Adherence to oral hormonal therapy in advanced prostate cancer: a scoping review.

Background: Orally administrated agents play a key role in the management of prostate cancer, providing a convenient and cost-effective treatment option for patients. However, they are also associated with adherence issues which can compromise therapeutic outcomes. This scoping review identifies and summarizes data on adherence to oral hormonal therapy in advanced prostate cancer and discusses associated factors and strategies for improving adherence. Methods: PubMed (inception to 27 January 2022) and conference databases (2020-2021) were searched to identify English language reports of real-world and clinical trial data on adherence to oral hormonal therapy in prostate cancer using the key search terms 'prostate cancer' AND 'adherence' AND 'oral therapy' OR respective aliases. Results: Most adherence outcome data were based on the use of androgen receptor pathway inhibitors in metastatic castration-resistant prostate cancer (mCRPC). Self-reported and observer-reported adherence data were used. The most common observer-reported measure, medication possession ratio, showed that the vast majority of patients were in possession of their medication, although proportion of days covered and persistence rates were considerably lower, raising the question whether patients were consistently receiving their treatment. Study follow-up for adherence was generally around 6 months up to 1 year. Studies also indicate that persistence may drop further with longer follow-up, especially in the non-mCRPC setting, which may be a concern when years of therapy are required. Conclusions: Oral hormonal therapy plays an important role in the treatment of advanced prostate cancer. Data on adherence to oral hormonal therapies in prostate cancer were generally of low quality, with high heterogeneity and inconsistent reporting across studies. Short study follow-up for adherence and focus on medication possession rates may further limit relevance of available data, especially in settings that require long-term treatment. Additional research is required to comprehensively assess adherence.

The Journey of Radiotherapy Dose Escalation in High Risk Prostate Cancer; Conventional Dose Escalation to Stereotactic Body Radiotherapy (SBRT) Boost Treatments.

High risk prostate cancer (HR-PrCa) is a subset of localized PrCa with significant potential for morbidity and mortality associated with disease recurrence and metastasis. Radiotherapy combined with Androgen Deprivation Therapy has been the standard of care for many years in HR-PrCa. In recent years, dose escalation, hypo-fractionation and high precision delivery with immobilization and image-guidance have substantially changed the face of modern PrCa radiotherapy, improving treatment convenience and outcomes. Ultra-hypo-fractionated radiotherapy delivered with high precision in the form of stereotactic body radiation therapy (SBRT) combines delivery of high biologically equivalent dose radiotherapy with the convenience of a shorter treatment schedule, as well as the promise of similar efficacy and reduced toxicity compared to conventional radiotherapy. However, rigorous investigation of SBRT in HR-PrCa remains limited. Here, we review the changes in HR-PrCa radiotherapy through dose escalation, hypo- and ultra-hypo-fractionated radiotherapy boost treatments, and the radiobiological basis of these treatments. We focus on completed and on-going trials in this disease utilizing SBRT as a sole radiation modality or as boost therapy following pelvic radiation.

Acute Toxicity and Quality of Life of Hypofractionated Radiation Therapy for Breast Cancer.

PURPOSE: To assess the acute toxicity and quality of life (QOL) of hypofractionation compared with conventional fractionation for whole breast irradiation (WBI) after breast-conserving surgery. METHODS AND MATERIALS: Women with node-negative breast cancer who had undergone breast-conserving surgery with clear margins were randomly assigned to conventional WBI of 5000 cGy in 25 fractions over 35 days or hypofractionated WBI of 4256 cGy in 16 fractions over 22 days. Acute skin toxicity and QOL were assessed at baseline and 2, 4, 6, and 8 weeks from the start of treatment for a subgroup of patients. QOL was assessed at baseline and 4 weeks posttreatment for all patients. In the acute toxicity substudy, repeated measures modeling was used to investigate treatment by time interactions over the 8-week period for acute toxicity and QOL mean change score. QOL mean change score from baseline to 4 weeks posttreatment was compared for all patients. RESULTS: In the acute toxicity substudy, 161 patients participated. In the main trial, 1152 patients participated. Acute skin toxicity was initially similar between groups but was less with hypofractionation compared with conventional fractionation toward the end of the 8-week period (P < .001). QOL at 6 weeks from the start of treatment was improved with hypofractionation for the skin side effects, breast side effects, fatigue, attractiveness, and convenience domains (all P < .05). In the main trial, hypofractionation resulted in improved overall QOL and QOL attributed to skin side effects, breast side effects, and attractiveness (all P < .01). CONCLUSIONS: Hypofractionated WBI compared with conventional WBI resulted in less acute toxicity and improved QOL. This further supports the benefits of hypofractionation.

