Understanding the incidence, duration, and severity of symptoms through daily symptom monitoring among frail and non-frail older patients receiving metastatic prostate cancer treatments.

INTRODUCTION: Older adults with metastatic prostate cancer (mPC) experience high symptom burden associated with treatment. Frailty may exacerbate treatment toxicity. The aim of this study was to explore short-term treatment toxicity in patients with metastatic prostate cancer. MATERIALS AND METHODS: Older adults with metastatic prostate cancer starting chemotherapy, androgen-receptor-axis targeted therapies, or radium-223 participated in a prospective, multicentre, observational study. Participants self-reported symptoms daily using the Edmonton Symptom Assessment System for one treatment cycle via internet or telephone. The most common moderate-to-severe symptoms (score≥4), their duration, and the proportion of participants who experienced improvements in symptom severity (score<4) after reporting moderate-to-severe symptoms at baseline were determined using descriptive statistics. Once-weekly symptom questionnaires were administered and analyzed using linear mixed effect models. Symptom incidence, duration, and frailty associations were assessed using t-tests and chi-square tests. RESULTS: Ninety participants completed the study (mean age=77 years [standard deviation=6.1], 42% frail [Vulnerable Elders Survey≥3]). The most common moderate-to-severe symptoms across cohorts were fatigue (46.8%), insomnia (42.9%), poor wellbeing (41.2%), pain (37.5%), and decreased appetite (37.1%). Poor wellbeing had a higher incidence in frail participants (62.5% in frail vs. 31.4% in non-frail, p=0.039). Symptom duration varied across cohorts and between frail and non-frail participants. Among participants who reported moderate-to-severe symptoms at baseline, no more than 15% improved in any symptom. There were statistically significant improvements in weekly symptoms for fatigue, decreased appetite, and insomnia in the chemotherapy cohort only. DISCUSSION: Limitations include a short follow-up duration, lack of a control group, and few radium-223 participants. Regular symptom monitoring can help clinicians understand temporal patterns and durations of symptoms and inform supportive care approaches.

Daily physical activity monitoring in older adults with metastatic prostate cancer on active treatment: Feasibility and associations with toxicity.

INTRODUCTION: Physical activity may be associated with cancer treatment toxicity, but generalizability to geriatric oncology is unclear. As many older adults have low levels of physical activity and technology use, this area needs further exploration. We evaluated the feasibility of daily step count monitoring and the association between step counts and treatment-emergent symptoms. MATERIALS AND METHODS: Adults aged 65+ starting treatment (chemotherapy, enzalutamide/abiraterone, or radium-223) for metastatic prostate cancer were enrolled in a prospective cohort study. Participants reported step counts (measured via smartphone) and symptoms (Edmonton Symptom Assessment Scale) daily for one treatment cycle (i.e., 3-4 weeks). Embedded semi-structured interviews were performed upon completion of the study. The feasibility of daily monitoring was evaluated with descriptive statistics and thematic analysis. The predictive validity of a decline in daily steps (compared to pre-treatment baseline) for the emergence of symptoms was examined using sensitivity and positive predictive value (PPV). Associations between a 15% decline in steps and the emergence of moderate (4-6/10) to severe (7-10/10) symptoms and pain in the next 24 h were assessed using logistic regression. RESULTS: Of 90 participants, 47 engaged in step count monitoring (median age = 75, range = 65-88; 52.2% participation rate). Daily physical activity monitoring was found to be feasible (94% retention rate; 90.5% median response rate) with multiple patient-reported benefits including increased self-awareness and motivation to engage in physical activity. During the first treatment cycle, instances of a 15% decline in steps were common (n = 37, 78.7%), as was the emergence of moderate to severe symptoms overall (n = 40, 85.1%) and pain (n = 26, 55.3%). The predictive validity of a 15% decline in steps on the emergence of moderate to severe symptoms was good (sensitivity = 81.8%, 95% confidence interval [CI] = 68.7-95.0; PPV = 73.0%, 95% CI = 58.7-87.3), although the PPV for pain was poor (sensitivity = 77.8%, 95% CI = 58.6-97.0; PPV = 37.8%, 95% CI = 22.2-53.5). In the regression models, changes in daily physical activity were not associated with symptoms or pain. DISCUSSION: Changes in physical activity had modest ability to predict moderate to severe symptoms overall. Although participation was suboptimal, daily activity monitoring in older adults with cancer appears feasible and may have other uses such as improving physical activity levels. Further studies are warranted.

