Informal caregiver quality of life in a palliative oncology population.

PURPOSE: Many patients with advanced cancer receive primary supports from informal caregivers (IC). As patient health deteriorates, IC assume increasing responsibility, often accompanied by distress. We investigated the quality of life (QOL) of IC of patients referred to a palliative radiotherapy (PRT) program. METHODS: IC accompanying patients to a dedicated PRT clinic completed a survey based on the validated Caregiver Quality of Life Index-Cancer (CQOLC). Demographics, burden, and engagement in support services were evaluated. Summary statistics were calculated, and parameters were assessed for association with CQOLC scores by a generalized linear model. RESULTS: Two hundred one surveys were analyzed representing 197 unique patients. The mean age was 68.3 years, with predominantly lung (25.0%) and prostate (19.3%) malignancies. 24.4% had been in hospital/long-term care within the previous 7 days. IC were 60.8% female, and 60.6% were the patient's spouse. 69.5% lived with the patient and 38.3% were additionally employed. IC spent a daily mean of 6.6 h (SD 7) assisting with instrumental (72.5%) and basic (37.5%) activities of daily living. Mean CQOLC score was 82.1/140 (SD 20). 63.8% of IC had previously accessed support service(s), most commonly home care (37.2%) and pharmacy (29.1%). 55.9% indicated interest in services not yet accessed. Multivariate analysis revealed additional employment, cohabitation, poor patient performance status, and interest in accessing more support services significantly correlated with higher IC burden. CONCLUSIONS: Employing the CQOLC to screen IC of patients referred to a PRT program permits early identification of vulnerable IC to facilitate linkage with appropriate supports.

Physical activity interests and preferences of cancer patients with brain metastases: a cross-sectional survey.

BACKGROUND: Physical activity has been shown to positively impact cancer-related fatigue, physical functioning and quality of life outcomes in early stage cancer patients, however its role at the end stage of cancer has yet to be determined. Brain metastases are amongst the most common neurological complications of advanced cancer, with significant deterioration in fatigue and quality of life. The purpose of the present study was to examine the physical activity interests and preferences of cancer patients with brain metastases initiating palliative whole brain radiotherapy. METHODS: Thirty-one patients aged 18 years or older, cognitively intact, diagnosed with brain metastases, and with Palliative Performance Scale scores of greater than 30%, were recruited from a multidisciplinary outpatient brain metastases clinic. An interviewer-administered survey was used to assess physical activity interests and preferences of participants who were embarking upon palliative whole brain radiotherapy. RESULTS: 87% (n = 27) of participants felt that physical activity was important, however there was limited interest in participating in a structured program at the onset of palliative whole brain radiotherapy. Lung cancer diagnosis was associated with being less interested in participating in a physical activity program, and feeling less able to participate in a physical activity program at the onset of palliative whole brain radiotherapy. CONCLUSIONS: Cancer patients with brain metastases demonstrate limited interest and varied preferences for physical activity during palliative whole brain radiotherapy. Additional pilot work with this patient population is needed before physical activity interventions can be tested in clinical research.

Correlates of objectively measured sedentary behavior in cancer patients with brain metastases: an application of the theory of planned behavior.

OBJECTIVE: The aim of this study is to examine the demographic, medical, and social-cognitive correlates of objectively measured sedentary behavior in advanced cancer patients with brain metastases. METHODS: Advanced cancer patients diagnosed with brain metastases, aged 18 years or older, cognitively intact, and with palliative performance scale greater than 30%, were recruited from a Rapid Access Palliative Radiotherapy Program multidisciplinary brain metastases clinic. A cross-sectional survey interview assessed the theory of planned behavior variables and medical and demographic information. Participants wore activPAL™ (PAL Technologies Ltd, Glasgow, United Kingdom) accelerometers recording time spent supine, sitting, standing, and stepping during 7 days encompassing palliative whole brain radiotherapy treatments. RESULTS: Thirty-one patients were recruited. Correlates of median time spent supine or sitting in hours per day were instrumental attitude (i.e., perceived benefits) of physical activity (r = -0.42; p = 0.030) and affective attitude (i.e., perceived enjoyment) of physical activity (r = -0.43; p = 0.024). Moreover, participants who sat or were supine for greater than 20.7 h per day reported significantly lower instrumental attitude (M = 0.7; 95% CI = 0.0-1.4; p = 0.051) and affective attitude (M = 0.7; 95% CI = 0.0-1.4; p = 0.041). Finally, participants who were older than 60 years of age spent more time sitting or being supine. CONCLUSIONS: Instrumental attitude and affective attitude were the strongest correlates of objectively measured sedentary behavior. This information could inform intervention studies to increase physical activity in advanced cancer patients with brain metastases.

