A Clinical Consensus Approach to Developing a New Funding Model for Radiation Services in Ontario.

In 2021, Ontario Health (Cancer Care Ontario) introduced a quality-based procedure model for the funding of radiation treatment (RT) in Ontario. This model ties reimbursement to patient care activities, ensuring equity and transparency in funding. Over 200 RT interprofessionals (oncologists, therapists and physicists) participated on 22 expert panels to establish or identify 288 evidence-based RT protocols and 672 quality expectations (QEs) to optimally deliver RT, which eventually led to the micro-costing of all protocols. Iterative review is required to ensure updated techniques and identify evolving standards of care, thereby providing the highest quality of RT care to Ontarians.

Role of Lactate Dehydrogenase in Identifying Relapse for Patients With Stage I Testicular Cancer on Surveillance.

PURPOSE: Tumor markers alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase assume a key role in the management of testicular germ cell tumors. While alpha-fetoprotein and human chorionic gonadotropin have modest sensitivity and specificity for germ cell tumors, lactate dehydrogenase has weak sensitivity and specificity. We explored the utility of lactate dehydrogenase in identifying relapse among stage I seminomatous and nonseminomatous germ cell tumors on surveillance. MATERIALS AND METHODS: Patients with a history of stage I testicular germ cell tumors were identified from a prospectively maintained database at the Princess Margaret Cancer Centre from December 1980 to May 2021 and surveyed according to established institutional algorithm guidelines. The utility of lactate dehydrogenase elevation to independently detect germ cell tumor relapse was examined. RESULTS: Among 1,014 seminoma and 676 nonseminomatous germ cell tumor patients, 176 and 176 patients relapsed with a median time to relapse of 13.6 and 8.9 months, respectively. Imaging alone was the most common mode of relapse detection in 144 and 74 of seminoma and nonseminomatous germ cell tumor patients, respectively. Lactate dehydrogenase was elevated in 49 cases of seminoma and 38 cases of nonseminomatous germ cell tumors at relapse, but was never the sole relapse indicator. Among 350 seminoma and 311 nonseminomatous germ cell tumor patients who never relapsed, 210 and 233, respectively, had at least 1 elevated lactate dehydrogenase value. CONCLUSIONS: Lactate dehydrogenase alone did not independently contribute to early relapse detection in stage I seminoma or nonseminomatous germ cell tumor. Elevated lactate dehydrogenase values were documented in a high proportion of nonrelapsing seminoma and nonseminomatous germ cell tumor cases.

Management of stage I testicular cancer.

PURPOSE OF REVIEW: Testicular cancer is the most common solid malignancy amongst young men, and a large proportion present with stage I disease. The options for management following radical orchiectomy are multifold. We review here approaches to treatment in this setting, providing an update on recent publications. RECENT FINDINGS: At Princess Margaret Cancer Centre, we maintain a nonrisk adapted active surveillance approach. With a dedicated surveillance program using low-dose computed tomography imaging, patients are appropriately identified early for treatment on relapse. There are ongoing investigations into minimizing toxicities of treatments for relapse, and in particular, retroperitoneal lymph node dissection (RPLND) presents an attractive alternative. This, though, remains investigational in the setting of seminoma. SUMMARY: Testicular cancer is a highly curable malignancy. In stage I disease, an active surveillance approach following radical orchiectomy is preferred, irrespective of risk-profile. This approach serves to limit the toxicity of adjuvant treatment in a significant proportion of patients, while maintaining excellent survival outcomes.

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.

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

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.

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

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.

Serum miRNA Predicts Viable Disease after Chemotherapy in Patients with Testicular Nonseminoma Germ Cell Tumor.