Validity of a self-administered G8 screening test for older patients with cancer.

INTRODUCTION: The Geriatric 8 (G8) is a brief cancer-specific tool which screens for patients who require a comprehensive geriatric assessment (CGA). The G8 test assesses patients on eight domains such as mobility, polypharmacy, age, and self-rated health. However, the current G8 requires a healthcare professional (nurse or physician) present to conduct the test, which limits its usefulness. The Self-G8 questionnaire (S-G8) is an adaptation of the original G8 test, assessing all the same domains, with questions modified to be appropriate for patients to self-complete. Our objective was to evaluate the performance of S-G8 compared to the G8 and CGA. MATERIALS AND METHODS: The initial S-G8 was designed by our team through review of the literature and questionnaire design principles, and was optimized through feedback from patients over the age of 70. The questionnaire subsequently underwent further refinement after undergoing pilot testing (N = 14). The diagnostic accuracy of the final iteration of the S-G8 was evaluated along with the standard G8 in a prospective cohort study (N = 52) in an academic geriatric oncology clinic at the Princess Margaret Cancer Centre, Toronto, Canada. Psychometric characteristics were evaluated including internal consistency, sensitivity, and specificity compared to the G8 and to the CGA. RESULTS: There was strong correlation between the G8 and S-G8 scores, with a Spearman correlation co-efficient of 0.76 (p < 0.001). Internal consistency was acceptable at 0.60. The frequency of abnormality (<14 score) for the G8 and S-G8 was 82.7% and 61.5%, respectively. The mean score for the original G8 and S-G8 was 11.9 and 13.5, respectively. The cut-off of 14 for the S-G8 yielded the best combination of sensitivity of 0.70 ± 0.07 and specificity of 0.78 ± 0.14 when compared to the G8. When compared to two or more abnormal domains on the CGA, the S-G8 performed at least as well as the G8 with a sensitivity of 0.77, specificity of 0.85, and a Youden's index of 0.62. DISCUSSION: The S-G8 questionnaire appears to be an acceptable alternative to the original G8 in identifying older adults with cancer who will benefit from a CGA. Large scale testing is warranted.

Implementation of clinical recommendations from the geriatric oncology clinic.

INTRODUCTION: While evidence on the value of routine geriatric assessment (GA) in cancer care for older patients is growing, there is limited data on the geriatric oncology (GO) clinic's specific recommendations and how they are implemented. In this study, we aimed to assess and evaluate the implementation of recommendations from the GO clinic at Princess Margaret Cancer Center, Toronto, Canada, within six months of the initial visit. MATERIALS AND METHODS: A retrospective chart review was conducted on 100 consecutive adults age 65+ visiting the GO clinic from 2018 to 2019. For each patient, we evaluated the number and type of recommendations from the GO clinic. Recommendations were grouped based on clinical judgement. Of the recorded recommendations, we measured the rate of implementation within six months of the initial visit including who implemented the recommendations and why recommendations were not implemented. Data were analyzed using descriptive statistics. RESULTS: One hundred patients visiting the GO clinic (mean age of 80.5 years, 62% male, 52% with planned curative intent, with the genitourinary site being most common) received a median of six recommendations (range of 2-12), regardless of sex, cancer stage, cancer site, and treatment intent. Medication optimization (27%), patient education (26%), and referral to allied health (14%) were the top recommendations from the GO clinic. At six-month follow-up, 83% of all recommendations were implemented, of which 94% were performed by the GO clinic team. Patient education was implemented at a 100% rate by the GO clinic at the time of initial assessment. GO follow-up visit and other diagnostic tests (hearing test, vision test) were the recommendations with the lowest implementation rates, at 51% and 31%, respectively. The most common reasons for recommendations not being implemented were patient transfer to palliative care/death and patient declining recommendations due to busy appointment schedules. DISCUSSION: A median of six recommendations were made per patient. The vast majority of recommendations were implemented, predominantly by the GO team. Overall, the study helps evaluate recommendations provided to patients visiting GO clinics, identify potential gaps, and assist with resource planning for optimal cancer care for older adults.