Minimal clinically important differences in the EORTC QLQ-BN20 in patients with brain metastases.

INTRODUCTION: Quality of life (QOL) is an important treatment endpoint in advanced cancer patients with brain metastases. In clinical trials, statistically significant changes can be reached in a large enough population; however, these changes may not be clinically relevant. OBJECTIVE: The objective of this study was to determine the minimal clinically important difference (MCID) for the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire brain module (EORTC QLQ-BN20) in patients with brain metastases. METHODS: Patients undergoing radiotherapy for brain metastases completed the EORTC QLQ-BN20 and QLQ-C30/C15-PAL at baseline and 1-month follow-up. MCIDs were calculated for both improvement and deterioration using anchor- and distribution-based approaches. The anchor of overall QOL (as assessed by question 30 or question 15 on the QLQ-C30 and QLQ-C15-PAL, respectively) was used to determine meaningful change. RESULTS: A total of 99 patients were included. The average age was 61 years, and the most common primary cancer sites were the lung and breast. Statistically significant meaningful differences were seen on two scales. A decrease of 6.1 (95 % confidence interval (CI) 0.8 to 11.4) units and 13.8 (0.2 to 27.4) units was required to represent clinically relevant deterioration of seizures and weakness of legs, respectively. Distribution-based MCID estimates tended to be closer to 0.5 SD on the EORTC QLQ-BN20. CONCLUSION: Understanding MCIDs allows physicians to determine the impact of treatment on patients' QOL and allows for determination of sample sizes for clinical trials. Future studies should be conducted to validate our findings in a larger population of patients with brain metastases.

Addressing controversial areas in the management of advanced prostate cancer in Canada Areas of consensus and controversy from the third Canadian consensus forum.

INTRODUCTION: The management of prostate cancer (PCa) is rapidly evolving. Treatment and diagnostic options grow annually, however, high-level evidence for the use of new therapeutics and diagnostics is lacking. In November 2022, the Genitourinary Research Consortium held its 3rd Canadian Consensus Forum (CCF3) to provide guidance on key controversial areas for management of PCa. METHODS: A steering committee of eight multidisciplinary physicians identified topics for discussion and adapted questions from the Advanced Prostate Cancer Consensus Conference 2022 for CCF3. Questions focused on management of metastatic castration-sensitive prostate cancer (mCSPC); use of novel imaging, germline testing, and genomic profiling; and areas of non-consensus from CCF2. Fifty-eight questions were voted on during a live forum, with threshold for "consensus agreement" set at 75%. RESULTS: The voting panel consisted of 26 physicians: 13 urologists/uro-oncologists, nine medical oncologists, and four radiation oncologists. Consensus was reached for 32 of 58 questions (one ad-hoc). Consensus was seen in the use of local treatment, to not use metastasis-directed therapy for low-volume mCSPC, and to use triplet therapy for synchronous high-volume mCSPC (low prostate-specific antigen). Consensus was also reached on sufficiency of conventional imaging to manage disease, use of germline testing and genomic profiling for metastatic disease, and poly (ADP-ribose) polymerase (PARP) inhibitors for BRCA-positive prostate cancer. CONCLUSIONS: CCF3 identified consensus agreement and provides guidance on >30 practice scenarios related to management of PCa and nine areas of controversy, which represent opportunities for research and education to improve patient care. Consensus initiatives provide valuable guidance on areas of controversy as clinicians await high-level evidence.

