An Updated Analysis of the Survival Endpoints of ASCENDE-RT.

PURPOSE: Using the primary endpoint of time to biochemical progression (TTP), Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (ASCENDE-RT) randomized National Comprehensive Cancer Network patients with intermediate and high-risk prostate cancer to low-dose-rate brachytherapy boost (LDR-PB) or dose-escalated external beam boost (DE-EBRT). Randomization to the LDR-PB arm resulted in a 2-fold reduction in biochemical progression compared with the DE-EBRT group at a median follow-up of 6.5 years (P < .001). Herein, the primary endpoint and secondary survival endpoints of the ASCENDE-RT trial are updated at a 10-year median follow-up. METHODS: Patients were randomly assigned to either the LDR-PB or the DE-EBRT arm (1:1). All patients received 1 year of androgen deprivation therapy and 46 Gy in 23 fractions of pelvic RT. Patients in the DE-EBRT arm received an additional 32 Gy in 16 fractions, and those in the LDR-PB arm received an 125I implant prescribed to a minimum peripheral dose of 115 Gy. Two hundred patients were randomized to the DE-EBRT arm and 198 to the LDR-PB arm. RESULTS: The 10-year Kaplan-Meier TTP estimate was 85% ± 5% for LDR-PB compared with 67% ± 7% for DE-EBRT (log rank P < .001). Ten-year time to distant metastasis (DM) was 88% ± 5% for the LDR-PB arm and 86% ± 6% for the DE-EBRT arm (P = .56). There were 117 (29%) deaths. Ten-year overall survival (OS) estimates were 80% ± 6% for the LDR-PB arm and 75% ± 7% for the DE-EBRT arm (P = .51). There were 30 (8%) patients who died of prostate cancer: 12 (6%) in the LDR-PB arm, including 2 treatment-related deaths, and 18 (9%) in the DE-EBRT arm. CONCLUSIONS: Men randomized to the LDR-PB boost arm of the ASCENDE-RT trial continue to experience a large advantage in TTP compared with those randomized to the DE-EBRT arm. ASCENDE-RT was not powered to detect differences in its secondary survival endpoints (OS, DM, and time to prostate cancer-specific death) and none are apparent.