Testosterone Breakthrough Rates during Androgen Deprivation Therapy for Castration Sensitive Prostate Cancer.

PURPOSE: Androgen deprivation therapy is an established therapy for castration sensitive prostate cancer and recent studies have observed that patients whose testosterone levels are suppressed below 0.7 nmol/l have improved outcomes. Testosterone breakthrough, or a rise in testosterone above a target threshold after the first month of androgen deprivation therapy, is generally associated with treatment deficiency. The purpose of this review is to summarize breakthrough rate data and explore the relationship to clinical outcomes in patients with castration sensitive prostate cancer receiving androgen deprivation therapy. MATERIALS AND METHODS: Our systematic search identified 45 studies with a total of 52 cohorts representing 6,047 total patients reporting testosterone breakthrough rates or derivative measures above the thresholds of 1.7 nmol/l (51 cohorts, 6,015 patients) or 0.7 nmol/l (15 cohorts, 2,495 patients). RESULTS: Significantly higher weighted mean breakthrough rates were seen for the 0.7 nmol/l threshold compared to 1.7 nmol/l (41.3% vs 6.9%, p <0.0001). A significant association between breakthrough rates and worse clinical outcomes overall was not found, although when larger trials (sample size greater than 100) and higher event rates (greater than 50%) were considered for the lowest threshold, significant associations between breakthrough rates and clinical outcomes were observed. Clinical factors such as administration and monitoring frequency, type of testosterone assay and type of androgen deprivation therapy did not significantly affect breakthrough rates, although nonvalidated assays were associated with a large degree of variability. CONCLUSIONS: Results from our analysis indicate that testosterone breakthroughs likely result in worse clinical outcomes and should be avoided. Moreover, there is a need to standardize assessment of testosterone levels both clinically and in the research context to better inform treatment decisions and improve the reliability and comparability of results across studies.

Cardiovascular Risk in Men with Prostate Cancer: Insights from the RADICAL PC Study.

PURPOSE: We describe the cardiovascular risk profile in a representative cohort of patients with prostate cancer treated with or without androgen deprivation therapy. MATERIALS AND METHODS: We prospectively characterized in detail 2,492 consecutive men (mean age 68 years) with prostate cancer (newly diagnosed or with a plan to prescribe androgen deprivation therapy for the first time) from 16 Canadian sites. Cardiovascular risk was estimated by calculating Framingham risk scores. RESULTS: Most men (92%) had new prostate cancer (intermediate risk 41%, high risk 50%). The highest level of education achieved was primary school in 12%. Most (58%) were current or former smokers, 22% had known cardiovascular disease, 16% diabetes, 45% hypertension, 31% body mass index 30 kg/m2 or greater, 24% low levels of physical activity, mean handgrip strength was 37.3 kg and 69% had a Framingham risk score consistent with high cardiovascular risk. Participants in whom androgen deprivation therapy was planned had higher Framingham risk scores than those not intending to receive androgen deprivation therapy, and this risk was abolished after adjustment for confounders. CONCLUSIONS: Two-thirds of men with prostate cancer are at high cardiovascular risk. There is a positive association between a plan to use androgen deprivation therapy and baseline cardiovascular risk factors. However, this association is explained by confounding factors.

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.

