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To evaluate the outcomes of unfavorable intermediate-risk (UIR) and high-risk (HR) prostate cancer patients treated with combined external beam radiation therapy (EBRT) and low-dose-rate prostate brachytherapy (LDR-PB).A population-based cohort of 568 prostate cancer patients treated with combined EBRT and LDR-PB from 2010 to 2016 was analyzed. All patients received EBRT followed by LDR-PB boost. Outcomes were compared with the results for the brachytherapy arm of the ASCENDE-RT trial.The median followup was 4.5 years. Sixty-nine percent (N = 391) had HR disease. Ninety-four percent of the HR and 57% of UIR were treated with androgen deprivation therapy (ADT) with a median duration of 12 months. The 5-year K-M biochemical progression-free survival (b-PFS), metastasis-free survival (MFS), and overall survival (OS) were 84 ± 2%, 90 ± 2%, and 88 ± 2%, similar to 89 ± 5%, 94 ± 4%, and 92 ± 4% for the ASCENDE-RT LDR-PB arm. The likelihood of achieving a PSA ≤0.2 ng/mL at 4 years was 88%, similar to 86% in the ASCENDE-RT LDR-PB arm. Thirty-three men (5.8%) would have been ineligible for ASCENDE-RT due to high-risk features. The 5-year K-M b-PFS, MFS and OS estimates were 86 ± 2%, 92 ± 1% and 89 ± 2% for the ASCENDE-RT eligible versus 56 ± 10% (p0.001), 73 ± 8% (p0.001), and 77 ± 9% (p = 0.098) for the ineligible patients.In this population-based cohort, combining LDR-PB with pelvic EBRT (+/- ADT) achieves very favorable b-PFS that compares to the LDR-PB arm of the ASCENDE-RT, supporting the generalizability of those results. Men ineligible for ASCENDE-RT, based on prognostic features, have a much higher risk of biochemical recurrence and metastatic relapse.

Background The reduction of overtreatment by active surveillance (AS) is limited in patients with low-risk prostate cancer (PCa) due to high rates of patients switching to radical treatment. MRI improves biopsy accuracy and could therewith affect inclusion in or continuation of AS. We aim to assess the effect of MRI with target biopsies on the total rate of patients discontinuing AS, and in particular discontinuation due to Grade Group (GG) reclassification. Methods Three subpopulations included in the prospective PRIAS study with GG 1 were studied. Group A consists of patients diagnosed before 2009 without MRI before or during AS. Group B consists of patients diagnosed without MRI, but all patients underwent MRI within 6 months after diagnosis. Group C consists of patients who underwent MRI before diagnosis and during follow-up. We used cumulative incidence curves to estimate the rates of discontinuation. Results In Group A (n = 500), the cumulative probability of discontinuing AS at 2 years is 27.5%; GG reclassification solely accounted for 6.9% of the discontinuation. In Group B (n = 351) these numbers are 30.9 and 22.8%, and for Group C (n = 435) 24.2 and 13.4%. The three groups were not randomized, however, baseline characteristics are highly comparable. Conclusions Performing an MRI before starting AS reduces the cumulative probability of discontinuing AS at 2 years. Performing an MRI after already being on AS increases the cumulative probability of discontinuing AS in comparison to not performing an MRI, especially because of an increase in GG reclassification. These results suggest that the use of MRI could lead to more patients being considered unsuitable for AS. Considering the excellent long-term cancer-specific survival of AS before the MRI era, the increased diagnostic accuracy of MRI could potentially lead to more overtreatment if definitions and treatment options of significant PCa are not adapted.

Purpose The purpose of the study was to assess the feasibility of performing intraoperative dosimetry for permanent prostate brachytherapy by combining transrectal ultrasound (TRUS) and fluoroscopy/cone beam CT [CBCT] images and accounting for the effect of prostate deformation. Methods and Materials 13 patients underwent TRUS and multiview two-dimensional fluoroscopic imaging partway through the implant, as well as repeat fluoroscopic imaging with the TRUS probe inserted and retracted, and finally three-dimensional CBCT imaging at the end of the implant. The locations of all the implanted seeds were obtained from the fluoroscopy/CBCT images and were registered to prostate contours delineated on the TRUS images based on a common subset of seeds identified on both image sets. Prostate contours were also deformed, using a finite-element model, to take into account the effect of the TRUS probe pressure. Prostate dosimetry parameters were obtained for fluoroscopic and CBCT-dosimetry approaches and compared with the standard-of-care Day-0 postimplant CT dosimetry. Results High linear correlation (R2 > 0.8) was observed in the measured values of prostate D90%, V100%, and V150%, between the two intraoperative dosimetry approaches. The prostate D90% and V100% obtained from intraoperative dosimetry methods were in agreement with the postimplant CT dosimetry. Only the prostate V150% was on average 4.1% (p-value Conclusions The results of this study have shown that both of the proposed dosimetric evaluation approaches have potential for real-time intraoperative dosimetry.

Background Active surveillance (AS) enrolment criteria and follow-up schedules for low-risk prostate cancer vary between institutions. However, uncertainty remains about adherence to these protocols. Objective To determine adherence to institution-specific AS inclusion criteria and follow-up schedules within the Movember Foundation’s Global Action Plan Prostate Cancer Active Surveillance (GAP3) initiative. Design, setting, and participants We retrospectively assessed the data of 15 101 patients from 25 established AS cohorts worldwide between 2014 and 2016. Outcome measurements and statistical analysis Adherence to individual AS inclusion criteria was rated on a five-point Likert scale ranging from poor to excellent. Nonadherence to follow-up schedules was defined as absence of repeat biopsy 1 yr after the scheduled date. Cohorts were pooled into annual and Prostate Cancer Research International: Active Surveillance (PRIAS)-based biopsy schedules, and a generalised linear mixed model was constructed to test for nonadherence. Results and limitations Serum prostate-specific antigen (PSA) inclusion criteria were followed in 92%, Gleason score (GS) criteria were followed in 97%, and the number of positive biopsy cores was followed in 94% of men. Both age and tumour stage (T stage) criteria had 99% adherence overall. Pooled nonadherence rates increased over time—8%, 16%, and 34% for annual schedules and 11%, 30%, and 29% for PRIAS-based schedules at 1, 4, and 7 yr, respectively—and did not differ between biopsy schedules. A limitation is that our results do not consider the use of multiparametric magnetic resonance imaging. Conclusions In on-going development of evidence-based AS protocols, variable adherence to PSA and GS inclusion criteria should be considered. Repeat biopsy adherence reduces with increased duration of surveillance, independent of biopsy frequency. This emphasises the importance of risk stratification at the commencement of AS. Patient summary We studied adherence to active surveillance protocols for prostate cancer worldwide. We found that inclusion criteria were generally followed well, but adherence to repeat biopsy reduced with time. This should be considered when optimising future active surveillance protocols.