PURPOSE: Retroperitoneal lymph node dissection is recommended for residual masses greater than 1 cm after chemotherapy of nonseminomatous germ cell tumors. Currently there is no reliable predictor of post-chemotherapy retroperitoneal lymph node dissection histology. Up to 50% of patients harbor necrosis/fibrosis only so that a potentially morbid surgery has limited therapeutic value. In this study we evaluated the ability of defined serum miRNAs to predict residual viable nonseminomatous germ cell tumors after chemotherapy. MATERIALS AND METHODS: Levels of serum miRNA, including miR-371a-3p, miR-373-3p and miR-367-3p, were measured using the ampTSmiR (amplification targeted serum miRNA) test in 82 patients, including 39 in cohort 1 and 43 in cohort 2, who were treated with orchiectomy, chemotherapy and post-chemotherapy retroperitoneal lymph node dissection. miRNA levels were compared to clinical characteristics and serum tumor markers, and correlated with the presence of viable germ cell tumor vs fibrosis/necrosis and teratoma. ROC analysis was done to determine miRNA discriminative capacity. RESULTS: miRNA levels were significantly associated with disease extent at chemotherapy and they decreased significantly after chemotherapy. Conventional serum tumor marker levels were uninformative after chemotherapy. However, after chemotherapy miRNA levels remained elevated in patients harboring viable germ cell tumor in post-chemotherapy retroperitoneal lymph node dissection specimens. miR-371a-3p demonstrated the highest discriminative capacity for viable germ cell tumors (AUC 0.874, 95% CI 0.774-0.974, p <0.0001). Using an adapted hypothetical cutoff of 3 cm or less for surgical intervention miR-371a-3p correctly stratified all patients with viable residual retroperitoneal germ cell tumors with 100% sensitivity (p = 0.02). CONCLUSIONS: Our study demonstrates for the first time the potential value of miR-371a-3p to predict viable germ cell tumors in residual masses after chemotherapy. Prospective studies are required to confirm clinical usefulness.

Protocol for a phase III RCT and economic analysis of two exercise delivery methods in men with PC on ADT.

BACKGROUND: Androgen deprivation therapy (ADT) is commonly used to treat prostate cancer. However, side effects of ADT often lead to reduced quality of life and physical function. Existing evidence demonstrates that exercise can ameliorate multiple treatment-related side effects for men on ADT, yet adherence rates are often low. The method of exercise delivery (e.g., supervised group in-centre vs. individual home-based) may be important from clinical and economic perspectives; however, few studies have compared different delivery models. Additionally, long-term exercise adherence and an understanding of predictors of adherence are critical to achieving sustained benefits, but such data are lacking. The primary aim of this multi-centre phase III non-inferiority randomized controlled trial is to determine whether a home-based delivery model is non-inferior to a group-based delivery model in terms of benefits in fatigue and fitness in this population. Two other key aims include examining cost-effectiveness and long-term adherence. METHODS: Men diagnosed with prostate cancer of any stage, starting or continuing on ADT for at least 6 months, fluent in English, and living close to a study centre are eligible. Participants complete five assessments over 12 months (baseline and every 3 months during the 6-month intervention and 6-month follow-up phases), including a fitness assessment and self-report questionnaires. Biological outcomes are collected at baseline, 6, and 12 months. A total of 200 participants will be randomized in a 1:1 fashion to supervised group training or home-based training supported by smartphones, health coaches, and Fitbit technology. Participants are asked to complete 4 to 5 exercise sessions per week, incorporating aerobic, resistance and flexibility training. Outcomes include fatigue, quality of life, fitness measures, body composition, biological outcomes, and program adherence. Cost information will be obtained using patient diary-based self-report and utilities via the EQ-5D. DISCUSSION: To disseminate publicly funded exercise programs widely, clinical efficacy and cost-effectiveness have to be demonstrated. The goals of this trial are to provide these data along with an increased understanding of adherence to exercise among men with prostate cancer receiving ADT. TRIAL REGISTRATION: The trial has been registered at clinicaltrials.gov (Registration # NCT02834416 ). Registration date was June 2, 2016.

Gene expression signatures prognostic for relapse in stage I testicular germ cell tumours.