Prostate Cancer Radiotherapy: An Evolving Paradigm.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A urologist referred a 69-year-old man for a radiotherapy opinion regarding a recently diagnosed adenocarcinoma of the prostate. Annual serum prostate-specific antigen (PSA) testing over 7 years demonstrated a rise in PSA from 1.36 ng/mL to 5.8 ng/mL, prompting a transrectal ultrasound that revealed a heterogeneous 37-mL gland containing no visualized hypoechoic nodules. Biopsy disclosed a Gleason score 3+4 (grade group 2) adenocarcinoma of the prostate. The synoptic report stated that six of 14 cores and 17% of the tissue were involved, with the greatest core involvement being 80% at the right apex. Perineural invasion was present without lymphovascular invasion. Disease was present bilaterally at the base, midgland, and apex.His medical history was significant only for treated peptic ulcer disease and he was taking no medication. His International Prostate Symptom Score was six of 35, and he reported being sexually active with good erectile function. There was no family history of prostate cancer. He is retired. Digital rectal examination revealed moderate benign prostatic hypertrophy with no suspicious nodules. A staging computerized tomography (CT) scan of the abdomen and pelvis and a whole-body bone scan ordered by his referring urologist reported no evidence of metastatic disease. The patient had discussed surgical options with his urologist and now wished to consider radiotherapy approaches.

External validation of the ProCaRS nomograms and comparison of existing risk-stratification tools for localized prostate cancer.

INTRODUCTION: The purpose of this study was to perform a direct comparison of several existing risk-stratification tools for localized prostate cancer in terms of their ability to predict for biochemical failure-free survival (BFFS). Two large databases were used and an external validation of two recently developed nomograms on an independent cohort was also performed in this analysis. METHODS: Patients who were treated with external beam radiotherapy (EBRT) and/or brachytherapy for localized prostate cancer were selected from the multi-institutional Genitourinary Radiation Oncologists of Canada (GUROC) Prostate Cancer Risk Stratification (ProCaRS) database (n=7974) and the Centre Hospitalier de l'Université de Montréal (CHUM) validation database (n=2266). The primary outcome was BFFS using the Phoenix definition. Concordance index (C-index) reported from Cox proportional hazards regression using 10-fold cross validation and decision curve analysis (DCA) were used to predict BFFS. RESULTS: C-index identified Cancer of the Prostate Risk Assessment (CAPRA) score and ProCaRS as superior to the historical GUROC and National Comprehensive Cancer Network (NCCN) risk-stratification systems. CAPRA modeled as five and three categories were superior to GUROC and NCCN only for the CHUM database. C-indices for CAPRA score, ProCaRS, GUROC, and NCCN were 0.72, 0.72, 0.71, and 0.72, respectively, for the ProCaRS database, and 0.66, 0.63, 0.57, and 0.60, respectively, for the CHUM database. However, many of these comparisons did not demonstrate a clinically meaningful difference. DCA identified minimal differences across the different risk-stratification systems, with no system emerging with optimal net benefit. External validation of the ProCaRS nomograms yielded favourable calibrations of R2=0.778 (low-dose rate [LDR]-brachytherapy) and R2=0.868 (EBRT). CONCLUSIONS: This study externally validated two ProCaRS nomograms for BFFS that may help clinicians in treatment selection and outcome prediction. A direct comparison between existing risk-stratification tools demonstrated minimal clinically significant differences in discriminative ability between the systems, favouring the CAPRA and ProCaRS systems. The incorporation of novel prognostic variables, such as genomic markers, is needed.

Randomized Trial of a Hypofractionated Radiation Regimen for the Treatment of Localized Prostate Cancer.