Applying Quality Indicators to Examine Quality of Care During Active Surveillance in Low-Risk Prostate Cancer: A Population-Based Study.

BACKGROUND: Although a few studies have reported wide variations in quality of care in active surveillance (AS), there is a lack of research using validated quality indicators (QIs). The aim of this study was to apply evidence-based QIs to examine the quality of AS care at the population level. METHODS: QIs were measured using a population-based retrospective cohort of patients with low-risk prostate cancer diagnosed between 2002 and 2014. We developed 20 QIs through a modified Delphi approach with clinicians targeting the quality of AS care at the population level. QIs included structure (n=1), process of care (n=13), and outcome indicators (n=6). Abstracted pathology data were linked to cancer registry and administrative databases in Ontario, Canada. A total of 17 of 20 QIs could be applied based on available information in administrative databases. Variations in QI performance were explored according to patient age, year of diagnosis, and physician volume. RESULTS: The cohort included 33,454 men with low-risk prostate cancer, with a median age of 65 years (IQR, 59-71 years) and a median prostate-specific antigen level of 6.2 ng/mL. Compliance varied widely for 10 process QIs (range, 36.6%-100.0%, with 6 [60%] QIs >80%). Initial AS uptake was 36.6% and increased over time. Among outcome indicators, significant variations were observed by patient age group (10-year metastasis-free survival was 95.0% for age 65-74 years and 97.5% in age <55 years) and physician average annual AS volume (10-year metastasis-free survival was 94.5% for physicians with 1-2 patients with AS and 95.8% for those with ≥6 patients with AS annually). CONCLUSIONS: This study establishes a foundation for quality-of-care assessments and monitoring during AS implementation at a population level. Considerable variations appeared with QIs related to process of care by physician volume and Qis related to outcome by patient age group. These findings may represent areas for targeted quality improvement initiatives.

Impact of treatment on elder-relevant physical function and quality of life outcomes in older adults with metastatic castration-resistant prostate cancer.

INTRODUCTION: Understanding physical function (PF) and quality of life (QoL) treatment effects are important in treatment decision-making for older adults with cancer. However, data are limited for older men with metastatic castration-resistant prostate cancer (mCRPC). We evaluated the effects of treatment on PF and QoL in older men with mCRPC. MATERIALS AND METHODS: Men aged 65+ with mCRPC were enrolled in this multicenter prospective observational study. PF measures included instrumental activities of daily living, grip strength, chair stands, and gait speed. QoL measures included fatigue, pain, mood, and Functional Assessment of Cancer Therapy (FACT)-General total and sub-scale scores. Outcomes were collected at baseline, three, and six months. Linear mixed effects regression models were used to examine PF and QoL differences over time across various treatment cohorts. RESULTS: We enrolled 198 men starting chemotherapy (n = 71), abiraterone (n = 37), enzalutamide (n = 67), or radium-223 (n = 23). At baseline, men starting chemotherapy had worse measures of PF, QoL, pain, and mood than the other groups. Over time, all PF measures remained stable, pain improved, but functional wellbeing (FWB) and mood worsened significantly for all cohorts. However, change over time in all outcomes was not appreciably different between treatment cohorts. Worst-case sensitivity analyses identified attrition (ranging from 22 to 42% by six months) as a major limitation of our study, particularly for the radium-223 cohort. DISCUSSION: FWB and mood were most prone to deterioration over time, whereas pain improved with treatment. Although patients initiating chemotherapy had worse baseline PF and QoL, chemotherapy was not associated with significantly greater worsening over time compared to other common therapies for mCRPC. These findings may assist in treatment discussions with patients. However, given the modest sample size, attrition, and timeframe of follow-up, the impact of treatment on PF and QoL outcomes in this setting requires further study, particularly for radium-223.