Metformin for Prevention of Anthropometric and Metabolic Complications of Androgen Deprivation Therapy in Prostate Cancer Patients Receiving Radical Radiotherapy: A Phase II Randomized Controlled Trial.

BACKGROUND: Patients with prostate cancer undergoing treatment with radical radiation therapy (RT) plus androgen deprivation therapy (ADT) experience a constellation of deleterious metabolic and anthropometric changes related to hypogonadism that are associated with increased morbidity and mortality. We assessed the effect of metformin versus placebo to blunt the adverse effects of ADT on body weight, waist circumference, and other metabolic parameters. METHODS AND MATERIALS: This phase 2, multicenter, randomized controlled trial (RCT) randomized normoglycemic men with locally advanced prostate cancer receiving radical RT and ADT (18-36 months) in a 1:1 ratio to receive metformin 500 mg by mouth 3 times a day (for 30-36 months) versus identical placebo. RESULTS: From December 2015 to October 2019, 83 men were randomized with median follow-up of 23 months. Baseline mean body mass Index (BMI) of the cohort was 30.2 (range 22.2-52.5). Change in mean weight relative to baseline was lower among men who received metformin compared with placebo at 5 months (-1.80 kg, P = .038), but was not significant with longer follow-up (1 year: +0.16 kg, P = .874). Although participants on ADT had increases in waist circumference in both study arms, metformin did not significantly reduce these changes (1 year: +2.79 cm (placebo) versus +1.46 cm (metformin), P = .336). Low-density lipoprotein (LDL) cholesterol was lower in the metformin arm (-0.32 mmol/L) compared with the placebo arm (-0.03 mmol/L) at 5 months (P = .022), but these differences were not significant with longer follow-up (1 year: -0.17 mmol/L vs -0.19 mmol/L, P = .896). There were no differences in HbA1C, triglyceride, high-density lipoprotein (HDL) cholesterol, and total cholesterol by study arm. CONCLUSIONS: Men receiving radical RT and ADT gained weight and had increases in waist circumference over time that metformin did not significantly mitigate. Although this study did not observe any preventive effect of metformin on the anthropometric and metabolic complications of ADT, metformin continues to be studied in phase 3 RCTs in this patient population to assess its potential antineoplastic effects.

Beyond palliative radiotherapy: a pilot multidisciplinary brain metastases clinic.

PURPOSE: The purpose of this study is to determine the feasibility of a multidisciplinary palliative radiotherapy clinic for patients with brain metastases. METHODS: We designed a 6-month pilot Rapid Access Palliative Radiotherapy Program (RAPRP) brain metastases clinic. The main goals of the clinic were: (1) to provide timely consultation and treatment, (2) to provide multidisciplinary assessment and care, (3) to facilitate accrual of patients to research studies, and (4) to be a positive experience for patients. Team members included a radiation oncologist, radiation therapist, nurse practitioner, social worker (SW), occupational therapist (OT), and registered dietitian (RD). Patients underwent multidimensional assessment with patient-reported questionnaires and completed a patient satisfaction survey. Data were collected in a prospective database and collated in a standardized fashion with descriptive statistics recorded as percentages, medians, and ranges. RESULTS: The pilot brain metastases clinic ran weekly from August 5, 2009 to January 27, 2010. In total, 33 patients were seen. The median time from referral date to clinic date was 6 days, with 76% of patients seen within 1 week. Most patients (94%) started their radiotherapy on clinic day. Fifteen patients (45%) required assessment by a SW, 36% by an OT, and 33% by a RD. Ninety-one percent of patients participated in a research study. Eighty-six percent of patients reported being very satisfied with the clinic experience, and 97% would recommend the clinic to a patient in a similar situation. CONCLUSIONS: The pilot RAPRP Brain Metastases Clinic was successful in providing patients with timely and multidisciplinary care and will continue beyond the pilot phase.

Conventional Versus Hypofractionated Radiation for High-Risk Prostate Cancer Patients (CHIRP): 24-Month Patient-Reported Outcomes of the Randomized Phase 2 CHIRP Trial.