Purpose Men with localized prostate cancer often are treated with external radiotherapy (RT) over 8 to 9 weeks. Hypofractionated RT is given over a shorter time with larger doses per treatment than standard RT. We hypothesized that hypofractionation versus conventional fractionation is similar in efficacy without increased toxicity. Patients and Methods We conducted a multicenter randomized noninferiority trial in intermediate-risk prostate cancer (T1 to 2a, Gleason score ≤ 6, and prostate-specific antigen [PSA] 10.1 to 20 ng/mL; T2b to 2c, Gleason ≤ 6, and PSA ≤ 20 ng/mL; or T1 to 2, Gleason = 7, and PSA ≤ 20 ng/mL). Patients were allocated to conventional RT of 78 Gy in 39 fractions over 8 weeks or to hypofractionated RT of 60 Gy in 20 fractions over 4 weeks. Androgen deprivation was not permitted with therapy. The primary outcome was biochemical-clinical failure (BCF) defined by any of the following: PSA failure (nadir + 2), hormonal intervention, clinical local or distant failure, or death as a result of prostate cancer. The noninferiority margin was 7.5% (hazard ratio, < 1.32). Results Median follow-up was 6.0 years. One hundred nine of 608 patients in the hypofractionated arm versus 117 of 598 in the standard arm experienced BCF. Most of the events were PSA failures. The 5-year BCF disease-free survival was 85% in both arms (hazard ratio [short v standard], 0.96; 90% CI, 0.77 to 1.2). Ten deaths as a result of prostate cancer occurred in the short arm and 12 in the standard arm. No significant differences were detected between arms for grade ≥ 3 late genitourinary and GI toxicity. Conclusion The hypofractionated RT regimen used in this trial was not inferior to conventional RT and was not associated with increased late toxicity. Hypofractionated RT is more convenient for patients and should be considered for intermediate-risk prostate cancer.

Acute and late urinary toxicity following radiation in men with an intact prostate gland or after a radical prostatectomy: A secondary analysis of RTOG 94-08 and 96-01.

INTRODUCTION: To estimate the contribution of the prostate gland and prostatic urethral inflammation to urinary symptoms after radiation therapy for prostate cancer, we performed a secondary analysis of urinary toxicity after primary radiation to an intact prostate vs. postprostatectomy radiation to the prostatic fossa in protocols RTOG 94-08 and 96-01, respectively. MATERIALS AND METHODS: Patients randomized to the radiation-alone arms (without hormone therapy) of the 2 trials were evaluated, including 104 men receiving primary prostate radiation to 68.4Gy on RTOG 94-08 and 371 men receiving 64.8Gy to the prostatic fossa on RTOG 96-01. Acute and late urinary toxicity were scored prospectively by RTOG scales. Chi-square test/logistic regression and cumulative incidence approach/Fine-Gray regression model were used for analyses of acute and late toxicity, respectively. RESULTS: Grade≥2 acute urinary toxicity was significantly higher after primary prostatic radiation compared with postprostatectomy radiation (30.8% vs. 14.0%; P<0.001), but acute grade≥3 toxicity did not differ (3.8% vs. 2.7%; P = 0.54). After adjusting for age, primary radiation resulted in significantly higher grade≥2 acute urinary toxicity (odds ratio = 3.72; 95% CI: 1.65-8.37; P = 0.02). With median follow-up of 7.1 years, late urinary toxicity was not significantly different with primary vs. postprostatectomy radiation (5-year grade≥2: 16.7% vs. 18.3%; P = 0.65; grade≥3: 6.0% vs. 3.3%; P = 0.24). CONCLUSIONS: Primary radiation to an intact prostate resulted in higher grade≥2 acute urinary toxicity than radiation to the prostatic fossa, with no difference in late urinary toxicity. Thus, a proportion of acute urinary toxicity in men with an intact prostate may be attributable to inflammation of the prostatic gland or urethra.

The Technique, Resources and Costs of Stereotactic Body Radiotherapy of Prostate Cancer: A Comparison of Dose Regimens and Delivery Systems.