OBJECTIVES: To identify differentially expressed genes between relapsed and non-relapsed clinical stage I testicular germ cell tumours (TGCTs). MATERIALS AND METHODS: We reviewed patients with clinical stage I non-seminoma and seminoma from an institutional database (2000-2012) who were managed by active surveillance. Patients with non-relapsed non-seminoma and non-relapsed seminoma were defined as being relapse-free after 2 and 3 years of surveillance, respectively. RNA extraction and gene expression analysis was performed on archival primary tumour samples and gene-set enrichment analysis (GSEA) was conducted in order to identify differentiating biological pathways. RESULTS: A total of 57 patients (relapsed non-seminoma, n = 12; relapsed seminoma, n =15; non-relapsed non-seminoma, n = 15; non-relapsed seminoma, n = 15) were identified, with a median (range) relapse time of 5.6 (2.5-18.1) and 19.3 (4.7-65.3) months in the relapsed non-seminoma and relapsed seminoma cohorts, respectively. A total of 1 039 differentially expressed genes were identified that separated relapsed and non-relapsed groups. In patients with relapse, GSEA revealed enrichment in pathways associated with differentiation, such as skeletal development (i.e. FGFR1, BMP4, GLI2, SPARC, COL2A1), tissue (i.e. BMP4, SPARC, COL13A1) and bone remodelling (i.e. CARTPT, GLI2, MGP). A discriminative gene expression profile between relapsed and non-relapsed cases was discovered when combining non-seminoma and seminoma samples using 10- and 30-probe signatures; however, this profile was not observed in the seminoma and non-seminoma cohorts individually. CONCLUSION: A discriminating signature for relapsed disease was identified for clinical stage I TGCT that we were not able to identify by histology alone. Further validation is required to determine if this signature provides independent prognostic information to standard pathological risk factors.

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

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.

Chemotherapy treatment decision-making experiences of older adults with cancer, their family members, oncologists and family physicians: a mixed methods study.

PURPOSE: Although comorbidities, frailty, and functional impairment are common in older adults (OA) with cancer, little is known about how these factors are considered during the treatment decision-making process by OAs, their families, and health care providers. Our aim was to better understand the treatment decision process from all these perspectives. METHODS: A mixed methods multi-perspective longitudinal study using semi-structured interviews and surveys with 29 OAs aged ≥70 years with advanced prostate, breast, colorectal, or lung cancer, 24 of their family members,13 oncologists, and 15 family physicians was conducted. The sample was stratified on age (70-79 and 80+). All interviews were analyzed using thematic analysis. RESULTS: There was no difference in the treatment decision-making experience based on age. Most OAs felt that they should have the final say in the treatment decision, but strongly valued their oncologists' opinion. "Trust in my oncologist" and "chemotherapy as the last resort to prolong life" were the most important reasons to accept treatment. Families indicated a need to improve communication between them, the patient and the specialist, particularly around goals of treatment. Comorbidity and potential side-effects did not play a major role in the treatment decision-making for patients, families, or oncologists. Family physicians reported no involvement in decisions but desired to be more involved. CONCLUSION: This first study using multiple perspectives showed neither frailty nor comorbidity played a role in the treatment decision-making process. Efforts to improve communication were identified as an opportunity that may enhance quality of care. In a mixed methods study multiple perspective study with older adults with cancer, their family members, their oncologist and their family physician we explored the treatment decision making process and found that most older adults were satisfied with their decision. Comorbidity, functional status and frailty did not impact the older adult's or their family members' decision.

PMH 9907: Long-term outcomes of a randomized phase 3 study of short-term bicalutamide hormone therapy and dose-escalated external-beam radiation therapy for localized prostate cancer.

BACKGROUND: The role of hormone therapy (HT) with dose-escalated external-beam radiotherapy (DE-EBRT) in the treatment of intermediate-risk prostate cancer (IRPC) remains controversial. The authors report the long-term outcome of a phase 3 study of DE-EBRT with or without HT for patients with localized prostate cancer (LPC). METHODS: From 1999 to 2006, 252 of an intended 338 patients with LPC were randomized to receive DE-EBRT with or without 5 months of neoadjuvant and concurrent bicalutamide 150 mg once daily. The study was closed early because of contemporary concerns surrounding bicalutamide. The primary outcome was biochemical failure (BF) incidence, and the secondary endpoints were overall survival (OS), local control (LC), and quality of life. The BF and OS rates were estimated using the cumulative incidence function and Kaplan-Meier methods and were compared using the Gray test and the log-rank test. RESULTS: Eleven patients were excluded from analysis. Characteristics were well balanced in each treatment arm. Ninety-five percent of patients had IRPC. The prescribed dose increased from 75.6 grays (Gy) in 42 fractions to 78 Gy in 39 fractions over the period. At a median follow-up of 9.1 years, 98 BFs occurred, with no significant effect of HT versus no HT on the BF rate (40% vs 47%; P = .32), the OS rate (82% vs 86%; P = .37), the LC rate (52% vs 48 %; P = .32) or quality of life, in the patients who completed the questionnaires. Dose escalation to 75.6 Gy versus >75.6 Gy reduced the BF rate by 26% (P = .004). CONCLUSIONS: For patients who predominantly have IRPC, the addition of HT to DE-EBRT did not significantly affect BF, OS, or LC. Bicalutamide appeared to be well tolerated. The conclusions from the study are limited by incomplete recruitment. Cancer 2016;122:2595-603. © 2016 American Cancer Society.