ACCORD: A Multicentre, Seamless, Phase 2 Adaptive Randomisation Platform Study to Assess the Efficacy and Safety of Multiple Candidate Agents for the Treatment of COVID-19 in Hospitalised Patients: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Stage 1: To evaluate the safety and efficacy of candidate agents as add-on therapies to standard of care (SoC) in patients hospitalised with COVID-19 in a screening stage. Stage 2: To confirm the efficacy of candidate agents selected on the basis of evidence from Stage 1 in patients hospitalised with COVID-19 in an expansion stage. TRIAL DESIGN: ACCORD is a seamless, Phase 2, adaptive, randomised controlled platform study, designed to rapidly test candidate agents in the treatment of COVID-19. Designed as a master protocol with each candidate agent being included via its own sub-protocol, initially randomising equally between each candidate and a single contemporaneous SoC arm (which can adapt into 2:1). Candidate agents currently include bemcentinib, MEDI3506, acalabrutinib, zilucoplan and nebulised heparin. For each candidate a total of 60 patients will be recruited in Stage 1. If Stage 1 provides evidence of efficacy and acceptable safety the candidate will enter Stage 2 where a total of approximately 126 patients will be recruited into each study arm sub-protocol. Enrollees and outcomes will not be shared across the Stages; the endpoint, analysis and sample size for Stage 2 may be adjusted based on evidence from Stage 1. Additional arms may be added as new potential candidate agents are identified via candidate agent specific sub-protocols. PARTICIPANTS: The study will include hospitalised adult patients (≥18 years) with confirmed SARS-CoV-2 infection, the virus that causes COVID-19, that clinically meet Grades 3 (hospitalised - mild disease, no oxygen therapy), Grades 4 (hospitalised, oxygen by mask or nasal prongs) and 5 (hospitalised, non-invasive ventilation or high flow oxygen) of the WHO Working Group on the Clinical Characteristics of COVID-19 9-point category ordinal scale. Participants will be recruited from England, Northern Ireland, Wales and Scotland. INTERVENTION AND COMPARATOR: Comparator is current standard of care (SoC) for the treatment of COVID-19. Current candidate experimental arms include bemcentinib, MEDI3506, acalabrutinib, zilucoplan and nebulised heparin with others to be added over time. Bemcentinib could potentially reduce viral infection and blocks SARS-CoV-2 spike protein; MEDI3506 is a clinic-ready anti-IL-33 monoclonal antibody with the potential to treat respiratory failure caused by COVID; acalabrutinib is a BTK inhibitor which is anti-viral and anti-inflammatory; zilucoplan is a complement C5 inhibitor which may block the severe inflammatory response in COVID-19 and; nebulised heparin has been shown to bind with the spike protein. ACCORD is linked with the UK national COVID therapeutics task force to help prioritise candidate agents. MAIN OUTCOMES: Time to sustained clinical improvement of at least 2 points (from randomisation) on the WHO 9-point category ordinal scale, live discharge from the hospital, or considered fit for discharge (a score of 0, 1, or 2 on the ordinal scale), whichever comes first, by Day 29 (this will also define the "responder" for the response rate analyses). RANDOMISATION: An electronic randomization will be performed by Cenduit using Interactive Response Technology (IRT). Randomisation will be stratified by baseline severity grade. Randomisation will proceed with an equal allocation to each arm and a contemporaneous SoC arm (e.g. 1:1 if control and 1 experimental arm; 1:1:1 if two experimental candidate arms etc) but will be reviewed as the trial progresses and may be changed to 2:1 in favour of the candidate agents. BLINDING (MASKING): The trial is open label and no blinding is currently planned in the study. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): This will be in the order of 60 patients per candidate agent for Stage 1, and 126 patients for Stage 2. However, sample size re-estimation may be considered after Stage 1. It is estimated that up to 1800 patients will participate in the overall study. TRIAL STATUS: Master protocol version ACCORD-2-001 - Master Protocol (Amendment 1) 22nd April 2020, the trial has full regulatory approval and recruitment is ongoing in the bemcentinib (first patient recruited 6/5/2020), MEDI3506 (first patient recruited 19/5/2020), acalabrutinib (first patient recruited 20/5/2020) and zilucoplan (first patient recruited 19/5/2020) candidates (and SoC). The recruitment dates of each arm will vary between candidate agents as they are added or dropped from the trial, but will have recruited and reported within a year. TRIAL REGISTRATION: EudraCT 2020-001736-95 , registered 28th April 2020. FULL PROTOCOL: The full protocol (Master Protocol with each of the candidate sub-protocols) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Pain response in a population-based study of radium-223 (Ra223) for metastatic castration-resistant prostate cancer.

INTRODUCTION: Clinical trials have shown that radium-223 (Ra223) can prolong survival and improve quality of life in patients with metastatic castration-resistant prostate cancer (mCRPC). The objectives of this study were to evaluate pain responses with Ra223 at a population-based level and to determine if there is an association between pain response and alkaline phosphatase (ALP) response. METHODS: All patients from the Vancouver and Kelowna Cancer Centers (CC) in British Columbia who were treated with Ra223 between June 2015 and December 2016 were identified. Patients completed the Brief Pain Inventory (BPI) just prior to each Ra223 injection. Pain response was defined as a two or more point improvement in worst pain relative to baseline, without an increase in pain medication level. ALP was determined at each visit, with a response threshold defined as a 30% decrease from baseline, consistent with the definition of response used in the ALSYMPCA trial. RESULTS: A total of 65 patients in Vancouver and Kelowna CC received Ra223 during the study period and 56 patients had at least one BPI record, of which 44 (79%) patients were assessable for change in worst pain. Of the assessable patients, 23 (52%, 95% confidence interval [CI] 38-67) had a pain response, although the use of concurrent external beam radiotherapy was a confounder in four cases. Of the 44 patients assessable for change in worst pain, 59% had ALP responses greater than 30%. An ALP response was seen in 56% of pain-responders vs. 43% of non-pain-responders. There was no association between pain response and ALP response (Phi =-0.05; p=0.77). CONCLUSIONS: Ra223 administration was associated with a meaningful pain response rate in this cohort. There was no correlation between pain response and ALP response.

The impact of comorbidities on the benefits of prolonged androgen ablation in patients with T3-4 prostate cancer treated with external beam radiation therapy.