Introduction: We aimed to describe the oncological outcomes after radical cystectomy and chemo-radiation for localized small cell bladder cancer (SCBC). Methods: This population-based analysis of localized SCBC from 1985–2018 in British Columbia included an analysis (analysis 1) of cancer-specific survival (CSS) and overall survival (OS) of patients treated with curative-intent radical cystectomy (RC) and radiation (RT), and an analysis (analysis 2) of CSS and OS in patients treated with RC and chemoRT consistent with the SCBC Canadian consensus guideline. Results: Seventy-seven patients who were treated with curative intent were identified: 33 patients had RC and 44 had RT. For analysis 1, five-year OS was 29% and 39% for RC and RT, respectively (p=0.51), and five-year CSS was 35% and 52% for RC and RT, respectively (p=0.29). On multivariable analysis, higher Charlson comorbidity index (CCI) and the lack of neoadjuvant chemotherapy (NACHT) were associated with worse OS, while higher CCI and Eastern Cooperative Oncology Group (ECOG) were associated with worse CSS. For analysis 2, five-year OS was 56% and 58% for the RC and chemoRT groups, respectively (p=0.90), and five-year CSS was 56% for RC and 71% for chemoRT (p=0.71). Four of 42 (9.5%) chemoRT patients had RC at relapse. Conclusions: SCBC is a rare entity with a poor prognosis. RC and chemoRT offer similar CSS and OS for localized SCBC, even when focusing the analysis on patients treated according to the modern consensus guidelines. NACHT should be considered for eligible patients. Both chemoRT and RC treatment options should be discussed with patients with SCBC.

e19518 Background: Classical Hodgkin lymphoma (cHL) is considered a highly curable cancer. With standard combination chemotherapy regimens, long-term survival exceeds 95% for limited-stage and 85% for advanced-stage patients. Despite these excellent outcomes some patients delay or decline conventional treatment for cHL. We retrospectively assessed the impact of initial treatment refusal on outcomes of patients with cHL in British Columbia (BC). Methods: Using the BC Cancer Lymphoid Cancer Database, we identified all patients aged 18-70 diagnosed between 1st Jan 1999- 31st Dec 2020 that had documented treatment refusal at initial presentation (‘refusers’ defined as not receiving or delaying treatment > 16 weeks). We identified a control cohort (min. 3 controls/refuser) treated within 8 weeks of diagnosis, matched for age, stage, diagnosis date within 3 years, and blinded for outcome. All patients had centrally reviewed biopsies and were treated with ABVD or ABVD-like regimens +/- radiotherapy if appropriate. Patient and disease characteristics at baseline and at time of treatment were analyzed with Chi-squared test and one-way ANOVA test. The Kaplan-Meier method was used to assess progression-free survival (PFS) and overall survival (OS), and statistical significance between groups was determined using the log-rank test. Results: We identified a cohort of 15 patients who initially refused treatment and 47 matched controls. The control cohort was well-matched, with no statistically significant differences in baseline characteristics (age, sex, Ann Arbor stage, B symptoms, International Prognostic Score (IPS) score, ECOG PS, and disease bulk) between groups. The most common reason for initial treatment refusal was to pursue alternative therapy (73%). 13 of 15 refusers eventually accepted treatment (mean time to treatment 76 weeks [range 26-214] vs. 5 weeks [range 1-8] for controls, p < 0.001). At time of treatment, the proportion of refusers with advanced-stage disease increased from 20% to 62% (p = 0.03) and had an associated alteration of treatment plan, and 62% of patients developed higher risk disease with increased IPS score (p = 0.02). At median follow-up of 5 years (0.4-21 years) for all living patients, estimated 5-year PFS was 65% vs 84%, and 5-year OS was 93% vs 98% for refusers and controls respectively. With extended follow up, 13% of refusers (1 late death at 8 years) compared to only 4% of controls died of cHL specifically. Conclusions: This study highlights the impact of treatment refusal in this highly curable malignancy. Initial refusal of treatment is associated with progression of stage, worsening prognostic score, escalation to more prolonged treatment than required at diagnosis, and increased risk of death from cHL. This analysis may help to provide guidance to counselling physicians, as well as inform patients who may be considering alternatives to standard of care for cHL.

Within the Movember Foundation's Global Action Plan Prostate Cancer Active Surveillance (GAP3) initiative, 25 centers across the globe collaborate to standardize active surveillance (AS) protocols for men with low-risk prostate cancer (PCa). A centralized PCa AS database, comprising data of more than 15000 patients worldwide, was created. Comparability of the histopathology between the different cohorts was assessed by a centralized pathology review of 445 biopsies from 15 GAP3 centers. Grade group 1 (Gleason score 6) in 85% and grade group ≥2 (Gleason score ≥7) in 15% showed 89% concordance at review with moderate agreement (κ=0.56). Average biopsy core length was similar among the analyzed cohorts. Recently established highly adverse pathologies, including cribriform and/or intraductal carcinoma, were observed in 3.6% of the reviewed biopsies. In conclusion, the centralized pathology review of 445 biopsies revealed comparable histopathology among the 15 GAP3 centers with a low frequency of high-risk features. This enables further data analyses-without correction-toward uniform global AS guidelines for men with low-risk PCa. PATIENT SUMMARY: Movember Foundation's Global Action Plan Prostate Cancer Active Surveillance (GAP3) initiative combines data from 15000 men with low-risk prostate cancer (PCa) across the globe to standardize active surveillance protocols. Histopathology review confirmed that the histopathology was consistent with low-risk PCa in most men and comparable between different centers.

Purpose Increasing the survival of patients with metastatic prostate cancer (PCa) may affect the demand for palliative radiation to bone (PRTB). Our aim was to characterize the use of PRTB in patients who died of PCa in British Columbia between 2003 and 2015. Methods and Materials All patients with a diagnosis of PCa who died during the study period (n = 23,260) were identified from a population-based provincial registry. Patient and treatment characteristics were analyzed. PRTB utilization rate was calculated by year and location. Survival was calculated from the first and the last course of PRTB. Results A total of 5701 patients died of PCa, with a median survival from diagnosis of 5.2 years. The overall PRTB utilization rate was 38.6%, with an increasing trend over time. Multiple courses of PRTB were frequent, with 51% of patients receiving ≥2 courses of PRTB. Of the patients who died of PCa (15.2% of the PRTB cohort), 5.4% received PRTB within the last 4 weeks of life, 60% of whom received multiple fractions. Rural areas had a lower referral rate and lower use of PRTB. Patients with longer survival tended to receive multiple courses of treatment. The median survival after the first course of PRTB increased from 8.2 months in 2003 to 2004 to 9.4 months in 2013 to 2014 (P = .04). Conclusions PRTB is only used in a minority of patients dying of PCa. The majority who die of PCa after PRTB do so within a year of their first course. The use of multifractionation was common in the last 4 weeks of life. Survival after first PRTB increased minimally over time, and additional research is required to identify its association with recent changes in practice. The referral rate and PRTB utilization rate differ between rural and nonrural locations, underlying the importance of accessibility and referral for utilization of PRTB. Investigating other barriers and ensuring equitable access to radiation are needed.

Purpose/objective(s) Approximately 50% of patients treated with curative intent radiotherapy for limited stage follicular lymphoma (FL) will have a lymphoma relapse. The ideal follow-up strategy for detecting relapse is uncertain. The purpose of this study was to evaluate the impact of surveillance imaging (SI) in patients treated with radiotherapy for limited stage follicular lymphoma (FL). Materials/methods Patients with limited stage IA-IIA, grade 1-3A, FL treated with curative intent radiotherapy alone between 2000-2015 were retrospectively reviewed. Relapse detection was categorized into clinical detection (investigations based on signs/symptoms or laboratory abnormalities) or SI detection (radiologic investigations in asymptomatic patients). Survival outcomes were stratified based on method of relapse detection. Results A total of 330 patients were included with a median follow-up of 8.1 (0.5-20.0) years. All patients received ≥20Gy of involved site radiotherapy (ISRT). 222 (67.3%) patients had SI investigations with a mean of 0.4 (0.1-1.7) per year of follow-up. The most common SI modality used was computed tomography (48.6%). Of all SI investigations (n = 830), 761 (91.7%) showed no evidence of relapse, 49 (5.9%) showed findings of suspected relapse that were that were subsequently found to be false positive, and 20 (2.4%) led to confirmed relapse. The resulting positive predictive value and specificity of SI was 29.0% and 94.0%, respectively. In the follow-up period, 146 (44.2%) patients had a relapse; 126 (86.3%) were detected clinically and 20 (13.7%) were detected with SI. In relapses that were clinically detected (n = 126), 11 (8.7%) were associated with clinically significant patient morbidity, manifesting as deep vein thrombosis (n = 2), pleural effusion (n = 1), biliary duct obstruction (n = 1), renal failure (n = 2), spinal cord or nerve root involvement (n = 4), or symptomatic hypercalcemia (n = 1). The 5- and 10-year overall survival (OS) from the date of diagnosis were 85.6% and 65.2% for clinically detected versus 84.7% and 74.1% for SI detected relapses (P = 0.71). The 5- and 10-year OS from the date of relapse were 70.1% and 50.6% for clinically detected versus 80.2% and 59.4% for SI detected relapses (P = 0.54). Conclusion This retrospective cohort revealed no significant OS differences between relapse detection by SI versus clinical assessment. The incidence of morbidity was low in relapses that were detected clinically. Only 2.4% of SI investigations led to a confirmed relapse suggesting they may have limited utility in the follow-up of limited stage FL patients treated with curative intent radiotherapy. A prospective analysis of cost-effectiveness and impact of SI on psychological and physical morbidity may help guide clinicians when considering a SI follow-up strategy.