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

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.

Intermittent androgen suppression for rising PSA level after radiotherapy.

BACKGROUND: Intermittent androgen deprivation for prostate-specific antigen (PSA) elevation after radiotherapy may improve quality of life and delay hormone resistance. We assessed overall survival with intermittent versus continuous androgen deprivation in a noninferiority randomized trial. METHODS: We enrolled patients with a PSA level greater than 3 ng per milliliter more than 1 year after primary or salvage radiotherapy for localized prostate cancer. Intermittent treatment was provided in 8-month cycles, with nontreatment periods determined according to the PSA level. The primary end point was overall survival. Secondary end points included quality of life, time to castration-resistant disease, and duration of nontreatment intervals. RESULTS: Of 1386 enrolled patients, 690 were randomly assigned to intermittent therapy and 696 to continuous therapy. Median follow-up was 6.9 years. There were no significant between-group differences in adverse events. In the intermittent-therapy group, full testosterone recovery occurred in 35% of patients, and testosterone recovery to the trial-entry threshold occurred in 79%. Intermittent therapy provided potential benefits with respect to physical function, fatigue, urinary problems, hot flashes, libido, and erectile function. There were 268 deaths in the intermittent-therapy group and 256 in the continuous-therapy group. Median overall survival was 8.8 years in the intermittent-therapy group versus 9.1 years in the continuous-therapy group (hazard ratio for death, 1.02; 95% confidence interval, 0.86 to 1.21). The estimated 7-year cumulative rates of disease-related death were 18% and 15% in the two groups, respectively (P=0.24). CONCLUSIONS: Intermittent androgen deprivation was noninferior to continuous therapy with respect to overall survival. Some quality-of-life factors improved with intermittent therapy. (Funded by the Canadian Cancer Society Research Institute and others; ClinicalTrials.gov number, NCT00003653.).

Lymph Node Yield in Primary Retroperitoneal Lymph Node Dissection for Nonseminoma Germ Cell Tumors.

PURPOSE: The number of lymph nodes removed at surgery for various malignancies has diagnostic and prognostic value. However, there are limited data on the significance of the number of nodes removed at retroperitoneal lymph node dissection performed for testicular nonseminoma germ cell tumors. MATERIALS AND METHODS: From 1979 to 2012 primary open retroperitoneal lymph node dissection was performed by a single experienced surgeon for clinical stage I/II testicular nonseminoma germ cell tumor in 157 patients. Node count was available in 111 cases (71%). Factors associated with total node count and nodes with viable cancer were assessed by linear regression. The association between node count and time to relapse was assessed by multivariate Cox proportional hazards models controlled for adjuvant chemotherapy. RESULTS: The median total lymph node count was 28 (IQR 19-38). Patient age, cancer laterality, body mass index, clinical stage, time from orchiectomy to retroperitoneal lymph node dissection, pathologist and lymph node dissection year were not associated with total lymph node count. A viable germ cell tumor was found in 70 patients (63%). Total node yield was not associated with nodal cancer metastasis. After lymph node dissection 17 patients (16%) received adjuvant chemotherapy. At a median 57-month followup 18 cases (17%) relapsed after primary retroperitoneal lymph node dissection. Increasing total node count was associated with a decreased risk of relapse on univariate and multivariate analysis (HR 0.96, 95% CI 0.92-0.99, p = 0.03 and HR 0.94, 95% CI 0.89-0.99, p = 0.017, respectively). CONCLUSIONS: No analyzed clinical or pathological variable was associated with the node yield of primary retroperitoneal lymph node dissection. However, there may be a relationship between the total node yield at retroperitoneal lymph node dissection and the risk of relapse.