PURPOSE: In this study, we report the 24-month patient-reported outcomes of the randomized phase 2 CHIRP trial that compared conventional and hypofractionated radiation therapy (RT) in the treatment of high-risk prostate cancer. METHODS AND MATERIALS: Men with high-risk localized prostate cancer were randomized to either conventional (78 Gy/39 fractions) or hypofractionated RT (68 Gy/25 fractions). All patients received pelvic nodal RT and adjuvant androgen deprivation therapy. Quality of life (QoL) data were collected through the expanded prostate cancer index composite and the short-form 12 (SF-12) health-related QoL questionnaire at baseline and at 3, 6, 12, 18, and 24 months posttreatment. We assessed change from baseline to account for differences in baseline comorbidities. Independent t test was used to identify differences between the 2 groups. RESULTS: Ninety-six participants were included in the QoL analysis, 49 in the hypofractionation arm and 47 in the standard fractionation arm. Urinary and sexual scores were similar between the 2 arms at all time points. Bowel bother scores exhibited a consistent trend favoring the standard arm from 3- to 18-months posttreatment and were statistically significant at 12 months (P = .016). SF-12 physical component scores showed a consistent trend favoring the hypofractionation arm from 6- to 18-months posttreatment and were statistically significant at 18 months (P = .017). At 24 months, there were no significant differences in QoL scores between the 2 groups. CONCLUSIONS: At 24 months post-RT, there were no major differences in patient-reported QoL between standard and hypofractionated RT. Early statistically significant differences in bowel bother and SF-12 physical component scores were no longer present at 24 months.

Stage migration of testicular germ cell tumours in Alberta, Canada, during the COVID-19 pandemic: a retrospective cohort study.

BACKGROUND: An absence of screening recommendations and the rapid progression of testicular germ cell tumours (TGCTs) offer a perspective on the potential impact of the COVID-19 pandemic on cancer presentations. We evaluated the presenting cancer stages of TGCTs in a real-world population before and during the pandemic to assess stage migration. METHODS: We performed a retrospective review of all new patients with TGCT diagnoses in Alberta, Canada, from Dec. 31, 2018, to Apr. 30, 2021, using the Alberta Cancer Registry. Because potential changes in staging should not occur instantaneously, we used a 6-month lag time from Apr. 1, 2020, for seminomas, and a 3-month lag time for nonseminomas, to compare initial cancer stages at presentation before and during the pandemic. We evaluated monthly rates of presentation by stage and histology. Exploratory outcomes included the largest tumour dimension, tumour markers and, for advanced disease, risk category and treatment setting. RESULTS: Of 335 patients with TGCTs, 231 were diagnosed before the pandemic and 104 during the pandemic (using a lag time). In total, 18 (7.8%) patients diagnosed before the pandemic presented with stage III disease, compared to 16 (15.4%) diagnosed during the pandemic (relative risk 1.97, 95% confidence interval [CI] 1.05-3.72). We observed no significant differences for secondary outcomes. Without a lag time, the rate ratio for a stage II presentation decreased significantly during the pandemic (0.40, 95% CI 0.21-0.72). INTERPRETATION: We observed signs of TGCT stage migration during the COVID-19 pandemic, driven by a decline in stage II disease and a potential rise in stage III disease. Management of TGCTs should remain a priority, even during a global pandemic.

The Influence of the Pretreatment Immune State on Response to Radiation Therapy in High-Risk Prostate Cancer: A Validation Study From NRG/RTOG 0521.