Radiotherapy (RT) is typically incorporated into the treatment of limited-stage nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), although it remains unknown whether chemotherapy alone may be suitable in select patients. We evaluated outcomes of limited-stage NLPHL at BC Cancer on the basis of era-specific guidelines: routine RT era, 1995 to 2005 (n = 36), combined modality with 2 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy followed by RT or RT alone; positron emission tomography (PET) era, after 2005 (n = 63), ABVD alone (4 cycles) if the PET scan after the second cycle of ABVD (PET2) is negative, or treatment is changed to RT if PET2 is positive. Median age of patients was 38 years (range, 16-82 years), 73% were male, and 43% had stage II. With a median follow-up of 10.5 years for all patients, 5-year progression-free survival (PFS) was 93% and was 97% for overall survival (OS), with no difference by treatment era (PFS, P = .13; OS, P = .35). For the 49 patients who had a PET2 scan, 86% were PET negative and 14% were PET positive by Deauville criteria with 5-year PFS rates of 92% and 80% (P = .70), respectively. This is the largest study of a PET-adapted approach in NLPHL and supports that ABVD alone may be a viable option in select patients with a negative PET2 scan, with consideration of acute and long-term toxicities.

Prostate cancer remains the 3rd leading cause of cancer-related mortality in Canadian men, and yet screening for prostate cancer continues to be controversial because the majority of men diagnosed with prostate cancer do not die of the disease. It also remains uncertain whether treatment of cases that can be treated with curative intent alters the mortality rate. There are very few studies describing the presenting stage, risk groups, and survival after diagnosis for men dying of prostate cancer in the literature. In this study, we explored these characteristics for all men who died of prostate cancer in British Columbia between 2013 and 2015. The population-based BC Cancer databases were used to identify all patients diagnosed between January 2013 and December 2015 who died of prostate cancer. Patient, tumour, and treatment characteristics were collected, and the risk grouping for each tumour was determined. The proportion of cases in each risk group at the time of diagnosis was determined. Survival time from diagnosis to death was calculated for all patients and for each risk group using the Kaplan&ndash, Meier method. A total of 1256 patients died of prostate cancer. Of patients who presented with metastatic disease, 57.2% presented with a Gleason score of 8 or more, compared with only 35.7% of patients who presented with nonmetastatic disease (p < 0.0001). The presenting stage and risk group of those dying of prostate cancer were as follows: 32% metastatic disease, 3% regional (defined as node-positive), 39% localized high risk, 9% localized intermediate risk, 4% localized low risk, 6% localized not otherwise specified, and 7% unknown. Therefore, 80.3% of those with a known risk group presented with either localized high-risk, regional, or metastatic disease at diagnosis. The median survival times from diagnosis to death were 12 years for localized low-risk, 10 years for localized intermediate-risk, 6.5 years for localized high-risk, 4 years for regional, and 1.7 years for metastatic disease at diagnosis. This population-based analysis demonstrates that patients with localized high-risk, regional, or metastatic disease at diagnosis constitute the overwhelming majority of patients who die of prostate cancer in British Columbia. Unless these disease states can reliably be identified at an earlier low- or intermediate-risk localized state in the future, it is unlikely that treatment of localized low- and intermediate-risk cancer will have an impact on survival. Furthermore, patients with de novo metastatic disease had identifiable risk factors of a higher prostate-specific antigen and Gleason score. Further studies are required to confirm these results.

Introduction: The biennial meeting of the Genitourinary Radiation Oncologists of Canada (GUROC) took place 22-23 November 2019. A consensus-building session was held during the meeting addressing topics of emerging interest or controversy in the management of genitourinary malignancies. Methods:Draft statements were debated among all meeting attendees in an open forum with anonymous live voting. Statements for which there was at least 75% agreement among attendees were adopted as GUROC consensus. Results: Four evidence-based consensus statements were developed. First, the use of prostate radiotherapy is recommended in the setting of de novo low-volume metastatic hormone-sensitive prostate cancer to improve overall survival. Second, the support of ongoing randomized trials evaluating metastasis-directed ablative local therapy in oligometastatic prostate cancer is recommended; where such trials are available, off-trial use of oligometastasis-directed ablative radiotherapy at this time is strongly discouraged. Third, routine use of prostate-rectal hydrogel spacer devices in patients with localized prostate cancer planned to receive external beam radiotherapy is not recommended; instead, selective use in patients at highest risk of rectal toxicity may be considered. Finally, multidisciplinary consultation is recommended for all patients with newly-diagnosed localized muscle-invasive bladder cancer. Conclusions: The GUROC consensus statements provide practical guidance to clinicians in areas of current controversy in the management of prostate and bladder cancer, and it is hoped that their implementation will contribute to improved outcomes in real-world practice and greater support of clinical trials.

The study objective was to investigate the effectiveness of palliative radiation therapy (RT) for patients with diffuse large B-cell lymphoma (DLBCL) and to identify factors, such as chemotherapy relapsed/refractory (R/R) disease, that may influence RT outcomes.Patients with DLBCL who received palliative RT from 2001 to 2015 in British Columbia were reviewed for patient characteristics, treatment details, and outcomes. Univariable and multivariable analyses for response and local progression were performed.Three-hundred and seventy courses of palliative RT in 217 patients were identified. Median equivalent dose in 2 Gy fractions was 19 Gy (range, 2-42 Gy). Clinical and/or radiologic response occurred in 230 (83%) of the 276 courses with response data available. Local control following palliative RT at 6 months was 66.7%. On univariable analysis, R/R disease was not associated with lower clinical response rates but had higher risk of progression (hazard ratio [HR], 0.5; P = .040). On multivariable analyses, patients with R/R disease who did not require concurrent steroids had greater response compared with those who received upfront palliative RT (odds ratio, 3.5; P = .011). Response to first-line chemotherapy and smaller lesion size were associated with improved local progression rates (HR, 0.2; P.001 and HR, 0.5; P = .020, respectively). RT dose fractionation factors were not significant on any analyses.Palliative RT for DLBCL is effective for symptom improvement, including in the chemotherapy R/R setting. Not requiring concurrent steroids, response to first-line chemotherapy, and smaller lesion size predicted better RT outcomes. There was no association between dose fractionation and response rates or local control to suggest that higher RT doses are more effective for palliation.

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).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.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 (p0.0001). 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).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.

Purpose To determine whether the risk of secondary breast cancer (SBC) is reduced in women with Hodgkin lymphoma (HL) treated with smaller field radiation therapy (SFRT) versus mantle field radiation therapy (MRT). Methods and Materials We used the BC Cancer Agency (BCCA) Lymphoid Cancer Database to identify female patients treated for HL between January 1961 and December 2009. Radiation therapy volumes were categorized as MRT or SFRT, which included involved field, involved site, or involved nodal radiation therapy. SBC risk estimates were compared using competing risk analysis and Fine and Gray multivariable model: MRT ± chemotherapy, SFRT ± chemotherapy, or chemotherapy-only. Results Of 734 eligible patients, 75% of the living patients have been followed up for more than 10 years, SBC has developed in 54, and 15 have died of breast cancer. The 20-year estimated risks (competing risk cumulative incidence) for SBC differed significantly: MRT 7.5% (95% confidence interval [CI] 4.4%-11.5%), SFRT 3.1% (95% CI 1.0%-7.7%), and chemotherapy-only 2.2% (95% CI 1.0%-4.8%) ( P =.01). Using a Fine and Gray model to control for death and patients lost to follow-up, MRT was associated with a higher risk of SBC (hazard ratio [HR] = 2.9; 95% CI 1.4%-6.0%; P =.004) compared with chemotherapy-only and with SFRT (HR = 3.3; 95% CI 1.3%-8.4%; P =.01). SFRT was not associated with a greater risk of SBC compared with chemotherapy-only (HR = 0.87; 95% CI 0.28%-2.66%; P =.80). Conclusion This study confirms that large-volume MRT is associated with a markedly increased risk of SBC; however, more modern small-volume RT is not associated with a greater risk of SBC than chemotherapy alone.