A phase II RCT and economic analysis of three exercise delivery methods in men with prostate cancer on androgen deprivation therapy.

BACKGROUND: Androgen deprivation therapy is commonly used to treat prostate cancer, the most common visceral cancer in men. However, various side effects often worsen physical functioning and reduce well-being among men on this treatment. Based on existing evidence, both resistance and aerobic training provide benefits for this population yet adherence rates are often low. The method of exercise delivery (supervised in-center or home-based) may be important, yet few studies have compared different models. Additionally, long-term exercise adherence is critical to achieve sustained benefits but long-term adherence data and predictors of adherence are lacking. The primary aim of this phase II, non-inferiority randomized controlled trial is to determine whether three exercise training delivery models are equivalent in terms of benefits in quality of life and physical fitness in this population. Secondary aims include examination of long-term adherence and cost-effectiveness. DESIGN: Men diagnosed with prostate cancer, starting or continuing on androgen deprivation therapy for at least 6 months, fluent in English, and living close to one of two experienced Canadian study centers are eligible. Participants complete five assessments over one year, including a fitness assessment and self-report questionnaires. Socio-demographic and clinical data collection occur at baseline, bone mineral density testing at two time points, and blood work is performed at three time points. Participants are randomized in a 1:1:1 fashion to supervised personal training, supervised group training, or home-based smartphone- and health coach-supported training. Each participant receives a detailed exercise manual, including illustrations of exercises and safety precautions. Participants are asked to complete 4 to 5 exercise sessions per week, incorporating aerobic, resistance and flexibility training. Participant intensity levels will be monitored. The intervention duration is 6 months, with 6 months additional follow-up. Outcomes include: body composition, fitness testing, quality of life and fatigue, biological outcomes, and program adherence. Cost information will be obtained using patient diary-based self-report. DISCUSSION: The goals of this study are to gain a better understanding of health benefits and costs associated with commonly used yet currently not compared exercise delivery models as well as an increased understanding of adherence to exercise. TRIAL REGISTRATION: The trial has been registered at clinicaltrials.gov (Registration # NCT02046837), registered January 20(th), 2014.

The prostate cancer risk stratification project: database construction and risk stratification outcome analysis.

This investigation reports on the biochemical and clinical outcomes of a newly created pan-Canadian Prostate Cancer Risk Stratification (ProCaRS) database developed by the Genitourinary Radiation Oncologists of Canada (GUROC). GUROC ProCaRS template-compliant data on 7974 patients who underwent radiotherapy were received from 7 unique databases. Descriptive analysis, Cox proportional hazards, and Kaplan-Meier analyses were performed using American Society for Radiation Oncology (ASTRO) biochemical failure-free survival (BFFS), prostate cancer-specific survival, and overall survival. Multivariable modeling for the primary ASTRO BFFS end point showed that age, prostate-specific antigen, T stage, and Gleason score and components such as hormonal therapy, and radiation treatment (brachytherapy with better outcome than external-beam) were predictive of outcome. Kaplan-Meier analysis of the existing GUROC and new NCCN classification system both showed good separation of all clinical outcome curves. The construction of a pan-Canadian database has informed important prostate cancer radiotherapy outcomes and risk stratification.

IMRT utilization in Ontario: qualitative deployment evaluation.

PURPOSE: The purpose of this paper is to describe a jurisdiction-wide implementation and evaluation of intensity-modulated radiation therapy (IMRT) in Ontario, Canada, highlighting innovative strategies and lessons learned. DESIGN/METHODOLOGY/APPROACH: To obtain an accurate provincial representation, six cancer centres were chosen (based on their IMRT utilization, geography, population, academic affiliation and size) for an in-depth evaluation. At each cancer centre semi-structured, key informant interviews were conducted with senior administrators. An electronic survey, consisting of 40 questions, was also developed and distributed to all cancer centres in Ontario. FINDINGS: In total, 21 respondents participated in the interviews and a total of 266 electronic surveys were returned. Funding allocation, guidelines and utilization targets, expert coaching and educational activities were identified as effective implementation strategies. The implementation allowed for hands-on training, an exchange of knowledge and expertise and the sharing of responsibility. Future implementation initiatives could be improved by creating stronger avenues for clear, continuing and comprehensive communication at all stages to increase awareness, garner support and encourage participation and encouraging expert-based coaching. IMRT utilization for has increased without affecting wait times or safety (from fiscal year 2008/2009 to 2012/2013 absolute increased change: prostate 46, thyroid 36, head and neck 29, sarcoma 30, and CNS 32 per cent). ORIGINALITY/VALUE: This multifaceted, jurisdiction-wide approach has been successful in implementing guideline recommended IMRT into standard practice. The expert based coaching initiative, in particular presents a novel training approach for those who are implementing complex techniques. This paper will be of interest to those exploring ways to fund, implement and sustain complex and evolving technologies.