Feasibility and acceptability of remote symptom monitoring (RSM) in older adults during treatment for metastatic prostate cancer.

INTRODUCTION: Emerging data support multiple benefits of remote symptom monitoring (RSM) during chemotherapy to improve outcomes. However, these studies have not focused on older adults and do not include treatments beyond chemotherapy. Although chemotherapy, androgen receptor axis-targeted therapies (ARATs), and radium-223 prolong survival, toxicities are substantial and increased in older adults with metastatic prostate cancer (mPC). We aimed to assess RSM feasibility among older adults receiving life-prolonging mPC treatments. MATERIALS AND METHODS: Older adults aged 65+ starting chemotherapy, an ARAT, or radium-223 for mPC were enrolled in a multicentre prospective cohort study. As part of the RSM package, participants completed the Edmonton Symptom Assessment Scale (ESAS) daily and detailed questionnaires assessing mood, anxiety, fatigue, insomnia, and pain weekly online or by phone throughout one treatment cycle (3-4 weeks). Alerts were sent to the clinical oncology team for severe symptoms (ESAS ≥7). Participants also completed an end of study questionnaire that assessed study burden and satisfaction. Descriptive statistics were used to determine recruitment and retention rates, participant response rates to daily and weekly questionnaires, clinician responses to alerts, and participant satisfaction rates. An inductive descriptive approach was used to categorize open-ended responses about study benefits, challenges, and recommendations into relevant themes. RESULTS: Ninety males were included (mean age 77 years, 48% ARAT, 38% chemotherapy, and 14% radium-223). Approximately 38% of patients preferred phone-based RSM. Patients provided RSM responses in 1216 out of 1311 daily questionnaires (93%). Over 93% of participants were satisfied (36%), very satisfied (43%), or extremely satisfied (16%) with RSM, although daily reporting was reported by several (8%) as burdensome. Nearly 45% of patients reported severe symptoms during RSM. Most symptom alerts sent to the oncology care team were acknowledged (97%) and 53% led to follow-ups with a nurse or physician for additional care. DISCUSSION: RSM is feasible and acceptable to older adults with mPC, but accommodation needs to be made for phone-based RSM. The optimal frequency and duration of RSM also needs to be established.

The role of frailty in modifying physical function and quality of life over time in older men with metastatic castration-resistant prostate cancer.