Primary cutaneous anaplastic large cell lymphoma (PCALCL) is a rare CD30+ lymphoproliferative disorder with excellent outcomes reported despite frequent cutaneous relapses. Limited information exists on the development of systemic lymphoma. The British Columbia Cancer Agency (BCCA) Lymphoid Cancer Database was searched to identify all adults diagnosed with PCALCL from 1993 to 2013. From 2005, the BCCA endorsed radiotherapy (RT) alone for limited stage with data failing to support chemotherapy. Forty-seven patients were identified with a male predominance (n = 31, 66%), median age of 64 years and predominantly limited stage (n = 40, 85%). Median follow-up was 8·4 years. The 5-year time to progression (TTP) was 58% (64% limited versus 29% advanced stage). The 5-year disease-specific survival (DSS) and overall survival was 86% and 75%, respectively. In an as-treated analysis, the 5-year DSS for limited stage patients was similar comparing RT to combined modality treatment or chemotherapy alone but the 5-year TTP favoured RT (82% vs. 33%, P = 0·004). The 5-year cumulative risk of developing systemic lymphoma was 14%. Our results confirm the favourable prognosis of PCALCL despite a high relapse rate. Limited stage patients treated with RT alone have excellent outcomes. There is a small risk of systemic lymphoma in PCALCL.

Purpose Studies in classical Hodgkin lymphoma (cHL) typically measure the time to events from diagnosis. We evaluated the risk of relapse at event-free survival time points in cHL and compared the risk of death to expected mortality rates in British Columbia (BC). Methods The BC Cancer Agency Lymphoid Cancer Database was screened to identify all patients age 16 to 69 years diagnosed with cHL between 1989 and 2012 treated with the chemotherapy regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (or equivalent). We compared the observed mortality to the general population using age-, sex-, and calendar period–generated expected mortality rates from BC life-tables. Relative survival was calculated using a conditional approach and expressed as a standardized mortality ratio of observed-to-expected deaths. Results One thousand four hundred two patients were identified; 749 patients were male (53%), the median age was 32 years, and 68% had advanced-stage disease. The median follow-up time was 8.4 years. Seventy-two percent of relapses occurred within the first 2 years of diagnosis. For all patients, the 5-year risk of relapse from diagnosis was 18.1% but diminished to 5.6% for patients remaining event free at 2 years. For advanced-stage patients who were event free at 2 years, the 5-year risk of relapse was only 7.6%, and for those who were event free at 3 years, it was comparable to that of limited-stage patients (4.1% v 2.5%, respectively; P = .07). Furthermore, international prognostic score ≥ 4 and bulky disease were no longer prognostic in patients who were event free at 1 year. Although the relative survival improved as patients remained in remission, it did not normalize compared with the general population. Conclusion Patients with cHL who are event free at 2 years have an excellent outcome regardless of baseline prognostic factors. All patients with cHL had an enduring increased risk of death compared with the general population.

To compare biochemical failure using a prostate-specific antigen (PSA) threshold of0.2 ng/mL to that using Phoenix threshold (nadir+2 ng/mL).Androgen suppression combined with elective nodal and dose-escalated radiation therapy (the ASCENDE-RT trial) is a randomized control trial in which 276 high-risk and 122 intermediate-risk patients were randomized to (1) a standard arm with 12 months of androgen deprivation therapy, pelvic external beam radiation therapy (EBRT) to 46 Gy, and an EBRT boost (dose-escalated EBRT [DE-EBRT]) to 78 Gy, or (2) an experimental arm which substituted a low-dose-rate prostate brachytherapy boost (LDR-PB). The primary endpoint was biochemical progression-free survival (b-PFS) using the Phoenix threshold. In this reanalysis of ASCENDE-RT, the b-PFS using phoenix is compared to the surgical PSA threshold of0.2 ng/mL.Compared to nadir+2 ng/mL, the0.2 ng/mL PSA threshold doubled the number of relapse events from 69 to 139. However, the increase was confined to the DE-EBRT subjects. The 7-year Kaplan-Meier b-PFS after DE-EBRT declined from 76% using nadir+2 ng/mL to 38% using the0.2 ng/mL threshold (p 0.001). Among the LDR-PB subset, there was no significant difference in b-PFS; the 7-year Kaplan-Meier b-PFS was 85% (0.2 ng/mL) versus 88% (nadir+2 ng/mL) (p = 0.319).Replacing Phoenix with a surgical threshold greatly increased biochemical failure after DE-EBRT boost but had no effect after LDR-PB. As a result of this finding, PSA outcomes after surgery or brachytherapy can be directly compared by using the surgical definition of PSA failure. In this context, a brachytherapy boost appears to produce superior b-PFS compared to contemporary surgical series.

Testosterone suppression, achieved through orchiectomy or medically induced androgen-deprivation therapy (ADT), is a standard treatment for men with recurrent and metastatic prostate cancer. Current assay methods demonstrate the capacity for testosterone suppression to

Rates of late toxicity are higher for salvage treatment of local recurrence after prior radiotherapy. We present our experience with salvage prostate brachytherapy (BT) for local recurrence after definitive external beam radiotherapy with attention to the relationship between dose and late toxicity.From 2005 to 2012, 18 patients with biopsy proven locally recurrent prostate cancer and negative staging received low-dose-rate BT with a prescribed dose of 130-144 Gy. Toxicities were graded using Common Terminology Criteria for Adverse Events, version 3.0.Median followup is 31.5 months (range, 12-104). International Prostate Symptom Scores peaked at 3 months (median, 21/35), returning to baseline by 24 months. Urinary catheterization rate was 33% (median duration, 14 days; range, 1-90 days). Late Grade 3/4 genitourinary toxicity occurred in 1 patient each, one of whom also had Grade 3 late gastrointestinal toxicity; urethral strictures developed in three others. These 5 patients with late toxicity had higher dose to the prostate (isodose enclosing 90% [D90] median, 151 Gy; range, 135-185 Gy) compared with those without late complications (median, 134 Gy; range, 105-165; p0.04). Acute gastrointestinal toxicity Grade3 occurred in 44%. Four patients (22%) experienced biochemical failure.Salvage low-dose-rate prostate BT can provide durable biochemical control. Care should be taken to select patients with higher likelihood of organ-confined disease. The goal of planning should be to treat the recurrent disease to an adequate dose with careful attention to maintain a conservative D90.

