 60+) patients with AML over 1year from diagnosis.

Materials And Methods: AML patients undergoing IC without stem-cell transplant at two tertiary care centers were enrolled in a prospective, longitudinal study. Assessments were done pre-IC and at 7 time points over the next year. QOL, fatigue, and physical performance (grip strength, 2-minute walk test (2MWT), timed chair stands) were measured in all patients whereas daily function was measured only in older patients. Data were analyzed using mixed effects regression models.

Results: 237 patients were recruited (140 younger and 97 older, 56% male). One-year survival was 79% and 60% among younger and older patients, respectively. For patients in remission, global QOL and fatigue improved significantly over time (p<0.001 for both); trends were similar between older and younger patients. Grip strength did not change over time (p=0.58) whereas both the 2MWT (p<0.001) and timed chair stands (p<0.001) improved significantly. Daily function improved significantly over time (p=0.003).

Conclusions: Survivors of AML in remission after IC achieve significant improvements in QOL, fatigue, and physical function over time with similar trajectories for older and younger patients. These data suggest that appropriately selected older patients do well following IC.
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http://dx.doi.org/10.1016/j.jgo.2015.04.002DOI Listing
July 2015

Long-term impact of androgen-deprivation therapy on physical function and quality of life.

Cancer 2015 Jul 24;121(14):2350-7. Epub 2015 Mar 24.

Department of Medicine, University Health Network, Toronto, Canada.

Background: This study examined the impact of androgen-deprivation therapy (ADT) on physical function and quality of life (QOL) over 36 months.

Methods: Eighty-seven men with nonmetastatic prostate cancer (PC) who were starting continuous ADT and 2 control groups (86 PC controls without ADT and 86 healthy controls), matched by age and education, were enrolled. Physical function was assessed with the 6-minute walk test (6MWT), grip strength, and Timed Up and Go (TUG) test. QOL was measured with the 36-Item Short Form Health Survey of the Medical Outcomes Study. Subjects were assessed at the baseline and at 3, 6, 12, 18, 24, 30, and 36 months. Mixed effects regression models were fitted with adjustments for baseline covariates.

Results: The 6MWT distance improved initially and then stabilized in both control groups but remained unchanged for ADT users (P = .0030). Grip strength remained stable in control groups but declined sharply in the ADT group by 3 months and then remained stable to 36 months (P = .0041). TUG scores declined gradually in the ADT group over 36 months but were unchanged in control groups (P = .0008). Aggregate physical QOL declined in ADT users over time but remained stable in control groups (P = .0001). Aggregate mental QOL was stable in all groups. Declines seen in the first year of ADT use generally persisted over 36 months and were independent of age.

Conclusions: Previously noted physical side effects over the first 12 months of ADT persisted or continued to worsen over an additional 2 years with no evidence of recovery. Exercise interventions to counteract these declines may be warranted.
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http://dx.doi.org/10.1002/cncr.29355DOI Listing
July 2015

Active surveillance in patients with a PSA >10 ng/mL.

Can Urol Assoc J 2014 Sep;8(9-10):E702-7

Department of Surgery (Urology), University of Toronto, Princess Margaret Hospital, Toronto, ON;

Introduction: The use of prostate-specific antigen (PSA) in active surveillance (AS) for prostate cancer is controversial. Some consider it an unreliable marker and others as sufficient evidence to exclude patients from AS. We analyzed our cohort of AS patients with a PSA over 10 ng/mL.

Methods: We included patients who had clinical T1c-T2a Gleason ≤6 disease, and ≤3 positive cores with ≤50% core involvement at diagnostic biopsy and ≥2 total biopsies. Patients were divided into 3 groups: (1) those with baseline PSA >10 ng/mL, (2) those with a PSA rise >10 ng/mL during follow-up; and (3) those with a PSA <10 ng/mL throughout AS. Adverse histology was defined as biopsy parameters exceeding the entry criteria limits. We further compared this cohort to a concurrent institutional cohort with equal biopsy parameters treated with immediate radical prostatectomy.

Results: Our cohort included 698 patients with a median follow-up of 46.2 months. In total, 82 patients had a baseline PSA >10 ng/mL and 157 had a PSA rise >10 ng/mL during surveillance. No difference in adverse histology incidence was detected between groups (p = 0.3). Patients with a PSA greater than 10 were older and had higher prostate volumes. Hazard ratios for groups with a PSA >10 were protective against adverse histology. Larger prostate volume and minimal core involvement appear as factors related to this successful selection of patients to be treated with AS.

Conclusion: These results suggest that a strict cut-off PSA value for all AS patients is unwarranted and may result in overtreatment. Though lacking long-term data and validation, AS appears safe in select patients with a PSA >10 ng/mL and low volume Gleason 6 disease.
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http://dx.doi.org/10.5489/cuaj.2121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4216302PMC
September 2014

Regular transition zone biopsy during active surveillance for prostate cancer may improve detection of pathological progression.

J Urol 2014 Oct 15;192(4):1088-93. Epub 2014 Apr 15.

Division of Surgical Oncology, Department of Uro-oncology, Princess Margaret Cancer Center, University Health Network; Department of Radiology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada; Department of Pathology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Urology, St. Vincent's Hospital and Austin Health, University of Melbourne, Victoria, Australia.

Purpose: We investigated the frequency of cancer and pathological progression in transition zone biopsies in men undergoing multiple rebiopsies while on active surveillance.