INTRODUCTION: As treatment options for metastatic castration-resistant prostate cancer (mCRPC) expand and its patient population ages, consideration of frailty is increasingly relevant. Using a novel frailty index (FI) and two common frailty screening tools, we examined quality of life (QoL) and physical function (PF) in frail versus non-frail men receiving treatment for mCRPC. MATERIALS AND METHODS: Men aged 65+ starting docetaxel chemotherapy, abiraterone, or enzalutamide for mCRPC were enrolled in a multicenter prospective cohort study. QoL, fatigue, pain, and mood were measured with the Functional Assessment of Cancer Therapy-General scale, the Edmonton Symptom Assessment System tiredness and pain subscales, and the Patient Health Questionnaire-9. PF was evaluated with grip strength, four-meter gait speed, five times Sit-to-Stand Test, and instrumental activities of daily living. Frailty was determined using the Vulnerable Elders Survey (VES-13), the Geriatric 8 (G8), and an FI constructed from 36 variables spanning laboratory abnormalities, geriatric syndromes, functional status, social support, as well as emotional, cognitive, and physical deficits. We categorized patients as non-frail (FI ≤ 0.2, VES < 3, G8 > 14), pre-frail (FI > 0.20, ≤0.35), or frail (FI > 0.35, VES ≥ 3, G8 ≤ 14); assessed correlation between the three tools; and performed linear mixed-effects regression analyses to examine longitudinal differences in outcomes (0, 3, 6 months) by frailty status. A sensitivity analysis with worst-case imputation was conducted to explore attrition. RESULTS: We enrolled 175 men (mean age 74.9 years) starting docetaxel (n = 71), abiraterone (n = 37), or enzalutamide (n = 67). Our FI demonstrated moderate correlation with the VES-13 (r = 0.607, p < 0.001) and the G8 (r = -0.520, p < 0.001). Baseline FI score was associated with worse QoL (p < 0.001), fatigue (p < 0.001), pain (p < 0.001), mood (p < 0.001), PF (p < 0.001), and higher attrition (p < 0.01). Over time, most outcomes remained stable, although pain improved, on average, regardless of frailty status (p = 0.007), while fatigue (p = 0.045) and mood (p = 0.015) improved in frail patients alone. DISCUSSION: Among older men receiving care for mCRPC, frailty may be associated with worse baseline QoL and PF, but over time, frail patients may experience largely similar trends in QoL and PF as their non-frail counterparts. Further study with larger sample size and longer follow-up may help elucidate how best to incorporate frailty into treatment decision-making for mCRPC.

Impact of patients' sex in assessments and treatment recommendations in an older adult cancer clinic.

INTRODUCTION: In multiple settings, sex disparities have been seen in diagnosis, treatment, and outcomes. This study sought to determine whether there are sex differences in a geriatric oncology clinic concerning results of the comprehensive geriatric assessment (CGA) and treatment recommendations. MATERIALS AND METHODS: This is a retrospective cohort study including patients ≥65 years old referred for consultation on cancer treatment decision-making who underwent a CGA between July 2015 and December 2020, in a single Canadian academic geriatric oncology (GO) clinic. We examined differences by sex, stratified by disease site, stage, treatment intent, CGA results by domain, final treatment plan, and referrals for abnormal CGA findings. Differences were assessed using chi-square, Fisher's exact, or t-test as appropriate. Multivariate logistic regression was performed to examine whether sex impacted recommendations to reduce treatment intensity. RESULTS: In the study period, 328 patients were assessed in the GO clinic (mean age 81 years). The most common cancer types were gastrointestinal (42.1%), hematologic (18.3%), and head and neck (17.3%). More males than females were assessed in the GO clinic (62.2% versus 37.8%, respectively). This proportion did not change over time (p = 0.58). The GO clinic recommended to reduce treatment intensity in 140 cases (42.7%), with no difference between sexes in adjusted models (43.6% of females and 42.2% of males, p = 0.80). There were no differences in any CGA domain by sex. There were also no differences in referrals made by the GO clinic to optimize abnormal CGA domains by sex. DISCUSSION: Sex itself did not impact treatment decision-making, nor referrals to optimize abnormal CGA domains in our GO clinic using CGA-based care.

Performance of the frailty index in predicting complete remission, intensive care unit admission, and overall mortality in older and younger patients with acute myeloid leukemia receiving intensive chemotherapy.

The frailty index (FI) predicts clinical outcomes in oncology. However, in the acute myeloid leukemia (AML) setting, its predictive ability is poorly understood. We assessed whether the FI predicts complete remission (CR), intensive care unit (ICU) admission, and 1-year all-cause mortality in younger and older adults with AML receiving intensity chemotherapy. This was a secondary analysis of a prospective study. In total, 237 patients (n = 140 younger and n = 97 older adults) were classified as non-frail, prefrail, or frail. Frail younger adults were less likely to achieve CR compared with non-frail younger adults. Pre-frail and frail younger adults were more likely to be admitted to the ICU compared with their non-frail counterparts. The FI was not predictive of 1-year all-cause mortality. The FI predicts CR and ICU admission in younger but not older adults. Disease biology may be more important than frailty in predicting 1-year overall mortality in patients with AML undergoing chemotherapy.