PURPOSE: The immunoinflammatory state has been shown to be associated with poor outcomes after radiation therapy (RT). We conducted an a priori designed validation study using serum specimens from Radiation Therapy Oncology Group (RTOG) 0521. It was hypothesized the pretreatment inflammatory state would correlate with clinical outcomes. METHODS AND MATERIALS: Patients on RTOG 0521 had serum banked for biomarker validation. This study was designed to validate previous findings showing an association between elevations in C-reactive protein (CRP) and shorter biochemical disease free survival (bDFS). CRP levels were measured in pretreatment samples. An exploratory panel of related cytokines was also measured including: monocyte chemotactic protein-1, granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin (IL)-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17A, IL-23, and tumor necrosis factor. The primary endpoint examined was bDFS. Additional exploratory endpoints included overall survival, distant metastases, and toxicity events attributed to RT. RESULTS: Two hundred and two patients in RTOG/NRG 0521 had serum samples available. Median age was 66 years (48-83), and 90% of patients were White. There was not an association between CRP and bDFS (adjusted hazard ratio [HR], 1.07 per 1 log increase in CRP; 95% confidence interval, 0.83-1.38; P = .60). In the exploratory, unplanned analysis, pretreatment IL-10 was significantly associated with worse bDFS (adjusted HR, 1.61 per log increase; P = .0027) and distant metastases (HR, 1.55 per log increase; P = .028). The association of IL-10 with bDFS was maintained on a multiplicity adjustment. The exploratory analyses of pretreatment levels of interferon-γ, IL-1b, IL-2, IL-13, IL-23 were negatively associated with grade 2 or higher pollakiuria (adjusted odds ratio, 0.64, 0.65, 0.71, 0.72, and 0.74, respectively, all P < .05), and IL-6 was negatively associated with grade 2 or higher erectile dysfunction (odds ratio, 0.62; P = .027). CONCLUSIONS: Pretreatment CRP was not associated with a poorer bDFS after RT. In a hypothesis- generating analysis, higher baseline levels of IL-10 were associated with lower rates of bDFS. These findings require additional prospective evaluation.

Gastrointestinal and genitourinary toxicity profiles of metformin versus placebo in men with prostate cancer receiving prostate radiotherapy: interim toxicity results of a double-blinded, multicenter, phase II randomized controlled trial.

Androgen deprivation therapy (ADT) used for prostate cancer (PCa) management is associated with metabolic and anthropometric toxicity. Metformin given concurrent to ADT is hypothesized to counteract these changes. This planned interim analysis reports the gastrointestinal and genitourinary toxicity profiles of PCa patients receiving ADT and prostate/pelvic radiotherapy plus metformin versus placebo as part of a phase 2 randomized controlled trial. Men with intermediate or high-risk PCa were randomized 1:1 to metformin versus placebo. Both groups were given ADT for 18-36 months with minimum 2-month neoadjuvant phase prior to radiotherapy. Acute gastrointestinal and genitourinary toxicities were quantified using CTCAE v4.0. Differences in ≥ grade 2 toxicities by treatment were assessed by chi-squared test. 83 patients were enrolled with 44 patients randomized to placebo and 39 randomized to metformin. There were no significant differences at any time point in ≥ grade 2 gastrointestinal toxicities or overall gastrointestinal toxicity. Overall ≥ grade 2 gastrointestinal toxicity was low prior to radiotherapy (7.9% (placebo) vs. 3.1% (metformin), p = 0.39) and at the end of radiotherapy (2.8% (placebo) vs 3.1% (metformin), p = 0.64). There were no differences in overall ≥ grade 2 genitourinary toxicity between treatment arms (19.0% (placebo) vs. 9.4% (metformin), p = 0.30). Metformin added to radiotherapy and ADT did not increase rates of ≥ grade 2 gastrointestinal or genitourinary toxicity and is generally safe and well-tolerated.

Clinical Outcomes of the CHIRP Trial: A Phase II Prospective Randomized Trial of Conventionally Fractionated Versus Moderately Hypofractionated Prostate and Pelvic Nodal Radiation Therapy in Patients With High-Risk Prostate Cancer.