Home-based versus supervised group exercise in men with prostate cancer on androgen deprivation therapy: A randomized controlled trial and economic analysis.

INTRODUCTION: Differences between health outcomes, participation/adoption, and cost-effectiveness of home-based (HOME) interventions and supervised group-based training (GROUP) in men with prostate cancer (PC) on androgen deprivation therapy (ADT) are currently unknown. The objective of this study was to assess the clinical efficacy, adherence, and cost-effectiveness of HOME versus GROUP in men on ADT for PC. MATERIALS AND METHODS: This was a multicentre, 2-arm non-inferiority randomized controlled trial and companion cost-effectiveness analysis. Men with PC on ADT were recruited from August 2016 to March 2020 from four Canadian centres and randomized 1:1 to GROUP or HOME. All study participants engaged in aerobic and resistance training four to five days weekly for six months. Fatigue [Functional Assessment of Cancer Therapy-Fatigue (FACT-F)] and functional endurance [6-min walk test (6MWT)] at six months were the co-primary outcomes. Secondary outcomes included quality of life, physical fitness, body composition, blood markers, sedentary behaviour, and adherence. Between-group differences in primary outcomes were compared to margins of 3 points for FACT-F and 40 m for 6MWT using a Bayesian analysis of covariance (ANCOVA). Secondary outcomes were compared with ANCOVA, Costs included Ministry of Health costs, program costs, patient out-of-pocket, and time costs. TRIAL REGISTRATION: #NCT02834416. RESULTS: Thirty-eight participants (mean [standard deviation (SD)] age, 70 [9.0] years) were enrolled (GROUP n = 20; HOME n = 18). There was an 89.8% probability that HOME was non-inferior to GROUP for both fatigue and functional endurance and a 9.5% probability that HOME reduced fatigue compared to GROUP (mean [SD] change, 12.1 [8.1] vs 3.6 [6.1]; p = 0.040) at six months. Adherence was similar among study arms. HOME was cost-saving (mean difference: -$4122) relative to GROUP. DISCUSSION: A HOME exercise intervention appears non-inferior to GROUP for fatigue and functional endurance and requires fewer resources to implement. HOME appears to ameliorate fatigue more than GROUP, but has comparable effects on other clinically relevant outcomes. Although limited by sample size and attrition, these results support further assessment of home-based programs.

Changes in apparent diffusion coefficient and T2 relaxation during radiotherapy for prostate cancer.

PURPOSE: To evaluate regional and temporal changes in apparent diffusion coefficient (ADC) and T2 relaxation during radiation therapy (RT) in patients with low and intermediate risk localized prostate cancer. MATERIALS AND METHODS: Seventeen patients enrolled on a prospective clinical trial where MRI was acquired every 2 weeks throughout eight weeks of image-guided prostate IMRT (78 Gy/39 fractions). ADC and T2 quantification used entire prostate, central gland, benign peripheral zone, and tumor-dense regions-of-interest, and mean values were evaluated for common response trends. RESULTS: Overall, the RT responses were greater than volunteer measurement repeatability, and week 6 appeared to be an optimum time-point for early detection. RT effects on the entire prostate were best detected using ADC (5-7% by week 2, P < 0.0125), effects on peripheral zone were best detected using T2 (19% reduction at week 6; P = 0.004) and effects on tumors were best detected using ADC (14% elevation at week 6; P = 0.004). CONCLUSION: ADC and T2 may be candidate biomarkers of early response to RT warranting further investigation against clinical outcomes.