A cost-utility analysis of apalutamide for metastatic castrationsensitive prostate cancer.

INTRODUCTION: Earlier application of oral androgen receptor-axis-targeted therapies in patients with metastatic castration-sensitive prostate cancer (mCSPC) has established improvements in overall survival, as compared to androgen deprivation therapy (ADT) alone. Recently, the use of apalutamide plus ADT has demonstrated improvement in mCSPC-related mortality vs. ADT alone, with an acceptable toxicity profile. However, the cost-effectiveness of this therapeutic option remains unknown. METHODS: We used a state-transition model with probabilistic analysis to compare apalutamide plus ADT, as compared to ADT alone, for mCSPC patients over a time horizon of 20 years. Primary outcomes included expected life-years (LY), quality-adjusted life-years (QALY), lifetime cost (2020 Canadian dollars), and incremental cost-effectiveness ratio (ICER). Parameter and model uncertainties were assessed through scenario analyses. Health outcomes and cost were discounted at 1.5%, as per Canadian guidelines. RESULTS: For the base-case analysis, expected LY for ADT and apalutamide plus ADT were 4.11 and 5.56, respectively (incremental LY 1.45). Expected QALYs were 3.51 for ADT and 4.84 for apalutamide plus ADT (incremental QALYs 1.33); expected lifetime cost was $36 582 and $255 633, respectively (incremental cost $219 051). ICER for apalutamide plus ADT, as compared to ADT alone, was $164 700/QALY. Through scenario analysis, price reductions ≥50% were required for apalutamide in combination with ADT to be considered cost-effective, at a cost-effectiveness threshold of $100 000/QALY. CONCLUSIONS: Apalutamide plus ADT is unlikely to be cost-effective from the Canadian healthcare perspective unless there are substantial reductions in the price of apalutamide treatment.

National consensus quality indicators to assess quality of care for active surveillance in low-risk prostate cancer: An evidence-informed, modified Delphi survey of Canadian urologists/radiation oncologists.

INTRODUCTION: Although many low-risk prostate cancer (PCa) patients worldwide currently receive active surveillance (AS), adherence to clinical guidelines on AS and variations in care at the population level remain poorly understood. We sought to develop system-level quality indicators (QIs) and performance measures for benchmarking the quality of care during AS. METHODS: Convenience sampling methods were used to identify an expert panel among practicing urologists and radiation oncologists across Canada. QI development involved two phases: 1) proposed QIs were identified through a literature search and published clinical guidelines on AS; and 2) indicators were selected through a modified Delphi process during which each panelist independently rated each indicator based on clinical importance. QI items were chosen as appropriate measures for quality of AS care if they met prespecified criteria (disagreement index <1 and median importance of ≥7 on a nine-point scale). RESULTS: Among 42 invited expert panel members, the response rate was 45% (n=19). Expert panel members were well-represented by type of physician (84% urologists, 16% radiation oncologists) and practice setting (79% academic, 21% non-academic). The expert panel endorsed 20 of 27 potential indicators as appropriate for measuring quality of AS care. CONCLUSIONS: We developed a set of QIs to measure AS care using published guidelines and clinical experts. Use of the indicators will be assessed for feasibility in healthcare databases. Reporting quality of care with these AS indicators may enhance adherence, reduce variation in care, and improve patient outcomes among low-risk PCa patients on AS.

The role of grip strength and short physical performance battery test in predicting chemotherapy-related outcomes in older adults with cancer.