Context: Active surveillance (AS) is an important strategy to reduce prostate cancer overtreatment. However, the optimal criteria for eligibility and predictors of progression while on AS are debated. Objective: To review primary data on markers, genetic factors, and risk stratification for patient selection and predictors of progression during AS. Evidence acquisition: Electronic searches were conducted in PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to April 2014 for original articles on biomarkers and risk stratification for AS. Evidence synthesis: Patient factors associated with AS outcomes in some studies include age, race, and family history. Multiple studies provide consistent evidence that a lower percentage of free prostate-specific antigen (PSA), a higher Prostate Health Index (PHI), a higher PSA density (PSAD), and greater biopsy core involvement at baseline predict a greater risk of progression. During follow-up, serial measurements of PHI and PSAD, as well as repeat biopsy results, predict later biopsy progression. While some studies have suggested a univariate relationship between urinary prostate cancer antigen 3 (PCA3) and transmembrane protease, serine 2-v-ets avian erythroblastosis virus E26 oncogene homolog gene fusion (TMPRSS2:ERG) with adverse biopsy features, these markers have not been consistently shown to independently predict AS outcomes. No conclusive data support the use of genetic tests in AS. Limitations of these studies include heterogeneous definitions of progression and limited follow-up. Conclusions: There is a growing body of literature on patient characteristics, biopsy features, and biomarkers with potential utility in AS. More data are needed on practical applications such as combining these tests into multivariable clinical algorithms and long-term outcomes to further improve AS in the future. Patient summary: Several PSA-based tests (free PSA, PHI, PSAD) and the extent of cancer on biopsy can help to stratify the risk of progression during active surveillance. Investigation of several other markers is under way. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

To compare the second malignancy incidence in prostate cancer patients treated with brachytherapy (BT) relative to radical prostatectomy (RP) and to compare both groups with the cancer incidence in the general population.From 1998 to 2010, 2418 patients were treated with Iodine 125 prostate BT monotherapy at the British Columbia Cancer Agency, and 4015 referred patients were treated with RP. Cancer incidence was compared with the age-matched general population using standardized incidence ratios (SIRs). Pelvic malignancies included invasive and noninvasive bladder cancer and rectal cancer. Cox multivariable analysis was performed with adjustment for covariates to determine whether treatment (RP vs BT) was associated with second malignancy risk.The median age at BT was 66 years and at RP 62 years. The SIR comparing BT patients with the general population was 1.06 (95% confidence interval [CI] 0.91-1.22) for second malignancy and was 1.53 (95% CI 1.12-2.04) for pelvic malignancy. The SIR comparing RP patients with the general population was 1.11 (95% CI 0.98-1.25) for second malignancy and was 1.11 (95% CI 0.82-1.48) for pelvic malignancy. On multivariable analysis, older age (hazard ratio [HR] 1.05) and smoking (HR 1.65) were associated with increased second malignancy risk (P.0001). Radical prostatectomy was not associated with a decreased second malignancy risk relative to BT (HR 0.90, P=.43), even when excluding patients who received postprostatectomy external beam radiation therapy (HR 1.13, P=.25). Older age (HR 1.09, P.0001) and smoking (HR 2.17, P=.0009) were associated with increased pelvic malignancy risk. Radical prostatectomy was not associated with a decreased pelvic malignancy risk compared with BT (HR 0.57, P=.082), even when excluding postprostatectomy external beam radiation therapy patients (HR 0.87, P=.56).After adjustment for covariates, BT patients did not have an increased second malignancy risk compared with RP patients. Further follow-up of this cohort is needed given the potential latency of radiation-induced malignancies.

Purpose: To determine late urinary toxicity (>12 months) in a large cohort of uniformly treated low-dose-rate prostate brachytherapy patients. Methods and Materials: From 1998 to 2009, 2709 patients with National Comprehensive Cancer Network–defined low-risk and low-tier intermediate-risk prostate cancer were treated with Iodine 125 ({sup 125}I) low-dose-rate prostate brachytherapy; 2011 patients with a minimum of 25 months of follow-up were included in the study. Baseline patients, treatment, implant factors, and late urinary toxicity (Radiation Therapy Oncology Group [RTOG] grading system and International Prostate Symptom Score [IPSS]) were recorded prospectively. Time to IPSS resolution, late RTOG genitourinary toxicity was examined with Kaplan-Meier and log-rank tests. Cox proportional hazards regression was done for individual covariates and multivariable models. Results: Median follow-up was 54.5 months (range, 2-13 years). Actuarial toxicity rates reached 27% and 10% (RTOG ≥2 and ≥3, respectively) at 9-13 years. Symptoms resolved quickly in the majority of patients (88% in 6-12 months). The prevalence of RTOG 0, 1, 2, 3, and 4 toxicity with a minimum of 7 years' follow-up was 70%, 21%, 6.4%, 2.3%, and 0.08%, respectively. Patients with a larger prostate volume, higher baseline IPSS, higher D90, acute toxicity, and age >70 years had more late RTOG ≥2 toxicity (all P≤.02). The IPSS resolved slower inmore » patients with lower baseline IPSS and larger ultrasound prostate volume, those not receiving androgen deprivation therapy, and those with higher D90. The crude rate of RTOG 3 toxicity was 6%. Overall the rate of transurethral resection of the prostate was 1.9%; strictures, 2%; incontinence, 1.3%; severe symptoms, 1.8%; late catheterization, 1.3%; and hematuria, 0.8%. The majority (80%) resolved their symptoms in 6-12 months. Conclusion: Long-term urinary toxicity after brachytherapy is low. Although actuarial rates increase with longer follow-up (27% RTOG 2 and 10% RTOG 3 at 13 years), symptoms resolve relatively quickly; between 5 and 13 years' follow-up, >90% of patients have minimal urinary toxicity. Refining patient selection criteria, planning, and treatment delivery may further reduce toxicity.« less

PURPOSE To determine whether the use of 6 months' adjuvant androgen deprivation therapy (ADT) combined with brachytherapy for intermediate-risk (IR) and low-risk (LR) prostate cancer is associated with an increased risk of cardiovascular death. METHODS AND MATERIALS This is a retrospective analysis of prospectively collected data from men treated in the British Columbia Cancer Agency brachytherapy program from 1998 to 2012. Men were categorized by risk group and ADT use. Cardiac and other comorbidities were recorded and compared between groups. Biochemical control (Phoenix definition, nadir + 2 ng/mL) was ascertained. Overall, prostate, cardiac, and other-cause mortality were analyzed by the Kaplan-Meier method and Fine and Gray competing-risk analysis. RESULTS The study included 3155 men (1142 with LR cancer and 2013 with IR cancer) who have been followed up for a median of 7.9 years. ADT was received by 47% of IR patients and 37% of LR patients for a median of 6 months. Men with IR cancer were older and had more cardiac and other comorbidities than LR cases (P

Purpose To describe outcomes of men with unfavorable (high-tier) intermediate risk prostate cancer (H-IR) treated with low-dose-rate (LDR) brachytherapy, with or without 6 months of androgen deprivation therapy (ADT). Methods and Materials Patients with H-IR prostate cancer, treated before 2012 with LDR brachytherapy without external radiation are included. Baseline tumor characteristics are described. Outcomes between groups receiving ADT are measured by Phoenix (nadir +2 ng/mL), and threshold 0.4 ng/mL biochemical relapse definitions (bNEDs), as well as clinical end points. Standard descriptive and actuarial statistics are used. Results Two hundred sixty men were eligible, 139 (53%) did not receive ADT and 121 (47%) did. Median follow-up was 5 years. Men treated with ADT had higher T stage and percent positive cores but lower pathologic grade group. bNED rates with and without ADT at 5 years are 86% and 85% ( p = 0.52) with the Phoenix definition, and 83% and 78% ( p = 0.13) with the threshold definition. Local recurrence or metastasis were rare in both groups ( p = not significant). Death from prostate cancer only occurred in 4 patients, 2 in each group. Overall survival was 85% in those treated with ADT and 93% without at 8 years, p = 0.15. Conclusions The addition of 6 months of ADT to LDR brachytherapy for H-IR prostate cancer does not improve 5 year prostate specific antigen control, and we no longer routinely recommended it.

Objective To evaluate the rates at which patients are offered and receive local salvage therapy (LST) after failure of primary radiotherapy for localized prostate cancer, as it is the only potentially curative treatment for localized recurrence but appears to be underutilized when compared with androgen-deprivation therapy (ADT) or observation. Materials and methods Patients with localized prostate cancer who received primary radiotherapy with curative intent between 1999 and 2000 were identified in the British Columbia Tumour Registry. Exclusion criteria included patient age >72 years, prostate-specific antigen>40 ng/ml, and clinical stage T4 at diagnosis. Data on clinicopathologic features, primary therapy, prostate-specific antigen kinetics, and salvage therapy were collected retrospectively. Radiation failure was defined as biochemical recurrence according to the Phoenix criteria or by initiation of salvage therapy. Results Of 1,782 patients treated in the study period, 1,067 met inclusion criteria. Of these, 257 failed radiation therapy. Radiation therapy failure was managed with observation (>12 mo) in 126 patients and ADT in 119. Of the observed patients, 66 subsequently received ADT. Five patients (1.8%) received LST (3 radical prostatectomy and 2 brachytherapy). Conclusions Only 2% of patients relapsing after radiation therapy for localized prostate cancer received LST. Although the benefits of LST are unproven, these findings reveal a possible underutilization of LST and indicate a need for enhanced collaboration between specialties to optimize care of this challenging cohort.