PURPOSE: To determine whether the survival benefit associated with prolonged androgen deprivation therapy (ADT) and radiotherapy (EBRT) varies with baseline estimates of overall survival in cT3-4 prostate cancer patients (PCa). METHODS AND MATERIALS: In 1997, the BC Cancer Agency adopted as standard a policy of prolonged ADT (>18months) with EBRT for locally advanced PCa. Two cohorts of cT3-T4 PCa treated with EBRT were selected: 1993-1995 (early: N=725) and 1999-2001 (late: N=584). Duration of ADT and baseline prognostic factors (age, clinical stage, grade, presenting PSA, and Charlson index (CCI)) were abstracted from charts. Estimates of 10-year (E10) survival using an age-adjusted CCI were calculated and patients were grouped into low (<60%), medium (60-90%) and high (>90%) E10. In each E10 group, actual overall survivals were compared by era using log rank test. RESULTS: There were 318 low, 544 medium, and 447 high E10 patients with median follow-up of 11.1years. Gleason grade and T stage were not statistically different between E10 groups. As expected, median age and baseline CCI were higher in lower E10 groups (p<0.0001). Overall survival was higher in the late era, but varied with E10 group: low (43% vs. 49%, p=0.54), medium (55% vs. 64%, p=0.02) and high (66% vs. 77%, p=0.01). CONCLUSION: The policy of prolonged ADT with EBRT provides a survival benefit that varies with baseline risk of death from other causes. Absolute benefit from ADT is largest in those with medium or high E10.

ASCENDE-RT: An Analysis of Health-Related Quality of Life for a Randomized Trial Comparing Low-Dose-Rate Brachytherapy Boost With Dose-Escalated External Beam Boost for High- and Intermediate-Risk Prostate Cancer.

PURPOSE: To report the patient-reported health-related quality of life (HR-QoL) outcomes for a multicenter randomized trial evaluating the safety and efficacy of 2 different techniques for dose escalation. METHODS AND MATERIALS: A total of 357 men with intermediate- and high-risk prostate cancer were stratified by risk group and randomized (1:1) to either a dose-escalated external beam (DE-EBRT) boost (n=177) or a low-dose-rate prostate brachytherapy (LDR-PB) boost (n=180) as part of combined modality therapy. The HR-QoL was assessed using the SF36v2 questionnaire, with additional scales for urinary, bowel, and sexual function. Date of starting androgen deprivation therapy was considered time zero, the median follow-up of 6 years. Scales were scored from 0 to 100; a decline in a mean score ≥10 compared with baseline was considered a clinically significant decline. This was an intent-to-treat analysis. RESULTS: Mean domain scores at baseline were well balanced between the 2 treatment arms. A clinically significant decline in mean scores in both the arms compared with baseline was noted for role physical (DE-EBRT [-11.4] and LDR-PB [-15.3]) and sexual function scale (DE-EBRT [-15.1] and LDR-PB [-19.2]). There was a significantly larger drop in mean scores in the LDR-PB group compared with the DE-EBRT group for physical function (-15.3 vs -6.9; P=.03), urinary function (-3.6 vs -0.5; P=.04). CONCLUSION: At 6 years' follow up, there were no significant differences in mean scores in 9 of 11 scales compared with baseline in both arms. A clinically significant decline in mean scores was noted in both arms for role physical and sexual function scales. There was a statistically significant decline in physical function and urinary function scales in the LDR-PB arm compared with the DE-EBRT arm.

ASCENDE-RT: An Analysis of Treatment-Related Morbidity for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost with a Dose-Escalated External Beam Boost for High- and Intermediate-Risk Prostate Cancer.