BACKGROUND: Grip strength (GS) and the Short Physical Performance Battery (SPPB) are brief objective tests used during a comprehensive geriatric assessment (CGA) to assess physical performance. Abnormal GS and SPPB scores are associated with greater morbidity and mortality in older adults with cancer but their relationship with chemotherapy tolerability is unclear. We explored the performance of GS and SPPB in predicting therapy delay, dose reduction, and treatment completion in older adults undergoing chemotherapy or chemoradiation. Additionally, we examined associations between GS, SPPB, and instrumental activities of daily living (IADLs). METHODS: Retrospective review of patients ≥65 years old who had undergone a pre-treatment CGA in a geriatric oncology clinic were retrieved from electronic charts and institutional databases. Abnormal GS was defined as <26 kg and < 16 kg for men and women, respectively. Abnormal SPPB was defined as ≤9 points. Logistic regression was used to examine the associations between abnormal GS or SPPB alone or combined with chemotherapy-related outcomes (e.g., delay, dose reduction, completion). Chi-squared tests were used to determine associations between physical performance measures (GS and SPPB) and IADLs. RESULTS: A total of 85 participants (mean age 79.1 years old) with mixed cancer diagnoses were included. Approximately 67% of participants exhibited abnormal GS or SPPB prior to treatment. Abnormal GS or SPPB (combined) was associated with treatment delay (odds ratio (OR) = 7.58, 95% confidence interval (CI) = 1.77, 32.43, P = 0.006). When physical performance measures were examined separately, only SPPB predicted treatment delay (OR = 3.26, 95%CI = 1.04, 10.21, P = 0.043). Abnormal GS or SPPB were not associated with dose reduction or treatment completion. Abnormal GS and SPPB alone or combined demonstrated only modest sensitivity (41.9-76.7%) and negative predictive value (57.9-64.2%) in identifying IADLs dependence. CONCLUSION: GS and SPPB may be used to predict treatment delay in older adults prior to chemotherapy and chemoradiation. Additional studies are warranted to examine whether GS and/or SPPB can predict dose reduction and treatment completion in older adults prior to receiving chemotherapy or chemoradiation.

Quality of care of consultations from the geriatric oncology clinic: "Are we addressing the needs of patients?"

INTRODUCTION: A comprehensive geriatric assessment (CGA) is recommended for older adults with cancer in the pre-treatment setting to optimize care. A CGA systematically evaluates multiple domains to develop a holistic view of the patient's health and facilitate timely interventions to ameliorate patient outcomes. For a CGA to be most effective, optimization of each abnormal domain should occur. However, there is limited literature exploring this issue. MATERIALS AND METHODS: Consultations of patients seen in a Geriatric Oncology clinic from June 2015 to June 2018 were reviewed. The percentage of "no recommendations made" in the consultation letter following the identification of impairment in each of eight geriatric domains was calculated. Trends over time were examined by stratifying the data into three periods ("Year 1", "Year 2", and "Year 3") and conducting a logistic regression analysis. RESULTS: A total of 365 consultation notes were reviewed. The patients were predominately older (mean age 79.9 years), male (66.9%), with genitourinary (38.6%) or gastrointestinal (23.3%) cancers. The most common stage was metastatic (40.6%). The most common treatment intent and modality were palliative (50.4%) and hormonal (50.9%), respectively. The geriatric domains that had the greatest frequency of impairments were medication optimization (76.2%), functional status (68.8%), and falls risk (64.9%). The domains that had the highest frequency of "no recommendations made" following identification of impairment were nutrition (39.8%), social support (39.5%), and mood (26.4%). The prevalence of "no recommendations made" decreased over time in social support (54.6% in Year 1 to 27.8% in Year 3, p = 0.043) and possibly nutrition (53.1% in Year 1 to 34.3% in Year 3, p = 0.088) but not for mood (p = 0.64). CONCLUSIONS: Nutrition, social supports and mood were the CGA domains with the highest proportion of "no recommendations made" following an identification of impairment. This is the first quality assurance study to identify social supports, mood, and nutrition domains as less frequently addressed following an identification of an impairment amongst older patients with cancer. Subsequent prospective research is required to understand reasons for these observations and identification of barriers to address these geriatric domains amongst older adults with cancer.

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

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.

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.

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.

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

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.

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

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.

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.

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.

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

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.