PURPOSE: Hypofractionated radiation therapy (HFRT) may offer treatment advantages for patients with prostate cancer. However, HFRT may also increase the risk of gastrointestinal (GI) or genitourinary (GU) toxicity compared with conventionally fractionated radiation therapy (CFRT). Several large trials have found that HFRT is well tolerated in mixed risk population studies. Here, we report on a phase II, randomized controlled study conducted to evaluate these endpoints in exclusively high-risk patients with prostate cancer treated with prostate and pelvic nodal radiation. METHODS AND MATERIALS: After giving informed consent, patients with high-risk prostate cancer were randomly assigned to prostate plus pelvic nodal radiation therapy with either HFRT (68 Gy in 25 fractions) or CFRT (78 Gy in 39 fractions) and 18 months of androgen suppression therapy. Toxicity was scored using the Common Terminology Criteria for Adverse Events (version 4.0). Biochemical failure was determined by the Phoenix definition. Patients were analyzed on an intention-to-treat basis. RESULTS: From 2012 to 2018, 111 patients with high-risk prostate cancer were enrolled and 109 patients were treated. The cumulative incidence of grade 2 or higher acute GI toxicity was not significantly different between the arms (HFRT 18.9% vs CFRT 21.8%; P = .812). Similarly, acute GU (HFRT 30.2% vs CFRT 30.9%; P = 1.00), late GI (HFRT 16.0% vs CFRT 10.0%; P = .554), and late GU (HFRT 16.0% vs CFRT 6.0%; P = .200) were not significantly different between the arms. Median follow-up was 38.0 months (4.8-77.8 months). The 3-year biochemical recurrence-free survival was not significantly different between the 2 arms (97.3% for HFRT vs 91.0% for CFRT; P = .606). The 3-year overall survival was 94.8% in the HFRT arm and 100.0% in the CFRT arm (P = .116). CONCLUSIONS: HFRT and CFRT using intensity modulated radiation therapy were both well tolerated for patients with high-risk prostate cancer and resulted in similar 3-year biochemical recurrence-free survival and overall survival.

Results from a Canadian consensus forum of key controversial areas in the management of advanced prostate cancer: Recommendations for Canadian healthcare providers.

INTRODUCTION: Rapid progress in diagnostics and therapeutics for the management of prostate cancer (PCa) has created areas where high-level evidence to guide practice is lacking. The Genitourinary Research Consortium (GURC) conducted its second Canadian consensus forum to address areas of controversy in the management of PCa and provide recommendations to guide treatment. METHODS: A panel of PCa specialists discussed topics related to the management of PCa. The core scientific committee finalized the design, questions, and analysis of the consensus results. Attendees then voted to indicate their management choice regarding each statement/topic. Questions for voting were adapted from the 2019 Advanced Prostate Cancer Consensus Conference. The thresholds for agreement were set at ≥75% for "consensus agreement," >50% for "near-consensus," and ≤50% for "no consensus." RESULTS: The panel was comprised of 29 PCa experts, including urologists (n=12), medical oncologists (n=12), and radiation oncologists (n=5). Voting took place for 65 predetermined questions and three ad hoc questions. Consensus was reached for 34 questions, spanning a variety of areas, including biochemical recurrence, treatment of metastatic castration-sensitive PCa, management of non-metastatic and metastatic castration-resistant PCa, bone health, and molecular profiling. CONCLUSIONS: The consensus forum identified areas of consensus or near-consensus in more than half of the questions discussed. Areas of consensus typically aligned with available evidence, and areas of variability may indicate a lack of high-quality evidence and point to future opportunities for further research and education.

Real-world evidence in patient-reported outcomes (PROs) of metastatic castrate-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate + prednisone (AA+P) across Canada: Final results of COSMiC.