PURPOSE: To report the genitourinary (GU) and gastrointestinal (GI) morbidity and erectile dysfunction in a randomized trial comparing 2 methods of dose escalation for high- and intermediate-risk prostate cancer. METHODS AND MATERIALS: ASCENDE-RT (Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy) enrolled 398 men, median age 68 years, who were then randomized to either a standard arm that included 12 months of androgen deprivation therapy and pelvic irradiation to 46 Gy followed by a dose-escalated external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost. At clinic visits, investigators recorded GU and GI morbidity and information on urinary continence, catheter use, and erectile function. Exclusion of 15 who received nonprotocol treatment and correction of 14 crossover events left 195 men who actually received a DE-EBRT boost and 188, an LDR-PB boost. Median follow-up was 6.5 years. RESULTS: The LDR-PB boost increased the risk of needing temporary catheterization and/or requiring incontinence pads. At 5 years the cumulative incidence of grade 3 GU events was 18.4% for LDR-PB, versus 5.2% for DE-EBRT (P<.001). Compared with the cumulative incidence, the 5-year prevalence of grade 3 GU morbidity was substantially lower for both arms (8.6% vs 2.2%, P=.058). The 5-year cumulative incidence of grade 3 GI events was 8.1% for LDR-PB, versus 3.2% for DE-EBRT (P=.124). The 5-year prevalence of grade 3 GI toxicity was lower than the cumulative incidence for both arms (1.0% vs 2.2%, respectively). Among men reporting adequate baseline erections, 45% of LDR-PB patients reported similar erectile function at 5 years, versus 37% after DE-EBRT (P=.30). CONCLUSIONS: The incidence of acute and late GU morbidity was higher after LDR-PB boost, and there was a nonsignificant trend for worse GI morbidity. No differences in the frequency of erectile dysfunction were observed.

Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An Analysis of Survival Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost for High- and Intermediate-risk Prostate Cancer.

PURPOSE: To report the primary endpoint of biochemical progression-free survival (b-PFS) and secondary survival endpoints from ASCENDE-RT, a randomized trial comparing 2 methods of dose escalation for intermediate- and high-risk prostate cancer. METHODS AND MATERIALS: ASCENDE-RT enrolled 398 men, with a median age of 68 years; 69% (n=276) had high-risk disease. After stratification by risk group, the subjects were randomized to a standard arm with 12 months of androgen deprivation therapy, pelvic irradiation to 46 Gy, followed by a dose-escalated external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost. Of the 398 trial subjects, 200 were assigned to DE-EBRT boost and 198 to LDR-PB boost. The median follow-up was 6.5 years. RESULTS: In an intent-to-treat analysis, men randomized to DE-EBRT were twice as likely to experience biochemical failure (multivariable analysis [MVA] hazard ratio [HR] 2.04; P=.004). The 5-, 7-, and 9-year Kaplan-Meier b-PFS estimates were 89%, 86%, and 83% for the LDR-PB boost versus 84%, 75%, and 62% for the DE-EBRT boost (log-rank P<.001). The LDR-PB boost benefited both intermediate- and high-risk patients. Because the b-PFS curves for the treatment arms diverge sharply after 4 years, the relative advantage of the LDR-PB should increase with longer follow-up. On MVA, the only variables correlated with reduced overall survival were age (MVA HR 1.06/y; P=.004) and biochemical failure (MVA HR 6.30; P<.001). Although biochemical failure was associated with increased mortality and randomization to DE-EBRT doubled the rate of biochemical failure, no significant overall survival difference was observed between the treatment arms (MVA HR 1.13; P=.62). CONCLUSIONS: Compared with 78 Gy EBRT, men randomized to the LDR-PB boost were twice as likely to be free of biochemical failure at a median follow-up of 6.5 years.

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.).

Spiritual care in a multicultural oncology environment.

PURPOSE OF REVIEW: Increasingly, oncology is practiced within multicultural environments. All aspects of care, including spiritual care should be delivered to patients with cancer in a culturally sensitive manner. In this article, we discuss the influence of culture on patients with cancer throughout the disease process by highlighting relevant reports in the literature. RECENT FINDINGS: Most articles focussing on culture and oncology are single-author or single-institution narrative reports pertaining to experiences with an individual racial, ethnic, religious or minority patient group. The majority of articles are found within the palliative care and nursing literature. SUMMARY: Health-related values vary widely across cultures, and the experience of spiritual care in oncology differs greatly across cultural groups. Although culture is generally recognized as an important health determinant that impacts the experience of care, the extent of different cultural influences is not well understood due to a paucity of relevant data, and reports on resources and educational strategies to optimize culturally competent spiritual care are similarly lacking.

Radiation oncology in undergraduate medical education: a literature review.