Purpose To compare disease-free survival (DFS) rates using a >0.4 ng/mL biochemical failure definition with the Phoenix (nadir+2 ng/mL) failure definition by analyzing a consecutive cohort of 1006 patients treated with low-dose-rate prostate brachytherapy (LDR-PB) monotherapy. Methods and Materials Data for first 1006 consecutive LDR-PB implants (1998–2003) were extracted from a prospective database. Patients had low- (58%) or intermediate (42%)-risk disease. Three months neoadjuvant and 3 months concomitant androgen deprivation therapy were used in 65% of cases. The Phoenix definition was modified to “unfail” patients who had a benign prostate-specific antigen (PSA) bounce. Results The median followup is 7.5 years. The median PSA at latest followup for disease-free patients was 0.04 ng/mL. The Phoenix definition yielded 5- and 10-year Kaplan–Meier DFS estimates of 96.5 ± 1.2% and 93.7 ± 2.0%, respectively. Applying the >0.4 ng/mL threshold reduced these estimates to 94.4 ± 1.6% and 88.8 ± 3.0% (log rank, p = 0.015). Conclusions Compared with Phoenix, applying a >0.4 ng/mL failure definition increased biochemical failure by ∼2% at 5 years and ∼5% at 10 years. These data show that Phoenix did not greatly exaggerate DFS estimates compared with a surgical-type threshold. However, this observation is a consequence of the exceptionally low residual PSA values characteristic of LDR-PB and cannot be generalized to other forms of radiation therapy.

Prostate-specific antigen (PSA) screening for prostate cancer may reduce mortality, but it incurs considerable risk of over diagnosis and potential harm to quality of life. Our objective was to evaluate the cost-effectiveness of PSA screening, with and without adjustment for quality of life, for the British Columbia (BC) population. We adapted an existing natural history model using BC incidence, treatment, cost and mortality patterns. The modeled mortality benefit of screening derives from a stage-shift mechanism, assuming mortality reduction consistent with the European Study of Randomized Screening for Prostate Cancer. The model projected outcomes for 40-year-old men under 14 combinations of screening ages and frequencies. Cost and utility estimates were explored with deterministic sensitivity analysis. The incremental cost-effectiveness of regular screening ranged from $36,300/LYG, for screening every four years from ages 55 to 69 years, to $588,300/LYG, for screening every two years from ages 40 to 74 years. The marginal benefits of increasing screening frequency to 2 years or starting screening at age 40 years were small and came at significant cost. After utility adjustment, all screening strategies resulted in a loss of quality-adjusted life years (QALYs); however, this result was very sensitive to utility estimates. Plausible outcomes under a range of screening strategies inform discussion of prostate cancer screening policy in BC and similar jurisdictions. Screening may be cost-effective, but the sensitivity of results to utility values suggests individual preferences for quality versus quantity of life should be a key consideration.

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.

To examine the relationship between whole prostate dose metrics and disease-free survival (DFS) after (125)I low-dose-rate prostate brachytherapy (LDR-PB).Data for the first 2000 LDR-PB monotherapy implants were extracted from a database containing patient, tumor, dosimetric, and outcomes information. By National Comprehensive Cancer Network criteria, half (n = 1006) had low-risk disease and half (n = 990) had intermediate-risk disease (four had high-risk disease). Most patients (58.4%) and 75.3% of intermediate-risk patients received 3 months neoadjuvant and 3 months concomitant androgen deprivation therapy (ADT). Univariate and multivariate analyses were conducted using recognized prognostic factors and the whole prostate dose metrics D90 (the minimum dose received by 90% of the postimplant CT-based prostate volume) and V100 (the percent of the postimplant CT-based prostate volume that received at least 100% of the prescription dose).The median followup is 5 years (maximum, 12.5 years); the 5-, 7-, and 10-year actuarial DFS estimates are 96.0%, 94.4%, and 93.0%, respectively. Of the recognized prognostic factors, only pretreatment prostate-specific antigen (p = 0.012) and Gleason sum (p = 0.010) were predictive of DFS. When analyzed as continuous variables, dose metrics were not predictive of DFS. However, most nonsignificant trends favored higher doses, and D90 values130 Gy were predictive of an increased risk of recurrence in the non-ADT subset (N = 833; log rank, p = 0.018).Although D90 values of130 Gy were predictive of an increased risk of recurrence in the non-ADT subset, neither D90 nor V100, when used as continuous variables, was predictive of DFS when applied to the entire cohort or in the subset analysis. This observation informs us that dose metrics are not equivalent to oncologic end points and must be calibrated against DFS for each physician and each institution offering LDR-PB.

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Background The Genitourinary Radiation Oncologists of Canada (GUROC) published a three-group risk stratification (RS) system to assist prostate cancer decision-making in 2001. The objective of this project is to use the ProCaRS database to statistically model the predictive accuracy and clinical utility of a proposed new multi-group RS schema. Methods The RS analyses utilized the ProCaRS database that consists of 7974 patients from four Canadian institutions. Recursive partitioning analysis (RPA) was utilized to explore the sub-stratification of groups defined by the existing three-group GUROC scheme. 10-fold cross-validated C-indices and the Net Reclassification Index were both used to assess multivariable models and compare the predictive accuracy of existing and proposed RS systems, respectively. Results The recursive partitioning analysis has suggested that the existing GUROC classification system could be altered to accommodate as many as six separate and statistical unique groups based on differences in BFFS (C-index 0.67 and AUC 0.70). GUROC low-risk patients would be divided into new favorable-low and low-risk groups based on PSA ⩽6 and PSA >6. GUROC intermediate-risk patients can be subclassified into low-intermediate and high-intermediate groups. GUROC high-intermediate-risk is defined as existing GUROC intermediate-risk with PSA >=10 AND either T2b/c disease or T1T2a disease with Gleason 7. GUROC high-risk patients would be subclassified into an additional extreme-risk group (GUROC high-risk AND (positive cores ⩾87.5% OR PSA >30). Conclusions Proposed RS subcategories have been identified by a RPA of the ProCaRS database.

5018Background: The TOAD (TROG 03.06; NCT00110162) phase 3 randomized trial showed that immediate androgen deprivation therapy (IADT) improved overall survival (OS) and time to clinical progression...

After publication of EORTC-22863 trial, prolonged androgen deprivation therapy (ADT) combined with radiation therapy (RT) became standard policy for high-risk prostate cancer patients in British Columbia (BC) in 1997. We evaluated whether population-based survival improved after this policy change.Two cohorts comprising all patients with T3-T4 prostate cancer treated with curative-intent RT in BC were reviewed. The Early cohort (n=730) was all patients treated between 1993 and 1995, and the Late cohort (n=584) was all patients treated between 1999 and 2001. The BC Cancer Registry, which collects data on survival, was linked to RT and pharmacy databases. Duration of ADT, age, stage, grade, presenting PSA, and Charlson comorbidity index (CCI; none=0, minor=1, major=2+), were abstracted from charts.Usage of ≥6 months and ≥18 months of neoadjuvant and adjuvant ADT increased from 14% and 1% to 97% and 59% (p0.0001). Baseline characteristics were similar, except for lower Gleason score (G2-6: 45% vs. 20%, G7: 35% vs. 48%, G8-10: 19% vs. 32%; p0.0001), higher T-stage (T4: 9% vs. 5%, p=0.004) and higher comorbidity (CCI 0: 62% vs. 71%, CCI 1: 26% vs. 20%, CCI 2+: 11% vs. 9%, p=0.002) in the Early cohort. Disease-specific survival adjusted for competing risks from other causes mortality was improved (90% vs. 86%, p=0.042). On multivariate analysis, the Late cohort was independently associated with improved 8-year overall survival (76% vs. 64%, p=0.0002).This population-based study demonstrated improved overall survival following a policy change to use of prolonged ADT with curative RT for patients with T3-T4 prostate cancer.