Robotic system has been used for stereotactic body radiotherapy (SBRT) of prostate cancer. Arc-based and fixed-gantry systems are used for hypofractionated regimens (10-20 fractions) and the standard regimen (39 fractions); they may also be used to deliver SBRT. Studies are currently underway to compare efficacy and safety of these systems and regimens. Thus, we describe the technique and required resources for the provision of robotic SBRT in relation to the standard regimen and other systems to guide investment decisions. Using administrative data of resource volumes and unit prices, we computed the cost per patient, cost per cure and cost per quality adjusted life year (QALY) of four regimens (5, 12, 20 and 39 fractions) and three delivery systems (robotic, arc-based and fixed-gantry) from a payer's perspective. We performed sensitivity analyses to examine the effects of daily hours of operation and in-room treatment delivery times on cost per patient. In addition, we estimated the budget impact when a robotic system is preferred over an arc-based or fixed-gantry system. Costs of SBRT were $6333/patient (robotic), $4368/patient (arc-based) and $4443/patient (fixed-gantry). When daily hours of operation were varied, the cost of robotic SBRT varied from $9324/patient (2 hours daily) to $5250/patient (10 hours daily). This was comparable to the costs of 39 fraction standard regimen which were $5935/patient (arc-based) and $7992/ patient (fixed-gantry). In settings of moderate to high patient volume, robotic SBRT is cost effective compared to the standard regimen. If SBRT can be delivered with equivalent efficacy and safety, the arc-based system would be the most cost effective system.

Inhibition of carbonic anhydrase IX (CA9) sensitizes renal cell carcinoma to ionizing radiation.

While normal kidneys are relatively sensitive to ionizing radiation (IR), renal cell carcinoma (RCC) is considered radioresistant. Carbonic anhydrase IX (CA9), an enzyme that maintains intracellular pH by carbon dioxide dissolution, is upregulated in the majority of RCC, but not in normal kidneys. Since regulation of intracellular pH may enhance radiation effects, we hypothesized that inhibition of CA9 may radiosensitize RCC. Clonogenic survival assay of human clear cell RCC 786-O and murine RCC RAG cells in the presence of a pharmacological CA9 inhibitor or with shRNA-mediated knockdown of CA9 was performed to investigate the response to IR in vitro (single dose or fractionated) and in vivo. Extracellular pH changes were measured in vitro. Treatment with AEBS [4-(2-aminoethyl)benzene sulfonamide], a sulfonamide, was used as a pharmacological inhibitor of the enzymatic activity of CA9. Nude mice bearing subcutaneous xenografts of 786-O cells stably expressing CA9 shRNA or scrambled control were irradiated (6 Gy). Tumor growth was followed longitudinally in the 786-O-bearing mice receiving AEBS (50-200 µg/ml drinking water) or control (vehicle only) which were irradiated (6 Gy) and compared with mice receiving either IR or AEBS alone. In vitro inhibition of CA9 activity or expression significantly sensitized RCC cells to the effects of IR (p<0.05), an effect even more significant when hypofractionated IR was applied. In vivo irradiated xenografts from RCC cells transfected with CA9 shRNA were significantly smaller compared to irradiated xenografts from the scrambled shRNA controls (p<0.05). RCC xenografts from mice treated with AEBS in combination with IR grew significantly slower than all controls (p<0.05). Inhibition of CA9 expression or activity resulted in radiation sensitization of RCC in a preclinical mouse model.

Development of ProCaRS Clinical Nomograms for Biochemical Failure-free Survival Following Either Low-Dose Rate Brachytherapy or Conventionally Fractionated External Beam Radiation Therapy for Localized Prostate Cancer.