PURPOSE: To review the published literature pertaining to radiation oncology in undergraduate medical education. METHODS AND MATERIALS: Ovid MEDLINE, Ovid MEDLINE Daily Update and EMBASE databases were searched for the 11-year period of January 1, 1998, through the last week of March 2009. A medical librarian used an extensive list of indexed subject headings and text words. RESULTS: The search returned 640 article references, but only seven contained significant information pertaining to teaching radiation oncology to medical undergraduates. One article described a comprehensive oncology curriculum including recommended radiation oncology teaching objectives and sample student evaluations, two described integrating radiation oncology teaching into a radiology rotation, two described multidisciplinary anatomy-based courses intended to reinforce principles of tumor biology and radiotherapy planning, one described an exercise designed to test clinical reasoning skills within radiation oncology cases, and one described a Web-based curriculum involving oncologic physics. CONCLUSIONS: To the authors' knowledge, this is the first review of the literature pertaining to teaching radiation oncology to medical undergraduates, and it demonstrates the paucity of published work in this area of medical education. Teaching radiation oncology should begin early in the undergraduate process, should be mandatory for all students, and should impart knowledge relevant to future general practitioners rather than detailed information relevant only to oncologists. Educators should make use of available model curricula and should integrate radiation oncology teaching into existing curricula or construct stand-alone oncology rotations where the principles of radiation oncology can be conveyed. Assessments of student knowledge and curriculum effectiveness are critical.

A phase II trial of a soy beverage for subjects without clinical disease with rising prostate-specific antigen after radical radiation for prostate cancer.

Our objective was to evaluate the tolerability and effect of a daily soy beverage in prostate cancer patients with biochemical failure after radiotherapy. Patients with rising prostate-specific antigen (PSA) after radical radiation for prostate cancer were instructed to consume 500 ml of soy beverage daily for 6 mo. Tolerability of the soy beverage and compliance were assessed. PSA doubling times before and after the consumption of soy were compared. Thirty-four subjects were enrolled; 5 withdrew before 1 mo of soy for reasons unrelated to soy consumption. All remaining 29 subjects were included in the analysis. Mean consumption of the assigned soy beverage was 93%. Mild gastrointestinal upset (38%) not affecting soy consumption was the commonest side effect. PSA showed a declining trend in 4 patients (13.8%), and there was a > 100% prolongation of PSA doubling time in 8 patients (27.6%). However, PSA doubling time also showed a 50% or more shortening in 5 patients (17.2%). In our cohort of North American subjects, 6 mo of a daily soy beverage was well tolerated and was associated with a declining trend or more than 2 times prolongation of PSA doubling time in 41% of subjects. Confirmatory studies are warranted.

Implementation of osteoporosis screening guidelines in prostate cancer patients on androgen ablation.

Androgen ablation (AA) therapy is one of the modalities used to treat prostate cancer. It is well known that AA therapy increases the risk of osteoporosis and fractures. In 2004, the British Columbia Cancer Agency published guidelines regarding bone health in these patients. A key recommendation was to arrange for bone mineral density (BMD) testing if AA was to be used for 6 mo or longer. Our objective was to evaluate how well these guidelines were implemented by reviewing the number of BMDs performed in patients who had been treated at one of the 4 cancer centers in British Columbia. We found that the overall number of BMDs documented after the implementation of the guidelines was significantly greater than the number documented before (25% vs 7.5%, p value < 0.0001). There appeared to be regional differences in implementation, with the greatest effect seen at the Vancouver center, which serves as the chief academic center for the province. The greater effect of guidelines at this center suggests a need for more effective dissemination peripherally. The care gap remaining at even the most impacted center indicates a need for greater efforts to both implement guidelines and monitor their implementation over time.

Inequities in Access: How Utilization of Palliative Radiation Therapy in British Columbia Varies with Geography.

PURPOSE: Referral and utilization rates are important measures of the quality of service offered by hospitals and clinics, specifically in regard to access to appropriate care. This study measured referral rates and utilization rates for palliative radiation therapy (PRT) for the different health authorities in British Columbia (BC), Canada, to establish areas where there were variations in access. METHODS AND MATERIALS: Incident data was taken from the British Columbia Cancer registry between 1986 and 1999. Radiation therapy (RT) data were extracted between 1986 and 2005. The extra years were included to allow time for any disease progression that may have occurred. Referral rates were defined as the percentage of incident cases that had a consultation at the British Columbia Cancer Agency. The PRT utilization rate was defined as the percentage of incident cases receiving at least one course of palliative radiation therapy. Data were analysed for each of the 16 Health Service Delivery Areas in BC. RESULTS: Significant geographical variations in both referral rates and utilization rates were identified. Generally, both referral rates and utilization rates were lower in areas where there is limited or difficult access to a cancer centre. After building a cancer centre in the Interior region of BC, both referral and utilization rates increased. INTERPRETATION: Utilization of palliative radiation varies depending on where people live. Access to RT is lower in remote geographical areas, implying a barrier to essential health care services. This seems to be related to lower referral rates in those areas.