Materials And Methods: Eligibility criteria of the active surveillance prostate cancer database (1997 to 2012) at our tertiary center includes prostate specific antigen 10 ng/ml or less, cT2 or less, no Gleason grade 4 or 5, 3 or fewer positive cores, no core with greater than 50% involvement, patient age 75 years or less and 1 or more biopsies after initial diagnostic biopsy. We excluded from analysis men with fewer than 10 cores at diagnostic biopsy and/or confirmatory biopsy greater than 24 months after diagnostic biopsy. Multiparametric magnetic resonance imaging was performed selectively to investigate incongruity between prostate specific antigen and biopsy findings. Pathological progression was defined by grade and/or volume (greater than 50% of core involved). Transition zone progression was subdivided into exclusively transition zone and combined transition zone (transition and peripheral zones). A multivariate Cox proportional hazards model was used to determine predictors of transition zone progression.

Results: A total of 392 men were considered in analysis. Median followup was 45.5 months. At each biopsy during active surveillance (confirmatory biopsy to biopsy 5+) there were transition zone positive cores in 18.6% to 26.7% of cases, all transition zone progression in 5.9% to 11.1% and exclusively transition zone progression in 2.7% to 6.7%. Volume related progression was noted more frequently than grade related progression (24 vs 9 cases). Predictors of only transition zone progression were the maximum percent in a single core (HR 1.99, 95% CI 1.30-3.04, p = 0.002) and cancer on magnetic resonance imaging (HR 3.19, 95% CI 1.23-8.27, p = 0.02).

Conclusions: Across multiple active surveillance biopsies 2.7% to 6.7% of men had only transition zone progression. We recommend that transition zone biopsy be considered in all men at confirmatory biopsy. Positive magnetic resonance imaging findings or a high percent of core involvement may subsequently be useful to identify patients at risk.
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http://dx.doi.org/10.1016/j.juro.2014.04.010DOI Listing
October 2014

A pilot phase II RCT of a home-based exercise intervention for survivors of AML.

Support Care Cancer 2014 Apr 16;22(4):881-9. Epub 2013 Nov 16.

Department of Medicine, University Health Network, Toronto, ON, Canada,

Background: Fatigue is the most common and disabling symptom affecting quality of life (QOL) and daily function in patients who have completed treatment for acute myeloid leukemia (AML). Although trials in patients with various solid tumors have reported improved fatigue and QOL following exercise interventions, there have been no studies in AML patients post treatment.

Methods: Forty patients aged ≥ 40 years who had completed treatment for AML were enrolled in a 12-week randomized phase II exercise intervention to determine feasibility (recruitment, retention, and adherence), efficacy, and safety of the intervention. Patients assigned to the exercise group received an individualized, moderate-intensity, 12-week home-based exercise program with weekly telephone support from a certified exercise physiologist. QOL, fatigue, and fitness outcomes were measured at baseline, 6 weeks, and 12 weeks. Between-group differences in 12-week change scores were calculated using linear regression adjusting for age and baseline function.

Results: Recruitment and retention rates were 38% and 91%, respectively. Adherence was low at 28%. Analyses did not suggest statistically significant or clinically important benefits in QOL, fatigue, or physical fitness with the intervention. The level of adherence did not appear to impact outcomes. There were no adverse events.

Conclusion: A home-based exercise program for post-treatment AML patients age 40 years or older can be safely delivered with reasonable recruitment and high retention. However, feasibility was hampered by low adherence. Further research and program modification are needed to better understand and overcome barriers to exercise delivery and adherence in AML survivors.
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http://dx.doi.org/10.1007/s00520-013-2044-8DOI Listing
April 2014

A population-based study of surgeon characteristics associated with the uptake of contemporary techniques in renal surgery.

Can Urol Assoc J 2013 Sep-Oct;7(9-10):E576-81

Division of Urologic Oncology, Princess Margaret Hospital, University of Toronto, Toronto, ON;

Introduction: We have witnessed the slow uptake of many contemporary techniques in the surgical management of renal tumours. We sought to evaluate surgeon-level characteristics associated with the uptake of laparoscopy, partial nephrectomy (PN) and adrenal-sparing approaches in surgically managing these tumours.

Methods: Using the Ontario Cancer Registry, we identified surgeons treating renal cell carcinoma (RCC) in the province of Ontario, Canada between 2002 and 2004. We then classified individuals within this cohort as either high or low utilizers of laparoscopy, PN or adrenal-sparing approaches. Further variables analyzed included academic status, surgeon graduation year and surgical volume status. We then used univariable and multivariable logistic regression models to assess predictors of uptake.

Results: We evaluated a total of 108 surgeons for their uptake of both laparoscopy and adrenal-sparing approaches and 94 surgeons for their uptake of PN. We identified 32 surgeons (30%) as high users of laparoscopy. Predictors of uptake of laparoscopy included graduation year after 1990 (odds ratio [OR] 4.81, confidence interval [CI] 1.57-14.8) and high-surgeon volume (OR 4.33, CI 1.60-10.4). We identified 41 surgeons (44%) as high users of PN. The only predictor of uptake of PN was academic status (OR 5.83, CI 1.96-17.3). We identified 69 surgeons (65%) as high users of adrenal-sparing approaches, but did not identify any significant predictors for uptake in this group.

Discussion: We identify unique factors contributing to the uptake of distinct surgical techniques in the management of RCC. This information sheds lights on the underlying mechanisms and helps us understand how to further encourage the dissemination of these practices.
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http://dx.doi.org/10.5489/cuaj.182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776032PMC
September 2013
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