Active surveillance (AS) is an important management strategy for men diagnosed with low-risk prostate cancer (PCa). The need for AS is increasing due to the awareness that many PCa are identified that show a low growth potential and therefore are likely to remain clinically asymptomatic during the lifetime of an individual. Currently there is no good method to prevent the overdiagnosis of indolent cancers upfront. During the last decade, several studies on AS around the world have made observations that feed the discussion on how to select and monitor these patients, how to proceed with the research to develop a better and more precise clinical definition of indolent cancers and how to manage men under AS clinically. Furthermore, patients' perspectives have become clearer, and quality of life studies give direction to the practical approach and care for patients and partners. This paper reflects the consensus on the state of the art and the future direction of AS, based on the Inside Track Conference "Active Surveillance for low risk prostate cancer" (Chairmen: C.H. Bangma, NL, and L. Klotz, CA; Co-Chairmen: L.J. Denis, BE, and C. Parker, UK; Scientific Coordinators: M. J. Roobol, NL, and E.W. Steyerberg, NL), organized by the European School of Oncology in collaboration with Europa Uomo in Rotterdam, the Netherlands in January 2012. Topics for discussion were the optimisation of patient selection based on indolent disease definition, the incorporation of therapeutic agents into AS programs, the optimisation of patient care, and the application of emerging technologies and biomarkers.

BACKGROUND. The objective of this study was to report the rates of disease-free survival (DFS), cause-specific survival (CSS), and overall survival after low-dose-rate (LDR) prostate brachytherapy (PB). METHODS. Data from 1006 consecutive patients with prostate cancer who received LDR-PB and underwent implantation on or before October 23, 2003 were extracted from a prospective database on November 11, 2011. The selected patients had low-risk (58%) or intermediate-risk (42%) disease according to National Comprehensive Cancer Network criteria. The Phoenix threshold was used to define biochemical relapse. Sixty-five percent of patients received 3 months of neoadjuvant androgen-deprivation therapy (ADT) and 3 months of concomitant ADT. Univariate and multivariate analyses are reported in relation to patient, tumor, and treatment variables. RESULTS. The median follow-up was 7.5 years. By using Fine and Gray competing risks analysis, the 5-year and 10-year actuarial DFS rates were 96.7% (95% confidence interval, 95.2%-97.7%) and 94.1% (95% confidence interval, 92%-95.6%), respectively. When applied to the whole cohort, none of the usual prognostic variables, including dose metrics, were correlated with DFS. However, in both univariate and multivariate models, increasing dose was the only covariate that correlated with improved DFS for the subset of men (N = 348) who did not receive ADT (P = .043). The actuarial 10-year CSS rate was 99.1% (95% confidence interval, 97.3%-99.7%). The overall survival rate was 93.8% at 5 years (95% confidence interval, 92%-95.1%) and 83.5% at 10 years (95% confidence interval, 79.8%-86.6%). Only age at implantation (P = .0001) was correlated with overall survival in multivariate analysis. CONCLUSIONS. In a consecutive cohort of 1006 men with National Comprehensive Cancer Network low-risk and intermediate-risk prostate cancer, the actuarial rate of recurrent disease after LDR-PB was approximately 3% at 5 years and 6% at 10 years. Cancer 2013. © 2012 American Cancer Society.

Aims To compare biochemical failure-free survival (BFFS) and overall survival for prostate cancer treated with stereotactic ablative radiotherapy (SABR), low dose rate (LDR) brachytherapy or external beam radiotherapy (EBRT) using a large Canadian multi-institutional database. Materials and methods Patients with low risk localised prostate cancer treated with SABR, LDR or EBRT and no androgen deprivation therapy were selected. Propensity score matching was used to create two sets of matched cohorts with LDR and EBRT serving as control groups. Kaplan–Meier survival analysis and Cox proportional hazards regression were used to compare differences in BFFS and overall survival between treatment groups. Results The pre-matched cohort contained 602 patients; the median follow-up was >5.0 years. There were no significant differences in BFFS before or after matching for SABR versus LDR but the prostate-specific antigen (PSA) nadir was lower after LDR. For the SABR versus EBRT, SABR had a BFFS trend before matching ( P = 0.08), which became significant after matching ( P Conclusions Using the Genitourinary Radiation Oncologists of Canada Prostate Cancer Risk Stratification database, low risk prostate cancer patients receiving SABR had similar BFFS compared with patients receiving LDR but better BFFS than EBRT patients. Further comparative studies of efficacy, quality of life and economic outcomes using a broader risk of patients are warranted.

Aim To describe the first case of a secondary meningioma in a patient after radiation treatment for thyroid eye disease (TED). Secondarily to identify any additional cases of secondary malignancy resulting from radiotherapy for thyroid eye disease from our institutional experience. Background Thyroid eye disease (TED) is a self-limiting auto-immune disorder causing expansion of orbital soft tissue from deposition of glycosaminoglycans and collagen, leading to significant cosmetic and functional morbidity. Established management options for TED include: glucocorticosteroids, orbital radiotherapy, and surgical orbital decompression. Two large series on radiotherapy for TED have been reported without any cases of secondary malignancy. Materials and methods The case of a patient with visual failure, found to have a sphenoid wing meningioma after previous TED radiotherapy is described. We then reviewed 575 patients with at least 3-year follow-up receiving radiotherapy for TED at British Columbia Cancer Agency to identify other possible secondary malignancies. Results The patient had postoperative improvement in her vision without any identified complications. Three additional cases of hematologic malignancy were identified. The calculated risk in our population of developing a radiation-induced meningioma after TED with at least 3 years of follow-up of is 0.17% (1/575); with hematopoetic malignancies the risk for secondary malignancy is 0.7% (4/575). Conclusions Our calculated risk for secondary malignancy (0.17%, 0.7%) is similar to the reported theoretical risk published in the literature (0.3–1.2%). There is real risk for the development of a secondary malignancy after radiotherapy treatment of TED and treatment options should include consideration for this potential.

Background and purpose To evaluate outcome in patients with Gleason 7 prostate cancer treated with iodine-125 brachytherapy at the British Columbia Cancer Agency. Materials and methods Between 20th July 1998 and 7th February 2006, 1500 patients underwent I-125 prostate brachytherapy without supplemental external beam radiation therapy. Of these, 439 had Gleason 7 disease; 362 had Gleason 3 + 4 and 77 had 4 + 3 disease. Generally, patients received 6 months of androgen suppression. We compared biochemical no evidence of disease (bNED) between patients with Gleason ⩽6 and Gleason 7 and between Gleason 3 + 4 and 4 + 3 using the Phoenix definition of biochemical recurrence. Results Median follow-up was 60 months. Estimated 5 year bNED was 97% for patients with Gleason score ⩽6 and 94% for patients with Gleason 7 disease ( p = 0.037). Estimated bNED was 95% and 94% for 3 + 4 and 4 + 3, respectively ( p = 0.791). There was no difference in bNED between implants achieving D90 ⩾ versus Conclusions I-125 brachytherapy with 6 months of ADT demonstrates excellent bNED rates in Gleason 7 disease. We found no evidence of a difference between patients with Gleason 3 + 4 versus 4 + 3 disease.