PURPOSE: Although several clinical nomograms predictive of biochemical failure-free survival (BFFS) for localized prostate cancer exist in the medical literature, making valid comparisons can be challenging due to variable definitions of biochemical failure, the disparate distribution of prognostic factors, and received treatments in patient populations. The aim of this investigation was to develop and validate clinically-based nomograms for 5-year BFFS using the ASTRO II "Phoenix" definition for two patient cohorts receiving low-dose rate (LDR) brachytherapy or conventionally fractionated external beam radiation therapy (EBRT) from a large Canadian multi-institutional database. METHODS AND MATERIALS: Patients were selected from the GUROC (Genitourinary Radiation Oncologists of Canada) Prostate Cancer Risk Stratification (ProCaRS) database if they received (1) LDR brachytherapy ≥ 144 Gy (n=4208) or (2) EBRT ≥ 70 Gy  (n=822). Multivariable Cox regression analysis for BFFS was performed separately for each cohort and used to generate clinical nomograms predictive of 5-year BFFS. Nomograms were validated using calibration plots of nomogram predicted probability versus observed probability via Kaplan-Meier estimates. RESULTS: Patients receiving LDR brachytherapy had a mean age of 64 ± 7 years, a mean baseline PSA of 6.3 ± 3.0 ng/mL, 75% had a Gleason 6, and 15% had a Gleason 7, whereas patients receiving EBRT had a mean age of 70 ± 6 years, a mean baseline PSA of 11.6 ± 10.7 ng/mL, 30% had a Gleason 6, 55% had a Gleason 7, and 14% had a Gleason 8-10. Nomograms for 5-year BFFS included age, use and duration of androgen deprivation therapy (ADT), baseline PSA, T stage, and Gleason score for LDR brachytherapy and an ADT (months), baseline PSA, Gleason score, and biological effective dose (Gy) for EBRT. CONCLUSIONS: Clinical nomograms examining 5-year BFFS were developed for patients receiving either LDR brachytherapy or conventionally fractionated EBRT and may assist clinicians in predicting an outcome. Future work should be directed at examining the role of additional prognostic factors, comorbidities, and toxicity in predicting survival outcomes.

Brachytherapy improves biochemical failure-free survival in low- and intermediate-risk prostate cancer compared with conventionally fractionated external beam radiation therapy: a propensity score matched analysis.

PURPOSE: To compare, in a retrospective study, biochemical failure-free survival (bFFS) and overall survival (OS) in low-risk and intermediate-risk prostate cancer patients who received brachytherapy (BT) (either low-dose-rate brachytherapy [LDR-BT] or high-dose-rate brachytherapy with external beam radiation therapy [HDR-BT+EBRT]) versus external beam radiation therapy (EBRT) alone. METHODS AND MATERIALS: Patient data were obtained from the ProCaRS database, which contains 7974 prostate cancer patients treated with primary radiation therapy at four Canadian cancer institutions from 1994 to 2010. Propensity score matching was used to obtain the following 3 matched cohorts with balanced baseline prognostic factors: (1) low-risk LDR-BT versus EBRT; (2) intermediate-risk LDR-BT versus EBRT; and (3) intermediate-risk HDR-BT+EBRT versus EBRT. Kaplan-Meier survival analysis was performed to compare differences in bFFS (primary endpoint) and OS in the 3 matched groups. RESULTS: Propensity score matching created acceptable balance in the baseline prognostic factors in all matches. Final matches included 2 1:1 matches in the intermediate-risk cohorts, LDR-BT versus EBRT (total n=254) and HDR-BT+EBRT versus EBRT (total n=388), and one 4:1 match in the low-risk cohort (LDR-BT:EBRT, total n=400). Median follow-up ranged from 2.7 to 7.3 years for the 3 matched cohorts. Kaplan-Meier survival analysis showed that all BT treatment options were associated with statistically significant improvements in bFFS when compared with EBRT in all cohorts (intermediate-risk EBRT vs LDR-BT hazard ratio [HR] 4.58, P=.001; intermediate-risk EBRT vs HDR-BT+EBRT HR 2.08, P=.007; low-risk EBRT vs LDR-BT HR 2.90, P=.004). No significant difference in OS was found in all comparisons (intermediate-risk EBRT vs LDR-BT HR 1.27, P=.687; intermediate-risk EBRT vs HDR-BT+EBRT HR 1.55, P=.470; low-risk LDR-BT vs EBRT HR 1.41, P=.500). CONCLUSIONS: Propensity score matched analysis showed that BT options led to statistically significant improvements in bFFS in low- and intermediate-risk prostate cancer patient populations.

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.