How gender, age, and geography influence the utilization of radiation therapy in the management of malignant melanoma.

PURPOSE: Comparing radiation therapy utilization rates (RTUR) to those predicted by best evidence is a useful measure of the equity and accessibility of service delivery. In this study the RTUR for melanoma was established for British Columbia, Canada, and compared with the rate suggested by the evidence. Demographic variables, specifically age, gender, and geography that influenced the RTUR were examined with a view to identifying methods of improving underutilization. METHODS AND MATERIALS: The RTUR in the management of malignant melanoma was taken from British Columbia Cancer registry data for 1986 to 1998. Variations in utilization based on age, gender, health authority, stage of disease, and referral patterns were analyzed. RESULTS: An RTUR of 11% was identified. This was consistent over time. Referral rates decreased between 1986 and 1998. RT is used mostly for later stage disease. Males were more likely to receive RT than females, related to later stage of disease in men. Referral rates decreased, but RTUR for referred cases increased, in health authorities that did not have a cancer center. CONCLUSIONS: Use of RT is influenced by age and by stage of disease. Overall RTUR in British Columbia is lower than suggested by best evidence. Referral patterns are influenced by geography. RTUR was higher in males, consistent with a different pattern of disease in males compared with females.

Relationship between delay in radiotherapy and biochemical control in prostate cancer.

PURPOSE: The aim of this study was to investigate whether a delay in radiotherapy is associated with a poorer biochemical control for prostate cancer. METHODS: The time to treatment (TTT) from diagnosis of prostate cancer to radiotherapy was analyzed with respect to prostate-specific antigen (PSA) control in 1024 hormone-naive patients. The Kaplan-Meier PSA control curves for patients with TTT less than the median were compared with those for patients with TTT greater than the median in 3 predefined risk groups. Statistical significant differences in PSA control were further analyzed using Cox multivariate analysis with pretreatment PSA, Gleason score, T stage, and radiotherapy dose as covariates. RESULTS: The median TTT and median follow-up are 3.7 months and 49 months respectively. Patients with a longer TTT have a statistically significant better PSA control than patients with a shorter TTT if they have intermediate- or high-risk disease. However in multivariate analysis TTT was not found to be significant in predicting PSA control, with pretreatment PSA and Gleason score emerging as highly significant in predicting PSA failure in both intermediate- and high-risk disease. CONCLUSION: In this study in prostate cancer patients in British Columbia, there was no evidence that a longer time interval between diagnosis and radiotherapy was associated with poorer PSA control.

EQUAL-quant: an international external quality assessment scheme for real-time PCR.

BACKGROUND: Quantitative gene expression analysis by real-time PCR is important in several diagnostic areas, such as the detection of minimum residual disease in leukemia and the prognostic assessment of cancer patients. To address quality assurance in this technically challenging area, the European Union (EU) has funded the EQUAL project to develop methodologic external quality assessment (EQA) relevant to diagnostic and research laboratories among the EU member states. We report here the results of the EQUAL-quant program, which assesses standards in the use of TaqMan probes, one of the most widely used assays in the implementation of real-time PCR. METHODS: The EQUAL-quant reagent set was developed to assess the technical execution of a standard TaqMan assay, including RNA extraction, reverse transcription, and real-time PCR quantification of target DNA copy number. RESULTS: The multidisciplinary EQA scheme included 137 participating laboratories from 29 countries. We demonstrated significant differences in performance among laboratories, with 20% of laboratories reporting at least one result lacking in precision and/or accuracy according to the statistical procedures described. No differences in performance were observed for the >10 different testing platforms used by the study participants. CONCLUSIONS: This EQA scheme demonstrated both the requirement and demand for external assessment of technical standards in real-time PCR. The reagent design and the statistical tools developed within this project will provide a benchmark for defining acceptable working standards in this emerging technology.