Purpose To identify subgroups of patients with carcinoma of the prostate treated with radical radiotherapy that have improved overall survival when disease is biochemically controlled. Methods and Materials A cohort of 1,060 prostate cancer patients treated with radical radiotherapy was divided into nine subgroups based on National Comprehensive Cancer Network risk category and estimated 10-year overall survival (eOS 10y) derived from the age adjusted Charlson Comorbidity Index. Patients with and without biochemical control were compared with respect to overall survival. Actuarial estimates of overall survival were calculated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used for analysis of overall survival. Results Median follow-up was 125 months (range, 51–176 months). Only the subgroups with high or intermediate risk disease and an eOS 10y of >90% had a statistically significantly improved overall survival when prostate cancer was biochemically controlled. In all other groups, biochemical control made no significant difference to overall survival. In the subgroup with high-risk disease and eOS 10y >90%, actuarial overall survival was 86.3% (95% confidence interval [CI] 78.5%–94.1%) and 62.1% (95% CI 52.9%–71.3%) for patients with biochemical control and biochemical relapse respectively ( p = 0.002). In the intermediate risk group with eOS >90%, actuarial overall survival was 95.3% (95% CI 89.0%–100%) and 79.8% (95% CI 68.0%–91.6%) for biochemically controlled and biochemically relapsed patients ( p = 0.033). On multivariate analysis, National Comprehensive Cancer Network risk group ( p = 0.005), biochemical control ( p = 0.033) and eOS 10y ( p Conclusion Biochemical control translates into improved overall survival in patients with high or intermediate risk disease and an estimated 10-year overall survival of >90%.

Introduction: The use of accepted prostate cancer risk stratification groups based on prostate-specific antigen, T stage and Gleason score assists in therapeutic treatment decision-making, clinical trial design and outcome reporting. The utility of integrating novel prognostic factors into an updated risk stratification schema is an area of current debate. The purpose of this work is to critically review the available literature on novel pre-treatment prognostic factors and alternative prostate cancer risk stratification schema to assess the feasibility and need for changes to existing risk stratification systems. Methods: A systematic literature search was conducted to identify original research publications and review articles on prognostic factors and risk stratification in prostate cancer. Search terms included risk stratification, risk assessment, prostate cancer or neoplasms, and prognostic factors. Abstracted information was assessed to draw conclusions regarding the potential utility of changes to existing risk stratification schema. Results: The critical review identified three specific clinically relevant potential changes to the most commonly used three-group risk stratification system: (1) the creation of a very-low risk category; (2) the splitting of intermediate-risk into a low- and highintermediate risk groups; and (3) the clarification of the interface between intermediate- and high-risk disease. Novel pathological factors regarding high-grade cancer, subtypes of Gleason score 7 and percentage biopsy cores positive were also identified as potentially important risk-stratification factors. Conclusions: Multiple studies of prognostic factors have been performed to create currently utilized prostate cancer risk stratification systems. We propose potential changes to existing systems.

Purpose The British Columbia Cancer Agency has been performing iodine-125 prostate brachytherapy since 1998, initially using loose seeds and phasing into the exclusive use of RAPIDStrand (RS) (Oncura Inc., Plymouth Meeting, PA) by November 2000. The aim of this study was to investigate rates of biochemical no evidence of disease (bNED) in patients treated with loose seeds compared with RS from this population-based cohort. Methods and materials Between July 1998 and February 2006, 1500 implants were performed (327 loose and 1173 RS). Biochemical failure is reported using the Phoenix definition and prostate-specific antigen (PSA) >0.4 ng/mL at ≥48 months postimplant. Actuarial estimates were calculated by the Kaplan–Meier method. Analysis was repeated with the first 100 loose and stranded implants excluded to assess the learning curve effect. Log-rank test was used to evaluate differences in bNED. Variables showing association with bNED were included in a multivariate model. Results There was no difference between loose and stranded seeds. Estimated rate of bNED was 93.5% (95% confidence interval [CI], 90.6–96.4) at 7 years for patients treated with loose seeds and 94.0% (95% CI, 91.8–96.2) for patients treated with RS according to Phoenix definition ( p = 0.846). Using the PSA >0.4 ng/mL definition, estimated rates were 91.3% (95% CI, 88.0–94.6) and 91.9% (95% CI, 89.7–94.1) for loose and stranded seeds, respectively ( p = 0.871). Exclusion of the first 100 loose and stranded implants also revealed no difference in bNED. Conclusion This study of 1500 patients treated with iodine-125 brachytherapy demonstrates no difference in bNED between loose and stranded seeds, using either Phoenix or PSA >0.4 ng/mL definitions of biochemical failure.

Objective: The purpose of this investigation was to explicate the content of primary treatmentconsultations in prostate oncology and examine the predictive relationships between patient,significant other, and oncologist consultation factors and patient satisfaction with communication.Methods: The recorded consultations of 156 newly diagnosed prostate cancer patients fromthree Canadian cancer centers were examined using the Medical Interaction Process System(MIPS). The MIPS findings, independent observer ratings of patient, significant other, andoncologist affective behavior, and derived consultation ratios of patient centeredness, patientdirectedness, and psychosocial focus, were used to predict patient satisfaction withcommunication post?consultation and at 12?weeks post?consultation.Results: Biomedical content categories were predominant in the consultations, accounting for86% of utterances, followed by administrative (9%) and psychosocial (5%) utterances. Postconsultationsatisfaction with communication was significantly lower for patients whose significantotherswere rated asmore assertive during the consultation, and those rated asmore anxious duringthe consultation. Patientswhowere rated as more anxious during the consultation, those with lowersatisfaction with communication immediately post?consultation and those with shorter consultationswere significantly less satisfied with communication at 12?weeks post?consultation.Conclusions: Adjuvant treatment consultations in prostate oncology are characterized by ahigh degree of information?giving by the physician, a predominance of biomedical discussion,and relatively minimal time addressing patients? psychosocial concerns. Patients may benefitfrom oncologists who address anxiety and emotional distress during the primary treatmentconsultation, allowing sufficient time to ensure that patients leave the consultation with theircommunication needs having been satisfied.

Over the past two decades, the fields of psychosocial oncology and supportive care have seen clinically effective tools as underutilized despite proven benefits to cancer patients and their families. The purpose of this paper is to discuss the reasons for the failure of psychosocial and supportive care interventions in oncology to realize broad clinical implementation and to demonstrate how a knowledge management framework offers several advantages for increasing the probability of successful implementation. This paper is based on a systematic review of the literature pertaining to efforts to implement psychosocial oncology and supportive care interventions. The struggle to develop, implement, and evaluate promising psychosocial oncology and supportive care innovations has moved academic thought toward the development of models and theories concerning the best ways to move new knowledge into clinical practice. There are critical and common barriers to the successful transfer and implementation of promising interventions, and implementation efforts may be maximized by using knowledge management frameworks to systematically identify and address these barriers. The successful implementation of empirically promising interventions requires research networks and practice groups to work together in a concerted, theory-guided effort to identify and address the contextual factors most relevant to any particular intervention. The growing support of knowledge implementation activities by research funders, policy-makers, opinion leaders, and advocates of psychosocial and supportive care interventions is a positive move in this direction.

Purpose To evaluate the response of clinically localized prostate cancer to various durations of planned androgen deprivation therapy (ADT) and to investigate subgroups predicting response. Methods and Materials Data of 3,666 prostate cancer patients treated with either combined ADT and external beam radiotherapy (EBRT) or EBRT alone at four institutions were examined. ADT consisted of neoadjuvant, concurrent, or adjuvant ADT or combinations of these regimens. The primary endpoint was time to biochemical failure (nadir plus 2 ng/ml), assessed from the end of therapy. Factors predictive for the need for ADT were examined with interaction analyses. Results The impact of increasing ADT duration was nonlinear with, on average, 6 months of adjuvant ADT resulting in a reduction of the risk of biochemical failure by 38% (95% confidence interval [CI], 29%–46%), while 12, 24, and 36 months of ADT resulted in a 58% (95% CI, 47%–67%), 66% (95% CI, 55%–75%), and 66% (95% CI, 51%–77%) relative failure reduction, respectively. Patients with higher T stage cancers and those treated with lower radiation doses had a significantly greater benefit for increasing ADT duration (interaction, p = 0.016 and p = 0.007, respectively). Pretreatment prostate-specific antigen values, Gleason score, age, and risk group did not modify the response to ADT. Conclusions The known ADT efficacy derived from randomized studies can be generalized to patients with different features, and individual predictions of potential benefit from ADT use and duration may be calculated to aid patient and physician decision making. Tumor stage and radiation dose variations were related to significantly different ADT duration effects. The validity of these predictive factors requires prospective evaluation.