INTRODUCTION: Abiraterone acetate plus prednisone (AA+P) has shown to significantly improve survival. COSMiC, a Canadian Observational Study in Metastatic Cancer of the Prostate, set out to prospectively amass real-world data on metastatic castration-resistant prostate cancer (mCRPC) patients managed with AA+P in Canada. Herein, we report their patient-reported outcomes (PROs). METHODS: After a median followup of 67.1 weeks, 254 patients were enrolled across 39 sites. Functional Assessment of Cancer Therapy-Prostate (FACT-P), Montreal Cognitive Assessment (MoCA), Brief Pain Inventory-Short Form (BPI-SF), Brief Fatigue Inventory (BFI), and Current Health Satisfaction in Prostate Cancer (CHS-PCa) were evaluated at baseline, as well as at weeks 12, 24, 48, and 72 after AA+P initiation. Descriptive analysis was used with continuous variables. Changes from baseline were summarized using mean (standard deviation [SD]). RESULTS: At a median age of 76.6 (8.94), baseline FACT-P total score was 111.3 (19.56) with no significant change in their functional status observed from baseline over time. The median baseline MoCA score was 25.2 (4.52), yet subsequent assessments showed an absence of cognitive decline while under treatment. Similarly, no meaningful changes were detected in BPI, BFI, and CHS-PCa during the 72-week study period, thus suggesting that patients' PROs were well-maintained throughout AA+P treatment. Prostate-specific antigen (PSA) response with >50% decline was 66.4%. Safety profile was consistent with the known side effect of AA+P. CONCLUSIONS: COSMiC represents the largest Canadian mCRPC cohort treated with AA+P with real-world, prospective evaluation of PROs. This data demonstrated the maintenance in quality of life and cognitive status over the course of the study and underscores the importance of PRO use in this complex patient population.

Controversial issues in the management of patients with advanced prostate cancer: Results from a Canadian consensus forum.

INTRODUCTION: The management of advanced prostate cancer (PCa) continues to evolve with the emergence of new diagnostic and therapeutic strategies. As a result, there are multiple areas in this landscape with a lack of high-level evidence to guide practice. Consensus initiatives are an approach to establishing practice guidance in areas where evidence is unclear. We conducted a Canadian-based consensus forum to address key controversial areas in the management of advanced PCa. METHODS: As part of a modified Delphi process, a core scientific group of PCa physicians (n=8) identified controversial areas for discussion and developed an initial set of questions, which were then reviewed and finalized with a larger group of 29 multidisciplinary PCa specialists. The main areas of focus were non-metastatic castration-resistant prostate cancer (nmCRPC), metastatic castration-sensitive prostate cancer (mCSPC), metastatic castration-resistant prostate cancer (mCRPC), oligometastatic prostate cancer, genetic testing in prostate cancer, and imaging in advanced prostate cancer. The predetermined threshold for consensus was set at 74% (agreement from 20 of 27 participating physicians). RESULTS: Consensus participants included uro-oncologists (n=13), medical oncologists (n=10), and radiation oncologists (n=4). Of the 64 questions, consensus was reached in 30 questions (n=5 unanimously). Consensus was more common for questions related to biochemical recurrence, sequencing of therapies, and mCRPC. CONCLUSIONS: A Canadian consensus forum in PCa identified areas of agreement in nearly 50% of questions discussed. Areas of variability may represent opportunities for further research, education, and sharing of best practices. These findings reinforce the value of multidisciplinary consensus initiatives to optimize patient care.

Management algorithms for prostate-specific antigen progression in prostate cancer: Biochemical recurrence after definitive therapy and progression to non-metastatic castrate-resistant prostate cancer.

INTRODUCTION: Current prostate cancer (PCa) guidelines primarily focus on localized or metastatic PCa. A multidisciplinary genitourinary oncology panel determined that additional guidance focusing on monitoring and management of biochemical recurrence (BCR) following radical therapy and non-metastatic castration-resistant prostate cancer (nmCRPC) was warranted. METHODS: The most up-to-date national and international guidelines, consensus statements, and emerging phase 3 trials were identified and used to inform development of algorithms by a multidisciplinary genitourinary oncology panel outlining optimal monitoring and treatment for patients with non-metastatic PCa. RESULTS: A total of eight major national and international guidelines/consensus statements published since 2015 and three phase 3 trials were identified. Working group discussions among the multidisciplinary genitourinary oncology panel led to the development of two algorithms: the first addressing management of patients with BCR following radical therapy (post-BCR), and the second addressing management of nmCRPC. The post-BCR algorithm suggests consideration of early salvage treatment in select patients and provides guidance regarding observation vs. intermittent or continuous androgen-deprivation therapy (ADT). The nmCRPC algorithm suggests continued ADT and monitoring for all patients, with consideration of treatment with apalutamide or enzalutamide for patients with high-risk disease (prostate-specific antigen [PSA] doubling time of ≤ 10 months). CONCLUSIONS: Two treatment algorithms have been developed to guide the management of non-metastatic PCa and should be considered in the context of local guidelines and practice patterns.