Hemoglobin levels do not predict biochemical outcome for localized prostate cancer treated with neoadjuvant androgen-suppression therapy and external-beam radiotherapy.

PURPOSE: To investigate whether hemoglobin (Hb) levels affect outcome in men with localized prostate adenocarcinoma (LPA) treated with neoadjuvant androgen-suppression therapy (NAST) and external-beam radiotherapy (EBRT). METHODS AND MATERIALS: A total of 563 men with LPA treated with NAST (median: 5.3 months) and EBRT who had Hb levels during treatment were retrospectively reviewed. Patient, tumor, and treatment variables, including the following Hb variables, were subjected to univariate and multivariable analyses to identify factors that predict biochemical control (bNED) and overall survival (OS): pre-EBRT Hb, Hb nadir during EBRT, and change in Hb from pre-EBRT to nadir during EBRT. RESULTS: Median PSA follow-up was 4.25 years. Forty-nine percent of men were anemic during EBRT, with a median Hb of 13.4 g/dL, and 68% experienced a decline in Hb from pre-EBRT to during EBRT of median 0.6 g/dL. Five-year Nadir+2 bNED and OS rates were similar for anemic and nonanemic patients during EBRT. High percent-positive biopsies, PSA and Gleason score, and use of AA monotherapy predicted worse bNED. High stage and age predicted worse OS. Hb variables were not predictive of bNED or OS. CONCLUSIONS: Anemia is a common side effect of NAST and is usually mild. Hb levels, however, do not predict biochemical control or survival.

GU radiation oncologists consensus on bone loss from androgen deprivation.

The majority of GU radiation oncologists in Canada attended a consensus meeting in November 2004. The topic of osteoporosis in men receiving androgen deprivation therapy (ADT) for prostate cancer was identified as a key theme. A chaired session with keynote speakers and review of the evidence took place followed by open debate. Participants were provided with background information. Osteoporosis was defined as a T-score < or = -2.5, but the importance of risk factors and clinical findings is noted. Dual DEXA is the current standard for assessment of bone density and relates well to fracture risk. The lifetime risk of fracture is 13% for men over the age of 50 years even without the influence of ADT. Lifestyle, dietary and supplementation advice are provided both to prevent and to manage osteoporosis. The role for prophylactic bisphosphonate therapy in men on ADT without osteoporosis has not been established. Follow-up DEXA scans are required to monitor density, risk and response to interventions. Fracture incidence and BMD should be considered in the trial design of studies involving prolonged ADT. Osteoporosis is a treatable condition and the oncologist should employ ADT with this knowledge. A follow-up e-mail survey was carried out regarding the consensus statement. Responses were received from 49 of the 69 attendees (71%), and overall there was an 89% agreement with the consensus statement. This is now adopted as national practice guidelines for radiation oncologists employed prolonged ADT in prostate cancer patients.

Surveillance of stage I testicular seminoma: British Columbia Cancer Agency Experience 1992 to 2002.

OBJECTIVES: To review the changes in the use of surveillance in Stage I seminoma in British Columbia during the past decade and to compare the relapse rates provincially against those in published reports. Postorchiectomy surveillance of Stage I seminoma is an alternative to adjuvant radiotherapy. The relapse rate from a pooled surveillance series was 18% at 5 years. METHODS: We reviewed the British Columbia Cancer Agency Tumour Registry records for all cases registered with a diagnosis of seminoma of the testes referred to the BCCA between 1992 and 2002. Patients not treated with radiotherapy within 4 months of referral were reviewed for patient and disease parameters (age, rete testes invasion, size, lymphatic invasion), relapse, salvage treatment, and survival. RESULTS: A total of 458 patients with Stage I seminoma were identified. Of these, 93 went onto surveillance. The annual percentage of patients going onto surveillance increased from 10% in 1992 to 33% by 2002. The median follow-up was 33 months. The 5-year actuarial relapse-free survival rate was 78%. Relapse was more common in those with known adverse prognostic factors (rete invasion or size greater than 4 cm). The actuarial 5-year relapse free rate was 86%, 71%, and 50% for patients with no risk factor, one risk factor, or both risk factors, respectively. The disease-specific survival rate at 5 years was 96%. CONCLUSIONS: Surveillance of patients with seminoma in British Columbia increased between 1992 and 2002. The relapse and survival rates in this population-based series were similar to those previously reported.