Evolution of the Radiation Therapist Role in a Multidisciplinary Palliative Radiation Oncology Clinic.

BACKGROUND: Palliative radiation therapists (PRTs) have been integrated in varying capacities into outpatient palliative radiation therapy (RT) services across Canada for over 2 decades. At our institution, PRTs have developed an essential role over 11 years within a palliative radiation oncology (PRO) clinic that focuses on integrating symptom management with radiation oncology assessment for palliative RT. PRTs have had direct clinical, technical, research, and administrative involvement as the clinic evolved from a pilot in 2007 supporting one half-day per week to the current model of five full clinical days. METHODS: Using collaborative reflection, we explored the PRTs' experience and insight. Twelve PRTs who contributed to the PRO clinic for varying lengths of time from 2007 through to 2016 were invited to participate in the development of a collective expression of the PRT experience. Seven PRTs consented to completing an electronic survey consisting of fifteen open-ended questions regarding individual roles and perspectives relating to our PRO clinic. Survey answers were enhanced by semistructured interviews when needed for clarification. Responses were contextualized within the operational changes to our multidisciplinary clinical model, from pilot to integrated service. RESULTS/DISCUSSION: Five respondents answered all of the questions. From the narratives, PRT roles and responsibilities were outlined and their insights and reflections included to contextualize clinical changes. Four phases of the clinic were identified and elucidated. Beginning in January 2007, three PRTs staffed a multidisciplinary clinical pilot one half-day per week for single-fraction, symptomatic bone metastases. The clinic has now evolved through various iterations to the current model with four PRTs sharing a "navigator" role with two registered nurses five full clinic days per week. The range of PRT experiences, responsibilities, and challenges encountered reflected specific clinical and operational conditions. CONCLUSION: As our clinical service model evolved from short-term pilot to fully integrated departmental service, so did the PRT role. PRTs contributing to RT as part of a multidisciplinary model support and advance nontraditional involvement in the holistic care of patients with advanced cancer.

Symptom assessment to guide treatment selection and determine progression in metastatic castration-resistant prostate cancer: Expert opinion and review of the evidence.

Multiple new agents to treat metastatic castration-resistant prostate cancer (mCRPC) have become available in recent years; however, the appropriate timing and sequencing of these agents have yet to be elucidated. Until accurate biomarkers become available to allow more focused therapeutic targeting for this population, treatment selection for men with mCRPC will continue to be driven largely by close assessment of patient-related factors and symptoms. Pain, as the predominant symptom of mCRPC, is often the focus when assessing progression and the need for a change in treatment. A myriad of other symptoms, including fatigue, impact on activities of daily living, sleep, and lower urinary tract symptoms, also affect men with mCRPC, and assessment of the composite of these symptoms provides an earlier signal for the need to adjust treatment. A number of tools are available for assessing symptoms in patients with advanced prostate cancer, but they are not routinely used, given their complexity and length. A new simplified questionnaire is proposed for the assessment of symptoms, beyond pain, to inform treatment decisions for men with mCRPC.

Avascular Necrosis of the Femoral Head After Palliative Radiotherapy in Metastatic Prostate Cancer: Absence of a Dose Threshold?

Avascular necrosis (AVN) is the final common pathway resulting from insufficient blood supply to bone, commonly the femoral head. There are many postulated etiologies of non-traumatic AVN, including corticosteroids, bisphosphonates, and radiotherapy (RT). However, it is unclear whether there is a dose threshold for the development of RT-induced AVN. In this case report, we describe a patient with prostate cancer metastatic to bone diagnosed with AVN after receiving single-fraction palliative RT to the left femoral head. Potential contributing factors are discussed, along with a review of other reported cases. At present, the RT dose threshold below which there is no risk for AVN is unknown, and therefore detrimental impact from the RT cannot be excluded. Given the possibility that RT-induced AVN is a stochastic effect, it is important to be aware of the possibility of this diagnosis in any patient with a painful hip who has received RT to the femoral head.